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Sample records for malignant pancreatic tumors

  1. Pancreatic Candidiasis That Mimics a Malignant Pancreatic Cystic Tumor on Magnetic Resonance Imaging: A Case Report in an Immunocompetent Patient.

    PubMed

    Seong, Minjung; Kang, Tae Wook; Ha, Sang Yun

    2015-01-01

    Candida is a commensal organism that is frequently found in the human gastrointestinal tract. It is the most common organism that causes pancreatic fungal infections. However, magnetic resonance imaging findings of Candida infection in the pancreas have not been described. We report imaging findings of pancreatic candidiasis in a patient in immunocompetent condition. It presented as a multi-septated cystic mass with a peripheral solid component in the background of pancreatitis and restricted diffusion on diffusion-weighted image that mimicked a malignant pancreatic cystic tumor.

  2. Expression of molecular targets for tyrosine kinase receptor antagonists in malignant endocrine pancreatic tumors.

    PubMed

    Fjällskog, Marie-Louise H; Lejonklou, Margareta H; Oberg, Kjell E; Eriksson, Barbro K; Janson, Eva T

    2003-04-01

    Molecular targeting with monoclonal antibodies and tyrosine kinase inhibitors is a novel approach to cancer treatment. We have examined the expression of molecular targets in patients with malignant endocrine pancreatic tumors, which is necessary to justify additional studies investigating the potential benefit from such treatment. Thirty-eight tumor tissues from malignant endocrine pancreatic tumors were examined with immunohistochemistry using specific polyclonal antibodies with regard to the expression pattern of platelet-derived growth factor receptors (PDGFRs) alpha and beta, c-kit, and epidermal growth factor receptor (EGFR). All 38 tissue specimens expressed PDGFRalpha on tumor cells, and 21 of 37 specimens (57%) expressed PDGFRalpha in tumor stroma (1 specimen was nonevaluable). Twenty-eight samples (74%) stained positive for PDGFRbeta on tumor cells, and 36 of 37 samples (97%) stained positive for PDGFRbeta in the stroma (1 specimen was nonevaluable). Thirty-five tumor tissues (92%) stained positive for c-kit, and 21 (55%) stained positive for EGFR on tumor cells. No differences were seen between syndromes or between poorly differentiated or well-differentiated tumors. Previous treatment did not influence expression pattern. Receptor expression pattern varied considerably between individuals. We have found that tyrosine kinase receptors PDGFRs alpha and beta, EGFR, and c-kit are expressed in more than half of the patients with endocrine pancreatic tumors. Because these receptors represent molecular targets for STI571 and ZD1839 (tyrosine kinase inhibitors) and IMC-C225 (a monoclonal antibody), we propose that patients suffering from EPTs might benefit from this new treatment strategy. However, because of great variability in receptor expression pattern, all patients' individual receptor expression should be examined.

  3. MicroRNAs Targeting Oncogenes Are Down-Regulated in Pancreatic Malignant Transformation from Benign Tumors

    PubMed Central

    Jiao, Long R.; Frampton, Adam E.; Jacob, Jimmy; Pellegrino, Loredana; Krell, Jonathan; Giamas, Georgios; Tsim, Nicole; Vlavianos, Panagiotis; Cohen, Patrizia; Ahmad, Raida; Keller, Andreas; Habib, Nagy A.; Stebbing, Justin; Castellano, Leandro

    2012-01-01

    Background MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. Methods Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. Results Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a “seedless” binding site within its 3′UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. Conclusions Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show

  4. Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD.

    PubMed

    Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K; Miyazaki, Hideki; Michael, Iacovos P; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

    2016-02-16

    Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis.

  5. Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD

    PubMed Central

    Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K.; Miyazaki, Hideki; Michael, Iacovos P.; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

    2016-01-01

    Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis. PMID:26831065

  6. Pancreatic neuroendocrine tumors.

    PubMed

    Varas Lorenzo, Modesto; Cugat Andorra, Esteban; Capdevila Castillón, Jaume

    2017-06-01

    Endocrine or pancreatic neuroendocrine tumors (PNET) were first cited in the 1950s; they may be sporadic or associated with hereditary syndromes, benign or malignant, functioning or non-functioning. Nowadays, NF-PNETs are the most frequent and their prevalence ranges from 50% to 91%. In our current series (including 70 cases, 33% malignant, 52 operated) the frequency was 72% as compared to 37% in the historical series.

  7. The tumor-educated-macrophage increase of malignancy of human pancreatic cancer is prevented by zoledronic acid.

    PubMed

    Hiroshima, Yukihiko; Maawy, Ali; Hassanein, Mohamed K; Menen, Rhiana; Momiyama, Masashi; Murakami, Takashi; Miwa, Shinji; Yamamoto, Mako; Uehara, Fuminari; Yano, Shuya; Mori, Ryutaro; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2014-01-01

    We previously defined macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as "tumor-educated-macrophages" (Edu) and macrophages harvested from mice without tumors as "naïve-macrophages" (Naïve), and demonstrated that Edu-macrophages promoted tumor growth and metastasis. In this study, Edu- and Naïve-macrophages were compared for their ability to enhance pancreatic cancer malignancy at the cellular level in vitro and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage-enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent compared to XPA1 cells cultured with Naïve-macrophages (P = 0.014). XPA1 cells exposed to conditioned medium harvested from Edu culture significantly increased proliferation (P = 0.016) and had more migration stimulation capability (P<0.001) compared to cultured cancer cells treated with the conditioned medium from Naïve. The mitotic index of the XPA1 cells, expressing GFP in the nucleus and RFP in the cytoplasm, significantly increased in vivo in the presence of Edu- compared to Naïve-macrophages (P = 0.001). Zoledronic acid (ZA) killed both Edu and Naïve in vitro. Edu promoted tumor growth and metastasis in an orthotopic mouse model of the XPA1 human pancreatic cancer cell line. ZA reduced primary tumor growth (P = 0.006) and prevented metastasis (P = 0.025) promoted by Edu-macrophages. These results indicate that ZA inhibits enhanced primary tumor growth and metastasis of human pancreatic cancer induced by Edu-macrophages.

  8. Diagnosis of pancreatic tumors by endoscopic ultrasonography

    PubMed Central

    Sakamoto, Hiroki; Kitano, Masayuki; Kamata, Ken; El-Masry, Muhammad; Kudo, Masatoshi

    2010-01-01

    Pancreatic tumors are highly diverse, as they can be solid or cystic, and benign or malignant. Since their imaging features overlap considerably, it is often difficult to characterize these tumors. In addition, small pancreatic tumors, especially those less than 2 cm in diameter, are difficult to detect and diagnose. For characterizing pancreatic tumors and detecting small pancreatic tumors, endoscopic ultrasonography (EUS) is the most sensitive of the imaging procedures currently available. This technique also provides good results in terms of the preoperative staging of pancreatic tumors. EUS-guided fine needle aspiration (EUS-FNA) has also proved to be a safe and useful method for tissue sampling of pancreatic tumors. Despite these advantages, however, it is still difficult to differentiate between benign and malignant, solid or cystic pancreatic tumors, malignant neoplasms, and chronic pancreatitis using EUS, even when EUS-FNA is performed. Recently, contrast-enhanced EUS with Doppler mode (CE-EUS) employing ultrasound contrast agents, which indicate vascularization in pancreatic lesions, has been found to be useful in the differential diagnosis of pancreatic tumors, especially small pancreatic tumors. However, Doppler ultrasonography with contrast-enhancement has several limitations, including blooming artifacts, poor spatial resolution, and low sensitivity to slow flow. Consequently, an echoendoscope was developed recently that has a broad-band transducer and an imaging mode that was designed specifically for contrast-enhanced harmonic EUS (CEH-EUS) with a second-generation ultrasound contrast agent. The CEH-EUS technique is expected to improve the differential diagnosis of pancreatic disease in the future. This review describes the EUS appearances of common solid and cystic pancreatic masses, the diagnostic accuracy of EUS-FNA, and the relative efficacies and advantages of CE-EUS and CEH-EUS along with their relative advantages and their complementary roles

  9. Putative tumor suppressor loci at 6q22 and 6q23-q24 are involved in the malignant progression of sporadic endocrine pancreatic tumors.

    PubMed

    Barghorn, A; Speel, E J; Farspour, B; Saremaslani, P; Schmid, S; Perren, A; Roth, J; Heitz, P U; Komminoth, P

    2001-06-01

    Our previous comparative genomic hybridization study on sporadic endocrine pancreatic tumors (EPTs) revealed frequent losses on chromosomes 11q, 3p, and 6q. The aim of this study was to evaluate the importance of 6q losses in the oncogenesis of sporadic EPTs and to narrow down the smallest regions of allelic deletion. A multimodal approach combining polymerase chain reaction-based allelotyping, double-target fluorescence in situ hybridization, and comparative genomic hybridization was used in a collection of 109 sporadic EPTs from 93 patients. Nine polymorphic microsatellite markers (6q13 to 6q25-q27) were investigated, demonstrating a loss of heterozygosity (LOH) in 62.2% of the patients. A LOH was significantly more common in tumors >2 cm in diameter than below this threshold as well as in malignant than in benign tumors. We were able to narrow down the smallest regions of allelic deletion at 6q22.1 (D6S262) and 6q23-q24 (D6S310-UTRN) with LOH-frequencies of 50.0% and 41.2 to 56.3%, respectively. Several promising tumor suppressor candidates are located in these regions. Additional fluorescence in situ hybridization analysis on 46 EPTs using three locus-specific probes (6q21, 6q22, and 6q27) as well as a centromere 6-specific probe revealed complete loss of chromosome 6 especially in metastatic disease. We conclude that the two hot spots found on 6q may harbor putative tumor suppressor genes involved not only in the oncogenesis but maybe also in the malignant and metastatic progression of sporadic EPTs.

  10. [Pancreatic tumors: recent developments].

    PubMed

    Lariño Noia, José

    2014-09-01

    Pancreatic cancer (PC) still typically has a poor prognosis. In addition to smoking, obesity and new-onset diabetes mellitus are considered to be significant risk factors. An endoscopic ultrasound (EUS) remains the mainstay for diagnosis and on which the majority of advances are based. In this sense, needle-based confocal laser endomicroscopy (nCLE) is gaining importance in the differential diagnosis of solid pancreatic lesions and studies comparing different needle types (cytology vs. histology) for EUS-guided puncture. Intravenous contrast (IC-EUS) and elastography are additional tools associated with EUS that can assist in diagnosing PC. Regarding prognostic factors, the importance of the role of mesenteric-portal vein resection was emphasized, given the limited advances in treatment, as in previous years. Regarding cystic tumors, work focuses on validating the new international guidelines from Fukuoka 2012 (revised Sendai criteria) and on determining predictors of cystic lesion malignancy, mainly of intraductal papillary mucinous neoplasm (IPMN). From a therapeutic point of view, there are theories regarding the usefulness of alcohol and the gemcitabine-paclitaxel combination in the ablation of small mucinous cystic lesions through EUS-injection. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  11. Is metastatic pancreatic cancer an untargetable malignancy?

    PubMed Central

    Kourie, Hampig Raphael; Gharios, Joseph; Elkarak, Fadi; Antoun, Joelle; Ghosn, Marwan

    2016-01-01

    Metastatic pancreatic cancer (MPC) is one of the most aggressive malignancies, known to be chemo-resistant and have been recently considered resistant to some targeted therapies (TT). Erlotinib combined to gemcitabine is the only targeted therapy that showed an overall survival benefit in MPC. New targets and therapeutic approaches, based on new-TT, are actually being evaluated in MPC going from immunotherapy, epigenetics, tumor suppressor gene and oncogenes to stromal matrix regulators. We aim in this paper to present the major causes rendering MPC an untargetable malignancy and to focus on the new therapeutic modalities based on TT in MPC. PMID:26989465

  12. Malignant tumors of childhood

    SciTech Connect

    Brooks, B.J.

    1986-01-01

    This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children.

  13. Minimally invasive surgical approach to pancreatic malignancies

    PubMed Central

    Bencini, Lapo; Annecchiarico, Mario; Farsi, Marco; Bartolini, Ilenia; Mirasolo, Vita; Guerra, Francesco; Coratti, Andrea

    2015-01-01

    Pancreatic surgery for malignancy is recognized as challenging for the surgeons and risky for the patients due to consistent perioperative morbidity and mortality. Furthermore, the oncological long-term results are largely disappointing, even for those patients who experience an uneventfully hospital stay. Nevertheless, surgery still remains the cornerstone of a multidisciplinary treatment for pancreatic cancer. In order to maximize the benefits of surgery, the advent of both laparoscopy and robotics has led many surgeons to treat pancreatic cancers with these new methodologies. The reduction of postoperative complications, length of hospital stay and pain, together with a shorter interval between surgery and the beginning of adjuvant chemotherapy, represent the potential advantages over conventional surgery. Lastly, a better cosmetic result, although not crucial in any cancerous patient, could also play a role by improving overall well-being and patient self-perception. The laparoscopic approach to pancreatic surgery is, however, difficult in inexperienced hands and requires a dedicated training in both advanced laparoscopy and pancreatic surgery. The recent large diffusion of the da Vinci® robotic platform seems to facilitate many of the technical maneuvers, such as anastomotic biliary and pancreatic reconstructions, accurate lymphadenectomy, and vascular sutures. The two main pancreatic operations, distal pancreatectomy and pancreaticoduodenectomy, are approachable by a minimally invasive path, but more limited interventions such as enucleation are also feasible. Nevertheless, a word of caution should be taken into account when considering the increasing costs of these newest technologies because the main concerns regarding these are the maintenance of all oncological standards and the lack of long-term follow-up. The purpose of this review is to examine the evidence for the use of minimally invasive surgery in pancreatic cancer (and less aggressive tumors

  14. Pancreatic tumor of mesenchymal origin--an unusual surgical finding.

    PubMed

    Peskova, M; Fried, M

    1994-04-01

    Recently, a patient with an unusual pancreatic tumor of smooth muscle origin, presented at the First Surgical Clinic, Charles University Hospital, Prague. Leiomyosarcoma, a malignant smooth muscle tumor, may arise almost anywhere in the body. Pancreatic localization is very unusual. A number of authors have surveyed the literature on pancreatic tumors of mesenchymal origin. As many as fifty cases have been reported in autopsy studies since 1882. Only six operated cases of pancreatic sarcomas were found in surgical series.

  15. Pancreatic neuroendocrine tumors

    PubMed Central

    Sun, Jian

    2017-01-01

    Summary Pancreatic neuroendocrine neoplasms (pNENs) are a heterogeneous group of tumors including well differentiated pancreatic neuroendocrine tumors (pNETs) and neuroendocrine carcinomas (pNECs). The incidence of pNENs has increased over the past few decades. Although, the understanding and interest for this tumor have also increased significantly, the debate about classification and diagnosis continues. Although the primary treatment for pNENs is surgical resection, there is still a lack of effective therapeutic options for patients with advanced unresectable pNENs. Although many therapeutic methods have proven effective, the choice of treatment and specific programs are still unclear. Our article presents an overview of pNENs, with a focus on their diagnostic work-up, clinical presentation and treatment options. PMID:28357177

  16. Application of a global proteomic approach to archival precursor lesions: deleted in malignant brain tumors 1 and tissue transglutaminase 2 are upregulated in pancreatic cancer precursors.

    PubMed

    Cheung, Wang; Darfler, Marlene M; Alvarez, Hector; Hood, Brian L; Conrads, Thomas P; Habbe, Nils; Krizman, David B; Mollenhauer, Jan; Feldmann, Georg; Maitra, Anirban

    2008-01-01

    Pancreatic cancer is an almost uniformly fatal disease, and early detection is a critical determinant of improved survival. A variety of noninvasive precursor lesions of pancreatic adenocarcinoma have been identified, which provide a unique opportunity for intervention prior to onset of invasive cancer. Biomarker discovery in precursor lesions has been hampered by the ready availability of fresh specimens, and limited yields of proteins suitable for large scale screening. We utilized Liquid Tissue, a novel technique for protein extraction from archival formalin-fixed material, and mass spectrometry to conduct a global proteomic analysis of an intraductal papillary mucinous neoplasm (IPMN). Tissue microarrays comprised of 38 IPMNs were used for validation of candidate proteins. The proteomic analysis of the IPMN Liquid Tissue lysate resulted in identification of 1,534 peptides corresponding to 523 unique proteins. A subset of 25 proteins was identified that had previously been reported as upregulated in pancreatic cancer. Immunohistochemical analysis for two of these, deleted in malignant brain tumors 1 (DMBT1) and tissue transglutaminase 2 (TGM2), confirmed their overexpression in IPMNs. Global proteomics analysis using the Liquid Tissue workflow is a feasible approach for unbiased biomarker discovery in limited archival material, particularly applicable to precursor lesions of cancer. Copyright 2008 S. Karger AG, Basel and IAP.

  17. Application of a Global Proteomic Approach to Archival Precursor Lesions: Deleted in Malignant Brain Tumors 1 and Tissue Transglutaminase 2 Are Upregulated in Pancreatic Cancer Precursors

    PubMed Central

    Cheung, Wang; Darfler, Marlene M.; Alvarez, Hector; Hood, Brian L.; Conrads, Thomas P.; Habbe, Nils; Krizman, David B.; Mollenhauer, Jan; Feldmann, Georg; Maitra, Anirban

    2008-01-01

    Background Pancreatic cancer is an almost uniformly fatal disease, and early detection is a critical determinant of improved survival. A variety of noninvasive precursor lesions of pancreatic adenocarcinoma have been identified, which provide a unique opportunity for intervention prior to onset of invasive cancer. Biomarker discovery in precursor lesions has been hampered by the ready availability of fresh specimens, and limited yields of proteins suitable for large scale screening. Methods We utilized Liquid Tissue®, a novel technique for protein extraction from archival formalin-fixed material, and mass spectrometry to conduct a global proteomic analysis of an intraductal papillary mucinous neoplasm (IPMN). Tissue microarrays comprised of 38 IPMNs were used for validation of candidate proteins. Results The proteomic analysis of the IPMN Liquid Tissue lysate resulted in identification of 1,534 peptides corresponding to 523 unique proteins. A subset of 25 proteins was identified that had previously been reported as upregulated in pancreatic cancer. Immunohistochemical analysis for two of these, deleted in malignant brain tumors 1 (DMBT1) and tissue transglutaminase 2 (TGM2), confirmed their overexpression in IPMNs. Conclusion Global proteomics analysis using the Liquid Tissue workflow is a feasible approach for unbiased biomarker discovery in limited archival material, particularly applicable to precursor lesions of cancer. PMID:18849643

  18. Autoimmune pancreatitis mimicking pancreatic tumor

    PubMed Central

    Dede, Kristóf; Salamon, Ferenc; Taller, András; Teknős, Dániel; Bursics, Attila

    2012-01-01

    Autoimmune pancreatitis (AIP) is a rare disease of unknown pathomechanism. It belongs to the IgG4-related disease family and responds well to steroids, although the relapse rate can reach up to 20–30%. Differentiating AIP from the more common pancreatic cancer can be very challenging. About 20% of AIP is diagnosed postoperatively during final histological examination. Each of the investigative tools can add something to the definitive diagnosis; the question remains whether it is possible to prevent an unnecessary resection. Through our case we would like to demonstrate the differential diagnostic opportunities and present the literary background of this issue. In conclusion, we can state that whenever a focal pancreatic lesion is encountered AIP should always be considered. PMID:24968399

  19. Two synchronous malignant tumors of the pancreas: a case report.

    PubMed

    De Silva, W S L; Pathirana, A A; Prematilleke, I; Rajapakse, S A P D; Hettiarachchi, P S H; Manawasinghe, D S; Dassanayake, B K

    2017-03-28

    Only a limited number of multiple synchronous primary malignancies of the pancreas have been reported in the medical literature. We report a case of two solid malignant tumors of the pancreas diagnosed preoperatively. We describe a 65-year-old Sri Lankan woman who presented with progressive obstructive jaundice. Initial contrast-enhanced computed tomography imaging detected a malignant tumor at the tail of her pancreas. A second tumor of the pancreatic head was detected with integrated imaging using multidetector computed tomography and multimodal magnetic resonance imaging. She underwent total pancreaticoduodenectomy and splenectomy. Gross examination of the specimen confirmed the presence of two separate tumors. Histology of the ampullary tumor showed pancreatic-type adenocarcinoma and the tumor in the tail of her pancreas showed a colloid-type adenocarcinoma. The possibility of multiple primary malignant solid tumors of different types with malignant potential has to be considered even without background pathology when managing multiple tumors in the pancreas.

  20. Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors

    PubMed Central

    Metz, David C.

    2008-01-01

    Pancreatic endocrine tumors (PETs) have long fascinated clinicians and investigators despite their relative rarity. Their clinical presentation varies depending upon whether the tumor is functional or not and also according to the specific hormonal syndrome produced. Tumors may be sporadic or inherited but little is known about their molecular pathology, especially the sporadic forms. Chromogranin A appears to be the most useful serum marker for diagnosis, staging and monitoring. Initially, therapy should be directed at the hormonal syndrome as this has the major initial impact on the patient's health. Most PETs are relatively indolent but ultimately malignant, except for insulinomas which are predominantly benign. Surgery is the only modality that offers the possibility of cure although it is generally noncurative in patients with Zollinger-Ellison syndrome or nonfunctional PETs with MEN1. Preoperative staging of disease extent is necessary to determine the likelihood of complete resection though debulking surgery is often felt to be useful in unresectable patients. Once metastatic, biotherapy is usually the first modality employed because it is generally well tolerated. Systemic or regional therapies are generally reserved until symptoms occur or tumor growth is rapid. Recently a number of newer agents, as well as receptor-directed radiotherapy, are being evalulated for patients with advanced disease. This review addresses a number of recent advances regarding the molecular pathology, diagnosis, localization and management of PETs including discussion of peptide receptor radionuclide therapy and other novel antitumor approaches. We conclude with a discussion of future directions and unsettled problems in the field. PMID:18703061

  1. [Hyperthermia of malignant tumors].

    PubMed

    Terashima, Hiromi

    2004-04-01

    The results of hyperthermia in the malignant tumors were reviewed. It is well known that hyperthermia enhances the effects of radiotherapy and chemotherapy for cancer patients. The clinical study on hyperthermia has been performed in the world since 1975. Several randomized clinical study revealed the benefits of hyperthermia in the head and neck cancers, recurrent breast cancers, and uterine cervical cancers. However, there are many difficulties to perform the hyperthermia in Japan because of lack of man-power and financial aid. Further clinical trials were recommended to obtain the evidences of hyperthermia.

  2. [Pancreatic ascariasis mimicking a pancreatic tumor].

    PubMed

    Casado Maestre, María Dolores; Alamo Martínez, José María; Segura Sampedro, Juan José; Gómez Bravo, Miguel Ángel; Padillo Ruiz, Francisco Javier; Durán Izquierdo, Elena; Gavilán Carrasco, Francisco

    2011-01-01

    Ascaris lumbricoides infection in Spain is anecdotal and is usually associated with travel to areas with high endemicity such as India and South America. Biliopancreatic disease caused by this parasite is both rare and one of the most feared complications. There are few publications in the literature about pancreatic involvement in ascariasis. We describe a case of pancreatic ascariasis diagnosed after a pancreaticoduodenectomy was performed for a suspected pancreatic adenocarcinoma. A 58-year-old man consulted for longstanding abdominal pain and diarrhea. Computed tomography and magnetic resonance scans, endoscopy, and endoscopic ultrasound-guided fine-needle cytology were performed. The pathological diagnosis was moderately differentiated adenocarcinoma of the pancreatic head. Cephalic pancreaticoduodenectomy was performed. The postoperative course was favorable. A pancreatic fistula type B (ISGPF classification) developed and was resolved with conservative treatment. Analysis of the surgical specimen revealed the presence of a pancreatic pseudotumor due to Ascaris lumbricoides. After these findings, treatment was completed with oral albendazole. Pancreatic ascariasis in our environment is unusual, but should be included in the differential diagnosis of tumors and inflammatory processes of the pancreas. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  3. The spectrum of hematologic malignancies involving the pancreas: potential clinical mimics of pancreatic adenocarcinoma.

    PubMed

    Rock, Jonathan; Bloomston, Mark; Lozanski, Gerard; Frankel, Wendy L

    2012-03-01

    Hematologic malignancies often involve the pancreas, causing potential diagnostic pitfalls and, rarely, potentially avoidable surgical resection. We review the spectrum of hematologic malignancies involving the pancreas and describe features useful in preoperative distinction from adenocarcinoma. Archived clinical, pathologic, and radiologic data (1965 to present) for hematologic malignancies involving the pancreas were reviewed and compared with the data for 157 surgically resected pancreatic adenocarcinomas. Of 42 cases, 27 (64%) were clinically "suspicious" for hematologic malignancies. Of the remaining 15 cases, 4 patients underwent resection for presumed pancreatic adenocarcinoma. Isolated pancreatic masses proved most difficult to identify clinically. Significant factors in distinguishing hematologic malignancies from adenocarcinoma included history of hematologic malignancy, young age, large tumor size, low CA19-9 level, B symptoms, and lack of jaundice or diabetes mellitus. Various hematologic malignancies involve the pancreas, most commonly diffuse large B-cell lymphoma. Pancreatic masses are usually correctly identified clinically. Preoperative and operative sampling is strongly recommended when hematologic malignancies cannot be excluded.

  4. Pancreatic islet autotransplantation for nonmalignant and malignant indications.

    PubMed

    Tanhehco, Yvette C; Weisberg, Stuart; Schwartz, Joseph

    2016-03-01

    The standard therapy for patients with chronic pancreatitis (CP) and severe abdominal pain is total pancreatectomy (TP) followed by islet autotransplantation (IAT) to prevent the development of brittle diabetes. In adult patients, narcotic independence is achieved in up to 73% of patients 1 to 5 years after transplantation whereas insulin independence is achieved in up to 40% of patients 1 to 2 years after transplantation. Pediatric patients have shown similar outcomes for narcotic independence (up to 79%) but better outcomes for insulin independence (up to 56% 1 year after transplantation). The quality of life of both adult and pediatric patients improved significantly after TP-IAT using the Medical Outcomes Study SF-36 survey. IAT after pancreatectomy is also performed for patients with benign and malignant disease of the pancreas. The limited studies in this patient population suggest that IAT may be potentially beneficial for carefully selected patients when sufficient numbers of islet cells can be isolated. Further studies involving a larger number of patients are needed to determine the risks and benefits of IAT in patients with malignancy. The feasibility of IAT depends on the availability of a laboratory that can isolate the pancreatic islet cells. An on-site laboratory is the traditional model; however, remote processing of pancreatic islets has been reported to result in successful outcomes. This review discusses the outcomes of adult and pediatric autologous pancreatic islet cell transplantation for CP and pancreatic tumors as well as laboratory processing of pancreatic islet cells. © 2015 AABB.

  5. Radiological description of cystic pancreatic tumors.

    PubMed

    Rodríguez Torres, C; Larrosa López, R

    2016-01-01

    Although most cystic pancreatic lesions are pseudocysts, it is important to do a thorough differential diagnosis with true cystic tumors because cystic tumors are potentially malignant. Sometimes computed tomography and magnetic resonance imaging cannot establish the definitive diagnosis, making it necessary to perform other imaging tests such as endoscopic ultrasound, which in addition to morphological information, can also enable cytologic and biochemical analysis of the lesion through puncture and aspiration of its contents. Combining all these findings nearly always provides enough diagnostic information to allow the appropriate approach in each case. This article describes the specific morphological characteristics for each cystic pancreatic tumor on computed tomography, magnetic resonance imaging, and endoscopic ultrasound and reviews the guidelines for managing these types of lesions.

  6. [Malignant soft tissue tumors].

    PubMed

    Schauer, A; Altmannsberger, M

    1984-01-01

    This article is a survey of actual aspects. With regard to frequency, the malignant fibrous histocytoma comes first, followed by lipo- and fibrosarcoma, synovial sarcoma, malignant schwannoma, malignant tumours proceeding from arteries and veins and the unstriated musculature. Staging and grading of these tumours are difficult. Until now their overall TNM-classification was not possible due to insufficient hard criteria.

  7. Pancreatic tumors imaging: An update.

    PubMed

    Scialpi, Michele; Reginelli, Alfonso; D'Andrea, Alfredo; Gravante, Sabrina; Falcone, Giuseppe; Baccari, Paolo; Manganaro, Lucia; Palumbo, Barbara; Cappabianca, Salvatore

    2016-04-01

    Currently, ultrasound (US), computed tomography (CT) and Magnetic Resonance imaging (MRI) represent the mainstay in the evaluation of pancreatic solid and cystic tumors affecting pancreas in 80-85% and 10-15% of the cases respectively. Integration of US, CT or MR imaging is essential for an accurate assessment of pancreatic parenchyma, ducts and adjacent soft tissues in order to detect and to stage the tumor, to differentiate solid from cystic lesions and to establish an appropriate treatment. The purpose of this review is to provide an overview of pancreatic tumors and the role of imaging in their diagnosis and management. In order to a prompt and accurate diagnosis and appropriate management of pancreatic lesions, it is crucial for radiologists to know the key findings of the most frequent tumors of the pancreas and the current role of imaging modalities. A multimodality approach is often helpful. If multidetector-row CT (MDCT) is the preferred initial imaging modality in patients with clinical suspicion for pancreatic cancer, multiparametric MRI provides essential information for the detection and characterization of a wide variety of pancreatic lesions and can be used as a problem-solving tool at diagnosis and during follow-up. Copyright © 2015. Published by Elsevier Ltd.

  8. Endoscopic approach to the diagnosis of pancreatic cystic tumor

    PubMed Central

    Kawaguchi, Yoshiaki; Mine, Tetsuya

    2016-01-01

    Because of the aging of the population, prevalence of medical checkups, and advances in imaging studies, the number of pancreatic cystic lesions detected has increased. Once these lesions are detected, neoplastic cysts should be differentiated from non-neoplastic cysts. Furthermore, because of the malignant potential of some neoplastic pancreatic cysts, further differentiation between benign and malignant cysts should be made regardless of their size. Although endoscopic ultrasound (EUS) has a very high diagnostic performance for pancreatic cystic lesions among the various imaging modalities, EUS findings alone are insufficient for the differentiation of pancreatic cysts and diagnosis of malignancy. In addition, cytology by EUS-guided fine-needle aspiration (FNA) has a high specificity but a low sensitivity for diagnosing malignancy in pancreatic cystic tumors. The levels of amylase, lipase, and tumor markers in pancreatic cystic fluid are considered auxiliary parameters for diagnosis of benign and malignant cysts, and a definitive diagnosis of malignancy using these parameters is difficult. Thus, in addition to EUS, cytology by EUS-FNA, and cystic fluid analysis, new techniques based on EUS-guided through-the-needle imaging, such as confocal laser endomicroscopy and cystoscopy, have been explored in recent years. PMID:26909130

  9. Pancreatic neuroendocrine tumors: biology, diagnosis, and treatment

    PubMed Central

    Ro, Cynthia; Chai, Wanxing; Yu, Victoria E.; Yu, Run

    2013-01-01

    Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized. PMID:23237225

  10. Malignant tumors

    Cancer.gov

    Main criteria for malignancy include size over 5 mm in diameter, invasion of airways, blood or lymphatic vessels, regional and distant metastasis, and ability to grow upon transplantation. Nuclear and cellular atypia, and loss of architecture should be considered as ancillary criteria for defining malignancy.

  11. Radiotherapy for Pancreatic Neuroendocrine Tumors

    SciTech Connect

    Contessa, Joseph N.; Griffith, Kent A.; Wolff, Elizabeth; Ensminger, William; Zalupski, Mark; Ben-Josef, Edgar

    2009-11-15

    Purpose: Pancreatic neuroendocrine tumors (PNTs) are rare malignant neoplasms considered to be resistant to radiotherapy (RT), although data on efficacy are scarce. We reviewed our institutional experience to further delineate the role of RT for patients with PNTs. Methods and Materials: Between 1986 and 2006, 36 patients with PNTs were treated with RT to 49 sites. Of these 36 patients, 23 had radiographic follow-up data, which were used to determine the tumor response rate and freedom from local progression. Long-term toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Results: The overall response rate to RT was 39% (13% complete response, 26% partial response, 56% stable disease, and 4% progressive disease). A significant difference in the freedom from local progression between the groups receiving either greater than or less than the median 2 Gy/fraction biologically equivalent dose of 49.6 Gy was found, with all radiographic progression occurring in patients who had received <=32 Gy. The actuarial 3-year local freedom from progression rate was 49%. Palliation was achieved in 90% of patients, with either improvement or resolution of symptoms after RT. Of 35 patients, 33 had metastatic disease at their referral for RT, and the median overall survival for this patient population was 2 years. Three long-term Grade 3 or greater toxicities were recorded. Conclusion: RT is an effective modality for achieving local control in patients with PNTs. RT produces high rates of symptomatic palliation and freedom from local progression. Prospective trials of radiotherapy for PNTs are warranted.

  12. Analysis of clinical characteristics and treatment of pancreatic cystic tumors

    PubMed Central

    You, Lei; Xiao, Jianchun; Cao, Zhe; Zhang, Wanying; Liao, Quan; Dai, Menghua; Zhang, Taiping; Zhao, Yupei

    2016-01-01

    Objective To summarize experience in the diagnosis and treatment of pancreatic cystic neoplasms. Methods This is a retrospective study of 207 patients who were diagnosed with pancreatic cystic tumors at Peking Union Medical College Hospital between Jan 2009 and Mar 2014. Clinical data, such as clinical manifestations, radiological and pathological images and surgical recordings, were collected. Results Of the 207 included patients, females accounted for 76.81%, and the mean patient age was 52.04 years. Malignancy was more common in older patients who presented with marasmus and jaundice. Other risk factors included solid components in the tumor, a large tumor size, and elevated levels of tumor markers. Surgical treatment was required when a malignant tumor was suspected. The operation approach was selected based on the location, size and characteristics of the tumor. The position of the tumor relative to the pancreatic duct also played a significant role. Conclusions No specific symptoms were observed for the patients with pancreatic cystic tumors. Imaging played an important role in making a differential diagnosis. Furthermore, surgical treatment should be proposed for patients with significant symptoms and potentially malignant tumors. The tumor resection rate is high, suggestive of good prognosis. PMID:27877011

  13. Malignant renal tumors in children

    PubMed Central

    Sanchez, Thomas Ray; Wootton-Gorges, Sandra

    2015-01-01

    Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. PMID:28326263

  14. Attenuated expression of menin and p27 (Kip1) in an aggressive case of multiple endocrine neoplasia type 1 (MEN1) associated with an atypical prolactinoma and a malignant pancreatic endocrine tumor.

    PubMed

    Ishida, Emi; Yamada, Masanobu; Horiguchi, Kazuhiko; Taguchi, Ryo; Ozawa, Atsushi; Shibusawa, Nobuyuki; Hashimoto, Koshi; Satoh, Tetsuro; Yoshida, Sachiko; Tanaka, Yoshiki; Yokota, Machiko; Tosaka, Masahiko; Hirato, Junko; Yamada, Shozo; Yoshimoto, Yuhei; Mori, Masatomo

    2011-01-01

    Tumors in multiple endocrine neoplasia type 1 (MEN1) are generally benign. Since information on the pathogenesis of MEN1 in malignant cases is limited, we conducted genetic analysis and compared the expression of menin, p27(Kip1)(p27)/CDKN1B and p18(Ink4C)(p18)/CDKN2C with levels in benign cases. We describe the case of a 56 year-old male with an atypical prolactinoma and malignant pancreatic neuroenocrine tumor. At age 50, he had undergone transsphenoidal surgery to remove a prolactinoma. However, the tumor relapsed twice. Histological analysis of the recurrent prolactinoma revealed the presence of prolactin, a high MIB-1 index (32.1 %), p53-positive cells (0.2%), and an unusual association with FSH-positive cells. A few years later, he was also found to have a non-functioning pancreatic tumor with probable metastasis to the extradullar region. The metastatic region tested positive for chromogranin and CD56, and negative for prolactin, with 1.2 % of cells p53-positive. Although genetic analyses of the MEN1, p27, and p18 genes demonstrated no mutation, numbers of menin, p27 and p18 immuno-positive cells were significantly down-regulated in the recurrent prolactinoma, but that of p18 was intact in the metastatic region. Furthermore, MEN1 and p27 mRNA levels of the recurrent prolactinoma were down-regulated, particularly the MEN1 mRNA level, compared to levels in 10 cases of benign prolactinoma, while the p18 mRNA level was similar to that of normal pituitary. The tumor in this case may be a subtype of MEN1 showing more aggressive and malignant features probably induced by low levels of menin and p27.

  15. Pancreatic islet cell tumor

    MedlinePlus

    ... functions. These include blood sugar level and the production of stomach acid. Tumors that arise from islet ... try and shrink the tumors. If the abnormal production of hormones is causing symptoms, you may receive ...

  16. Imaging probe for tumor malignancy

    NASA Astrophysics Data System (ADS)

    Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Hasahiro

    2009-02-01

    Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia"). Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers. Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo, we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1α). It can therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection. These results suggest that POHA can be used an imaging probe for tumor malignancy.

  17. Heterotopic Pancreatic Pseudocyst Radiologically Mimicking Gastrointestinal Stromal Tumor

    PubMed Central

    Sarsenov, Dauren; Tırnaksız, Mehmet Bülent; Doğrul, Ahmet Bülent; Tanas, Özlem; Gedikoglu, Gökhan; Abbasoğlu, Osman

    2015-01-01

    Heterotopic pancreas is a relatively common variant of foregut embryologic dystopia that can be described as pancreatic tissue found outside the normal anatomic location, being independent from vascular supply of normal pancreas. Having all features of pancreatic tissue except for the major duct structures, this ectopic tissue may be clinically recognized when pathologic changes take place. Inflammation, hemorrhagic or obstructive states, and eventually malignancy-related problems may become a diagnostic challenge for clinician and finally lead to consequences of misdiagnosis. In this article we will discuss a case of heterotopic pancreatic tissue located in gastric cardia, which was diagnosed preoperatively as gastrointestinal stromal tumor. PMID:25785332

  18. Circulating Tumor Cells and Circulating Tumor DNA Provide New Insights into Pancreatic Cancer

    PubMed Central

    Gao, Yang; Zhu, Yayun; Yuan, Zhou

    2016-01-01

    Pancreatic cancer has a rather dismal prognosis mainly due to high malignance of tumor biology. Up to now, the relevant researches on pancreatic cancer lag behind seriously partly due to the obstacles for tissue biopsy, which handicaps the understanding of molecular and genetic features of pancreatic cancer. In the last two decades, liquid biopsy, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), is promising to provide new insights into the biological and clinical characteristics of malignant tumors. Both CTCs and ctDNA provide an opportunity for studying tumor heterogeneity, drug resistance, and metastatic mechanism for pancreatic cancer. Furthermore, they can also play important roles in detecting early-stage tumors, providing prognostic information, monitoring tumor progression and guiding treatment regimens. In this review, we will introduce the latest findings on biological features and clinical applications of both CTCs and ctDNA in pancreatic cancer. In a word, CTCs and ctDNA are promising to promote precision medicine in pancreatic cancer. PMID:27994495

  19. Pancreatic endocrine tumors.

    PubMed

    Asa, Sylvia L

    2011-04-01

    The endocrine cells of the pancreas and their related cells throughout the gastrointestinal tract give rise to a variety of tumors that pose a diagnostic challenge. There has been progress in understanding their histogenesis, morphology, immunohistochemistry, molecular biology and classifications. This review will focus on nomenclature/terminology, classification, the role of immunohistochemistry, molecular advances, including genetic predisposition, and potential therapeutic targets to define the role of pathology in the application of prognostic and predictive markers for this disease.

  20. The Potential for Circulating Tumor Cells in Pancreatic Cancer Management

    PubMed Central

    Pimienta, Michael; Edderkaoui, Mouad; Wang, Ruoxiang; Pandol, Stephen

    2017-01-01

    Pancreatic cancer is one the most lethal malignancies. Only a small proportion of patients with this disease benefit from surgery. Chemotherapy provides only a transient benefit. Though much effort has gone into finding new ways for early diagnosis and treatment, average patient survival has only been improved in the order of months. Circulating tumor cells (CTCs) are shed from primary tumors, including pre-malignant phases. These cells possess information about the genomic characteristics of their tumor source in situ, and their detection and characterization holds potential in early cancer diagnosis, prognosis, and treatment. Liquid Biopsies present an alternative to tumor biopsy that are hard to sample. Below we summarize current methods of CTC detection, the current literature on CTCs in pancreatic cancer, and future perspectives. PMID:28626429

  1. Isolated Pancreatic Metastasis from Malignant Melanoma: Is Pancreatectomy Worthwile?

    PubMed Central

    Birnbaum, David Jérémie; Moutardier, Vincent; Turrini, Olivier; Gonçalves, Anthony; Delpero, Jean Robert

    2013-01-01

    Isolated pancreatic metastasis from malignant melanoma (IPMMM) is rare because most melanoma patients already have a widespread disease at diagnosis. No adjuvant systemic treatment is known to be efficient in this setting. Experience with pancreatic resection for IPMMM is limited and controversial. We report here the case of an IPMMM patient successfully treated by pancreaticoduodenectomy with a prolonged survival of 6 years. PMID:24741425

  2. Malignant Peripheral Nerve Sheath Tumors.

    PubMed

    Durbin, Adam D; Ki, Dong Hyuk; He, Shuning; Look, A Thomas

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are tumors derived from Schwann cells or Schwann cell precursors. Although rare overall, the incidence of MPNST has increased with improved clinical management of patients with the neurofibromatosis type 1 (NF1) tumor predisposition syndrome. Unfortunately, current treatment modalities for MPNST are limited, with no targeted therapies available and poor efficacy of conventional radiation and chemotherapeutic regimens. Many murine and zebrafish models of MPNST have been developed, which have helped to elucidate the genes and pathways that are dysregulated in MPNST tumorigenesis, including the p53, and the RB1, PI3K-Akt-mTOR, RAS-ERK and Wnt signaling pathways. Preclinical results have suggested that new therapies, including mTOR and ERK inhibitors, may synergize with conventional chemotherapy in human tumors. The discovery of new genome editing technologies, like CRISPR-cas9, and their successful application to the zebrafish model will enable rapid progress in the faithful modeling of MPNST molecular pathogenesis. The zebrafish model is especially suited for high throughput screening of new targeted therapeutics as well as drugs approved for other purposes, which may help to bring enhanced treatment modalities into human clinical trials for this devastating disease.

  3. Head mass in chronic pancreatitis: Inflammatory or malignant

    PubMed Central

    Dutta, Amit K; Chacko, Ashok

    2015-01-01

    Chronic pancreatitis increases the risk of developing pancreatic cancer. This often presents as a mass lesion in the head of pancreas. Mass lesion in the head of pancreas can also occur secondary to an inflammatory lesion. Recognising this is crucial to avoid unnecessary surgery. This is sometimes difficult as there is an overlap in clinical presentation and conventional computed tomography (CT) abdomen findings in inflammatory and malignant mass. Advances in imaging technologies like endoscopic ultrasound in conjunction with techniques like fine needle aspiration, contrast enhancement and elastography as well as multidetector row CT, magnetic resonance imaging and positron emission tomography scanning have been shown to help in distinguishing inflammatory and malignant mass. Research is ongoing to develop molecular techniques to help characterise focal pancreatic mass lesions. This paper reviews the current status of imaging and molecular techniques in differentiating a benign mass lesion in chronic pancreatitis and from malignancy. PMID:25789097

  4. Systemic Therapies for Advanced Pancreatic Neuroendocrine Tumors

    PubMed Central

    Raj, Nitya; Reidy-Lagunes, Diane

    2016-01-01

    SYNOPSIS Pancreatic neuroendocrine tumors are a rare tumor type, and comprise 1-2% of all pancreatic neoplasms. When nonfunctional (i.e. nonhormone secreting), these tumors generally cause few symptoms and often go unnoticed for several years; for this reason, they are rarely localized at presentation, and are typically diagnosed in the presence of metastatic disease, most commonly to the liver. Although pancreatic neuroendocrine tumors can be less aggressive than other tumor types, the management poses a significant challenge because of the heterogeneous clinical presentations and varying degrees of aggressiveness. The therapy of pancreatic neuroendocrine tumors includes a multimodality approach and can often include surgery, liver-directed therapies (i.e. embolization), as well as targeted and cytotoxic systemic treatments. A variety of systemic therapies have been developed for the management of pancreatic neuroendocrine tumors. These therapies include somatostatin analogs (octreotide or lanreotide), a select group of cytotoxic chemotherapy agents (alkylating, fluorouracil and platinum drugs), as well as targeted or biologic agents (everolimus and sunitinib). This chapter will review the available systemic therapy options for advanced pancreatic neuroendocrine tumors. PMID:26614372

  5. Stereotaxic interstitial irradiation of malignant brain tumors

    SciTech Connect

    Gutin, P.H.; Leibel, S.A.

    1985-11-01

    The authors discuss the feasibility of treatment of malignant tumors with brachytherapy. The history of brain tumor brachytherapy, its present day use, and future directions are detailed. 24 references.

  6. Intrasellar malignant peripheral nerve sheath tumor (MPNST).

    PubMed

    Krayenbühl, N; Heppner, F; Yonekawa, Y; Bernays, R L

    2007-02-01

    Intracranial malignant peripheral nerve sheath tumors (MPNST) and intrasellar schwannomas are rare tumors. We describe a case of an intrasellar schwannoma with progression to a MPNST, a finding that, although very rare, extends the differential diagnosis of intrasellar lesions.

  7. Metastatic malignant phyllodes tumor involving the cerebellum.

    PubMed

    Rowe, J Jordi; Prayson, Richard A

    2015-01-01

    Brain metastases from malignant phyllodes tumors of the breast are a rare occurrence. We report a patient with a malignant phyllodes tumor of the right breast which subsequently metastasized to the right lower lobe of the lung 1 year after initial presentation, and to the right cerebellar hemisphere 2 years after diagnosis of her breast mass. After both chemotherapy and whole brain radiotherapy the patient is tumor free at most recent follow-up, 116 months after the breast tumor diagnosis was made. The literature is briefly reviewed and the differential diagnosis of malignant spindle cell brain tumors is discussed.

  8. [Management of malignant vulvar tumors].

    PubMed

    Mahjoub, S; Ben Brahim, F; Ben Hmid, R; Zghal, D; Kallel, N; Sébai, N; Zouari, Faouzia

    2008-12-01

    Vulva anatomy--FIGO classification--Vulva tumors anatomopathology--Tretments of vulva cancers. Our stady is a retrospective, longitudinal and continuous one. It concerns 11 malignant vulva tumors whith were treated in the département "C" of the centre of maternity of Tunis. The period of stady is fifty four months (2002-2006). The aim of our study is to analyse the charactéristics of the vulva cancer and to compare our results to littérature. Mean age of our patients is 67 years old. They are all menaused. The principal signs are vulva tuméfaction in 72.7% of the cases, vulva prurit in 27.3% of the cases and genital bleeding in 27.3% of the cases. The mean period of consultation is of 14 months. We have ten cases of vulvar epidermoid carcinoma and one melanoma. The treatment was surgical in the eleven cases (10 total vulvectomy and one hemivulvectomy) They all benefited of an inguinal bilateral curage. The adjuvant radiotérapie was indicated in 3 cases. A patient was classed stage Ib of FIGO, 7 stage II, one stage III and one stage IVa. Nine patients are in remission, 3 are dead: 2 because of their cancer and one due to a pulmonar embolism. The survival of 6 month is 72.2%. The prevention of this cancer passes by the close follow of dystrophic states and viral pathologies of the vulva.

  9. Utility of preoperative dynamic magnetic resonance imaging of the pancreas in diagnosing tumor-forming pancreatitis that mimics pancreatic cancer: report of a case.

    PubMed

    Kuroki, Tamotsu; Tajima, Yoshitsugu; Tsuneoka, Noritsugu; Adachi, Tomohiko; Kanematsu, Takashi

    2010-01-01

    The differential diagnosis of pancreatic carcinoma and tumor-forming pancreatitis remains difficult, and this situation can cause serious problems because the management and prognosis of these two focal pancreatic masses are entirely different. We herein report a case of tumor-forming pancreatitis that mimics pancreatic carcinoma in an 80-year-old woman. Computed tomography showed a solid mass in the head of the pancreas, and endoscopic retrograde cholangiopancreatography showed a complete obstruction of the main pancreatic duct in the head of the pancreas. Dynamic contrastenhanced magnetic resonance imaging (MRI) demonstrated a time-signal intensity curve (TIC) with a slow rise to a peak (1 min after the administration of the contrast material), followed by a slow decline at the pancreatic mass, indicating a fibrotic pancreas. Under the diagnosis of tumor-forming pancreatitis, the patient underwent a segmental pancreatectomy instead of a pancreaticoduodenectomy. The histopathology of the pancreatic mass was chronic pancreatitis without malignancy. The pancreatic TIC obtained from dynamiccontrast MRI can be helpful to differentiate tumor-forming pancreatitis from pancreatic carcinoma and to avoid any unnecessary major pancreatic surgery.

  10. Vascular invasion does not discriminate between pancreatic tuberculosis and pancreatic malignancy: a case series.

    PubMed

    Rana, Surinder S; Sharma, Vishal; Sampath, Sathosh; Sharma, Ravi; Mittal, Bhagwant R; Bhasin, Deepak K

    2014-01-01

    Pancreatic tuberculosis is very rare and most commonly involves the head and uncinate process of the pancreas. It closely mimics pancreatic malignancy and is often diagnosed after pancreatico-duodenectomy. Vascular invasion is believed to be a hallmark of malignant lesions and described as a point of differentiating benign lesions from malignant lesions. We herein retrospectively evaluated the patients with pancreatic tuberculosis seen at our unit over the last 4 years for features of vascular invasion. We retrospectively analyzed the collected database of all patients diagnosed with pancreatic tuberculosis at our unit over the last four years and identified patients who had evidence of local vascular invasion and their clinical and imaging findings were retrieved. Over the last four years, 16 patients (12 males) with pancreatic tuberculosis were seen and five of these 16 patients had imaging features of vascular invasion by the pancreatic head mass. Of these five patients, four were males and the mean age was 32.0±5.47 years. Of these five patients, three had involvement of portal vein and superior mesenteric vein and two had involvement of hepatic artery. Presence of vascular invasion does not distinguish pancreatic tuberculosis and malignancy, and, therefore, cytopathological confirmation is mandatory to differentiate between the two.

  11. Malignant phyllodes tumor of the prostate.

    PubMed

    Kim, H S; Lee, J H; Nam, J H; Lee, M C; Park, C S; Juhng, S W; Ro, J Y; Choi, C

    1999-12-01

    Phyllodes tumor of the prostate is rare. We have recently experienced a case of phyllodes tumor of the prostate in a 57-year-old man who complained of urinary retention for 1 year. The epithelial components were positive reactivity for prostate specific antigen. The stromal cells showed nuclear atypia with increased mitotic activity. The tumor was diagnosed as a malignant phyllodes tumor as it invaded into the urinary bladder and rectum, and grew rapidly immediately after operation. We describe the morphological features and immunohistochemical findings of malignant phyllodes tumor and review the literature.

  12. Update on Malignant Sweat Gland Tumors.

    PubMed

    van der Horst, Michiel P J; Brenn, Thomas

    2017-06-01

    Malignant sweat gland tumors are rare cutaneous neoplasms, traditionally separated according to their behavior into low- and high-grade malignant. There is significant morphologic overlap, and outright malignant tumors may show relatively bland histologic features. They may, therefore, be mistaken easily for benign neoplasms. Recognition of these tumors and accurate diagnosis is important for early treatment to prevent aggressive behavior and adverse outcome. This article provides an overview of 4 important entities with emphasis on diagnostic pitfalls, differential diagnosis and recent developments. Microcystic adnexal carcinoma, squamoid eccrine ductal carcinoma, aggressive digital papillary adenocarcinoma, and spiradenocarcinoma are discussed in detail. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Malignant tumors in an ancient Egyptian population.

    PubMed

    Zink, A; Rohrbach, H; Szeimies, U; Hagedorn, H G; Haas, C J; Weyss, C; Bachmeier, B; Nerlich, A G

    1999-01-01

    Since it is still an open debate whether malignant tumors are mainly influenced by environmental factors, the frequency of such malignant tumors in historic populations with different living conditions is of particular interest. In the present study, we investigated the occurrence of malignant tumors affecting bone tissue in a population of mumrnies and skeletons, which had been excavated from the large necropolis of Thebes-West, Upper Egypt. Our study material comprised a series of at least 415 individuals (thereof 325 adults) dating from approx. 1500-500 B.C. All individuals had been mummified, but were severely damaged and partially broken by grave robbers, so that often only parts of the mummies/skeletons were available for investigation. The available specimens were subjected to careful macroscopic examination, while isolated findings were radiologically analyzed. Using this approach, we identified at least 4 cases showing malignant tumors affecting the skeleton. In two cases, multiple mixed osteolytic-osteoblastic lesions suggested multiple metastases from carcinomas. Two further individuals presented with multiple osteolyses (vertebra, pelvis, skull) most suggestive of multiple myeloma. The observation of at least 4 cases of malignant tumors with osseous manifestation in a series of 325 adult individuals provides clear evidence that malignant tumors were not a rare event in the ancient Egyptian study population, particularly when the limitations of a study of tumors manifested only in osseous remnants are taken into consideration. A calculation of the age- and sex-adjusted tumor frequency in our material in comparison with a recent model for such a material by Waldron (1996) indicates that the rate of malignant tumors with bone affection in our series is higher than in an English population from 1901-1905, although lower than in a comparable present day population. This clearly indicates that important factors affecting malignant tumors were effective even

  14. Capecitabine, Temozolomide and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2016-09-21

    Gastrinoma; Glucagonoma; Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Islet Cell Carcinoma; Recurrent Pancreatic Cancer; Somatostatinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  15. Malignant solitary fibrous tumor in retroperitoneum

    PubMed Central

    Zhou, Yihong; Chu, Xi; Yi, Ye; Tong, Liang; Dai, Yingbo

    2017-01-01

    Abstract Rationale: Solitary fibrous tumor (SFT) is a rare mesenchymal tumor occurs in various sites. Malignant SFT in retroperitoneum is extremely rare. Patient concerns: We report a case of malignant retroperitoneal SFT in a 59-year-old man presented with right flank pain for 1 month. Diagnoses, interventions and outcomes: A laparotomy and resection of the tumor were performed, the histopathologic and immunohistochemical findings were consistent with malignant retroperitoneal SFT. No adjuvant treatment was performed, and the patient had no signs of recurrence or metastasis at the 12 months follow-up. Lessons: Complete surgical excision is the basic treatment principle for malignant retroperitoneal SFT. The histologic features and the Ki-67 label index are helpful for the diagnosis of malignant SFT. PMID:28296778

  16. EUS-Guided Antitumor Therapy for Pancreatic Tumors.

    PubMed

    Seo, Dong Wan

    2010-09-01

    Endoscopic ultrasound (EUS) is a very useful modality for the diagnosis and staging of pancreatic masses. With the advent of EUS-guided fine-needle aspiration technology, this modality has made a tremendous leap from imaging modality to histologic diagnosis and therapeutic intervention. EUS offers high-resolution images of and unparalleled access to the pancreas. After locating the tip of the echoendoscope in the duodenum or stomach, several drugs or local treatment modalities can be delivered directly into the pancreas. EUS-guided ethanol lavage with/without paclitaxel injection has been tested for the treatment of cystic tumors of the pancreas, with complete resolution of cystic tumor being observed in up to 70-80% of patients. Ethanol injection is also performed for the management of solid neuroendocrine tumors of the pancreas. Various type of EUS-guided injection have also been investigated for the treatment of pancreatic cancer. An activated allogenic mixed lymphocyte culture (Cytoimplant) was injected in patients with advanced pancreatic cancer. A replication-deficient adenovirus vector carrying the tumor necrosis factor-alpha gene was also delivered intratumorally by EUS. ONYX-015 is an oncolytic attenuated adenovirus that exhibits replication preferentially in malignant cells, causing cell death, and this has also been injected into pancreatic cancers under EUS guidance. EUS-guided local ablation therapies such as radiofrequency ablation, photodynamic therapy, and brachytherapy are also under investigation. EUS-guided fine-needle injection for various solid or cystic lesions is a rapidly expanding field. This article reviews the various applications of EUS for the treatment of pancreatic tumors.

  17. EUS-Guided Antitumor Therapy for Pancreatic Tumors

    PubMed Central

    2010-01-01

    Endoscopic ultrasound (EUS) is a very useful modality for the diagnosis and staging of pancreatic masses. With the advent of EUS-guided fine-needle aspiration technology, this modality has made a tremendous leap from imaging modality to histologic diagnosis and therapeutic intervention. EUS offers high-resolution images of and unparalleled access to the pancreas. After locating the tip of the echoendoscope in the duodenum or stomach, several drugs or local treatment modalities can be delivered directly into the pancreas. EUS-guided ethanol lavage with/without paclitaxel injection has been tested for the treatment of cystic tumors of the pancreas, with complete resolution of cystic tumor being observed in up to 70-80% of patients. Ethanol injection is also performed for the management of solid neuroendocrine tumors of the pancreas. Various type of EUS-guided injection have also been investigated for the treatment of pancreatic cancer. An activated allogenic mixed lymphocyte culture (Cytoimplant) was injected in patients with advanced pancreatic cancer. A replication-deficient adenovirus vector carrying the tumor necrosis factor-alpha gene was also delivered intratumorally by EUS. ONYX-015 is an oncolytic attenuated adenovirus that exhibits replication preferentially in malignant cells, causing cell death, and this has also been injected into pancreatic cancers under EUS guidance. EUS-guided local ablation therapies such as radiofrequency ablation, photodynamic therapy, and brachytherapy are also under investigation. EUS-guided fine-needle injection for various solid or cystic lesions is a rapidly expanding field. This article reviews the various applications of EUS for the treatment of pancreatic tumors. PMID:21103299

  18. Tumor antigens as related to pancreatic cancer.

    PubMed

    Chu, T M; Holyoke, E D; Douglass, H O

    1980-01-01

    Data are presented suggesting the presence of pancreas tumor-associated antigens. Slow progress has been made during the past few years in the identification of pancreatic tumor antigens that may be of clinical usefulness and it seems unlikely that many of the practical problems now being faced in identification and isolation of these antigens and in development of a specific, sensitive assay will be solved by conventional immunochemical approaches. The study of antigen and/or antibody purified from immune complexes in the host and the application of leukocyte adherence inhibition techniques to immunodiagnosis of pancreatic cancer are among the new approaches that may provide effective alternatives in the study of pancreatic tumor antigens.

  19. Pancreatic endocrine neoplasms: Epidemiology and prognosis of pancreatic endocrine tumors

    PubMed Central

    Halfdanarson, Thorvardur R.; Rubin, Joseph; Farnell, Michael B.; Grant, Clive S.; Petersen, Gloria M.

    2009-01-01

    Pancreatic endocrine neoplasms (PETs) are uncommon tumors with an annual incidence less than 1 per 100,000 persons per year in the general population. PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are nonfunctional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis and established and novel prognostic markers of PETs are reviewed. PMID:18508996

  20. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1.

    PubMed

    Machado, Marcel Cerqueira Cesar

    2012-01-01

    Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and localization of

  1. Overexpression of CD90 (Thy-1) in pancreatic adenocarcinoma present in the tumor microenvironment.

    PubMed

    Zhu, Jianhui; Thakolwiboon, Smathorn; Liu, Xinhua; Zhang, Min; Lubman, David M

    2014-01-01

    CD90 (Thy-1) plays important roles in oncogenesis and shows potential as a candidate marker for cancer stem cells (CSCs) in various malignancies. Herein, we investigated the expression of CD90 in pancreatic adenocarcinoma (PDAC), with a comparison to normal pancreas and non-malignant pancreatic disease, by immunohistochemical (IHC) analysis of tissue microarrays containing 183 clinical tissue specimens. Statistical analysis was performed to evaluate the correlation between CD90 expression and the major clinicopathological factors after adjustment of age and gender. The IHC data showed that CD90 was significantly overexpressed in PDAC and its metastatic cancers as compared to chronic pancreatitis and benign islet tumors, while it was negative in normal pancreas and 82.7% of adjacent normal pancreas tissues. The abundant CD90 expression was predominantly present in PDAC stroma, such as fibroblasts and vascular endothelial cells, which could serve as a promising marker to distinguish pancreatic adenocarcinoma from normal pancreas and non-malignant pancreatic diseases. Double immunostaining of CD90 with CD24, a CSC marker for PDAC, showed that there was little overlap between these two markers. However, CD90+ fibroblast cells were clustered around CD24+ malignant ducts, suggesting that CD90 may be involved in the tumor-stroma interactions and promote pancreatic cancer development. Furthermore, CD90 mostly overlapped with α-smooth muscle actin (αSMA, a marker of activated pancreatic stellate cells (PSCs)) in PDAC stroma, which demonstrated that CD90+ stromal cells consist largely of activated PSCs. Double immunostaining of CD90 and a vascular endothelial cell marker CD31 demonstrated that CD90 expression on vascular endothelial cells was significantly increased in PDACs as compared to normal pancreas and non-malignant pancreatic diseases. Our findings suggest that CD90 could serve as a promising marker for pancreatic adenocarcinoma where desmoplastic stroma plays an

  2. Genetics of Bladder Malignant Tumors in Childhood

    PubMed Central

    Zangari, Andrea; Zaini, Johan; Gulìa, Caterina

    2016-01-01

    Bladder masses are represented by either benign or malignant entities. Malignant bladder tumors are frequent causes of disease and death in western countries. However, in children they are less common. Additionally, different features are found in childhood, in which non epithelial tumors are more common than epithelial ones. Rhabdomyosarcoma is the most common pediatric bladder tumor, but many other types of lesions may be found, such as malignant rhabdoid tumor (MRT), inflammatory myofibroblastic tumor and neuroblastoma. Other rarer tumors described in literature include urothelial carcinoma and other epithelial neoplasms. Rhabdomyosarcoma is associated to a variety of genetic syndromes and many genes are involved in tumor development. PAX3-FKHR and PAX7-FKHR (P-F) fusion state has important implications in the pathogenesis and biology of RMS, and different genes alterations are involved in the pathogenesis of P-F negative and embryonal RMS, which are the subsets of tumors most frequently affecting the bladder. These genes include p53, MEF2, MYOG, Ptch1, Gli1, Gli3, Myf5, MyoD1, NF1, NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, IGF1R, PDGFRA, ERBB2/4, MET, BCOR. Malignant rhabdoid tumor (MRT) usually shows SMARCB1/INI1 alterations. Anaplastic lymphoma kinase (ALK) gene translocations are the most frequently associated alterations in inflammatory myofibroblastic tumor (IMT). Few genes alterations in urothelial neoplasms have been reported in the paediatric population, which are mainly related to deletion of p16/lnk4, overexpression of CK20 and overexpression of p53. Here, we reviewed available literature to identify genes associated to bladder malignancies in children and discussed their possible relationships with these tumors. PMID:27013922

  3. [Diabetes in patients with malignant tumors].

    PubMed

    Lengyel, Zoltán; Boér, Katalin; Halászlaki, Csaba; Németh, Zsuzsanna

    2013-09-01

    Disturbances of the carbohydrate metabolism are fairly common is patients with malignancy. On the other hand, diabetes appears to have an effect on the development and progression of various tumors. Malignant diseases and the therapies used in their treatment often have an impact on carbohydrate metabolism, while diabetes may hinder specific oncotherapy or influence oncological therapeutic decisions. Several complications of malignant diseases and some of the medications used in their treatment, such as steroids or parenteral nutrition, may raise blood glucose levels. The various obstacles of oral nutrition frequently seen in patients with malignancy can lead to hypoglycaemia in patients with diabetes. Our article endeavours to review the pathophysiological and clinical connection between diabetes and malignant diseases and the use of insulin, oral antidiabetic drugs and diet in patients with malignant disease.

  4. Cerebral malignant nerve sheath tumor, triton tumor variant: case report.

    PubMed

    Bornstein-Quevedo, Leticia; Peralta-Olvera, Fabiola; Marhx-Bracho, Alfonso; Rodríguez-Jurado, Rodolfo; De Leon-Bojorge, Beatriz

    2003-01-01

    A case of a cerebral malignant triton tumor in a 3-year-old boy with a 2-month history of frontal headache and no clinical evidence of neurofibromatosis is reported. The computed tomography (CT) scan showed a large, irregular tumor in the right parietooccipital lobe. A partial surgical resection was performed. Histologically, the tumor was highly cellular and consisted of spindle cells with hyperchromatic and pleomorphic nuclei. Focally, neoplastic cells with rhabdomyoblastic features were found. The immunohistochemical study showed that tumor cells were positive for S-100 protein and CD57, and the rhabdomyoblasts expressed desmin, Myo-D1, and myoglobin. During the postoperative period, a massive intraparenchymal hemorrhage was identified and surgical drainage was performed. The patient worsened and died 10 days after the first surgery. Postmortem study was not authorized. Six cases of cerebral malignant nerve sheath tumor have been described; however, primary intraparenchymal malignant triton tumor has not been previously described.

  5. The Yolk Sac Feeds Pancreatic Tumors.

    PubMed

    Pollard, Jeffrey W

    2017-08-15

    In this issue of Immunity, Zhu et al. (2017) report that tumor-associated macrophages in a mouse model of pancreatic ductal adenocarcinoma (PDAC) originate from both the yolk sac (YS) and bone marrow. Differential ablation of these populations indicates that only the YS-derived macrophages promote PDAC progression and growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Prostate-Specific Membrane Antigen (PSMA) Avid Pancreatic Neuroendocrine Tumor.

    PubMed

    Vamadevan, Shankar; Shetty, Deepa; Le, Ken; Bui, Chuong; Mansberg, Robert; Loh, Han

    2016-10-01

    Ga-PSMA PET/CT is increasingly used to evaluate recurrent prostatic malignancy due to its high specificity. A 75-year-old man with a previous history of treated prostate cancer 3 years earlier presented with rising prostate-specific antigen (PSA) level and underwent Ga-PSMA PET/CT which demonstrated a PSMA-avid focus in the neck of the pancreas. Triple-phase abdominal CT demonstrated enhancement in the arterial phase and to a lesser extent the venous phase of a soft tissue mass in the neck of the pancreas. Cytological and histopathological examination of the soft tissue mass confirmed a low-grade pancreatic neuroendocrine tumor.

  7. [DIAGNOSIS OF VASCULAR INVASION BY PANCREATIC TUMORS].

    PubMed

    Dronov, O I; Zemskov, S V; Bakunets, P P

    2016-02-01

    Basing on analysis of own material (84 patients) and data of literature there was established, that vascular invasion by pancreatic tumors constitutes the main obstacle for conduction of the patients' radical treatment. Early diagnosis permits radical resectability of the patients, what constitutes the only one effective method of treatment. In vascular invasion by tumor a surgeon experience and professional preparation determines possibility of the extended operation performance with intervention on affected main vessel, enhancing the treatment radicalism.

  8. Malignant tumors of Stensen's duct.

    PubMed

    Steiner, M; Gould, A R; Miller, R L; Johnson, J A

    1999-01-01

    A rare case of squamous cell carcinoma arising in Stensen's duct is reported. The literature concerning malignant neoplasia originating in this site is reviewed, with attention given to the histopathologic diversity of neoplasms occurring in the duct, criteria for determination of origin in the duct, and outcomes of therapy.

  9. Criteria for malignancy in gastrointestinal endocrine tumors.

    PubMed

    Bordi, Cesare; D'Adda, Tiziana; Azzoni, Cinzia; Pizzi, Silvia; Bottarelli, Lorena; Mormandi, Francesca; Antonetti, Tommaso; Luong, Tu Vinh; Rindi, Guido

    2006-01-01

    In contrast with the large amount of data generated from endocrine tumors of the pancreas, sparse and mostly unconfirmed data are available on the criteria for the assessment of malignancy risk and patient outcome in endocrine tumors of the gastrointestinal tract. In these conditions the 2000 WHO classification with its standardized scheme of pathologic report constitutes a framework facilitating the assessment of tumor malignancy and has been regarded as useful for clinical purposes, providing the basis for proper management of the patients and for the design of treatment protocols. The classification is based on a combination of pathological and clinical features with parameters specific for each organ in which the endocrine tumors originate. Three main categories, one further subdivided into two subgroups, are considered: (1) well-differentiated endocrine tumors, further subdivided into tumors with benign and with uncertain behavior; (2) well-differentiated endocrine carcinomas, low grade; and (3) poorly differentiated endocrine carcinomas, high grade. In this review the differential tumor characteristics between the different categories are summarized. Moreover, the relevance of additional features with respect to tumor prognostication, chiefly the Ki-67 proliferation index and malignancy-associated genetic changes, is discussed with emphasis on the discrepancies emerging between tumors of foregut and of midgut origin.

  10. Expression of maspin in benign and malignant salivary gland tumors: an immunohistochemical study.

    PubMed

    Reshma, V; Rao, Kavita; Priya, N S; Umadevi, H S; Smitha, T; Sheethal, H S

    2014-01-01

    Maspin is a novel serine protease inhibitor (serpin) with multifaceted tumor-suppressive activities. It was originally identified in normal human breast myoepithelial cells and shows variable expression in different types of cancer cells. Maspin displays anti-metastatic properties in mammary and prostate cancer. Its expression is maintained during ovarian, lung and pancreatic carcinogenesis, indicating that Maspin regulated metastatic potential is tissue specific. Thus, it is possible that Maspin participates in salivary gland tumor biology as well. In this study, expression pattern of maspin in benign and malignant salivary gland tumors is analyzed, to understand the biological behavior of salivary gland tumors with respect to maspin expression. The aim of this study was to demonstrate, record, and correlate the expression pattern of maspin in benign and malignant salivary gland tumors. A retrospective study of maspin expression in 30 diagnosed cases of benign and malignant salivary gland tumors retrieved from archives of our department. Anti-maspin antibody and horseradish peroxidase detection system. Descriptive statistical analysis and Chi-square/Fisher Exact test. Intense expression with P < 0.001 is associated with benign tumors, nuclear staining with P < 0.001 is significantly associated with benign tumors and cytoplasmic staining with P = 0.020 is associated with malignant tumors. Intensity of expression is more in benign tumors when compared with malignant tumors. The benign tumors showed both nuclear and cytoplasmic expression. Some malignant tumors did express maspin, but mainly in the cytoplasm.

  11. Morbidity and mortality of pancreatic tumors undergoing surgical treatment

    PubMed Central

    ZENI, Luiza Bueno; RUSSI, Ricardo Fantazzini; FIALHO, Alexandre Faleiro; FONSECA, Ana Luiza Pagani; SOMBRIO, Lyara Schaefer; ROCHA, Igor Cunha

    2014-01-01

    Background Pancreatic cancer has a high mortality rate due to late diagnosis and aggressive behavior. The prognosis is poor, with 5-year survival occurring in less than 5% of cases. Aim To analyze demographic characteristics, comorbidities, type of procedure and early postoperative complications of patients with pancreatic cancer submitted to surgical treatment. Methods Cross-sectional study with analysis of 28 medical records of patients with malignant tumors of the pancreas in a 62 month. Data collection was performed from the medical records of the hospital. Results Of the total, 53,6% were male and the mean age was 60.25 years. According to the procedure, 53,6% was submitted to duodenopancreactectomy the remainder to biliodigestive derivation or distal pancreatectomy. The ductal adenocarcinoma occurred in 82,1% and 92,9% of tumors were located in the pancreatic head. Early postoperative complications occurred in 64,3% of cases and the most prevalent was intra-abdominal abscess (32,1%). Among duodenopancreactectomies 77,8% had early postoperative complications. Conclusion Its necessary to encourage early detection of tumors of the pancreas to raise the number operations with curative intent. Refinements in surgical techniques and surgical teams can diminish postoperative complications and, so, operative morbimortality can also decrease over time. PMID:25626938

  12. The Role of Gastrin and CCK Receptors in Pancreatic Cancer and other Malignancies

    PubMed Central

    Smith, Jill P.; Fonkoua, Lionel K.; Moody, Terry W.

    2016-01-01

    The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in growth of the gastrointestinal tract. It has become apparent that gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of GI cancers as well as other malignancies through activation of the cholecystokinin-B (CCK-B) receptor. Of interest, gastrin is expressed in the embryologic pancreas but not in the adult pancreas; however, gastrin becomes re-expressed in pancreatic cancer where it stimulates growth of this malignancy by an autocrine mechanism. Strategies to down-regulate gastrin or interfere with its interface with the CCK receptor with selective antibodies or receptor antagonists hold promise for the treatment of pancreatic cancer and other gastrin - responsive tumors. PMID:26929735

  13. The Role of Gastrin and CCK Receptors in Pancreatic Cancer and other Malignancies.

    PubMed

    Smith, Jill P; Fonkoua, Lionel K; Moody, Terry W

    2016-01-01

    The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in growth of the gastrointestinal tract. It has become apparent that gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of GI cancers as well as other malignancies through activation of the cholecystokinin-B (CCK-B) receptor. Of interest, gastrin is expressed in the embryologic pancreas but not in the adult pancreas; however, gastrin becomes re-expressed in pancreatic cancer where it stimulates growth of this malignancy by an autocrine mechanism. Strategies to down-regulate gastrin or interfere with its interface with the CCK receptor with selective antibodies or receptor antagonists hold promise for the treatment of pancreatic cancer and other gastrin--responsive tumors.

  14. Autocrine growth factors and solid tumor malignancy.

    PubMed Central

    Walsh, J. H.; Karnes, W. E.; Cuttitta, F.; Walker, A.

    1991-01-01

    The ability of malignant cells to escape the constraint that normally regulate cell growth and differentiation has been a primary focus of attention for investigators of cancer cell biology. An outcome of this attention has been the discovery that the protein products of oncogenes play a role in the activation of growth signal pathways. A second outcome, possibly related to abnormal oncogene expression, has been the discovery that malignant cells frequently show an ability to regulate their own growth by the release of autocrine growth modulatory substances. Most important, the growth of certain malignant cell types has been shown to depend on autocrine growth circuits. A malignant tumor whose continued growth depends on the release of an autocrine growth factor may be vulnerable to treatment with specific receptor antagonists or immunoneutralizing antibodies designed to break the autocrine circuit. Information is rapidly emerging concerning autocrine growth factors in selected human solid tissue malignancy. Images PMID:1926844

  15. Long-standing malignant pancreatic carcinoid treated with octreotide.

    PubMed

    Varas-Lorenzo, M J

    2010-11-01

    A male presented with a metastatic, plasma serotonin-secreting (high 5-HIAA in urine), malignant pancreatic carcinoid with a carcinoid-like syndrome, and was assessed using ultrasounds (US), computerized tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS) and Octreoscan; he sequentially received chemotherapy, interferon and octreotide, with long-term, 12-year survival after diagnosis. Given this unusual case, the second reported in our country, the overall literature is reviewed.

  16. Malignant Peripheral Nerve Sheath Tumor -A Rare Malignancy in Mandible

    PubMed Central

    Majumdar, Sumit; Kotina, Sreekanth; Uppala, Divya; Kumar, Singam Praveen

    2016-01-01

    Malignant Peripheral Nerve Sheath Tumor (MPNST) is biologically an aggressive tumor that is usually found in the extremities, trunk and infrequently found in the head and neck area particularly in the jaws, arising from the cells allied with nerve sheath. Mandibular MPNST may either arise from a preexisting neurofibroma or develop de novo. Because of the greater variability from case to case in overall appearance both clinically and histologically, a case of MPNST of the mandible in a 25-year-old female patient is reported. The lesion was excised and immunohistological studies (S-100 & Neuron specific enolase) were conducted to confirm the neural origin. PMID:27504425

  17. Implications of Incidentally Discovered, Nonfunctioning Pancreatic Endocrine Tumors

    PubMed Central

    Haynes, Alex B.; Deshpande, Vikram; Ingkakul, Thun; Vagefi, Parsia A.; Szymonifka, Jackie; Thayer, Sarah P.; Ferrone, Cristina R.; Wargo, Jennifer A.; Warshaw, Andrew L.; Castillo, Carlos Fernández-del

    2011-01-01

    Objectives To describe the characteristics and outcomes after resection of incidentally discovered, nonfunctioning pancreatic endocrine tumors (PETs). Design Case series. Setting Academic hospital. Patients Consecutive patients with an incidentally identified, nonfunctioning PET resected from May 1, 1977, through July 31, 2009. Main Outcome Measures Operative morbidity and survival after resection. Results A total of 139 patients with median age of 56 years (range, 21–85 years) underwent resection; tumor size ranged from 0.4 to 17.0 cm, with median size of 3.0 cm. No perioperative deaths were reported. Sixty-one patients (43.9%) experienced a perioperative complication. Twenty-six tumors (18.7%) were classified as benign, 39 (28.1%) as malignant, and 72 (51.8%) as uncertain. We were unable to confidently classify 2 tumors due to lack of information regarding mitotic rate in the pathology report. Complete follow-up was available for 112 patients (80.6%) (median, 34.2 months). Five-year actuarial survival rates were 88.8% for patients with benign disease, 92.5% for patients with tumors of uncertain biology, and 49.8% for those with malignant tumors (P=.01). Late metastasis, tumor recurrence, or disease progression were seen in 1 patient (3.8%) with tumors initially classified as benign, 8 patients (11.1%) with uncertain tumors, and 15 patients (38.5%) with tumors classified as malignant (P<.001). Of the 39 patients with tumors 2 cm or smaller, 3 (7.7%) had late metastases or recurrence. When compared with patients with symptomatic, nonfunctioning PETs, no large difference was observed in tumor size, patient age, disease, or survival. Conclusions Incidentally detected, nonfunctioning PETs can display aggressive behavior, even when small. Although patients with malignant disease had diminished survival and increased rates of recurrence, benign histologic findings did not eliminate the possibility of progression. Patients with incidentally discovered, nonfunctioning

  18. Successful selective internal radiotherapy (SIRT) in a patient with a malignant solid pseudopapillary pancreatic neoplasm (SPN).

    PubMed

    Krug, S; Bartsch, D K; Schober, M; Librizzi, D; Pfestroff, A; Burbelko, M; Moll, R; Michl, P; Gress, T M

    2012-01-01

    Solid pseudopapillary neoplasms of the pancreas (SPNs, Gruber-Frantz-Tumor) are a rare entity representing 1-5% of all exocrine pancreatic tumors. The pseudocystic lesions preferentially affect young females <30 years, are mostly benign (∼90%) and normally present with unspecific symptoms. We describe the case of a 16-years-old Asian woman that was initially diagnosed with an SPN in the pancreatic head with mesenterial and hepatic metastases. After diagnosis, an extensive tumor resection was performed including pyloric-preserving pancreatic head resection followed by sequential resection of all hepatic metastases. After the patient was diagnosed with a hepatic recurrence and high intrahepatic tumor load, we chose a multimodal procedure and performed a selective internal radiotherapy (SIRT). Four years after SIRT and 10 years after initial diagnosis of metastatic SPN, the patient is in a good condition without any evidence for hepatic recurrence. This case represents a rare clinical course of a malignant and invasive SPN with an exceptionally long survival despite of high initial tumor burden. The selective internal radiotherapy is a suitable approach for inducing long-term remissions of the strongly vascularized liver metastases.

  19. The use of pancreatic ductoscopy in the operative management of benign and malignant pancreatic disorders.

    PubMed

    Branum, G D; Pappas, T N; Meyers, W C

    1995-01-01

    Direct visualization of the pancreatic duct was helpful in decision making during complex pancreaticobiliary operations. Two-, 3-, or 5-mm scopes were introduced into the pancreatic ducts of 32 patients with pancreatic disorders. Scopes were passed into the ductal system of: (1) 16 patients undergoing pancreaticojejunostomy; (2) six patients undergoing pancreaticoduodenectomy; (3) four patients with pancreatic pseudocysts or choledochal cysts: (4) two patients undergoing resection of the pancreatic tail; and (5) two patients undergoing accessory ductoplasty for pancreas divism or stricture. Eight patients had calculi removed utilizing the scope, and multiple strictures were identified and filleted. Pancreatic ductoscopy was used in two patients to document successful sphincteroplasty of an accessory duct. In two instances benign pancreatic duct tumors were removed. Pancreatic ductoscopy was used to search for coexistent duct neoplasms in the eight patients who underwent resection. The technique permits intraoperative inspection, biopsy, and removal of lesions intrinsic to the ductal system. Combined with surgical procedures this endoscopic method proved a useful adjunct in difficult cases.

  20. Malignant transformation of breast fibroadenoma to malignant phyllodes tumor: long-term outcome of 36 malignant phyllodes tumors.

    PubMed

    Abe, Makoto; Miyata, Satoshi; Nishimura, Seiichiro; Iijima, Kotaro; Makita, Masujiro; Akiyama, Futoshi; Iwase, Takuji

    2011-10-01

    Malignant phyllodes tumor of the breast is a rare neoplasm for which clinical findings remain insufficient for determination of optimal management. We examined the clinical behavior of these lesions in an attempt to determine appropriate management. We evaluated long-term outcome and clinical characteristics of malignant phyllodes tumors arising from fibroadenomas of the breast. A total of 173 patients were given a diagnosis of phyllodes tumor and underwent surgery at the Cancer Institute Hospital in Japan between January 1980 and December 1999. Of these patients, 39 (22.5%) were given a diagnosis of malignant phyllodes tumor; in three of these cases, detailed medical records were lost. Malignant phyllodes tumors were classified into two groups based on history of malignant transformation. Of the 36 malignant cases, 11 (30.6%) were primary and were given a diagnosis of fibroadenoma, experienced recurrence during the follow-up period, and were diagnosed with malignant phyllodes tumor (cases with a history of fibroadenoma). The other group was defined as cases without history of fibroadenoma and in whom lesions initially occurred as malignant phyllodes tumors. Based on differences between the two groups, overall survival curves were plotted using the Kaplan–Meier method, and statistical comparisons were performed using the log-rank test and Peto and Peto’s test. The outcome of cases with history of fibroadenoma was significantly better than that of cases without history of fibroadenoma. Patients with malignant phyllodes tumors but without prior history of malignant transformation who exhibit rapid growth within 6 months require aggressive treatment.

  1. Robotic left pancreatectomy for pancreatic solid pseudopapillary tumor.

    PubMed

    Ntourakis, Dimitrios; Marzano, Ettore; De Blasi, Vito; Oussoultzoglou, Elie; Jaeck, Daniel; Pessaux, Patrick

    2011-03-01

    Solid pseudopapillary pancreatic tumors of pancreas are a rare entity, seen most often in females in their second or third decades. Although previously believed to be benign, this tumor is currently considered a low-grade malignant epithelial neoplasm with low metastatic rate and high overall survival.1,2 Its resection could be performed by robotic technique with respect to oncological principles to avoid tumor cell dissemination.3 In this multimedia article, we present a 28-year-old female with a history of hyperthyroidism who underwent a computed tomography (CT) scan because of a persistent high C-reactive protein level following caesarean section. This CT scan revealed a 7-cm cystic lesion of the pancreatic tail. The serum tumor marker CA 19-9 was normal. Further investigation with an magnetic resonance imaging (MRI) scan showed that the lesion was macrocystic with internal septas compatible with a solid pseudopapillary neoplasm.4 The patient was treated with robotic distal splenopanceatectomy (video). The operative time was 5 h with an estimated blood loss of 250 mL. No blood transfusion was necessary. The postoperative period was uneventful, and she was discharged on postoperative day 8. The histological finding revealed a solid pseudopapillary tumor of the pancreas pT2pN0 (0/14 lymph nodes removed). There was no evidence of clinical, biological, and radiological pancreatic fistula, and a control CT scan on postoperative day 8 did not show any abdominal fluid collection. The patient's 1 month follow-up was normal. The robotic distal splenopancreatectomy is a procedure that offers some technical and oncological advantages over the already described minimally invasive techniques for distal pancreatic tumors.5,6 These advantages are mainly due to the stability of the operative field, to the 3D and magnified vision, and to the articulated robotic arms.7-9 The 3D representation and the stability of the operative field facilitate the performance of operative

  2. Propofol attenuates pancreatic cancer malignant potential via inhibition of NMDA receptor.

    PubMed

    Chen, Xiangyuan; Wu, Qichao; You, Li; Chen, Sisi; Zhu, Minmin; Miao, Changhong

    2017-01-15

    Propofol is a commonly used intravenous anesthetic, and could attenuate cancer cells malignant potential via inhibiting hypoxia-inducible factor-1α (HIF-1α) expression. However, the mechanism is still inclusive. In the present study, we mainly focus on the mechanism by which propofol down-regulated HIF-1α expression and malignant potential in pancreatic cancer cells. Human pancreatic cancer cells (Miapaca-2 and Panc-1) in vitro and murine pancreatic cancer cell (Panc02) in vivo were used to assess the effect of propofol on vascular endothelial growth factor (VEGF) expression and migration of pancreatic cancer cells. Propofol inhibited cells migration, expression of VEGF and HIF-1α, phosphorylation of extracellular regulated protein kinases (ERK), AKT, Ca(2+)/calmodulin dependent protein kinases II (CaMK II), and Ca(2+) concentration in a concentration-dependent manner (5, 25, 50, 100μM). Furthermore, MK801, an inhibitor of NMDA receptor, and KN93, an inhibitor of CaMK II, could inhibit the expression of VEGF, HIF-1a, p-AKT, p-ERK, p-CaMK II in vitro, growth of tumor and VEGF expression in vivo, which were similar to the effect of propofol. In addition, the anti-tumor effect of propofol could be counteracted by rapastinel, an activator of NMDA receptor. Our study indicated that propofol suppressed VEGF expression and migration ability of pancreatic cancer cells in vitro and in vivo, probably via inhibiting NMDA receptor. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Outcome of stenting in biliary and pancreatic benign and malignant diseases: A comprehensive review

    PubMed Central

    Mangiavillano, Benedetto; Pagano, Nico; Baron, Todd H; Luigiano, Carmelo

    2015-01-01

    Endoscopic stenting has become a widely method for the management of various malignant and benign pancreatico-biliary disorders. Biliary and pancreatic stents are devices made of plastic or metal used primarily to establish patency of an obstructed bile or pancreatic duct and may also be used to treat biliary or pancreatic leaks, pancreatic fluid collections and to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis. In this review, relevant literature search and expert opinions have been used to evaluate the outcome of stenting in biliary and pancreatic benign and malignant diseases. PMID:26290631

  4. Intravital characterization of tumor cell migration in pancreatic cancer

    PubMed Central

    Beerling, Evelyne; Oosterom, Ilse; Voest, Emile; Lolkema, Martijn; van Rheenen, Jacco

    2016-01-01

    ABSTRACT Curing pancreatic cancer is difficult as metastases often determine the poor clinical outcome. To gain more insight into the metastatic behavior of pancreatic cancer cells, we characterized migratory cells in primary pancreatic tumors using intravital microscopy. We visualized the migratory behavior of primary tumor cells of a genetically engineered pancreatic cancer mouse model and found that pancreatic tumor cells migrate with a mesenchymal morphology as single individual cells or collectively as a stream of non-cohesive single motile cells. These findings may improve our ability to conceive treatments that block metastatic behavior. PMID:28243522

  5. Comparison of multidetector CT and endoscopic ultrasonography in malignant pancreatic mass lesions.

    PubMed

    Arabul, Mahmut; Karakus, Funda; Alper, Emrah; Kandemir, Altay; Celik, Mustafa; Karakus, Volkan; Yucel, Kamil; Unsal, Belkis

    2012-01-01

    Endoscopic ultrasonography (EUS) has been shown to be superior to conventional CT in detecting and staging pancreatic cancer. We conducted a prospective trial to compare EUS and MDCT, in discriminating benign/malignant, in determining local and vascular invasion of a suspected pancreatic cancer and deciding its resectability. The study was performed at the Gastroenterology Department of Izmir Ataturk Training and Research Hospital, from June 2009 to June 2010, all patients with suspected pancreatic and periampullary tumors referred to our department were enrolled. A total of 56 patients were evaluated at the beginning. Five patients having distal CBD tumor (n=2), gallbladder tumor (n=1) and papillary tumor (n=2) were excluded from the study. Analysis was done for the remaining 51 patients. For the diagnosis of resectability/unresectability, EUS alone demonstrated a definite role in 4 (9%) of the 43 patients in confirming surgical and pathologic results and MDCT alone demonstrated a definite role in 6 (14%) of the 43 patients in confirming their results. An accurate diagnostic decision regarding resectability/unresectability was accomplished in 27 (63%) patients with EUS and MDCT. While MDCT is clinically quite effective, in terms of a correct resectability/unresectability decision, EUS should also be used.

  6. Resection or cryosurgery relates with pancreatic tumor type: primary pancreatic cancer with previous non-pancreatic cancer or secondary metastatic cancer within the pancreas.

    PubMed

    Jin, Peng; Ji, Xiaoyan; Ren, He; Tang, Yong; Hao, Jihui

    2014-01-01

    We investigated the incidence of primary pancreatic cancer with previous non-pancreatic cancer (PPC) and secondary metastatic cancer within the pancreas (SMC) to elucidate the differential diagnosis and treatment of these lesions. The clinical data of 2539 patients with pancreatic mass in Tianjin Cancer Hospital from January 2000 to December 2012 were retrospectively analyzed. All of the 66 patients who showed double or multiple primary cancers or metastatic pancreatic malignancies were included into the PPC group or SMC group, respectively. In addition, PPC patients were compared with 570 patients suffering from pancreatic cancer (PC) alone. For the PPC group (n = 34), the most common previous non-pancreatic cancers were gastric cancer, breast cancer, and thyroid cancer. For the SMC group (n = 32), the most common metastatic tumors were lung cancer, renal cell carcinoma (RCC), and gastric cancer. Multivariate analysis identified age (OR = 1.099; 95% CI, 1.007-1.199), previous tumor type (OR = 1.164; 95% CI, 1.046-1.296), and time interval between two tumors (OR = 1.021; 95% CI, 1.003-1.039) as significant indicators. Significantly better survival times were observed after resection than after cryosurgery in the PPC group (p < 0.001) but not in the SMC group (p = 0.670). Overall, primary pancreatic cancers are as common as metastasis to the pancreas in patients with a previous cancer. A longer time interval between two tumors indicates a higher possibility that a new pancreatic cancer will occur. Some cancers (particularly RCC) are more likely to metastasize to the pancreas than other cancers. For metastatic cancers, cryosurgery is as effective as resection as a treatment option. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  7. Primary malignant tumors of the small bowel.

    PubMed

    Mittal, V K; Bodzin, J H

    1980-09-01

    Primary malignant tumors of the small bowel are uncommon and are often diagnosed at an advanced stage. A 10 year survey (1967 to 1977) of the clinical records at one hospital revealed 39 cases of primary malignant tumors of the small bowel. The most common symptoms were abdominal pain (89.7 percent) and weight loss (77 percent). Six patients presented with complications of enterovesical fistula, bleeding and perforation. Preoperative diagnosis was suspected in 27 cases (69.2 percent). Adenocarcinoma was the most common tumor, followed by carcinoid tumor, lymphoma, leiomyosarcoma and melanoma. The treatment of choice was surgical resection whenever possible. Curative resection was attempted in 25 cases. Adjuvant radiotherapy and chemotherapy was used in four patients with lymphoma. Twenty-seven patients (69.2 percent) are alive from 1 to 6 years after diagnosis and treatment. The 5 year survival rate is 35 percent. Earlier diagnosis is essential if the prognosis for patients with small bowel malignancy is to be improved.

  8. Afatinib Dimaleate and Capecitabine in Treating Patients With Advanced Refractory Solid Tumors, Pancreatic Cancer or Biliary Cancer

    ClinicalTrials.gov

    2017-08-04

    Advanced Malignant Solid Neoplasm; Bile Duct Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer

  9. Malignant Tumors of Tongue in Iranian Population

    PubMed Central

    Akbari, Mohammad Esmaeil; Atarbashi Moghadam, Saede; Atarbashi Moghadam, Fazele; Bastani, Zahra

    2016-01-01

    Background The incidence of oral cancers varies from one country to another, which can be clarified by the difference in the distribution of the risk factors and the possible etiologies. Tongue is a main segment of oral cavity and malignant lesions of this region accounts for nearly 30% of all oral cancers. Objectives In the present study, we evaluated the pattern of tongue cancer in Iranian population and compared these findings with those previously reported in the other countries. Methods In this multicenter, retrospective cross-sectional study recorded cases of the malignant tongue tumors in the cancer research center (CRC) of Shahid Beheshti University of Medical Sciences were extracted. The patient records and their microscopic reports were retrieved from the archives and age, sex and microscopic types were evaluated. It is to be noted that the CRC has been serving as a cancer registry center for major hospitals all over the country since the year of 2003. Thus, the obtained statistics are highly reliable. Results During the years 2003 to 2008, a total number of 952 new cases of the tongue cancer were recorded in the CRC. Most cases are diagnosed in the sixth and seventh decades of life. 450 cases (47.2%) occurred in men and 489 cases (51.36%) in women. Four different types of malignant lesions (epithelial, salivary gland, hematopoietic and mesenchymal) were diagnosed. Epithelial tumors were the most prevalent malignancies (93%) of which squamous cell carcinoma (SCC) made up 87.39% of all lesions. Salivary gland tumors had the second place with 3.15% of the total lesions. Conclusions In Iranian population, squamous cell carcinoma is the most prevalent malignancy of tongue and it is notable that the ratio of female to male population was equal. These lesions were prevalent in the sixth and seventh decades of life. Thus screening examination of tongue by dentist especially in elderly patients is necessary for early detection of cancerous lesions. PMID:27761209

  10. [Primary Malignant Cardiac Tumors: Surgical results].

    PubMed

    Saraiva, Joana; Antunes, Pedro Engrácia; Carvalho, Lina; Antunes, Manuel Jesus

    2016-04-01

    To characterize primary malignant cardiac tumors operated on in our center and to analyze patient survival. Between January 1994 and August 2014, 123 patients with cardiac tumors underwent surgery, of which 12 (9.8%) were primary malignant tumors - eight sarcomas (67%), three B-cell lymphomas (25%) and one epithelioid hemangioendothelioma (8.3%). The tumor affected the left atrium in five cases (42%), the right atrium in four (33%), the right ventricle in two (17%) and the pulmonary valve in one (8%). Patients' mean age was 55.4 ± 16.9 years, 67% were female and 75% presented in New York Heart Association class III-IV. Resection was complete (negative margins) in five cases and partial in seven (five sarcomas and two lymphomas), and 11 patients needed adjuvant therapy, surgery alone being curative in only one (epithelioid hemangioendothelioma). Mean follow-up was 41.7 ± 61.3 months: 24.8 ± 30.0 months (3.8-95.7) for sarcomas, 70.1 ± 118.0 months (1-206.3) for lymphomas and 91.9 months for the epithelioid hemangioendothelioma. During follow-up, 10 patients died (83%) and two were alive (17%). Overall survival at 30 days, six months, one year and two years was 91.7%, 66.7%, 58.3% and 41.7%, respectively. In the sarcoma group, 1-year and 2-year survival were 62.5% and 37.5%, respectively. Resection of primary malignant cardiac tumors, even partial, is safe, provides relief of obstructive symptoms and improves quality of life, but is rarely curative and has a low survival rate. Due to the rarity of such tumors, a multicenter database could improve knowledge and help clarify the indications for cardiac surgery as a treatment option. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  11. Ameloblastic fibrosarcoma: a rare malignant odontogenic tumor.

    PubMed

    Gilani, S M; Raza, A; Al-Khafaji, B M

    2014-02-01

    Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic tumor. It can arise de novo, however one-third of cases may arise from a recurrent ameloblastic fibroma, in which case they appear to present at an older age. A 16-year-old female presented with one month history of right mandibular mass. Computerized tomography (CT) scan showed a large destructive mass. A biopsy of the mass was performed. Histologically, it consisted of a mixed epithelial-mesenchymal odontogenic neoplasm composed of benign islands of well-differentiated ameloblastic epithelium within a malignant fibrous stroma consisting of spindle cells or fibroblasts with a brisk mitotic activity. The malignant spindle cell proliferation showed positive staining with p-53 and a high proliferation index with ki-67. A diagnosis of AFS was rendered. The differential diagnosis includes other odontogenic sarcomas, ameloblastic carcinosarcoma and spindle cell carcinoma. Treatment of choice is wide surgical excision, with long-term follow-up. Postoperative chemotherapy and radiotherapy has been used successfully in a few reported cases. AFS is a locally aggressive malignant tumor, with regional and distant metastases being uncommon. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  12. [Infection in patients with malignant tumors].

    PubMed

    Zhang, Xuhua; Cao, Peiguo

    2010-11-01

    To investigate the characters of infection in patients with malignant tumors, especially the distribution, yearly change of pathogens, and pathogen resistance to common antibacterial agents. We respectively analyzed the characters of infection in 489 patients with malignant tumors. The respiratory tract was the most frequent infection site (61.1%). The infection was mainly caused by opportunistic pathogens. The Gram-negative bacterias mainly consisted of Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii (46.3%). The Gram-positive bacteria mainly consisted of Staphylococcus aureus and Staphylococcus epidermidis (29.9%), and the rest 23.8% of the infection was caused by different fungi, mainly consisting of Candida albicans. The ratio of the Gram-negative bacteria resistance to antibiotics such as penicillins, cephalosporins (except ceftazidime), sulfanilamides, tetracyclines and quinolones was higher. The ratio of the Gram-positive bacteria resistance to antibiotics such as penicillins, macrolides and quinolones was higher. The ratio of fungus resistance to antibacterial agents such as fluconazol and itraconazole was higher. The infection caused by fungi obviously increased in the past 5 years. The infection in patients with malignant tumors is mainly caused by opportunistic pathogens, and the pathogen resistance to antibacterial agents is serious. The infection caused by fungi is increasing.

  13. Antisense therapeutics for tumor treatment: the TGF-beta2 inhibitor AP 12009 in clinical development against malignant tumors.

    PubMed

    Schlingensiepen, K H; Fischer-Blass, B; Schmaus, S; Ludwig, S

    2008-01-01

    Overexpression of the cytokine transforming growth factor-beta 2 (TGF-beta2) is a hallmark of various malignant tumors including pancreatic carcinoma, malignant glioma, metastasizing melanoma, and metastatic colorectal carcinoma. This is due to the pivotal role of TGF-beta2 as it regulates key mechanisms of tumor development, namely immunosuppression, metastasis, angiogenesis, and proliferation. The antisense technology is an innovative technique offering a targeted approach for the treatment of different highly aggressive tumors and other diseases. Antisense oligonucleotides are being developed to inhibit the production of disease-causing proteins at the molecular level. The immunotherapeutic approach with the phosphorothioate oligodeoxynucleotide AP 12009 for the treatment of malignant tumors is based on the specific inhibition of TGF-beta2. After providing preclinical proof of concept, the safety and efficacy of AP 12009 were assessed in clinical phase I/II open-label dose-escalation studies in recurrent or refractory high-grade glioma patients. Median survival time after recurrence exceeded the current literature data for chemotherapy. Currently, phase I/II study in advanced pancreatic carcinoma, metastatic melanoma, and metastatic colorectal carcinoma and a phase IIb study in recurrent or refractory high-grade glioma are ongoing. The preclinical as well as the clinical results implicate targeted TGF-beta2 suppression as a promising therapeutic approach for malignant tumor therapy.

  14. Carcinoma of the pancreatic head and periampullary region. Tumor staging with laparoscopy and laparoscopic ultrasonography.

    PubMed Central

    John, T G; Greig, J D; Carter, D C; Garden, O J

    1995-01-01

    OBJECTIVE: The authors performed a prospective evaluation of staging laparoscopy with laparoscopic ultrasonography in predicting surgical resectability in patients with carcinomas of the pancreatic head and periampullary region. SUMMARY BACKGROUND DATA: Pancreatic resection with curative intent is possible in a select minority of patients who have carcinomas of the pancreatic head and periampullary region. Patient selection is important to plan appropriate therapy and avoid unnecessary laparotomy in patients with unresectable disease. Laparoscopic ultrasonography is a novel technique that combines the proven benefits of staging laparoscopy with high resolution intraoperative ultrasound of the liver and pancreas, but which has yet to be evaluated critically in the staging of pancreatic malignancy. METHODS: A cohort of 40 consecutive patients referred to a tertiary referral center and with a diagnosis of potentially resectable pancreatic or periampullary cancer underwent staging laparoscopy with laparoscopic ultrasonography. The diagnostic accuracy of staging laparoscopy alone and in conjunction with laparoscopic ultrasonography was evaluated in predicting tumor resectability (absence of peritoneal or liver metastases; absence of malignant regional lymphadenopathy; tumor confined to pancreatic head or periampullary region). RESULTS: "Occult" metastatic lesions were demonstrated by staging laparoscopy in 14 patients (35%). Laparoscopic ultrasonography demonstrated factors confirming unresectable tumor in 23 patients (59%), provided staging information in addition to that of laparoscopy alone in 20 patients (53%), and changed the decision regarding tumor resectability in 10 patients (25%). Staging laparoscopy with laparoscopic ultrasonography was more specific and accurate in predicting tumor resectability than laparoscopy alone (88% and 89% versus 50% and 65%, respectively). CONCLUSIONS: Staging laparoscopy is indispensable in the detection of "occult" intra

  15. A retroperitoneal neuroendocrine tumor in ectopic pancreatic tissue.

    PubMed

    Okasha, Hussein Hassan; Al-Bassiouni, Fahim; El-Ela, Monir Abo; Al-Gemeie, Emad Hamza; Ezzat, Reem

    2013-07-01

    Ectopic pancreas is the relatively uncommon presence of pancreatic tissue outside the normal location of the pancreas. We report a case of abdominal pain due to retroperitoneal neuroendocrine tumor arising from heterotopic pancreatic tissue between the duodenal wall and the head of the pancreas. Patient underwent surgical enucleation of the tumor.

  16. Malignant thoracopulmonary small-cell (Askin) tumor

    SciTech Connect

    Fink, I.J.; Kurtz, D.W.; Cazenave, L.; Lieber, M.R.; Miser, J.S.; Chandra, R.; Triche, T.J.

    1985-09-01

    The clinical, radiographic, and pathologic features of 10 patients with documented malignant small-cell tumor of the thoracopulmonary region (Askin tumor) were reviewed. The tumor represents a distinct pathologic entity of neuroectodermal origin. Clinically, it presents as a chest-wall mass with or without pain. Its radiographic appearance is that of a soft-tissue mass with or without pleural or rib involvement, often with metastatic disease - to the skeletal system, bone marrow, thorax, and sympathetic chain. Two patients developed metastases to the adrenal gland and liver, one after autologous bone marrow transplantation. The radiologist should be aware of this entity and its pattern of metastatic spread since metastases are treated aggressively.

  17. [Ovarian tumors of low malignant potential (borderline ovarian tumors)].

    PubMed

    Luchian, Alina-Mihaela; Pricop, M

    2011-01-01

    Ovarian borderline tumors are rare, their good prognosis depending on their stage at the time of diagnosis, and the presence of invasive implants. There is little information on tumor type identified intra-surgically, as well as on the most favorable treatment in borderline ovarian tumors. To determine the criteria of identification and presurgery and intra-surgery differentiation of the ovarian borderline tumors from the invasive carcinoma and benign ovarian tumors. This study included 54 patients with TPMS (ovarian borderline tumors) surgically treated in the past 22 years (January 1988-December 2009) at the 4th Gynecological Clinic of the lasi "Gr. T. Popa" University of Medicine and Pharmacy. In this interval 1,107 ovarian tumors: 575 benign, 478 malignant, and 54 TPMS (4.87%) were recorded. The age of the patients with borderline tumors ranged between 20 and 78 years, mean age 46 years, and the histological types were: mucinous (27 cases), serous (18 cases), mixed (8 cases), and Brenner tumor (1 case). We have analyzed the distribution of these cases according to the time when surgical treatment was performed. The frequency of borderline ovarian tumors in our study is 4.87%, lower than in the literature. We believe that this low percentage in our study is due to missing the microscopic data in some macroscopic benign tumors. By this research we aimed at elaborating a therapeutic strategy for each case using with discernment the modern treatment (surgery, chemotherapy, radiotherapy), as well as new chemical drugs with the goal of obtaining better results and longer survival. There are no tumor markers which could predict the progression of a borderline ovarian tumor to invasive tumors, but the invasive course is only 0.7%.

  18. [Pancreatic tumors--pessimism, optimism or realism?].

    PubMed

    Leffler, J; Dvorák, J

    1998-08-01

    Among 35 patients with the preoperative diagnosis of a tumour of the head of the pancreas who had a radical operation at the Surgical Clinic of the Second Medical Faculty Charles University in Prague-Motol between January 1995 and March 1998 a malignant tumour was confirmed in 24 instances. Another nine patients had a histological finding of chronic pancreatitis and the remaining two patients a benign cystadenoma of the pancreas. The 30-day mortality in the whole group is 5.7% (2/35). Both deaths within 30 days after surgery were due to massive haemorrhage into the upper GIT in patients with pancreatic cancer. The haemorrhage developed within 21 and 30 days after surgery. The source of haemorrhage was not proved unequivocally, neither clinically nor post mortem. Obviously late haemorrhage from some gastrointestinal anastomosis was involved. From a total of 24 patients after Whipple's operation on account of a malignant tumour of the head of the pancreas nine died. The mean survival period was seven months after surgery. Fifteen patients survive and after a mean follow-up period of 14 months the median of survival calculated to the date of March 31 1998 is 17 months for stage UICC I and five months for stage UICC III. Because of the short follow-up period the results cannot be compared properly with data in the contemporary literature but they are promising for further work in this sphere of surgery and evidence that it is correct to refute the nihilist view held in the past. Hitherto achieved therapeutic results in this country and abroad certainly do not justify yet an optimistic view as regards the perspective of patients with carcinoma of the pancreas.

  19. Pancreatic neuroendocrine tumors: does chemotherapy work?

    PubMed

    Tejani, Mohamedtaki Abdulaziz; Saif, Muhammad Wasif

    2014-03-10

    Pancreatic neuroendocrine tumors (pNETs) are rare well-differentiated neoplasms which can be functional or non-functional. They tend to have a worse prognosis than their counterpart carcinoid tumors. Current systemic treatment options for advanced, unresectable disease include somatostatin analogs, everolimus and sunitinib. Low response rates and toxicity profiles have, thus far, limited the widespread use of cytotoxic chemotherapy in this setting. In this update, we review three abstracts from the 2014 ASCO Gastrointestinal Cancers Symposium that present outcomes of the use of combination capecitabine and temozolomide in patients with advanced pNET. We summarize their results and discuss the role of this regimen in treatment algorithms for metastatic pNET.

  20. Current medical treatment of pancreatic neuroendocrine tumors.

    PubMed

    Yalcin, Suayib; Oyan, Basak; Bayraktar, Yusuf

    2007-01-01

    Pancreatic neuroendocrine tumors (NETs) consist of a wide group of neoplasms, with different biological behaviors in terms of aggressiveness and hormone production. In the last two decades, significant progress has been observed in our understanding of their biology, diagnosis and treatment. Surgery remains to be the only curative approach, but unfortunately the diagnosis is often delayed due to the slow growth of these tumors and the difficulty in identifying the symptoms related to the tumor-released hormones. In addition to surgery, other approaches to control the disease are biological therapy consisting of somatostatin analogs and interferon (IFN), systemic chemotherapy, radioligand therapy and local therapy with chemoembolization. Several newer cytotoxic agents, including irinotecan, gemcitabine, taxanes, oxaliplatin, capecitabine and PS-341 have been studied in metastatic patients. Considering the high vascularity of these tumors, antiangiogenic agents like endostatin and thalidomide have also been evaluated in advanced NETs. Although these agents seem to have potential activity in NETs and may increase progression free survival, none of these currently available medical therapeutic options are curative. While more efficient novel strategies are to be developed, the rationale use of the current therapeutic options may improve quality of life, control the symptoms related to the hypersecretion of hormones and/or peptides, control tumor proliferation and prolong survival in patients suffering from NETs.

  1. Irreversible Electroporation of Hepatic and Pancreatic Malignancies: Radiologic-Pathologic Correlation.

    PubMed

    Gonzalez-Beicos, Aldo; Venkat, Shree; Songrug, Tanakorn; Poveda, Julio; Garcia-Buitrago, Monica; Poozhikunnath Mohan, Prasoon; Narayanan, Govindarajan

    2015-09-01

    Irreversible electroporation (IRE) is a novel therapy that has shown to be a feasible and promising alternative to conventional ablative techniques when treating tumors near vital structures or blood vessels. The clinical efficacy of IRE has been evaluated using established imaging criteria. This study evaluates the histologic and imaging response of hepatic and pancreatic malignancies that were surgically resected after IRE. In total, 12 lesions ablated with IRE were included, including 3 pancreatic carcinomas, 5 primary tumors of the liver, and 4 metastatic tumors of the liver. The rate of complete response to IRE was 25% based on the histologic evaluation of the resected tumors. Although treatment-related vessel wall changes were noted in several cases in histologic findings, there was no evidence of vascular luminal narrowing or obliteration in any of the specimens. The imaging response to IRE before surgical resection usually resulted in underestimation of disease burden when compared with the histologic response seen on the resected specimens. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Carcinosarcoma of parotid gland (malignant mixed tumor).

    PubMed

    Feng, Duan; Fidele, Nyimi Bushabu; Agustin, Mansthumba Milolo; Jian, Guan; Bourleyi, Sekele Isouradi; Augustin, Lamwe; Olivier, Ngueji Kakubu

    2015-01-01

    Salivary gland carcinosarcoma is a rare neoplasm; with a poor prognosis. The most common epithelial components are adenocarcinoma or squamous cell carcinoma, whereas the most common mesenchymal components are chondrosarcoma. It should not be confused with the most common carcinoma ex-pleomorphic adenoma, in which the epithelial component alone is malignant. This condition might exhibit with a wide variety of presentation and symptoms along with associated conditions. We present a case of an old patient who presented with a very unusual type clinically with confusing presentation which was eventually diagnosed as carsinosarcoma. In addition, the literature is reviewed, and the possible clinical signs and management of malignant mixed tumor of the salivary gland are briefly discussed.

  3. Pathways of metastatic spread of malignant tumors.

    PubMed

    del Regato, J A

    1977-03-01

    In order to produce viable metastases, the neoplastic cells must first be able to survive in the fluid system that they attain and that transport them. An important circumstance that has escaped the attention of most observers is the fact that the establishment of metastatic colonies is favored by the sluggish transportation of the detached neoplastic cells. Such leisurely transport is provided by lymphatic channels and peritoneal fluid; in the peritoneal cavity, the favorable circumstance aids the spread of relatively benign tumors such as pseudomyxoma peritonei and ovarian adenomas. In the blood, the slow transport is assured only by the venous access to the vertebral vein system; this avenue to blood-borne spread is particularly favorable to well differentiated tumors with a slow rate of growth and explains the widespread bone metastases from tumors with a low degree of malignancy, such as well differentiated adenocarcinomas of the thyroid and prostate. In contrast, neoplastic cells that enter the swift arterial circulation from the left heart are not often successfully implanted, in spite of their high degree of malignancy, and more often perish. Otherwide, we should observe a greater number of metastases in the small bones of the wrists and hands and of the ankles and feet, where the arterial circulation would bring them.

  4. Photodynamic Therapy for Malignant Brain Tumors.

    PubMed

    Akimoto, Jiro

    2016-01-01

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area.

  5. [Chronic pancreatitis or pancreatic malignancy: clinical and radiological differential diagnosis of pancreas head space-occupying mass].

    PubMed

    Nieß, H; Albertsmeier, M; Thomas, M; Kleespies, A; Angele, M; Bruns, C J

    2013-02-01

    Chronic pancreatitis can be complicated both by an inflammatory benign mass and by the development of pancreatic cancer. The distinction of these complications is not only difficult but also crucial as patients suffering from either of the two have significantly different prognoses. This article describes typical clinical and radiological findings, which may help the physician in differentiating these two maladies. Furthermore, we conducted a retrospective study where we evaluated the clinical patterns in patients with chronic pancreatitis who underwent resection for a pancreatic mass. Although certain findings may be indicative for benign tumors, none of the diagnostic tools available offers a sufficient degree of certainty. In cases of tumors secondary to autoimmune pancreatitis the diagnostic error is exceptionally high. Because of the poor prognosis related to untreated pancreatic cancer, the general recommendation is to perform resection of the tumor when technically possible and when carcinoma cannot be ruled out completely.

  6. Photodynamic therapy of advanced malignant tumors

    NASA Astrophysics Data System (ADS)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  7. Gastrointestinal stromal tumors (GISTs) and second malignancies

    PubMed Central

    Rodriquenz, Maria Grazia; Rossi, Sabrina; Ricci, Riccardo; Martini, Maurizio; Larocca, Mario; Dipasquale, Angelo; Quirino, Michela; Schinzari, Giovanni; Basso, Michele; D’Argento, Ettore; Strippoli, Antonia; Barone, Carlo; Cassano, Alessandra

    2016-01-01

    Abstract Several evidences showed that patients with gastrointestinal stromal tumors (GISTs) develop additional malignancies. However, thorough incidence of second tumors remains uncertain as the possibility of a common molecular pathogenesis. A retrospective series of 128 patients with histologically proven GIST treated at our institution was evaluated. Molecular analysis of KIT and PDGFR-α genes was performed in all patients. Following the involvement of KRAS mutation in many tumors’ pathogenesis, analysis of KRAS was performed in patients with also second neoplasms. Forty-six out of 128 GIST patients (35.9%) had a second neoplasm. Most second tumors (52%) raised from gastrointestinal tract and 19.6% from genitourinary tract. Benign neoplasms were also included (21.7%). Molecular analysis was available for 29/46 patients with a second tumor: wild-type GISTs (n. 5), exon 11 (n. 16), exon 13 (n. 1), exon 9 (n. 1) KIT mutations, exon 14 PDGFR-α mutation (n. 2) and exon 18 PDGFR-α mutation (n. 4). KIT exon 11 mutations were more frequent between patients who developed a second tumor (P = 0.0003). Mutational analysis of KRAS showed a wild-type sequence in all cases. In metachronous cases, the median time interval between GIST and second tumor was 21.5 months. The high frequency of second tumors suggests that an unknown common molecular mechanism might play a role, but it is not likely that KRAS is involved in this common pathogenesis. The short interval between GIST diagnosis and the onset of second neoplasms asks for a careful follow-up, particularly in the first 3 years after diagnosis. PMID:27661019

  8. Comparison of loss of heterozygosity patterns between ovarian tumors of low malignant potential and malignant ovarian tumors

    SciTech Connect

    Crawford, E.C.; Miller, D.M.; Finley, W.H.

    1994-09-01

    Ovarian tumors of low malignant potential (LMP) represent a pathologic subtype of ovarian tumor that possess many features common to malignant tumors including epithelial stratification, increased mitotic activity and atypical cellularity. These tumors, however, do not invade the ovarian stroma and have a much improved patient prognosis. Utilizing dinucleotide repeats, loss of heterozygosity (LOH) studies were performed on a total of 12 ovarian tumors of LMP in 5 regions found to have significant levels of LOH in malignant ovarian tumors. The regions chosen for study were 3p, 6q, 11p, 17p and 17q. LOH could be demonstrated in malignant ovarian tumors in loci from 3p, 11p and both chromosomal arms of 17 when compared to normal tissue from the same patient. Loss in malignant tumors was more common in loci mapped to 3p21 and to 11p15. OH was not noted in any samples for a repeat in the TP53 gene even though flanking markers on 17p were lost in 1 patient with a malignant tumor. Loss was not demonstrated in any of the loci examined from 6q in malignant ovarian tumors. LOH was not demonstrated in any of the 39 loci examined from any of the five chromosomal regions in the ovarian tumors of LMP. Cytogenetic analyses of these LMP tumors were consistent with lack of involvement in these chromosomal regions. These data suggest the mechanism of tumorigenesis is different in tumors of LMP from that in malignant ovarian tumors.

  9. Association of Chronic Pancreatitis and Malignant Main Duct IPMN: A Rare but Difficult Clinical Problem.

    PubMed

    Berger, Zoltán; De La Fuente, Hernán; Meneses, Manuel; Matamala, Fernanda; Sepúlveda, Makarena; Rojas, Claudia

    2017-01-01

    We report the case of a 70-year-old woman who consulted for recurrent short episodes of mild-to-moderate abdominal pain. Dilated main pancreatic duct was seen on CAT scan and magnetic resonance, with multiple calcifications and intraductal stones, typical in CP. However, for a more pronounced cystic dilatation in the pancreatic head, we could not exclude the coexistence of a main duct IPMN. ERCP was performed, with pancreatic sphincterotomy and extraction of pancreatic stones, but, at the same time, mucin extrusion was seen from the dilated duct through the papilla. Pancreatoduodenectomy was performed. Surgery and histology confirmed malignant IPMN with the typical image of chronic pancreatitis and intraductal stones in the vicinity. The patient is doing well 4 years after the surgery, without recurrence of the malignant disease, with changes of chronic pancreatitis in the pancreatic remnant. This paper discusses the possible relationships between the two entities and emphasizes the need of differential diagnosis.

  10. Association of Chronic Pancreatitis and Malignant Main Duct IPMN: A Rare but Difficult Clinical Problem

    PubMed Central

    De La Fuente, Hernán; Meneses, Manuel; Matamala, Fernanda; Sepúlveda, Makarena; Rojas, Claudia

    2017-01-01

    We report the case of a 70-year-old woman who consulted for recurrent short episodes of mild-to-moderate abdominal pain. Dilated main pancreatic duct was seen on CAT scan and magnetic resonance, with multiple calcifications and intraductal stones, typical in CP. However, for a more pronounced cystic dilatation in the pancreatic head, we could not exclude the coexistence of a main duct IPMN. ERCP was performed, with pancreatic sphincterotomy and extraction of pancreatic stones, but, at the same time, mucin extrusion was seen from the dilated duct through the papilla. Pancreatoduodenectomy was performed. Surgery and histology confirmed malignant IPMN with the typical image of chronic pancreatitis and intraductal stones in the vicinity. The patient is doing well 4 years after the surgery, without recurrence of the malignant disease, with changes of chronic pancreatitis in the pancreatic remnant. This paper discusses the possible relationships between the two entities and emphasizes the need of differential diagnosis. PMID:28321347

  11. Malignant phyllodes tumor of the breast: a case study.

    PubMed

    Keim-Malpass, Jessica; Mills, Anne M; Showalter, Shayna L

    2014-10-01

    Malignant phyllodes tumors of the breast are rare, fast-growing tumors that can be difficult to diagnose. A case study is featured about a young adult patient who lacked insurance and received a delayed diagnosis of malignant phyllodes tumor of the breast. This article includes pertinent clinical and age-specific considerations for comprehensive management.

  12. Collision tumors: pancreatic adenocarcinoma and mantle cell lymphoma.

    PubMed

    Dasanu, Constantin A; Shimanovsky, Alexei; Rotundo, Edyta K; Posteraro, Anthony F; Cooper, Dennis L; Atienza, Jonessa A

    2013-07-10

    Collision tumors are very rare entities composed of two or more distinct tumor components, each separated by normal tissue. Perhaps due to technical advances in the last decade, the incidence of collision tumors has been on the rise. To the best of our knowledge, collision tumors featuring mantle cell lymphoma and pancreatic adenocarcinoma have not been previously described in the scientific literature. For the first time, we describe herein the clinical course of a collision tumor between pancreatic adenocarcinoma and mantle cell lymphoma. We hypothesize several aspects in the pathogenesis of a such event and review the existing literature on collision tumors.

  13. Malignant salivary gland tumors in Quito, Ecuador.

    PubMed

    Pacheco-Ojeda, L; Domeisen, H; Narvaez, M; Tixi, R; Vivar, N

    2000-01-01

    Malignant salivary gland tumors (MSGT) are uncommon. Age-standardized incidence rates are 0.5 and 0.3 per 100,000 in Quito, Ecuador; and 1.0 and 0.7 per 100,000 in the USA (SEER Program), for males and females, respectively. The goal of this study was to review a 16-year experience of a major general hospital in the treatment of these lesions. From 1982 to 1998, 308 salivary gland tumors were surgically treated at the Hospital 'Carlos Andrade Marin' of the Ecuadorian Institute of Social Security in Quito, Ecuador, an Andean city of approximately 2 million inhabitants. Malignant lesions were found in 58 cases (19%): 37 out of 194 parotid gland tumors (19%), 7 out of 86 submandibular tumors (8%) and 14 out of 28 minor salivary gland tumors (50%). Adenoid cystic carcinoma and mucoepidermoid carcinoma were the most common histologic types. Twenty-two cases were classified as stage I, 13 as stage II, 1 as stage III and 20 as stage IV (UICC TNM staging classification). Thirty-one (53%) patients were treated by surgery alone; postoperative radiation therapy was additionally given to 22 (38%), and surgery, radiotherapy and chemotherapy were applied in 5 cases (9%). Local (LR) and/or regional recurrences were detected in 13 patients (22%). Twelve patients (21%) developed distant metastasis (DM; 2 in more than one site): 7 in the lungs, 2 in the brain, 2 in the bone and 1 each in the liver, subcutaneous tissue and pleura. Thirty-five patients are alive, 33 disease free. Twenty-three patients are deceased: 6 with LR, 7 with DM, 3 with both LR and DM, 1 with locoregional recurrence and DM, 2 with a second neoplasm, 3 with intercurrent disease and 1 from unknown causes. Five- and 10-year overall survival rates were 75 and 68%, respectively. There were no significant differences in mortality according to the site of the primary tumor or histologic type, but stage and involved surgical margins were important prognostic factors (p = 0.006 and 0.003). The surgical or multimodality

  14. Dosimetric comparison of volumetric modulated arc therapy and intensity-modulated radiation therapy for pancreatic malignancies

    SciTech Connect

    Ali, Arif N.; Dhabaan, Anees H.; Jarrio, Christie S.; Siddiqi, Arsalan K.; Landry, Jerome C.

    2012-10-01

    Volumetric-modulated arc therapy (VMAT) has been previously evaluated for several tumor sites and has been shown to provide significant dosimetric and delivery benefits when compared with intensity-modulated radiation therapy (IMRT). To date, there have been no published full reports on the benefits of VMAT use in pancreatic patients compared with IMRT. Ten patients with pancreatic malignancies treated with either IMRT or VMAT were retrospectively identified. Both a double-arc VMAT and a 7-field IMRT plan were generated for each of the 10 patients using the same defined tumor volumes, organs at risk (OAR) volumes, dose, fractionation, and optimization constraints. The planning tumor volume (PTV) maximum dose (55.8 Gy vs. 54.4 Gy), PTV mean dose (53.9 Gy vs. 52.1 Gy), and conformality index (1.11 vs. 0.99) were statistically similar between the IMRT and VMAT plans, respectively. The VMAT plans had a statistically significant reduction in monitor units compared with the IMRT plans (1109 vs. 498, p < 0.001). In addition, the doses to the liver, small bowel, and spinal cord were comparable between the IMRT and VMAT plans. However, the VMAT plans demonstrated a statistically significant reduction in the mean left kidney V{sub 25} (9.4 Gy vs. 2.3 Gy, p = 0.018), mean right kidney V{sub 15} (53.4 Gy vs. 45.9 Gy, p = 0.035), V{sub 20} (32.2 Gy vs. 25.5 Gy, p = 0.016), and V{sub 25} (21.7 Gy vs. 14.9 Gy, p = 0.001). VMAT was investigated in patients with pancreatic malignancies and compared with the current standard of IMRT. VMAT was found to have similar or improved dosimetric parameters for all endpoints considered. Specifically, VMAT provided reduced monitor units and improved bilateral kidney normal tissue dose. The clinical relevance of these benefits in the context of pancreatic cancer patients, however, is currently unclear and requires further investigation.

  15. Tumor suppressor Fbxw7 antagonizes WNT signaling by targeting β-catenin for degradation in pancreatic cancer.

    PubMed

    Jiang, Jian-Xin; Sun, Cheng-Yi; Tian, She; Yu, Chao; Chen, Mei-Yuan; Zhang, Hao

    2016-10-01

    Pancreatic cancer is one of the deadliest solid malignancies associated with aberrant Wnt signaling activation. Fbxw7 mutations have been implicated in the development of pancreatic cancer, whereas the exact mechanism of this ubiquitin ligase as a tumor suppressor remains unclear in pancreatic carcinogenesis. Here, we describe that Fbxw7 is downregulated upon pancreatic cancer development. Depletion of Fbxw7 results in tumor suppression in pancreatic cancer cells, while Fbxw7 overexpression inhibits pancreatic cancer cell proliferation and invasion. Considering the negative correlation between Fbxw7 and β-catenin, we find that Fbxw7 antagonizes Wnt signaling through targeting β-catenin for its degradation. Moreover, the inhibitory effect of Fbxw7 on pancreatic cancer cell proliferation is mainly executed by the destruction of the Wnt/β-catenin signaling pathway. We also reveal that c-myc, a widely accepted target of Fbxw7, is also transcriptionally regulated by the Fbxw7/β-catenin axis in pancreatic cancer cells. Collectively, our results demonstrate that Fbxw7 is a novel regulator of Wnt/β-catenin signaling-dependent regulation of pancreatic cancer cell growth and invasion, and inactivation of Fbxw7 in pancreatic cancer tissues might be the reason for the aberrant activation of Wnt signaling.

  16. More Complete Removal of Malignant Brain Tumors by Fluorescence-Guided Surgery

    ClinicalTrials.gov

    2016-05-13

    Benign Neoplasms, Brain; Brain Cancer; Brain Neoplasms, Benign; Brain Neoplasms, Malignant; Brain Tumor, Primary; Brain Tumor, Recurrent; Brain Tumors; Intracranial Neoplasms; Neoplasms, Brain; Neoplasms, Intracranial; Primary Brain Neoplasms; Primary Malignant Brain Neoplasms; Primary Malignant Brain Tumors; Gliomas; Glioblastoma

  17. Endogenously Expressed IL-4Rα Promotes the Malignant Phenotype of Human Pancreatic Cancer In Vitro and In Vivo.

    PubMed

    Traub, Benno; Sun, Lie; Ma, Yongsu; Xu, Pengfei; Lemke, Johannes; Paschke, Stephan; Henne-Bruns, Doris; Knippschild, Uwe; Kornmann, Marko

    2017-03-28

    Exogenous interleukin-4 (IL-4) has been demonstrated to affect the growth of different human malignancies including pancreatic cancer cells. The aim of our study was to determine the role of endogenously expressed IL-4-receptor-α-chain (IL-4Rα) in pancreatic cancer cells. IL-4Rα-suppression was achieved by generating Capan-1 cells stably expressing shRNA targeting IL-4Rα. The malignant phenotype was characterized by assessing growth properties, directional and non-directional cell movement in vitro and tumor growth in vivo. Signaling pathways were analyzed upon IL-4 and IL-13 stimulation of wildtype (WT) and control-transfected cells compared to IL-4Rα-knockdown cells. Silencing of IL-4Rα resulted in reduced anchorage-dependent cell growth (p < 0.05) and reduced anchorage-independent colony size (p < 0.001) in vitro. Moreover, cell movement and migration was inhibited. IL-4 and IL-13 stimulation of Capan-1-WT cells induced activation of similar pathways like stimulation with Insulin-like growth factor (IGF)-I. This activation was reduced after IL-4Rα downregulation while IGF-I signaling seemed to be enhanced in knockdown-clones. Importantly, IL-4Rα silencing also significantly suppressed tumor growth in vivo. The present study indicates that endogenously expressed IL-4 and IL-4Rα contribute to the malignant phenotype of pancreatic cancer cells by activating diverse pro-oncogenic signaling pathways. Addressing these pathways may contribute to the treatment of the disease.

  18. Lymphoepithelial cysts of the pancreas. Can preoperative imaging distinguish this benign lesion from malignant or pre-malignant cystic pancreatic lesions?

    PubMed

    Kavuturu, Srinivas; Sarwani, Nabeel E; Ruggeiro, Fransesca M; Deshaies, Isabelle; Kimchi, Eric T; Kaifi, Jussuf T; Staveley-O'Carroll, Kevin F; Gusani, Niraj J

    2013-05-10

    Lymphoepithelial cysts of the pancreas are rare true benign cystic tumors of the pancreas of uncertain etiology. Cystic neoplasms of the pancreas present a significant diagnostic dilemma in differentiating benign from premalignant or malignant variants. Since the first description of lymphoepithelial cysts in 1985, 109 cases have been reported in the literature. We describe 6 cases of this rare tumor, the preoperative imaging results, and a review the literature. Five males and one female ranging in age from 47 to 76 years underwent resection for lymphoepithelial cysts. Five patients presented with abdominal pain related to the lesion and in one patient the lesion was discovered incidentally. Four patients had elevated serum CA 19-9 levels. Pre-operative imaging with a CT scan and MRI of the abdomen typically revealed a well defined hypodense mass with Hounsfield units (HU) in the range of 15 to 20. One patient had papillary projections into the lesion. The mean size was 3.3 cm (ranging from 1.8 cm to 4 cm). All lesions were exophytic off the pancreatic parenchyma (1 cyst was located in the head of the pancreas, 2 were in the body, and 3 were in the tail region). Pre-operative EUS-guided/CT-guided needle aspiration, when performed, was not diagnostic. All patients underwent resection (one pancreaticoduodenectomy, five left pancreatectomies) to remove these cystic neoplasms. Pathology revealed a cyst lined by non-dysplastic squamous cells surrounded by sheets of benign lymphocytes. No evidence of malignancy was found. Lymphoepithelial cysts of the pancreas are rare and are characteristically seen in men. While a hypodense mass (less than 20 HU) with papillary projections should be considered suspicious for lymphoepithelial cyst, a definitive diagnosis cannot be made solely based on preoperative imaging. EUS-guided biopsy coupled with biochemical/tumor marker studies are increasingly being used as a diagnostic tool to help differentiate between the various types of

  19. [Transformation of trigeminal nerve tumor into malignant peripheral nerve sheath tumor (MPNST)].

    PubMed

    Nenashev, E A; Cherekaev, V A; Kadasheva, A B; Kozlov, A V; Rotin, D L; Stepanian, M A

    2012-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare entity with only 18 cases of trigeminal nerve MPNST described by now and only one report of malignant transformation of trigeminal nerve tumor into MPNST published up to date. One more case of malignant transformation of trigeminal nerve (1st division) tumor into MPNST is demonstrated.

  20. [Risks factors for pediatric malignant liver tumors].

    PubMed

    Ferrís I Tortajada, J; Ortega García, J A; Garcia I Castell, J; López Andreu, J A; Ribes Koninckx, C; Berbel Tornero, O

    2008-04-01

    Pediatric Hepatic Malignancies (PHMs) are the result of the interaction between constitutional and environmental risk factors (RFs). We review the evidence on the main RFs associated to PHMs. Systematic review of the literature published in the last 25 years on Medline, Embase, Cancerlit, Lilacs and SciElo using the following key words: "etiology/risk factor/epidemiology" and "malignant liver tumors/hepatic cancer" or "hepatoblastoma/hepatocarcionoma". PHMs account for 1 % of all pediatric malignancies. The main types, hepatoblastoma (HB) and hepatocarcionma (HCC) make up 98-99 % of PHM. The main constitutional RFs are: a) Beckwith-Wiedemann (BW) syndrome; b) isolated hemihyperplasia syndrome (IHS); c) adenomatous polyps of the colon; d) hemochromatosis; e) Hereditary Tyrosinemia Type 1; f) a -1-antitrypsin deficiency; g) porphyrias; h) cirrhosis; i) nonalcoholic steatosis; and j) primary sclerosing cholangitis. The main environmental RFs are: a) hepatitis B virus (HBV) and C virus (HCV); b) B1 aflatoxin (B1AF); c) ionizing radiation; d) alcohol; e) hormonal treatments; f) occupational exposure to pesticides, solvents, vinyl chloride and metals; g) smoking; h) arsenic; i) prematury and very low birth weight; and j) trematodes. The clinical, analytical and ultrasound screening facilitate the early diagnosis of HB in the previously mentioned genetic syndromes, particularly BW and IHS during the first years of life. HBV universal vaccination of newborns provides the biggest opportunity to prevent a substantial proportion of PHMs. Also systematic monitoring of HBV and HCV in blood, hemoderivates, donated organs and drug addicts, are very useful. Other effective measures are: the reduction/elimination of B(1)AF in food, zero alcohol intake during childhood and adolescence as well decreasing prenatal exposure to the tobacco, solvents, pesticides, vinyl chloride, metals, ionizing radiation and hormonal treatments.

  1. Chondroitin sulfate proteoglycan CSPG4 as a novel hypoxia-sensitive marker in pancreatic tumors.

    PubMed

    Keleg, Shereen; Titov, Alexandr; Heller, Anette; Giese, Thomas; Tjaden, Christine; Ahmad, Sufian S; Gaida, Matthias M; Bauer, Andrea S; Werner, Jens; Giese, Nathalia A

    2014-01-01

    CSPG4 marks pericytes, undifferentiated precursors and tumor cells. We assessed whether the shed ectodomain of CSPG4 (sCSPG4) might circulate and reflect potential changes in CSPG4 tissue expression (pCSPG4) due to desmoplastic and malignant aberrations occurring in pancreatic tumors. Serum sCSPG4 was measured using ELISA in test (n = 83) and validation (n = 221) cohorts comprising donors (n = 11+26) and patients with chronic pancreatitis (n = 11+20) or neoplasms: benign (serous cystadenoma SCA, n = 13+20), premalignant (intraductal dysplastic IPMNs, n = 9+55), and malignant (IPMN-associated invasive carcinomas, n = 4+14; ductal adenocarcinomas, n = 35+86). Pancreatic pCSPG4 expression was evaluated using qRT-PCR (n = 139), western blot analysis and immunohistochemistry. sCSPG4 was found in circulation, but its level was significantly lower in pancreatic patients than in donors. Selective maintenance was observed in advanced IPMNs and PDACs and showed a nodal association while lacking prognostic relevance. Pancreatic pCSPG4 expression was preserved or elevated, whereby neoplastic cells lacked pCSPG4 or tended to overexpress without shedding. Extreme pancreatic overexpression, membranous exposure and tissue(high)/sera(low)-discordance highlighted stroma-poor benign cystic neoplasm. SCA is known to display hypoxic markers and coincide with von-Hippel-Lindau and Peutz-Jeghers syndromes, in which pVHL and LBK1 mutations affect hypoxic signaling pathways. In vitro testing confined pCSPG4 overexpression to normal mesenchymal but not epithelial cells, and a third of tested carcinoma cell lines; however, only the latter showed pCSPG4-responsiveness to chronic hypoxia. siRNA-based knockdowns failed to reduce the malignant potential of either normoxic or hypoxic cells. Thus, overexpression of the newly established conditional hypoxic indicator, CSPG4, is apparently non-pathogenic in pancreatic malignancies but might mark distinct

  2. Chondroitin Sulfate Proteoglycan CSPG4 as a Novel Hypoxia-Sensitive Marker in Pancreatic Tumors

    PubMed Central

    Keleg, Shereen; Titov, Alexandr; Heller, Anette; Giese, Thomas; Tjaden, Christine; Ahmad, Sufian S.; Gaida, Matthias M.; Bauer, Andrea S.; Werner, Jens; Giese, Nathalia A.

    2014-01-01

    CSPG4 marks pericytes, undifferentiated precursors and tumor cells. We assessed whether the shed ectodomain of CSPG4 (sCSPG4) might circulate and reflect potential changes in CSPG4 tissue expression (pCSPG4) due to desmoplastic and malignant aberrations occurring in pancreatic tumors. Serum sCSPG4 was measured using ELISA in test (n = 83) and validation (n = 221) cohorts comprising donors (n = 11+26) and patients with chronic pancreatitis (n = 11+20) or neoplasms: benign (serous cystadenoma SCA, n = 13+20), premalignant (intraductal dysplastic IPMNs, n = 9+55), and malignant (IPMN-associated invasive carcinomas, n = 4+14; ductal adenocarcinomas, n = 35+86). Pancreatic pCSPG4 expression was evaluated using qRT-PCR (n = 139), western blot analysis and immunohistochemistry. sCSPG4 was found in circulation, but its level was significantly lower in pancreatic patients than in donors. Selective maintenance was observed in advanced IPMNs and PDACs and showed a nodal association while lacking prognostic relevance. Pancreatic pCSPG4 expression was preserved or elevated, whereby neoplastic cells lacked pCSPG4 or tended to overexpress without shedding. Extreme pancreatic overexpression, membranous exposure and tissuehigh/seralow-discordance highlighted stroma-poor benign cystic neoplasm. SCA is known to display hypoxic markers and coincide with von-Hippel-Lindau and Peutz-Jeghers syndromes, in which pVHL and LBK1 mutations affect hypoxic signaling pathways. In vitro testing confined pCSPG4 overexpression to normal mesenchymal but not epithelial cells, and a third of tested carcinoma cell lines; however, only the latter showed pCSPG4-responsiveness to chronic hypoxia. siRNA-based knockdowns failed to reduce the malignant potential of either normoxic or hypoxic cells. Thus, overexpression of the newly established conditional hypoxic indicator, CSPG4, is apparently non-pathogenic in pancreatic malignancies but might mark distinct epithelial

  3. Targeted Therapies Improve Survival for Patients with Pancreatic Neuroendocrine Tumors

    Cancer.gov

    In 2011, based on initial findings from two clinical trials, the Food and Drug Administration approved sunitinib and everolimus for patients with pancreatic neuroendocrine tumors. Updated results from the everolimus trial were published in September 2016.

  4. What Is the Best Way to Identify Malignant Transformation Within Pancreatic IPMN: A Systematic Review and Meta-Analyses

    PubMed Central

    Sultana, Asma; Jackson, Richard; Tim, Gilbert; Bostock, Emma; Psarelli, Eftychia E; Cox, Trevor F; Sutton, Robert; Ghaneh, Paula; Raraty, Michael G T; Neoptolemos, John P; Halloran, Christopher M

    2015-01-01

    Objectives: Pancreatic intraductal papillary mucinous neoplasias (IPMNs) represent 25% of all cystic neoplasms and are precursor lesions for pancreatic ductal adenocarcinoma. This study aims to identify the best imaging modality for detecting malignant transformation in IPMN, the sensitivity and specificity of risk features on imaging, and the usefulness of tumor markers in serum and cyst fluid to predict malignancy in IPMN. Methods: Databases were searched from November 2006 to March 2014. Pooled sensitivity and specificity of diagnostic techniques/imaging features of suspected malignancy in IPMN using a hierarchical summary receiver operator characteristic (HSROC) approach were performed. Results: A total of 467 eligible studies were identified, of which 51 studies met the inclusion criteria and 37 of these were incorporated into meta-analyses. The pooled sensitivity and specificity for risk features predictive of malignancy on computed tomography/magnetic resonance imaging were 0.809 and 0.762 respectively, and on positron emission tomography were 0.968 and 0.911. Mural nodule, cyst size, and main pancreatic duct dilation found on imaging had pooled sensitivity for prediction of malignancy of 0.690, 0.682, and 0.614, respectively, and specificity of 0.798, 0.574, and 0.687. Raised serum carbohydrate antigen 19-9 (CA19-9) levels yielded sensitivity of 0.380 and specificity of 0903. Combining parameters yielded a sensitivity of 0.743 and specificity of 0.906. Conclusions: PET holds the most promise in identifying malignant transformation within an IPMN. Combining parameters increases sensitivity and specificity; the presence of mural nodule on imaging was the most sensitive whereas raised serum CA19-9 (>37 KU/l) was the most specific feature predictive of malignancy in IPMNs. PMID:26658837

  5. Immunohistochemical study of pancreatic neuroendocrine tumor in Panthera tigris tigris.

    PubMed

    Nyska, A; Goldstein, J; Eshkar, G; Klein, B

    1996-07-01

    The histological and immunohistochemical characteristics of a case of pancreatic neuroendocrine tumor are described in a 14-yr-old female Bengal tiger (Panthera tigris tigris) housed at the New Biblical Zoo of Jerusalem, Jerusalem, Israel, 1994. The neoplastic cells were immunohistochemically negative for insulin and glucagon, slightly positive for neuron-specific enolase, moderately positive for serotonin and somatostatin, and markedly positive for chromogranine A and gastrin. This is the first documentation of a pancreatic neuroendocrine tumor in the tiger.

  6. Emerging concepts in pancreatic cancer medicine: targeting the tumor stroma

    PubMed Central

    Neesse, Albrecht; Krug, Sebastian; Gress, Thomas M; Tuveson, David A; Michl, Patrick

    2014-01-01

    Pancreatic ductal adenocarcinoma is a stroma-rich and highly challenging cancer to treat. Over recent years, it has become increasingly evident that the complex network of soluble cytokines, growth factors, proteases, and components of the extracellular matrix collaboratively interact within the tumor microenvironment, sustaining and driving cancer cell proliferation, invasion, and early metastasis. More recently, the tumor microenvironment has also been appreciated to mediate therapeutic resistance in pancreatic ductal adenocarcinoma, thus opening numerous avenues for novel therapeutic explorations. Inert and soluble components of the tumor stroma have been targeted in order to break down the extracellular matrix scaffold, relieve vessel compression, and increase drug delivery to hypovascular tumors. Moreover, targeting of antiapoptotic, immunosuppressive, and pro-proliferative effects of the tumor stroma provides novel vantage points of attack. This review focuses on current and future developments in pancreatic cancer medicine, with a particular emphasis on biophysical and biochemical approaches that target the tumor microenvironment. PMID:24379681

  7. [Pelvic actinomycosis simulating adnexal malignant tumor].

    PubMed

    Benkiran, L; Gamra, L; Lamalmi, N; Essouyeh, M; Regragui, A; Amrani, M; Souadka, A; Melabbas, M A

    2002-01-01

    The purpose of this report is to describe the case of a 35-year-old patient admitted to the National Oncology Institute in Rabat, Morocco for pelvic pain and deteriorating general status ongoing for 8 months. Clinical and ultrasonographic examination showed a heterogenous mass measuring 7 cm in maximum width located inferior and lateral to the inferior aspect of the right side of the uterus. These findings were suggestive of a malignant tumor of the right ovary. Ovariectomy and omentectomy were performed. Histological examination of surgical specimens demonstrated right tubo-ovarian actinomycosis associated with peritonitis. Genital tract actinomycosis is an uncommon finding in women of childbearing age. It is due to colonization by a pyogenic bacteria (Actinomyces) usually secondary to a gastrointestinal infection, e.g. ileocecum, and sometimes in association with the presence of an intrauterine device or foreign body. Based on this case report, the authors discuss abdominopelvic actinomyocosis with emphasis on tumor-like findings that can lead to misdiagnosis by clinicians and radiologists.

  8. Radiopathological evaluation of primary malignant skull tumors: a review.

    PubMed

    Gangadhar, Kiran; Santhosh, Deepa

    2012-09-01

    Skull tumors comprise a wide variety of entities, ranging from chronic inflammatory disease to primary and secondary neoplasms. There is no valid incidence or data about the incidence of skull tumors in general. Primary malignant skull tumors are rare, with most articles reporting single cases. We would discuss some of the frequent tumors in this group and review of the literature for the same.

  9. Targeting pancreatic expressed PAX genes for the treatment of diabetes mellitus and pancreatic neuroendocrine tumors.

    PubMed

    Martin-Montalvo, Alejandro; Lorenzo, Petra I; López-Noriega, Livia; Gauthier, Benoit R

    2017-01-01

    Four members of the PAX family, PAX2, PAX4, PAX6 and PAX8 are known to be expressed in the pancreas. Accumulated evidences indicate that several pancreatic expressed PAX genes play a significant role in pancreatic development/functionality and alterations in these genes are involved in the pathogenesis of pancreatic diseases. Areas covered: In this review, we summarize the ongoing research related to pancreatic PAX genes in diabetes mellitus and pancreatic neuroendocrine tumors. We dissect the current knowledge at different levels; from mechanistic studies in cell lines performed to understand the molecular processes controlled by pancreatic PAX genes, to in vivo studies using rodent models that over-express or lack specific PAX genes. Finally, we describe human studies associating variants on pancreatic-expressed PAX genes with pancreatic diseases. Expert opinion: Based on the current literature, we propose that future interventions to treat pancreatic neuroendocrine tumors and diabetes mellitus could be developed via the modulation of PAX4 and/or PAX6 regulated pathways.

  10. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    ClinicalTrials.gov

    2017-02-07

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

  11. Radiation-induced malignant and atypical peripheral nerve sheath tumors

    SciTech Connect

    Foley, K.M.; Woodruff, J.M.; Ellis, F.T.; Posner, J.B.

    1980-04-01

    The reported peripheral nerve complications of therapeutic irradiation in humans include brachial and lumbar plexus fibrosis and cranial and peripheral nerve atrophy. We have encountered 9 patients with malignant (7) and atypical (2) peripheral nerve tumors occurring in an irradiated site suggesting that such tumors represent another delayed effect of radiation treatment on peripheral nerve. In all instances the radio-theray was within an acceptable radiation dosage, yet 3 patients developed local radiation-induced skin and bony abnormalities. The malignant peripheral nerve sheath tumors developed only in the radiation port. Animal studies support the clinical observation that malignant peripheral nerve sheath tumors can occur as a delayed effect of irradiation.

  12. Penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis

    PubMed Central

    Ranjan, Alok; Srivastava, Sanjay K.

    2016-01-01

    Pancreatic tumors exhibit enhanced autophagy as compared to any other cancer, making it resistant to chemotherapy. We evaluated the effect of penfluridol against pancreatic cancer. Penfluridol treatment induced apoptosis and inhibited the growth of Panc-1, BxPC-3 and AsPC-1, pancreatic cancer cells with IC50 ranging between 6–7 μM after 24 h of treatment. Significant autophagy was induced by penfluridol treatment in pancreatic cancer cells. Punctate LC3B and autophagosomes staining confirmed autophagy. Inhibiting autophagy by chloroquine, bafilomycin, 3-methyladenine or LC3BsiRNA, significantly blocked penfluridol-induced apoptosis, suggesting that autophagy lead to apoptosis in our model. Penfluridol treatment suppressed the growth of BxPC-3 tumor xenografts by 48% as compared to 17% when treated in combination with chloroquine. Similarly, penfluridol suppressed the growth of AsPC-1 tumors by 40% versus 16% when given in combination with chloroquine. TUNEL staining and caspase-3 cleavage revealed less apoptosis in the tumors from mice treated with penfluridol and chloroquine as compared to penfluridol alone. Penfluridol treatment also suppressed the growth of orthotopically implanted Panc-1 tumors by 80% by inducing autophagy-mediated apoptosis in the tumors. These studies established that penfluridol inhibits pancreatic tumor growth by autophagy-mediated apoptosis. Since penfluridol is already in clinic, positive findings from our study will accelerate its clinical development. PMID:27189859

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

    ClinicalTrials.gov

    2017-01-19

    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

  14. Targeted Disruption of Orchestration between Stroma and Tumor Cells in Pancreatic Cancer: Molecular Basis and Therapeutic Implications

    PubMed Central

    Kong, Xiangyu; Li, Lei; Li, Zhaoshen; Xie, Keping

    2012-01-01

    Pancreatic cancer is one of the most lethal malignancies, with a prominent desmoplastic reaction as the defining hallmark of the disease. The past several decades have seen dramatic progress in understanding of pancreatic cancer pathogenesis, including the identification of precursor lesions, sequential transformation from normal pancreas to invasive pancreatic cancer and corresponding signature genetic events, and the biological impact of those alterations on malignant behaviors. However, the current therapeutic strategies for epithelial tumor cells, which have exhibited potent antitumor activity in cell culture and animal models, have failed to have significant effects in the clinic. The desmoplastic stroma surrounding pancreatic cancer cells, which accounts for about 90% of a tumor’s mass, clearly is not a passive scaffold for cancer cells but an active contributor to carcinogenesis. Improved understanding of the dynamic interaction between cancer cells and their stroma will be important to designing new, effective therapeutic strategies for pancreatic cancer. This review focuses on the origination of stromal molecular and cellular components in pancreatic tumors, their biological effects on pancreatic cancer cells, and the orchestration between these two components. PMID:22749856

  15. Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors.

    PubMed

    Hall, MacLean; Liu, Hao; Malafa, Mokenge; Centeno, Barbara; Hodul, Pamela J; Pimiento, José; Pilon-Thomas, Shari; Sarnaik, Amod A

    2016-01-01

    We evaluated whether tumor infiltrating lymphocytes (TIL) could be expanded from surgically resected tumors from pancreatic cancer patients. Tumors were resected from pancreatic cancer patients. Tumors were minced into fragments and cultured in media containing high dose interleukin-2 (IL-2) for up to 6 weeks. T cell phenotype, activation markers, and reactivity were measured. TIL expansion was measured in 19 patient samples. The majority of these TIL were CD4(+) T cells and were highly activated. Purified CD8(+) T cells produced IFN-γ in response to HLA-matched pancreatic tumor targets. PD-1 blockade and 4-1BB stimulation were demonstrated as effective strategies to improve effective TIL yield, including the production of tumor-reactive pancreatic TIL. TIL expanded from pancreatic tumors are functional and able to respond to pancreatic tumor associated antigens. PD-1 blockade, 41BB stimulation, and CD8(+) T cell enrichment are effective strategies to improve TIL yield and tumor reactivity. These results support the development of adoptive cell therapy strategies using TIL for the treatment of pancreatic cancer.

  16. Malignant transformation of biliary adenofibroma: a rare biliary cystic tumor

    PubMed Central

    Zendejas-Mummert, Benjamin; Hartgers, Mindy L.; Venkatesh, Sudhakar K.; Smyrk, Thomas C.; Mahipal, Amit; Smoot, Rory L.

    2016-01-01

    Biliary adenofibromas (BAFs) are rare, benign biliary cystic tumors with potential for malignant transformation. Of the eleven prior cases of BAF reported in the literature, six showed evidence of malignant transformation. We describe the clinical, imaging and pathology features of two cases of malignant BAF and review the existing literature to raise awareness of this entity and provide additional tools for diagnosing this rare tumor Additionally, we identified a loss of function mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) tumor suppressor gene in a malignant caudate lobe BAF, thereby providing potential insight into the molecular pathogenesis of BAF malignant transformation. Although additional cases and longer-term follow-up are needed, our cases suggest that recurrence or metastasis of malignant BAF is not common and that complete surgical resection can be curative. PMID:28078134

  17. Calcitonin-secreting pancreatic neuroendocrine tumors: a case report and review of the literature.

    PubMed

    Kováčová, Martina; Filková, Marta; Potočárová, Mária; Kiňová, Soňa; Pajvani, Utpal B

    2014-08-01

    We report the presentation and novel therapy of a calcitonin-secreting pancreatic neuroendocrine tumor (PNET) and review the literature on this unusual neoplasm. We cite the history of a 38-year-old male who presented with fatigue, weight loss, and diarrhea and was found to have a pancreatic head mass on cross-sectional imaging, as well as liver metastases. The patient's laboratory evaluation was notable for a >100-fold elevation of the peptide hormone calcitonin in serum. As calcitonin is typically secreted by thyroid C-cells, hypercalcitoninemia is considered a marker for medullary thyroid cancer (MTC) or C-cell hyperplasia, but it may be present in several physiologic or pathologic conditions or may be ectopically secreted in rare PNETs. An octreotide scan confirmed the presence of somatostatin (SST) receptors on the pancreatic mass and liver metastases, leading to the diagnosis of a calcitonin-secreting PNET. We initiated treatment with long-acting SST analogs and peptide receptor radionuclide therapy (90Yttrium-DOTATOC) and achieved disease regression while maintaining a high quality of life. Functional PNETs that secrete calcitonin are exceedingly rare, but they are important to consider in the differential diagnosis of nonthyroid-mediated hypercalcitonemia or pancreatic tumors that present with diarrhea, as the management differs markedly from both MTC and other pancreatic malignancies.

  18. Targeting pancreatitis blocks tumor-initiating stem cells and pancreatic cancer progression

    PubMed Central

    Madka, Venkateshwar; Brewer, Misty; Ritchie, Rebekah L.; Lightfoot, Stan; Kumar, Gaurav; Sadeghi, Michael; Patlolla, Jagan Mohan R.; Yamada, Hiroshi Y.; Cruz-Monserrate, Zobeida; May, Randal; Houchen, Courtney W.; Steele, Vernon E.; Rao, Chinthalapally V.

    2015-01-01

    Recent development of genetically engineered mouse models (GEMs) for pancreatic cancer (PC) that recapitulates human disease progression has helped to identify new strategies to delay/inhibit PC development. We first found that expression of the pancreatic tumor-initiating/cancer stem cells (CSC) marker DclK1 occurs in early stage PC and in both early and late pancreatic intraepithelial neoplasia (PanIN) and that it increases as disease progresses in GEM and also in human PC. Genome-wide next generation sequencing of pancreatic ductal adenocarcinoma (PDAC) from GEM mice revealed significantly increased DclK1 along with inflammatory genes. Genetic ablation of cyclo-oxygenase-2 (COX-2) decreased DclK1 in GEM. Induction of inflammation/pancreatitis with cerulein in GEM mice increased DclK1, and the novel dual COX/5-lipoxygenase (5-LOX) inhibitor licofelone reduced it. Dietary licofelone significantly inhibited the incidence of PDAC and carcinoma in situ with significant inhibition of pancreatic CSCs. Licofelone suppressed pancreatic tumor COX-2 and 5-LOX activities and modulated miRNAs characteristic of CSC and inflammation in correlation with PDAC inhibition. These results offer a preclinical proof of concept to target the inflammation initiation to inhibit cancer stem cells early for improving the treatment of pancreatic cancers, with immediate clinical implications for repositioning dual COX/5-LOX inhibitors in human trials for high risk patients. PMID:25906749

  19. Systematic comparison of sporadic and syndromic pancreatic islet cell tumors.

    PubMed

    Erlic, Zoran; Ploeckinger, Ursula; Cascon, Alberto; Hoffmann, Michael M; von Duecker, Laura; Winter, Aurelia; Kammel, Gerit; Bacher, Janina; Sullivan, Maren; Isermann, Berend; Fischer, Lars; Raffel, Andreas; Knoefel, Wolfram Trudo; Schott, Matthias; Baumann, Tobias; Schaefer, Oliver; Keck, Tobias; Baum, Richard P; Milos, Ioana; Muresan, Mihaela; Peczkowska, Mariola; Januszewicz, Andrzej; Cupisti, Kenko; Tönjes, Anke; Fasshauer, Mathias; Langrehr, Jan; von Wussow, Peter; Agaimy, Abbas; Schlimok, Günter; Lamberts, Regina; Wiech, Thorsten; Schmid, Kurt Werner; Weber, Alexander; Nunez, Mercedes; Robledo, Mercedes; Eng, Charis; Neumann, Hartmut P H

    2010-12-01

    Pancreatic islet cell tumors (ICTs) occur as sporadic neoplasias or as a manifestation of multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau disease (VHL). Molecular classification of ICTs is mandatory for timely diagnosis and surveillance. Systematic comparison of VHL-ICTs and sporadic ICTs has been lacking. Our registry-based approaches used the German NET-Registry with 259 patients with neuroendocrine tumors (NETs), who were primarily diagnosed with NETs, and the German VHL-Registry with 485 molecular genetically confirmed patients who had undergone magnetic resonance imaging or computed tomography of the abdomen. All patients provided blood DNA for testing of the MEN1 and VHL genes for intragenic mutations and large deletions. In the NET-Registry, 9/101 patients (8.9%) with ICTs had germline mutations, 8 in MEN1 and 1 in VHL. In the VHL-Registry, prevalence of NETs was 52/487 (10.6%), and all were ICTs. Interestingly, of those with VHL p.R167W, 47% developed ICTs, compared to 2% of those with p.Y98H. In total, there were 92 truly sporadic, i.e. mutation-negative ICT patients. Comparing these with the 53 VHL-ICT patients, the statistically significant differences were predominance of female gender (P=0.01), multifocal ICTs (P=0.0029), and lower malignancy rate (P<0.001) in VHL-ICTs compared to sporadic cases. VHL was prevalent in <0.5% of NETs, while NETs occur in ∼10% of VHL, virtually exclusively as ICTs, which are rarely the first presentation. Patients with NETs should not be subjected to genetic testing of the VHL gene, unless they have multifocal ICTs, other VHL-associated tumors, and/or a family history for VHL.

  20. Targeting Malignant Brain Tumors with Antibodies.

    PubMed

    Razpotnik, Rok; Novak, Neža; Čurin Šerbec, Vladka; Rajcevic, Uros

    2017-01-01

    Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood-brain barrier (BBB) makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain delivery platforms for antibodies have been studied such as liposomes, nanoparticle-based systems, cell-penetrating peptides (CPPs), and cell-based approaches. We have already shown the successful delivery of single-chain fragment variable (scFv) with CPP as a linker between two variable domains in the brain. Antibodies normally face poor penetration through the BBB, with some variants sufficiently passing the barrier on their own. A "Trojan horse" method allows passage of biomolecules, such as antibodies, through the BBB by receptor-mediated transcytosis (RMT). Such examples of therapeutic antibodies are the bispecific antibodies where one binding specificity recognizes and binds a BBB receptor, enabling RMT and where a second binding specificity recognizes an antigen as a therapeutic target. On the other hand, cell-based systems such as stem cells (SCs) are a promising delivery system because of their tumor tropism and ability to cross the BBB. Genetically engineered SCs can be used in gene therapy, where they express anti-tumor drugs, including antibodies. Different types and sources of SCs have been studied for the delivery of therapeutics to the brain; both mesenchymal stem cells (MSCs) and neural stem cells (NSCs) show great potential. Following the success in treatment of leukemias and lymphomas, the adoptive T-cell therapies, especially the chimeric antigen receptor-T cells (CAR-Ts), are making their way into glioma treatment as another type of cell-based therapy using the

  1. Inflammatory myofibroblastic tumor of the distal bile duct associated with lymphoplasmacytic sclerosing pancreatitis. Case report and review of the literature.

    PubMed

    Martín Malagón, Antonio; López-Tomassetti Fernández, Eudaldo; Arteaga González, Iván; Carrillo Pallarés, Angel; Díaz Luis, Hermogenes

    2006-01-01

    Inflammatory myofibroblastic tumor (IMT) or inflammatory pseudotumor has been described in various organs such as the liver, intestinal tract, spleen, kidney, bladder, lung, peritoneum and heart. However, its appearance in the periampullary region is uncommon and has rarely been reported in the literature. It is characterized histologically by myofibroblastic cell proliferation together with a mixed inflammatory infiltrate that clinically and radiologically mimics a malignant tumor. We report a case of IMT located in the distal common bile duct of a 51-year-old woman. She underwent Whipple resection with the initial diagnosis of cholangiocarcinoma; the pathologic diagnosis of the tumor was IMT of the distal bile duct associated with lymphoplasmacytic sclerosing pancreatitis. Referring to previously reported cases, suspected diagnosis of a malignant tumor made surgical excision the primary choice for symptom relief and in order to obtain a definitive diagnosis. IMT relationship with lymphoplasmacytic sclerosing pancreatitis is discussed.

  2. Integrated clinicopathological features and gene microarray analysis of pancreatic neuroendocrine tumors.

    PubMed

    Zhou, Huaqiang; Chen, Qinchang; Tan, Wulin; Qiu, Zeting; Li, Si; Song, Yiyan; Gao, Shaowei

    2017-08-20

    Pancreatic neuroendocrine tumors are relatively rare pancreatic neoplasms over the world. Investigations about molecular biology of PNETs are insufficient for nowadays. We aimed to explore the expression of messenger RNA and regulatory processes underlying pancreatic neuroendocrine tumors from different views. The expression profile of GSE73338 were downloaded, including samples with pancreatic neuroendocrine tumors. First, the Limma package was utilized to distinguish the differentially expressed messenger RNA. Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to explore the functions and pathways of target genes. In addition, we constructed a protein-protein interaction network. NEK2, UBE2C, TOP2A and PPP1R1A were revealed with continuous genomic alterations in higher tumor stage. 91 up-regulated and 36 down-regulated genes were identified to be differentially expressed in malignant PNETs. Locomotory behavior was significantly enriched for biological processes of metastasis PNETs. GCGR and GNAS were identified as the hub of proteins in the protein-protein interaction sub-network of malignant PNETs. We showed the gene expression differences in PNETs according to different clinicopathological aspects. NEK2, UBE2C, TOP2A are positively associated with high tumor grade, and PPP1R1A negatively. GCGR and GNAS are regarded as the hub of the PPI sub-network. CXCR4 may affect the progression of PNETs via the CXCR4-CXCL12-CXCR7 chemokine receptor axis. However, more studies are required. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. [Neuroendocrine pancreatic tumors and helpfulness of targeted therapies].

    PubMed

    Vaysse, Thibaut; Coriat, Romain; Perkins, Géraldine; Dhooge, Marion; Brezault, Catherine; Chaussade, Stanislas

    2013-06-01

    The neuroendocrine pancreatic tumors are rare tumors, but their incidence is constantly rising. Even if the management of these tumors has to be surgical as soon as possible, the disease is most often metastatic at the stage of the diagnostic. The prognostic and the therapeutic options differ from pancreatic adenocarcinoma. Available treatments have evolved over the last years with recent publications of studies that bring to light the benefits of targeted therapies in this pathology. This has resulted in modifications of both practices and either French and international guidelines. Therefore, we focus on the management of the grade 1 and grade 2 well-differentiated neuroendocrine pancreatic tumors as classified in new WHO classification of neuroendocrine neoplasms published in 2010.

  4. Malignant granular cell tumor with unusual histological features.

    PubMed

    Behzatoğlu, Kemal; Bahadir, Burak

    2007-02-01

    Malignant granular cell tumor, although uncommon, should be differentiated from a number of granular cell-containing tumors. Reported herein is a distinctive variant of malignant granular cell tumor, clinically presenting as a rapidly enlarging scrotal mass, in which some areas morphologically displayed features indistinguishable from Kaposi sarcoma. Cells in areas simulating Kaposi sarcoma were immunohistochemically the same as typical granular cells in other portions of the tumor. The recognition of this pattern is important because it may predominate and overshadow the original nature of tumor.

  5. Melanocytic Malignant Peripheral Nerve Sheath Tumor of the Male Breast.

    PubMed

    Wang, Haijun; Ge, Jing; Chen, Lirong; Xie, Panpan; Chen, Fangfang; Chen, Yiding

    2009-01-01

    SUMMARY: BACKGROUND: Malignant peripheral nerve sheath tumors are rare tumor entities that originate from peripheral nerve sheaths and have an unfavorable prognosis. Common sites include deeper soft tissues, usually in the proximity of a nerve trunk. Breast is an absolutely rare location of this lesion, and presentation as a breast lump in the male breast is even rarer. CASE REPORT: A 65-year-old man presented with a 6-month history of a painless mass of the left breast. Tissue biopsy was performed. Histopathology revealed a malignant spindle cell tumor which was confirmed to be a melanocytic malignant peripheral nerve sheath tumor on the basis of immunopositivity for HMB45 and S-100. CONCLUSION: There are no generally accepted guidelines for the treatment of malignant peripheral nerve sheath tumors in the male breast. The patient was referred for radiation therapy after simple mastectomy.

  6. CHIP is a novel tumor suppressor in pancreatic cancer and inhibits tumor growth through targeting EGFR

    PubMed Central

    Wang, Tianxiao; Yang, Jingxuan; Xu, Jianwei; Li, Jian; Cao, Zhe; Zhou, Li; You, Lei; Shu, Hong; Lu, Zhaohui; Li, Huihua; Li, Min; Zhang, Taiping; Zhao, Yupei

    2014-01-01

    Carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is an E3 ubiquitin ligase that is involved in protein quality control and mediates several tumor-related proteins in many cancers, but the function of CHIP in pancreatic cancer is not known. Here we show that CHIP interacts and ubiquitinates epidermal growth factor receptor (EGFR) for proteasome-mediated degradation in pancreatic cancer cells, thereby inhibiting the activation of EGFR downstream pathways. CHIP suppressed cell proliferation, anchor-independent growth, invasion and migration, as well as enhanced apoptosis induced by erlotinib in vitro and in vivo. The expression of CHIP was decreased in pancreatic cancer tissues or sera. Low CHIP expression in tumor tissues was correlated with tumor differentiation and shorter overall survival. These observations indicate that CHIP serves as a novel tumor suppressor by down-regulating EGFR pathway in pancreatic cancer cells, decreased expression of CHIP was associated with poor prognosis in pancreatic cancer. PMID:24722501

  7. Use of cinacalcet and sunitinib to treat hypercalcaemia due to a pancreatic neuroendocrine tumor.

    PubMed

    Valdes-Socin, Hernan; Almanza, Matilde Rubio; Fernández-Ladreda, Mariana Tomé; Daele, Daniel Van; Polus, Marc; Chavez, Marcela; Beckers, Albert

    2017-09-18

    Neuroendocrine tumors (NETs) can secrete hormones, including ectopic secretions, but they have been rarely associated with malignant hypercalcemia. A 52-year-old man with a history of diabetes mellitus was diagnosed with a pancreatic tumor. A pancreatic biopsy confirmed a well-differentiated pancreatic NET (pNET). The patient subsequently developed liver metastasis and hypercalcemia with high 1,25 OH vitamin D and suppressed parathyroid hormone (PTH) levels. Hypercalcemia was refractory to chemotherapy, intravenous saline fluids, diuretics, calcitonin and zoledronate. Cinacalcet administration (120 mg/day) resulted in a significant calcium reduction. Hypocalcemia was observed when sunitinib was added three months later and cinacalcet was stopped. Subsequently, the calcium and PTH levels normalized. After six months, we observed 20% shrinkage of the pancreatic tumor and necrosis of a liver metastasis. Cinacalcet is an allosteric activator of the calcium receptor agonist, and it is used for severe hypercalcemia in patients with primary (benign and malignant) hyperparathyroidism. In this patient, cinacalcet demonstrated a calcium lowering effect, normalized hypophosphatemia, and improved the clinical condition of the patient. The mechanism through which cinacalcet improved PTH-rp mediated hypercalcemia is still unclear, but studies have suggested that a potential mechanism is the activation of calcitonin secretion. Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used to treat advanced pNETs. The hypocalcemic effects of sunitinib have not been previously described in a patient with pNET. Here, we report for the first time the successful combination of cinacalcet and sunitinib in the treatment of a pNET patient presenting with malignant hypercalcemia.

  8. Pancreatic solid cystic desmoid tumor: case report and literature review.

    PubMed

    Xu, Bin; Zhu, Ling-Hua; Wu, Jia-Guo; Wang, Xian-Fa; Matro, Erik; Ni, Jun-Jun

    2013-12-14

    Desmoid tumors (DTs) are nonmetastatic, locally aggressive neoplasms with a high rate of postoperative recurrence. Pancreatic DTs are especially rare; only a few cases have been reported to date. This paper describes a case of a sporadic cystic DT of the pancreas managed successfully with central pancreatectomy, with no signs of recurrence 40 mo after surgery. According to the literature, this is the first reported case in China of a pancreatic DT presenting as a solid cystic lesion, as well as the first pancreatic DT managed with central pancreatectomy and pancreaticogastrostomy. We report the case for its rarity and emphasize disease management by concerted application of clinical, pathological, radiological and immunohistochemical analyses.

  9. Pancreatic neuroendocrine tumors in twelve baboons (Papio spp.).

    PubMed

    Owston, M A; LaRue, M K; Dick, E J; Ambrus, A; Porter, B F

    2016-04-01

    Pancreatic neuroendocrine tumors (PNETs) are rare in nonhuman primates and in humans. Twenty-one PNETs from twelve female baboons (Papio spp.) from the Southwest National Primate Research Center were evaluated using histopathology and immunohistochemistry. Histologically, all tumors were benign and had neuroendocrine packeting. Immunohistochemical staining for synaptophysin and chromogranin was positive in all tumors evaluated (17/17). Insulin was positive in 16 of 21 tumors. Somatostatin was positive in 9 of 20 tumors. Multifocal staining for glucagon and pancreatic polypeptide was evident in a minority of tumors (6/20 and 2/17, respectively). Gastrin and vasoactive intestinal peptide were negative in all tumors evaluated. Nine tumors expressed more than one hormone marker. This is the first detailed pathologic study of pancreatic endocrine tumors in the baboon. The findings suggest that these tumors are generally benign and have similar morphologic and immunohistochemical features as those described in people, including the ability to express multiple hormones. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Pancreatic Neuroendocrine Tumors in Twelve Baboons (Papio spp.)

    PubMed Central

    Owston, M.A.; LaRue, M.K.; Dick, E.J.; Ambrus, A.; Porter, B.F.

    2016-01-01

    Background Pancreatic neuroendocrine tumors (PNETs) are rare in nonhuman primates and in humans. Methods Twenty-one PNETs from twelve female baboons (Papio spp.) from the Southwest National Primate Research Center were evaluated using histopathology and immunohistochemistry. Results Histologically, all tumors were benign and had neuroendocrine packeting. Immunohistochemical staining for synaptophysin and chromogranin was positive in all tumors evaluated (17/17). Insulin was positive in 16/21 tumors. Somatostatin was positive in 9/20 tumors. Multifocal staining for glucagon and pancreatic polypeptide was evident in a minority of tumors (6/20 and 2/17, respectively). Gastrin and vasoactive intestinal peptide were negative in all tumors evaluated. Nine tumors expressed more than one hormone marker. Conclusions This is the first detailed pathologic study of pancreatic endocrine tumors in the baboon. The findings suggest that these tumors are generally benign and have similar morphologic and immunohistochemical features as those described in people, including the ability to express multiple hormones. PMID:26899153

  11. Pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome.

    PubMed

    Murakami, Keigo; Nakamura, Yasuhiro; Felizola, Saulo J A; Morimoto, Ryo; Satoh, Fumitoshi; Takanami, Kentaro; Katakami, Hideki; Hirota, Seiichi; Takeda, Yoshiyu; Meguro-Horike, Makiko; Horike, Shin-Ichi; Unno, Michiaki; Sasano, Hironobu

    2016-11-15

    Solitary fibrous tumors occasionally present with hypoglycemia because of the excessive release of insulin-like growth factor II. We report the first case of pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome. An 82-year-old Japanese man presented with lower limb edema, uncontrolled hypertension, hypokalemia, and baseline hypercortisolism. Distal pancreatectomy was performed after the clinical diagnosis of a neuroendocrine tumor with ectopic secretion of adrenocorticotropic hormone. On histological examination, the tumor showed spindle cells in a fascicular arrangement. The diagnosis of the solitary fibrous tumor was confirmed by the identification of the NAB2-STAT6 fusion gene and positive immuno-histochemical staining for STAT6 and CD34. Using quantitative real-time polymerase chain reaction, mRNA that encoded proopiomelanocortin, precursor of adrenocorticotropic hormone, was detected. Proopiomelanocortin production through the demethylation of the promoter region Domain IV was detected. Pancreatic solitary fibrous tumors represent a new cause of ectopic adrenocorticotropic hormone syndrome.

  12. Unusual malignant tumors of the thyroid gland.

    PubMed

    Diaconescu, M R; Costea, I; Glod, M; Grigorovici, M; Diaconescu, S

    2013-01-01

    Although situated on the last places among the statistical hierarchy of human malignancies, thyroid cancers (TC) are the most common tumors of the endocrine system. Follicular epithelium neoplasms account for more than 90% of these lesions with a favourable prognosis, while resting tumors (medullary, anaplastic, lymphoma, sarcoma etc) generally present a rapid unfavorable evolution with a low rate of survival. In a series of 464 thyropathies personally treated, 72 cases of TC (15.5%) were identified. Fifty-seven patients presented epithelial TC a 34 papillary variant, 20 follicular variant and 8 mixed forms. Alongside these there were two medullary TC, 9 anaplastic TC and insular TC, and primary lymphoma and metastasis to the thyroid of a lung carcinoma each single case. Four cases have been described in patients who were aged 2-6 years at the time of the Chernobyl disaster. Out of the common types, based on our own taxonomic criteria, we selected a group of 36 TC with unusual clinical, histological and behavioural characteristics or particular pathological associations. Seven cases of occult TC, 7 cases with precessive adenopathy TC and 11 patients with TC associated with hyperthyroidism were registered. All of them underwent adapted thyroidectomies in which the presence of cancer was decisive for the extent of surgery. Medullary, insular and anaplastic TC were the most aggressive lesions and even extended surgery and complementary therapy failed to improve the prognosis of these patients. In the same category we included the cases presenting the coexistence of two TC types, pathologic dedifferentiation in recurrences and concurrent presence of another endocrine or nonendocrine cervical lesion. The a surgical dogma of total thyroidectomy cannot always be respected, so complementary therapeutic solutions must be applied. RESULTS were complex, registering steady recoveries in occult, hyperfunctioning and even in coexisting pathological lesions, but many recurrences

  13. Malignant insulinoma presenting as metastatic liver tumor. Case report and review of the literature.

    PubMed

    Baldelli, R; Ettorre, G; Vennarecci, G; Pasimeni, G; Carboni, F; Lorusso, R; Barnabei, A; Appetecchia, M

    2007-12-01

    Insulin-secreting tumors are the commonest hormone-producing neoplasm of the gastrointestinal tract. They occur with an incidence of 4 cases per million per year. About 10% of them are metastatic and malignant insulinomas very rarely observed in children and in elderly. We report a rare case of very large malignant insulinoma in a 71-year-old woman admitted in our Oncological Institute on October 2005. She presented with fasting hypoglicemia (blood glucose 35 mg/dl) and high serum insulin levels (insulin 115.9 microU/ml). A computerized tomographic scan showed a pancreatic tail lesion of about 6 cm in max diameter and multiple liver metastases. A whole body scintiscan using 111In-DTPA-D-Phe1-octreotide was made and an increased uptake in the tail of the pancreas has been found. The patient was submitted to liver biopsy and the diagnosis of a metastatic insulin-secreting tumor was immunoistochemically confirmed. Due to the presence of some hypoglicemic episodes uncontrolled by medical treatment, on December 2005 the patient was admitted to surgical intervention with a body and tail pancreatic resection. Post-operatively the patient experienced again syncope with hypoglycemia and hyperinsulinemia. It was then decided to start a schedule of treatment with somatostatin analog (octreotide subcutaneously 500 microg three times a day) with a good control of blood glucose levels (101 mg/dl). A trans-arterial chemioembolization was planned but the patient died for pancreatic and cardiovascular complications before this treatment started.

  14. Intraoperative methods to stage and localize pancreatic and duodenal tumors.

    PubMed

    Norton, J A

    1999-01-01

    Intraoperative methods to stage and localize tumors have dramatically improved. Advances include less invasive methods to obtain comparable results and precise localization of previously occult tumors. The use of new technology including laparoscopy and ultrasound has provided some of these advances, while improved operative techniques have provided others. Laparoscopy with ultrasound has allowed for improved staging of patients with pancreatic cancer and exclusion of patients who are not resectable for cure. We performed laparoscopy with ultrasound on 50 consecutive patients with adenocarcinoma of the pancreas or liver who appeared to have resectable tumors based on preoperative computed tomography. 22 patients (44%) were found to be unresectable because of tumor nodules on the liver and/or peritoneal surfaces or unsuspected distant nodal or liver metastases. The site of disease making the patient unresectable was confirmed by biopsy in each case. Of the 28 remaining patients in whom laparoscopic ultrasound predicted to be resectable for cure, 26 (93%) had all tumor removed. Thus laparoscopy with ultrasound was the best method to select patients for curative surgery. Intraoperative ultrasound (IOUS) has been a critical method to identify insulinomas that are not palpable. Nonpalpable tumors are most commonly in the pancreatic head. Because the pancreatic head is thick and insulinomas are small, of 9 pancreatic head insulinomas only 3 (33%) were palpable. However, IOUS precisely identified each (100%). Others have recommended blind distal pancreatectomy for individuals with insulinoma in whom no tumor can be identified. However, our data suggest that this procedure is contraindicated as these occult tumors are usually within the pancreatic head. Recent series suggest that previously missed gastrinomas are commonly in the duodenum. IOUS is not able to identify these tumors, but other methods can. Of 27 patients with 31 duodenal gastrinomas, palpation identified 19

  15. Imaging Review of Skeletal Tumors of the Pelvis Malignant Tumors and Tumor Mimics

    PubMed Central

    Girish, Gandikota; Finlay, Karen; Fessell, David; Pai, Deepa; Dong, Qian; Jamadar, David

    2012-01-01

    Malignant lesions of the pelvis are not uncommon and need to be differentiated from benign lesions and tumor mimics. Appearances are sometimes nonspecific leading to consideration of a broad differential diagnosis. Clinical history, anatomic location, and imaging characterization can help narrow the differential diagnosis. The focus of this paper is to demonstrate the imaging features and the role of plain films, computed tomography, and magnetic resonance imaging for detecting and characterizing malignant osseous pelvic lesions and their common mimics. PMID:22593667

  16. Rare Malignant Tumors of the Breast

    PubMed Central

    Miller, Trevor; Albarracin, Constance; Carkaci, Selin; Whitman, Gary J; Adrada, Beatriz E

    2015-01-01

    While the more common forms of breast cancer are well understood and recognized, there are many important rare malignancies that are less appreciated. Many of these cancers have imaging findings that, when understood, help to formulate a more educated differential diagnosis. In this article, the clinical features, imaging, and pathologic findings of rare breast malignancies will be discussed. PMID:26664775

  17. Rare Malignant Tumors of the Breast.

    PubMed

    Miller, Trevor; Albarracin, Constance; Carkaci, Selin; Whitman, Gary J; Adrada, Beatriz E

    2015-01-01

    While the more common forms of breast cancer are well understood and recognized, there are many important rare malignancies that are less appreciated. Many of these cancers have imaging findings that, when understood, help to formulate a more educated differential diagnosis. In this article, the clinical features, imaging, and pathologic findings of rare breast malignancies will be discussed.

  18. 99mTc-HYNIC-TOC imaging in the evaluation of pancreatic masses which are potential neuroendocrine tumors.

    PubMed

    Qiao, Zhen; Zhang, Jingjing; Jin, Xiaona; Huo, Li; Zhu, Zhaohui; Xing, Haiqun; Li, Fang

    2015-05-01

    The aim of this investigation was to determine the accuracy of the findings and the diagnoses of Tc-hydrazinonicotinyl-Tyr3-octreotide scan (Tc-HYNIC-TOC imaging) in patients with pancreatic masses which were potential neuroendocrine tumors. Records of total 20 patients with pancreatic masses were retrospectively reviewed. All of the patients had been revealed by abdominal contrast CT and possibility of neuroendocrine tumors could not be excluded by CT imaging before Tc-HYNIC-TOC imaging. Tc-HYNIC-TOC imaging was performed at 1 and 4 hours post-tracer injection, and SPECT/CT images of the abdomen were also acquired. The image findings were compared to final diagnoses which were made from pathological examination. Among all 20 pancreatic masses evaluated, there were 16 malignant lesions which included 1 ductal adenocarcinoma and 15 neuroendocrine tumors. Tc-HYNIC-TOC imaging identified 14 of 15 pancreatic neuroendocrine tumors and excluded 4 of 5 lesions which were not neuroendocrine tumors. The overall sensitivity, specificity, and accuracy was therefore 93.3% (14 of 15), 80% (4 of 5), and 90.0% (18 of 20), respectively, in our patient population. Tc-HYNIC-TOC imaging provides reasonable accuracy in the evaluation pancreatic mass suspected to be neuroendocrine tumors.

  19. Transformation of benign fibroadenoma to malignant phyllodes tumor

    PubMed Central

    Daigle, Megan E; Tortora, Matthew; Panasiti, Ryane

    2015-01-01

    The transformation of a benign fibroadenoma into a phyllodes tumor is uncommon and unpredictable. We report the case of a 40-year-old woman with a core biopsy proven fibroadenoma that underwent transformation into a malignant phyllodes tumor after 3 years of size stability. We present ultrasound and magnetic resonance images, as well as pathology slides from core biopsy and surgical excision, to illustrate this transformation. It has been suggested that phyllodes tumors may be misdiagnosed as fibroadenomas by core biopsy. However, in this case, pathology supports correct initial diagnosis of fibroadenoma and demonstrates a portion of the original fibroadenoma along the periphery of the malignant phyllodes tumor. PMID:26331090

  20. Considerable pancreatic tumor motion during breath-holding.

    PubMed

    Lens, Eelco; van der Horst, Astrid; Versteijne, Eva; Bel, Arjan; van Tienhoven, Geertjan

    2016-11-01

    Breath-holding (BH) is often used to reduce abdominal organ motion during radiotherapy. However, for inhale BH, abdominal tumor motion during BH has not yet been investigated. The aim of this study was to quantify tumor motion during inhale BH and tumor position variations between consecutive inhale BHs in pancreatic cancer patients. Twelve patients with intratumoral fiducials were included and asked to perform three consecutive 30-second inhale BHs on each of three measurement days. During BH, lateral fluoroscopic movies were obtained and a two-dimensional (2D) image correlation algorithm was used to track the fiducials and the diaphragm, yielding the tumor and diaphragm motion during each BH. The tumor position variation between consecutive BHs was obtained from the difference in initial tumor position between consecutive BHs on a single measurement day. We observed tumor motion during BH with a mean absolute maximum displacement over all BHs of 4.2 mm (range 1.0-11.0 mm) in inferior-superior (IS) direction and 2.7 mm (range 0.5-8.0 mm) in anterior-posterior (AP) direction. We found only a moderate correlation between tumor and diaphragm motion in the IS direction (Pearson's correlation coefficient |r|>0.6 in 45 of 76 BHs). The mean tumor position variation between consecutive BHs was 0.2 [standard deviation (SD) 1.7] mm in the inferior direction and 0.5 (SD 0.8) mm in the anterior direction. We observed substantial pancreatic tumor motion during BH as well as considerable position variation between consecutive BHs on a single day. We recommend further quantifying these uncertainties before introducing breath-hold during radiation treatment of pancreatic cancer patients. Also, the diaphragm cannot be used as a surrogate for pancreatic tumor motion.

  1. Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment.

    PubMed

    Gomez-Chou, Sobeyda; Swidnicka-Siergiejko, Agnieszka; Badi, Niharika; Chavez-Tomar, Myrriah; Lesinski, Gregory B; Bekaii-Saab, Tanios; Farren, Matthew R; Mace, Thomas A; Schmidt, Carl; Liu, Yan; Deng, Defeng; Hwang, Rosa F; Zhou, Liran; Moore, Todd T; Chatterjee, Deyali; Wang, Huamin; Leng, Xiaohong; Arlinghaus, Ralph B; Logsdon, Craig D; Cruz-Monserrate, Zobeida

    2017-03-01

    Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated in patients with pancreatic ductal adenocarcinoma (PDAC) and in obese individuals, but whether it contributes to PDAC development is unclear. In this study, we investigated the effects of Lcn2 depletion on diet-induced obesity, inflammation and PDAC development. Mice with acinar cell-specific expression of KrasG12D were crossed with Lcn2-depleted animals and fed isocaloric diets with varying amounts of fat content. Pancreas were collected and analyzed for inflammation, pancreatic intraepithelial neoplasia (PanIN) and PDAC. We also used a syngeneic orthotopic PDAC mouse model to study tumor growth in the presence or absence of Lcn2 expression. In addition, to understand the mechanistic role of how LCN2 could be mediating PDAC, we studied LCN2 and its specific receptor solute carrier family 22 member 17 (SLC22A17) in human pancreatic cancer stellate cells (PSC), key mediators of the PDAC stroma. Depletion of Lcn2 diminished extracellular matrix deposition, immune cell infiltration, PanIN formation and tumor growth. Notably, it also increased survival in both obesity-driven and syngeneic orthotopic PDAC mouse models. LCN2 modulated the secretion of pro-inflammatory cytokines in PSC of the PDAC tumor microenvironment, while downregulation of LCN2-specific receptor SLC22A17 blocked these effects. Our results reveal how LCN2 acts in the tumor microenvironment links obesity, inflammation and PDAC development.

  2. Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update

    PubMed Central

    Gurzu, Simona; Turdean, Sabin; Kovecsi, Attila; Contac, Anca Otilia; Jung, Ioan

    2015-01-01

    Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelial-to-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail. PMID:25984514

  3. Particulate debris osteolysis simulating malignant tumor.

    PubMed

    Brand, Richard A; Marsh, J Lawrence

    2004-01-01

    Osteolysis induced by particulate debris from total joint implants is typically confined to bone and benign in radiographic appearance even when extensive. However, they can extend well beyond bone in which case they can simulate malignancies owing either to mass effects and pressure on adjacent tissues or owing to the radiographic appearance. We report two cases which presented as possible malignancy, and review the literature on extensive osteolysis. Recognition of this possibility may aid in interpretation of the clinical presentation and imaging studies.

  4. The Role of Tumor Cell-Derived Connective Tissue Growth Factor (CTGF/CCN2) in Pancreatic Tumor Growth

    PubMed Central

    Bennewith, Kevin L.; Huang, Xin; Ham, Christine M.; Graves, Edward E.; Erler, Janine T.; Kambham, Neeraja; Feazell, Jonathan; Yang, George P.; Koong, Albert

    2009-01-01

    Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA-expressing clones showed dramatically reduced growth in soft agar and when implanted subcutaneously. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by PET imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed co-localization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell-derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer. PMID:19179545

  5. Cystic pancreatic neuroendocrine tumors: To date a diagnostic challenge.

    PubMed

    Caglià, Pietro; Cannizzaro, Maria Teresa; Tracia, Angelo; Amodeo, Luca; Tracia, Luciano; Buffone, Antonino; Amodeo, Corrado; Cannizzaro, Matteo Angelo

    2015-09-01

    Cystic PNETs are an uncommon neoplasms increasingly detected in current clinical practice which often present a diagnostic challenges to both the experienced radiologist and pathologist. The aim of this study was to review the available literature to summarize current data that compare and evaluate both the clinical and pathologic features of cystic pancreatic neuroendocrine tumors. A systematic review of the current literature was performed using the search engines EMBASE and PubMed to identify all studies reporting on cystic pancreatic neuroendocrine tumors. The MeSH search terms used were "cystic pancreatic neuroendocrine tumors", "endocrine neoplasms", and "pancreatic cysts". Multiple combinations of the keywords and MeSH terms were used. The clinical evaluation of cystic pancreatic lesions appears to suffer from same limitations despite the improvement in the diagnostic tools. Subsequently, we highlight diagnostic pitfalls and differential diagnosis of these cystic tumors. In this review we discuss current advances in the application of the imaging modalities and characteristics features with special emphasize on endoscopic ultrasound (EUS), and EUS guide fine needle aspiration (EUS-FNA). Cystic neuroendocrine tumor in the pancreas underlines the clinical impact of endoscopic ultrasound in the work-up of patients with unclear lesions in the pancreas. EUS-FNA cytology and cyst fluid analysis is a useful adjunct to abdominal imaging for the diagnosis of pancreatic cystic lesions. Due to the evident diagnostic difficulties, we hypothesize that cyst fluid characteristics, including cytomorphological features, is the most accurate test to achieve a preoperative diagnosis and to provide a basis for prognostic prediction. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  6. Transcriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy

    PubMed Central

    Stoy, Christian; Sundaram, Aishwarya; Rios Garcia, Marcos; Wang, Xiaoyue; Seibert, Oksana; Zota, Annika; Wendler, Susann; Männle, David; Hinz, Ulf; Sticht, Carsten; Muciek, Maria; Gretz, Norbert; Rose, Adam J; Greiner, Vera; Hofmann, Thomas G; Bauer, Andrea; Hoheisel, Jörg; Berriel Diaz, Mauricio; Gaida, Matthias M; Werner, Jens; Schafmeier, Tobias; Strobel, Oliver; Herzig, Stephan

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures in PDAC. Here, we show that transcriptional co-factor Transducin beta-like (TBL) 1 was over-expressed in both human and murine PDAC. Inactivation of TBL1 in human and mouse pancreatic cancer cells reduced cellular proliferation and invasiveness, correlating with diminished glucose uptake, glycolytic flux, and oncogenic PI3 kinase signaling which in turn could rescue TBL1 deficiency-dependent phenotypes. TBL1 deficiency both prevented and reversed pancreatic tumor growth, mediated transcriptional PI3 kinase inhibition, and increased chemosensitivity of PDAC cells in vivo. As TBL1 mRNA levels were also found to correlate with PI3 kinase levels and overall survival in a cohort of human PDAC patients, TBL1 was identified as a checkpoint in the malignant behavior of pancreatic cancer and its expression may serve as a novel molecular target in the treatment of human PDAC. PMID:26070712

  7. Treatment of malignant salivary gland tumors with fast neutrons

    SciTech Connect

    Catterall, M.

    1981-12-01

    The results of fast neutron therapy for malignant tumors of the salivary glands are very satisfactory and on present evidence, fast neutrons are the treatment of first choice for tumors in these sites, when compared with the results from surgery and conventional radiotherapy. In this article, confirmation of results of neutron therapy already published from Hammersmith are given by workers at the Fermi Laboratory.

  8. [Contribution on the familial occurrence of malignant testicular tumors].

    PubMed

    Kleinteich, B; Marx, G

    1983-01-01

    Eight cases of testis tumors in monozygote twin brothers are described in the bibliography. One case is added here. Nearly at the same age, two twin brothers got a right side embryonal teratocarcinoma. The histories of diseases were approximately identical. The brothers died two years later. The possibility of genetic factors causing or influencing the development of malignant testicular tumors are briefly discussed.

  9. Everolimus and pancreatic neuroendocrine tumors (PNETs): Activity, resistance and how to overcome it.

    PubMed

    Capozzi, Monica; Caterina, Ieranò; De Divitiis, Chiara; von Arx, Claudia; Maiolino, Piera; Tatangelo, Fabiana; Cavalcanti, Ernesta; Di Girolamo, Elena; Iaffaioli, Rosario Vincenzo; Scala, Stefania; Tafuto, Salvatore

    2015-09-01

    Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors (PNETs) can be functional, hormone secreting tumors, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNETs, usually present later either incidentally or due to tumor bulk symptoms. Currently Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), is the most promising drug for patients with unresectable, metastatic disease, in progressive well-differentiated PNETs and many studies are ongoing to demonstrate its effects on the other neuroendocrine histotipes. Food and Drug Administration (FDA) and European Medicines Agency (EMA) registered Everolimus in advanced/metastatic breast cancer, in advanced/metastatic renal cell carcinoma and in well/moderately differentiated pancreatic neuroendocrine tumors. Nevertheless only a subset of patients respond to the therapy due to the development of drug resistance. Thus the powerful Everolimus antitumor activity have prompted extensive efforts to overcome drug resistance and to maximize clinical benefit. In this review we aim to summarize current knowledge on mechanisms of Everolimus and other mTOR inhibitors molecules resistance with the intent to overcome it.

  10. A multicenter study of oral malignant tumors from Thailand

    PubMed Central

    Dhanuthai, Kittipong; Rojanawatsirivej, Somsri; Subarnbhesaj, Ajiravudh; Thosaporn, Watcharaporn; Kintarak, Sompid

    2016-01-01

    Background: Oral malignant tumors in Thailand have not been extensively studied. Hence the following study was conducted. Aims: To determine the prevalence and clinicopathologic data of the oral malignant tumors from Thailand. Subjects and Methods: Biopsy records of the Oral Pathology Department, Chulalongkorn University; Department of Oral Biology and Diagnostic Sciences, Chiang Mai University; Department of Oral Diagnosis, Khon Kaen University and Department of Stomatology, Prince of Songkla University, were reviewed for lesions diagnosed in the category of oral malignant tumors from 2005–2014. Demographic data and site of the lesions were collected. Statistical Analysis Used: Data were analyzed by descriptive statistics using SPSS software version 17.0. Results: Of the 22,639 accessioned cases, 1411 cases (6.23%) were diagnosed as oral malignant tumors. The mean age of the patients was 59.13 ± 17.32 years. A total of 651 cases (46.14%) were diagnosed in males, whereas 759 cases (53.79%) were diagnosed in females. The male-to-female ratio was 0.86:1. The sites of predilection for oral malignant tumors were the gingiva, followed by tongue and alveolar mucosa. The three most common oral malignant tumors in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Conclusions: This study provides extensive data on the oral malignant tumors from several university biopsy services located in virtually all parts of Thailand. The data from the present study show some similarities with previous studies; however, differences such as gender and site of predilection still exist. PMID:27721612

  11. Tumor Initiation in Human Malignant Melanoma and Potential Cancer Therapies

    PubMed Central

    Ma, Jie; Frank, Markus H.

    2010-01-01

    Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment. PMID:20184545

  12. Tumor initiation in human malignant melanoma and potential cancer therapies.

    PubMed

    Ma, Jie; Frank, Markus H

    2010-02-01

    Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment.

  13. Radical resection and enucleation in Chinese adolescents with pancreatic tumors

    PubMed Central

    Yao, Lie; Xie, Zhi-Bo; Jin, Chen; Jiang, Yong-Jian; Li, Ji; Yang, Feng; Lin, Quan-Jun; Fu, De-Liang

    2017-01-01

    Abstract Pancreatic tumors rarely occur in adolescents, and the appropriateness of radical resection for these patients remains controversial. Medical records were retrospectively reviewed for patients younger than 19 years who underwent radical resection or limited resection (enucleation) between 2000 and 2015. Patient demographics, clinical characteristics, operative details, growth, and survival were analyzed. During the study period, 11 adolescents (mean age, 16.18 years; standard deviation, 1.99; interquartile range, 15.0–18.0) underwent radical resection (n = 7) or enucleation (n = 4) to treat solid pseudopapillary tumors (n = 5), pancreatic neuroendocrine tumors (n = 5), or pancreatic ductal adenocarcinoma (n = 1). None of the 7 patients who underwent radical resection experienced recurrence or serious complications, while 3 of 4 patients who underwent enucleation experienced recurrence (P = 0.02). Recurrence-free survival was slightly longer in patients who underwent radical resection, and this procedure did not appear to affect adolescent growth and development. Radical resection might be safe and effective for adolescents with pancreatic tumors. PMID:28328854

  14. Particulate Debris Osteolysis Simulating Malignant Tumor

    PubMed Central

    Brand, Richard A; Marsh, J Lawrence

    2004-01-01

    Osteolysis induced by particulate debris from total joint implants is typically confined to bone and benign in radiographic appearance even when extensive. However, they can extend well beyond bone in which case they can simulate malignancies owing either to mass effects and pressure on adjacent tissues or owing to the radiographic appearance. We report two cases which presented as possible malignancy, and review the literature on extensive osteolysis. Recognition of this possibility may aid in interpretation of the clinical presentation and imaging studies. PMID:15296216

  15. Small bowel metastasis from pancreatic cancer in a long-term survival patient with synchronous advanced malignant pleural mesothelioma: A case report and literature review

    PubMed Central

    Fasano, Morena; Corte, Carminia Maria Della; Vicidomini, Giovanni; Scotti, Valerio; Rambaldi, Pier Francesco; Fiorelli, Alfonso; Accardo, Marina; De Vita, Ferdinando; Santini, Mario; Ciardiello, Fortunato; Morgillo, Floriana

    2016-01-01

    Diffuse malignant pleural mesothelioma (MPM) is an aggressive tumor that originates from the surface of the pleura. Approximately 70% of cases are associated with chronic asbestos exposure. MPM is regarded as an incurable disease, with a median survival of ~2 years following intensive multimodality treatment. Pancreatic cancer is a malignancy also associated with a poor prognosis, with only 2% of patients surviving for 5 years. The majority of patients with pancreatic cancer are diagnosed with an advanced stage of disease and experience a poor response to therapy. The development of synchronous MPM and other types of cancer is rare. The present study describes a patient with synchronous, biphasic MPM and pancreatic adenocarcinoma, who was treated with a multimodal therapeutic approach with stereotactic body radiation therapy. Due to a suspected diagnosis of ‘acute abdomen’, an emergency small intestine resection was performed and a subsequent diagnosis of moderately-differentiated adenocarcinoma was confirmed. During a further immunohistochemical examination, pathologists determined that the small bowel metastasis descended from pancreatic cancer. The onset of bowel metastasis is an event rarely associated with MPM, and has not been previously described in the literature for cases of pancreatic cancer. Therefore, to the best of our knowledge, the present study describes the first case of intestinal metastasis from pancreatic cancer in a long-term survival patient with biphasic MPM. PMID:28105159

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

    PubMed Central

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

    2016-01-01

    Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC) and engrailed-1 (EN-1) promoters is frequently detected in pancreatic tumor cells. The aim of the present study was to assess their prevalence in pancreatic juice of carcinomas of the pancreas and periampullary area. A total of 135 pancreatic juices obtained from 85 pancreatic cancer (PC), 26 ampullary carcinoma (AC), 10 intraductal papillary mucinous neoplasm (IPMN) and 14 chronic pancreatitis (CP) patients were analyzed. The methylation status of the APC, HRH2, CDH13, SPARC and EN-1 promoters was analyzed using methylation specific-melting curve analysis (MS-MCA). Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were also tested with allele-specific quantitative polymerase chain reaction amplification. Out of the 5 promoters analyzed, APC (71%) and HRH2 (65%) were the most frequently methylated in PC juice. APC methylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%). APC methylation had a high sensitivity (71–80%) for all types of cancer analyzed. The panel (where a sample scored as positive when ≥2 markers were methylated) did not outperform APC as a single marker. Finally, KRAS detection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer. APC hypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms. PMID:27602165

  17. Tumor-specific gene therapy for pancreatic cancer using human neural stem cells encoding carboxylesterase

    PubMed Central

    Choi, Seon-A; Yoon, Seung-Bin; Kim, Seung U.; Lee, Hong J.

    2016-01-01

    Advanced pancreatic cancer is one of the most lethal malignant human diseases lacking effective treatment. Its extremely low survival rate necessitates development of novel therapeutic approach. Human neural stem cells (NSCs) are known to have tumor-tropic effect. We genetically engineered them to express rabbit carboxyl esterase (F3.CE), which activates prodrug CPT-11(irinotecan) into potent metabolite SN-38. We found significant inhibition of the growth of BxPC3 human pancreatic cancer cell line in vitro by F3.CE in presence of CPT-11. Apoptosis was also markedly increased in BxPC3 cells treated with F3.CE and CPT-11. The ligand VEGF and receptor VEGF-1(Flt1) were identified to be the relevant tumor-tropic chemoattractant. We confirmed in vivo that in mice injected with BxPC3 on their skin, there was significant reduction of tumor size in those treated with both F3.CE and BxPC3 adjacent to the cancer mass. Administration of F3.CE in conjunction with CPT-11 could be a new possibility as an effective treatment regimen for patients suffering from advanced pancreatic cancer. PMID:27659534

  18. Tumor-specific gene therapy for pancreatic cancer using human neural stem cells encoding carboxylesterase.

    PubMed

    Choi, Sung S; Yoon, Kichul; Choi, Seon-A; Yoon, Seung-Bin; Kim, Seung U; Lee, Hong J

    2016-11-15

    Advanced pancreatic cancer is one of the most lethal malignant human diseases lacking effective treatment. Its extremely low survival rate necessitates development of novel therapeutic approach. Human neural stem cells (NSCs) are known to have tumor-tropic effect. We genetically engineered them to express rabbit carboxyl esterase (F3.CE), which activates prodrug CPT-11(irinotecan) into potent metabolite SN-38. We found significant inhibition of the growth of BxPC3 human pancreatic cancer cell line in vitro by F3.CE in presence of CPT-11. Apoptosis was also markedly increased in BxPC3 cells treated with F3.CE and CPT-11. The ligand VEGF and receptor VEGF-1(Flt1) were identified to be the relevant tumor-tropic chemoattractant. We confirmed in vivo that in mice injected with BxPC3 on their skin, there was significant reduction of tumor size in those treated with both F3.CE and BxPC3 adjacent to the cancer mass. Administration of F3.CE in conjunction with CPT-11 could be a new possibility as an effective treatment regimen for patients suffering from advanced pancreatic cancer.

  19. PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma.

    PubMed

    Laury, Anna R; Hornick, Jason L; Perets, Ruth; Krane, Jeffrey F; Corson, Joseph; Drapkin, Ronny; Hirsch, Michelle S

    2010-05-01

    Ovarian serous neoplasms can have morphologic overlap with malignant mesothelioma. The distinction is clinically important, yet most studies have failed to identify immunostains that reliably distinguish these 2 tumor types. Recently, transcription factor PAX8 was shown to be a sensitive and relatively specific marker for Müllerian tumors. In addition, some studies suggest that h-caldesmon is sensitive and specific for mesothelioma when compared with serous ovarian tumors. The goal of this study was to evaluate whether PAX8 and h-caldesmon expression can successfully distinguish mesothelioma from serous ovarian tumors. Immunohistochemistry was carried out using PAX8 and h-caldesmon antibodies on archival tissue from 254 ovarian serous tumors and 50 mesothelial tumors. Nuclear and cytoplasmic immunoreactivity were considered positive for PAX8 and h-caldesmon, respectively. PAX8 staining was present in 99% of high-grade serous ovarian carcinomas and all (100%) low-grade ovarian carcinomas and serous borderline tumors; however, only 74% of these cases (188/254) were diffusely positive in more than 50% of tumors cells, and intensity ranged from strong to weak. None of the pleural malignant mesotheliomas were reactive with PAX8. However, 2/23 (9%) peritoneal malignant mesotheliomas showed focal and/or weak staining for PAX8; the remaining cases were negative. Two well-differentiated papillary mesotheliomas and 1 multicystic mesothelioma each showed some staining for PAX8. h-caldesmon was negative in all serous neoplasms and all mesothelial neoplasms, except 1 pleural malignant mesothelioma which showed patchy immunoreactivity. Strong PAX8 staining is highly specific (P<0.00001) for ovarian serous tumors when compared with malignant mesotheliomas of the peritoneum and pleura. The presence of weak staining for PAX8 in the 3 "noninvasive" mesotheliomas questions the use for PAX8 in this differential diagnosis. On the basis of this study, h-caldesmon is not a useful marker

  20. KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

    SciTech Connect

    Laurila, Eeva; Vuorinen, Elisa; Savinainen, Kimmo; Rauhala, Hanna; Kallioniemi, Anne

    2014-03-10

    Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. - Highlights: • KPNA7 expression is elevated in several pancreatic cancer cell lines. • KPNA7 silencing in high expressing cancer cells leads to growth inhibition. • The cell growth reduction is associated with p21 induction and G1 arrest. • KPNA7 silencing is also accompanied with increased autophagy.

  1. Targeting GIPC/synectin in pancreatic cancer inhibits tumor growth.

    PubMed

    Muders, Michael H; Vohra, Pawan K; Dutta, Shamit K; Wang, Enfeng; Ikeda, Yasuhiro; Wang, Ling; Udugamasooriya, D Gomika; Memic, Adnan; Rupasinghe, Chamila N; Rupashinghe, Chamila N; Baretton, Gustavo B; Aust, Daniela E; Langer, Silke; Datta, Kaustubh; Simons, Michael; Spaller, Mark R; Mukhopadhyay, Debabrata

    2009-06-15

    Various studies have shown the importance of the GAIP interacting protein, COOH-terminus (GIPC, also known as Synectin) as a central adaptor molecule in different signaling pathways and as an important mediator of receptor stability. GIPC/Synectin is associated with different growth-promoting receptors such as insulin-like growth factor receptor I (IGF-IR) and integrins. These interactions were mediated through its PDZ domain. GIPC/Synectin has been shown to be overexpressed in pancreatic and breast cancer. The goal of this study was to show the importance of GIPC/Synectin in pancreatic cancer growth and to evaluate a possible therapeutic strategy by using a GIPC-PDZ domain inhibitor. Furthermore, the effect of targeting GIPC on the IGF-I receptor as one of its associated receptors was tested. The in vivo effects of GIPC/Synectin knockdown were studied after lentiviral transduction of luciferase-expressing pancreatic cancer cells with short hairpin RNA against GIPC/Synectin. Additionally, a GIPC-PDZ--targeting peptide was designed. This peptide was tested for its influence on pancreatic cancer growth in vitro and in vivo. Knockdown of GIPC/Synectin led to a significant inhibition of pancreatic adenocarcinoma growth in an orthotopic mouse model. Additionally, a cell-permeable GIPC-PDZ inhibitor was able to block tumor growth significantly without showing toxicity in a mouse model. Targeting GIPC was accompanied by a significant reduction in IGF-IR expression in pancreatic cancer cells. Our findings show that targeting GIPC/Synectin and its PDZ domain inhibits pancreatic carcinoma growth and is a potential strategy for therapeutic intervention of pancreatic cancer.

  2. Biochemical prognostic indicators for pancreatic neuroendocrine tumors and small bowel neuroendocrine tumors

    PubMed Central

    Cavaness, Keith; Celinski, Scott; Preskitt, John

    2014-01-01

    Pancreatic neuroendocrine tumors (PNETs) and small bowel neuroendocrine tumors (SBNETs) are rare tumors that are frequently diagnosed late in the course of the disease. Several biomarkers have been proposed in the literature as prognostic factors for patients with these tumors. This article discusses a recent publication in Annals of Surgical Oncology from the University of Iowa analyzing the effect of different biomarkers on survival in patients with PNETs and SBNETs. PMID:25493250

  3. [Clinical features of solid malignant tumors in childhood].

    PubMed

    Koshinaga, Tsugumichi; Ohashi, Kensuke; Sugitou, Kiminobu; Ikeda, Tarou

    2013-07-01

    The pathogenesis of pediatric malignant tumors is associated with congenital abnormalities. Oncogenes and antioncogenes are identified in some of these cases. Neuroblastoma arises from the adrenal medulla and sympathetic ganglia. Most neuroblastomas produce catecholamine. Urinary vanillylmandelic acid(VMA)and homovanillic acid(HVA), metabolites of catecholamine, are sensitive tumor markers. Risk stratification according to tumor stage and a combination of prognostic factors helps determine the appropriate therapeutic strategy in clinical settings. Nephroblastoma(Wilms tumor)is the most common pediatric renal tumor and is often accompanied by congenital anomalies. Surgical resection of the tumor and the involved kidney is the initial treatment recommendation in the US and Japan. Consecutive chemotherapy and radiotherapy are administered after surgical staging and a definite histopathological diagnosis. Prognosis is relatively good for most nephroblastoma cases with a favorable histology. In addition to nephroblastoma, clear cell sarcoma of the kidney, characterized by a tendency to metastasize to the bone, is a renal tumor with poor prognosis. Rhabdoid tumor of the kidney is another tumor type; however, its pathogenesis is still unknown and it is associated with extremely poor prognosis because of the lack of effective therapeutic measures. Hepatoblastoma is the most common malignant liver tumor. The serum alpha-fetoprotein level is the most effective tumor marker. Complete surgical resection of the involved liver lobe is the definitive approach for cure. Preoperative chemotherapy increases the possibility of complete surgical resection. High-risk patients have a poor prognosis.

  4. [Multiple primary malignant tumors involving the liver].

    PubMed

    Tiszlavicz, L; Tasnádi, T

    1993-01-31

    In the Department of Pathology of the Albert Szent-Györgyi Medical University in Szeged during the last 30 years 1770 (19.4% of the cancers) primary malignant lung tumours were observed in autopsy material, from which 86 patients (4.9%) had other malignancies as well. In 81 cases other extrapulmonary and in 5 cases other primary lung tumours were observed. The male predominance in these cases was significant. All of the patients were heavy smokers. Amongst these synchronous tumour-associations the most frequent extrapulmonary tumours arose in the urogenital tract, in the head and neck, relatively frequently also in the breast, liver, stomach, intestine and thyroid. These cases caused diagnostic dilemmas both for the clinician and even for the pathologist. Several signs help to distinguish a new primary tumour from a metastasis. Multiplicity itself does not mean poorer prognosis. Each cancer should possibly receive adequate treatment.

  5. Distinguishing benign from malignant pulmonary nodules with helical chest CT in children with malignant solid tumors.

    PubMed

    McCarville, M Beth; Lederman, Henrique M; Santana, Victor M; Daw, Najat C; Shochat, Stephen J; Li, Chin-Shang; Kaufman, Robert A

    2006-05-01

    To retrospectively assess whether computed tomographic (CT) findings can indicate the benign or malignant nature of pulmonary nodules in pediatric patients with malignant solid primary tumors. With institutional review board approval, waived parental and patient consent, and HIPAA compliance, the authors determined the incidence of malignancy among 81 pulmonary nodules that were sampled at biopsy within 3 weeks after chest CT (January 1999 to September 2003) in 41 young patients with malignant solid tumors. Three radiologists independently and retrospectively reviewed these scans and the available previously obtained scans, classifying nodules as benign, malignant, or indeterminate on the basis of their number, unilateral versus bilateral distribution, size, margins (indistinct vs distinct), calcification, growth, and associated adenopathy. These classifications were compared with nodule histologic type, and interreviewer agreement was assessed. The median patient age was 14.8 years (mean, 13.7 years; range, 5-21 years). Twenty-four of the 41 patients (58%) had at least one biopsy-proved malignant nodule. Four (10%) patients had both benign and malignant nodules; 17 (42%) had only benign nodules. Reviewer 1 classified 65% (39 of 60) of nodules correctly; reviewer 2, 57% (37 of 65); and reviewer 3, 67% (43 of 64). Interreviewer agreement was slight to moderate (kappa malignant (P = .03) and nodule size was not associated with malignancy (P >/= .32). The frequency of benign nodules and the inconsistency of predictions based on CT features suggest the need for better predictors of pulmonary nodules being malignant or benign, so as to reduce unnecessary thoracotomy in pediatric patients with solid malignancy. . (c) RSNA, 2006.

  6. [Multiple primary malignant tumors involving the liver].

    PubMed

    Tiszlavicz, L

    1991-11-17

    In the autopsy material of the Department of Pathology of Albert Szent-Györgyi Medical University 167 primary liver cancers were observed in 30 years, from which 13 patients (7.8%) had also other primary malignancies. The tumour-associations were mainly synchronously, there was strong male predominance. In 9 cases the hepatocellular carcinoma originated in cirrhotic liver. The most frequent extrahepatic tumours were found in the lungs (5 cases), smoking was among the anamnestic data.

  7. Immunotherapy of Malignancy by in vivo Gene Transfer into Tumors

    NASA Astrophysics Data System (ADS)

    Plautz, Gregory E.; Yang, Zhi-Yong; Wu, Bei-Yue; Gao, Xiang; Huang, Leaf; Nabel, Gary J.

    1993-05-01

    The immune system confers protection against a variety of pathogens and contributes to the surveillance and destruction of neoplastic cells. Several cell types participate in the recognition and lysis of tumors, and appropriate immune stimulation provides therapeutic effects in malignancy. Foreign major histocompatibility complex (MHC) proteins also serve as a potent stimulus to the immune system. In this report, a foreign MHC gene was introduced directly into malignant tumors in vivo in an effort to stimulate tumor rejection. In contrast to previous attempts to induce tumor immunity by cell-mediated gene transfer, the recombinant gene was introduced directly into tumors in vivo. Expression of the murine class I H-2K^s gene within the CT26 mouse colon adenocarcinoma (H-2K^d) or the MCA 106 fibrosarcoma (H-2K^b) induced a cytotoxic T-cell response to H-2K^s and, more importantly, to other antigens present on unmodified tumor cells. This immune response attenuated tumor growth and caused complete tumor regression in many cases. Direct gene transfer in vivo can therefore induce cell-mediated immunity against specific gene products, which provides an immunotherapeutic effect for malignancy, and potentially can be applied to the treatment of cancer and infectious diseases in man.

  8. Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression.

    PubMed

    Zhu, Yu; Herndon, John M; Sojka, Dorothy K; Kim, Ki-Wook; Knolhoff, Brett L; Zuo, Chong; Cullinan, Darren R; Luo, Jingqin; Bearden, Audrey R; Lavine, Kory J; Yokoyama, Wayne M; Hawkins, William G; Fields, Ryan C; Randolph, Gwendalyn J; DeNardo, David G

    2017-08-15

    Tumor-associated macrophages (TAMs) are essential components of the cancer microenvironment and play critical roles in the regulation of tumor progression. Optimal therapeutic intervention requires in-depth understanding of the sources that sustain macrophages in malignant tissues. In this study, we investigated the ontogeny of TAMs in murine pancreatic ductal adenocarcinoma (PDAC) models. We identified both inflammatory monocytes and tissue-resident macrophages as sources of TAMs. Unexpectedly, significant portions of pancreas-resident macrophages originated from embryonic development and expanded through in situ proliferation during tumor progression. Whereas monocyte-derived TAMs played more potent roles in antigen presentation, embryonically derived TAMs exhibited a pro-fibrotic transcriptional profile, indicative of their role in producing and remodeling molecules in the extracellular matrix. Collectively, these findings uncover the heterogeneity of TAM origin and functions and could provide therapeutic insight for PDAC treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. [MALIGNANT TUMORS IN OVARIAN MATURE CYSTIC TERATOMAS INTRAOPERATIVE DIAGNOSTIC BASIS].

    PubMed

    Khachatryan, A

    2016-11-01

    Extremely rare ovarian primary tumors formed in a mature cystic teratomaare described in the literature. This research work studies the frequency of malignant mature cystic teratoma, as well as their clinical and morphological features and necessity of intraoperative histological examination of all teratomas. Cases histories of 56 patients, suffering from ovarian mature cystic teratomahave been studied in MC Shengavit in the period of 2003 - 2015. Among them 4 patients with the somatic malignancies were identified. Morphological methods, which are considered to be "gold standard" of tumor investigation, were used in staining the slides with hematoxylin - eosin. According to the literature the secondary malignant transformation rarely occurs and is typical in postmenopausal women, with a frequency of 0.17-3%. According to the results of our study, malignant tumors in mature cystic teratomas were observed in 4 (7,14%) from the total number of mature cystic teratomas (n=56). There was not revealed a correlation between the duration of the complaints, age of the patients, sizes of ovarian mature teratoma and malignization degree. Thus, the greatest difficulties of clinical diagnosis of malignant tumors in the ovarian mature cystic teratomas were in the early stage of the disease, because of a variety of clinical manifestations, not pathognomonic for malignization. All mentioned symptoms may be observed in the patients with usual mature cystic teratomas. Тhis cases confirm the necessity to take tissue samples from the other ovary for intraoperative histopathological evaluation in each case of mature cystic teratomas. It is necessary to examine a large number of tumor sites, to prevent errors in the assessment of the maturity degree of teratoma.

  10. [The observatory of rare malignant gynecologic tumors].

    PubMed

    Devouassoux-Shisheboran, Mojgan; Vacher-Lavenu, Marie-Cécile

    2014-02-01

    The observatory of gynecological rare tumors (TMRG) has been initially created for ovarian rare neoplasms (TMRO). Because of the similarities between ovarian and other gynecological tumors, this observatory has been then extended to all gynecological rare tumors. The recognition by INCa of three national expert centers (centre Léon-Bérard, hôpitaux de Paris, institut Gustave-Roussy) in rare gynecological cancers and a network of regional expert centers in 2010, expend the experience of the website "Observatoire francophone des tumeurs rares de l'ovaire". The major goals of this gynecology rare tumors experts network, are to promote systematic second opinion for initial diagnostic by experts in gynecopathology, systematic multidisciplinary advice by surgeons and medical oncologist experts, to disseminate clinical guidelines dedicated to rare gynecological tumors, to promote specific fundamental and translational research within clinical trials dedicated to rare tumors. At the end, we would like to improve benefit in term of survival and/or fertility for all these potential young patients.

  11. Malignant tumors of the liver in children.

    PubMed

    Aronson, Daniel C; Meyers, Rebecka L

    2016-10-01

    This article aims to give an overview of pediatric liver tumors; in particular of the two most frequently occurring groups of hepatoblastomas and hepatocellular carcinomas. Focus lays on achievements gained through worldwide collaboration. We present recent advances in insight, treatment results, and future questions to be asked. Increasing international collaboration between the four major Pediatric Liver Tumor Study Groups (SIOPEL/GPOH, COG, and JPLT) may serve as a paradigm to approach rare tumors. This international effort has been catalyzed by the Children's Hepatic tumor International Collaboration (CHIC) formation of a large collaborative database. Interrogation of this database has led to a new universal risk stratification system for hepatoblastoma using PRETEXT/POSTTEXT staging as a backbone. Pathologists in this international collaboration have established a new histopathological consensus classification for pediatric liver tumors. Concomitantly there have been advances in chemotherapy options, an increased role of liver transplantation for unresectable tumors, and a web portal system developed at www.siopel.org for international education, consultation, and collaboration. These achievements will be further tested and validated in the upcoming Paediatric Hepatic International Tumour Trial (PHITT). Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Characterization of pancreatic glucagon-producing tumors and pituitary gland tumors in transgenic mice overexpressing MYCN in hGFAP-positive cells

    PubMed Central

    Fielitz, Kathrin; Althoff, Kristina; De Preter, Katleen; Nonnekens, Julie; Ohli, Jasmin; Elges, Sandra; Hartmann, Wolfgang; Klöppel, Günter; Knösel, Thomas; Schulte, Marc; Klein-Hitpass, Ludger; Beisser, Daniela; Reis, Henning; Eyking, Annette; Cario, Elke; Schulte, Johannes H.

    2016-01-01

    Amplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the spectrum of MYCN-driven neoplasms in mice, we transgenically overexpressed MYCN under the control of the human GFAP-promoter that, among other targets, drives expression in neural progenitor cells. However, LSL-MYCN;hGFAP-Cre double transgenic mice did neither develop neural crest tumors nor tumors of the central nervous system, but presented with neuroendocrine tumors of the pancreas and, less frequently, the pituitary gland. Pituitary tumors expressed chromogranin A and closely resembled human pituitary adenomas. Pancreatic tumors strongly produced and secreted glucagon, suggesting that they derived from glucagon- and GFAP-positive islet cells. Interestingly, 3 out of 9 human pancreatic neuroendocrine tumors expressed MYCN, supporting the similarity of the mouse tumors to the human system. Serial transplantations of mouse tumor cells into immunocompromised mice confirmed their fully transformed phenotype. MYCN-directed treatment by AuroraA- or Brd4-inhibitors resulted in significantly decreased cell proliferation in vitro and reduced tumor growth in vivo. In summary, we provide a novel mouse model for neuroendocrine tumors of the pancreas and pituitary gland that is dependent on MYCN expression and that may help to evaluate MYCN-directed therapies. PMID:27769070

  13. Lymphoepithelial cyst of the pancreas mimicking malignant cystic tumor: report of a case.

    PubMed

    Ryu, Dong Hee; Sung, Ro Hyun; Kang, Min Ho; Choi, Jae Woon

    2015-08-01

    Lymphoepithelial cysts of the pancreas are a type of true cyst that can mimic pseudocysts and cystic neoplasms. They are very rare, non-malignant lesions that are unilocular or multilocular cystic lesions lined predominantly by mature squamous epithelium and surrounded by non-neoplastic lymphoid elements. We, herein, present a patient with a cystic pancreas tumor mimicking a malignant cystic neoplasm. The patient was admitted with upper abdominal discomfort. Computed tomography showed a 64×39 mm cystic mass in the pancreas tail. She underwent distal pancreatectomy and splenectomy. In the fluid analysis of the pancreas cystic mass, the CEA and CA19-9 were 618 ng/ml and 3.9 U/ml, respectively. The resected pancreas specimen showed a 6.5 cm-sized cyst the pancreas tail. The cyst was well circumscribed and multilocular. The final pathology report of the resected pancreas specimen noted that the cyst was multilocular, and the cyst lining was showing stratified squamous epithelium covering the lymphoid tissue (containing lymphoid follicles), which was consistent with a lymphoepithelial cyst. The patient recovered uneventfully from surgery and has been doing well for the past 3 months. A differential diagnosis of cystic pancreatic lesions is important. We suggest that lymphoepithelial cysts, although very rare, may be included in the differential diagnosis of cystic pancreatic tumors.

  14. [Classification of gastro-entero-pancreatic neuroendocrine tumors].

    PubMed

    Perren, A; Schmitt, A; Komminoth, P; Pavel, M

    2009-03-01

    Tumors of the disseminated/diffuse neuroendocrine system (NET) are characterized by a common phenotype. However, the biology varies according to histomorphology, endocrine symptoms and organ of origin. The WHO classification takes these differences into account and uses a common framework, where the parameters size and extent of invasion vary according to the organ of origin. In order to achieve a further standardization of reporting the European Neuroendocrine Tumor Society (ENETS) recently proposed a tumor-node-metastasis (TNM) staging and grading system for gastro-entero-pancreatic NET.

  15. Pancreastatin producing cell line from human pancreatic islet cell tumor.

    PubMed

    Funakoshi, A; Tateishi, K; Tsuru, M; Jimi, A; Wakasugi, H; Ikeda, Y; Kono, A

    1990-04-30

    It has been characterized that cell line QGP-1 derived from human non-functioning pancreatic islet cell tumor produces human pancreastatin. Exponentially growing cultures produced 5.7 fmol of pancreastatin/10(6) cells/hr. Human pancreastatin immunoreactivities in plasma and tumor after xenografting with QGP-1 into nude mouse were 92.7 fmol/ml and 160.2 pmol/g wet weight, respectively. Immunocytochemical study revealed both chromogranin A and pancreastatin immunoreactive cells in the tumor. Gel filtrations of culture medium and tumor extract identified heterogenous molecular forms of PST-LI which eluted as large and smaller molecular species. These results suggest that plasma pancreastatin levels may be useful as a tumor marker of endocrine tumor of the pancreas, and the pancreastatin producing cell line may be useful for studies of the mechanism of secretions and processing of chromogranin A and pancreastatin.

  16. Concise review: genetically engineered stem cell therapy targeting angiogenesis and tumor stroma in gastrointestinal malignancy.

    PubMed

    Keung, Emily Z; Nelson, Peter J; Conrad, Claudius

    2013-02-01

    Cell-based gene therapy holds considerable promise for the treatment of human malignancy. Genetically engineered cells if delivered to sites of disease could alleviate symptoms or even cure cancer through expression of therapeutic or suicide transgene products. Mesenchymal stem cells (MSCs), nonhematopoietic multipotent cells found primarily in bone marrow, have garnered particular interest as potential tumor-targeting vehicles due to their innate tumortropic homing properties. However, recent strategies go further than simply using MSCs as vehicles and use the stem cell-specific genetic make-up to restrict transgene expression to tumorigenic environments using tumor-tissue specific promoters. This addresses one of the concerns with this novel therapy that nonselective stem cell-based therapy could induce cancer rather than treat it. Even minimal off-target effects can be deleterious, motivating recent strategies to not only enhance MSC homing but also engineer them to make their antitumor effect selective to sites of malignancy. This review will summarize the advances made in the past decade toward developing novel cell-based cancer therapies using genetically engineered MSCs with a focus on strategies to achieve and enhance tumor specificity and their application to targeting gastrointestinal malignancies such as hepatocellular carcinoma and pancreatic adenocarcinoma. Copyright © 2012 AlphaMed Press.

  17. Primary malignant mixed tumor of bone: a case report

    PubMed Central

    Su, Zhansan; Li, Zhi; Liu, Baoan

    2015-01-01

    Background: An extremely rare primary mixed tumor occurring in left proximal femurs of a 47-year old female is reported. Case report: She had left hip pain for three months in April 2004. Radiological examinations revealed that a translucent expansive lesion in the left greater trochanter. She received the curettage of lesion and bone graft surgery. Curettage specimens were diagnosed as malignant mixed tumor, considered to be metastatic. Five months late the lesion recurred. She underwent obturator neurotomy plus total hip replacement of left hip. A long-term of more than ten years follow-up showed there were no evidence of disease recurrence or metastasis and no any signs of other tumor in her body. Discussion: The tumor contained myoepithelial component with positive immunostain of S-100 protein, p63, CK-pan, and vimentin, epithelial component confirmed by CK-pan, CK-LMW and cartilage, which indicated the tumor was a mixed tumor. Cellular atypia, relative high mitosis index, cartilage consistent with grade I chordrosarcoma, focal coagulative necrosis, and infiltration between trabeculae found in the tumor indicated that the tumor had a low grade malignant nature. During long-time follow-up there were no signs of any tumor found in the patient, which strongly suggested that the tumor be a primary one. PMID:26339414

  18. An approach to malignant mammary phyllodes tumors detection.

    PubMed

    Ilić, Ivan; Randelović, Pavle; Ilić, Ratko; Katić, Vuka; Milentijević, Maja; Velicković, Ljubinka; Krstić, Miljan

    2009-04-01

    Mammary phyllodes tumors (MPT) are uncommon fibroepithelial (biphasic) neoplasms whose clinical behavior is difficult to predict on the basis of histological criteria only. They are divided into benign, borderline malignant and malignant groups. Sometimes it appears difficult to distinguish these tumors from other types of soft tissue sarcomas. Because of the relatively scant data on the role of biological markers in MPT histogenesis, we have decided to undertake the following study, trying to shed more light on the issue by investigating the following elements that make up MPT: their histological patterns, biological behavior, enzymohistochemical, histochemical and immunohistochemical characteristics (ICH) together with the mast cell analysis. We examined the biopsy material of 35 MPT in our laboratory. Enzymohistochemistry was performed on frozen sections (method of Crowford, Nachlas and Seligman). The used methods were classical hematoxylin-eosin (H & E); histochemical Massontrichrome, Alcian-blue, Periodic acid Schiff and immunohistochemical LSAB2 method (DacoCytomation). Ki-67, c-kit, vimentin, estrogen receptor (ER), progesterone receptor (PR) and Her-2 oncoprotein immunohistochemistry was performed on all tumors. The patients were ranged per age from 30--62 years (mean 43.3 years, median 39 years). A total of 35 cases of MPT were included: 20 benign (57%), 6 borderline malignant (17%) and 9 malignant (26%). Twenty-two patients (62.8%) underwent segmental mastectomy, while 13 (37.2%) had total mastectomies. Twenty-eight patients had negative surgical margins at original resection. The mean size of malignant MPT (7.8 cm) was larger than that of benign MPT (4.5 cm). Significant features of the malignant MPT were: stromal cellularity, stromal cellular atypism, high mitotic activity, atypic mitoses, stromal overgrowth, infiltrative tumor contour and heterologous stromal elements. Benign MPT showed strong enzymohistochemical Leucine Amino Peptidase (LAP) activity

  19. Targeting GIPC/Synectin in Pancreatic Cancer Inhibits Tumor Growth

    PubMed Central

    Muders, Michael H.; Vohra, Pawan K.; Dutta, Shamit K; Wang, Enfeng; Ikeda, Yasuhiro; Wang, Ling; Udugamasooriya, D. Gomika; Memic, Adnan; Rupashinghe, Chamila N.; Baretton, Gustavo B.; Aust, Daniela E.; Langer, Silke; Datta, Kaustubh; Simons, Michael; Spaller, Mark R.; Mukhopadhyay, Debabrata

    2009-01-01

    Translational Relevance The five year survival rate in patients with ductal adenocarcinoma of the pancreas is less than 4%. Accordingly, new targets for the treatment of this deadly disease are urgently needed. In this study, we show that targeting GAIP interacting protein C-terminal (GIPC, also known as Synectin) and its PDZ-domain reduces pancreatic cancer growth significantly in vitro and in vivo. Additionally, the blockage of GIPC/Synectin was accompanied by a reduction of IGF-1R protein levels. In summary, the use of a GIPC-PDZ domain inhibitor may be a viable option in the treatment of pancreatic adenocarcinoma in future. Purpose Various studies have demonstrated the importance of GAIP interacting protein, C-terminus (GIPC, also known as Synectin) as a central adaptor molecule in different signaling pathways and as an important mediator of receptor stability. GIPC/Synectin is associated with different growth promoting receptors like IGF-1R and integrins. These interactions were mediated through its PDZ domain. GIPC/Synectin has been shown to be overexpressed in pancreatic and breast cancer. The goal of this study was to demonstrate the importance of GIPC/Synectin in pancreatic cancer growth and to evaluate a possible therapeutic strategy by using a GIPC-PDZ domain inhibitor. Furthermore, the effect of targeting GIPC on the IGF-1 receptor as one of its associated receptors was tested. Experimental Design In vivo effects of GIPC/Synectin knockdown were studied after lentiviral transduction of luciferase-expressing pancreatic cancer cells with shRNA against GIPC/Synectin. Additionally, a GIPC-PDZ-targeting peptide was designed. This peptide was tested for its influence on pancreatic cancer growth in vitro and in vivo. Results Knockdown of GIPC/Synectin led to a significant inhibition of pancreatic adenocarcinoma growth in an orthotopic mouse model. Additionally, a cell-permeable GIPC-PDZ inhibitor was able to block tumor growth significantly without showing

  20. Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein

    PubMed Central

    Kamphorst, Jurre J.; Nofal, Michel; Commisso, Cosimo; Hackett, Sean R.; Lu, Wenyun; Grabocka, Elda; Vander Heiden, Matthew G.; Miller, George; Drebin, Jeffrey A.; Bar-Sagi, Dafna; Thompson, Craig B.; Rabinowitz, Joshua D.

    2014-01-01

    Glucose and amino acids are key nutrients supporting cell growth. Amino acids are imported as monomers, but an alternative route induced by oncogenic KRAS involves uptake of extracellular proteins via macropinocytosis and subsequent lysosomal degradation of these proteins as a source of amino acids. In this study, we examined the metabolism of pancreatic ductal adenocarcinoma (PDAC), a poorly vascularized lethal KRAS-driven malignancy. Metabolomic comparisons of human PDAC and benign adjacent tissue revealed that tumor tissue was low in glucose, upper glycolytic intermediates, creatine phosphate and the amino acids glutamine and serine, two major metabolic substrates. Surprisingly, PDAC accumulated essential amino acids. Such accumulation could arise from extracellular proteins being degraded through macropinocytosis in quantities necessary to meet glutamine requirements, which in turn produces excess of most other amino acids. Consistent with this hypothesis, active macropinocytosis is observed in primary human PDAC specimens. Moreover, in the presence of physiological albumin, we found that cultured murine PDAC cells grow indefinitely in media lacking single essential amino acids, and replicate once in the absence of free amino acids. Growth under these conditions was characterized by simultaneous glutamine depletion and essential amino acid accumulation. Overall, our findings argue that the scavenging of extracellular proteins is an important mode of nutrient uptake in PDAC. PMID:25644265

  1. [Autoimmune Encephalitis Associated with Malignant Tumors].

    PubMed

    Inuzuka, Takashi

    2016-09-01

    Autoimmune encephalitis consists of limbic symptoms and signs associated with antibodies against neuronal cell-surface antigens or intracellular antigens. Some cases are known to be associated with anti-channel or anti-receptor-related molecule antibodies. Whether these cases are paraneoplastic depends on the kinds of antigens that the antibodies are produced against. Other cases due to well-characterized onco-neural antibodies are almost always paraneoplastic and are generally resistant to anti-tumor therapy and/or immunotherapy. An exception is anti-Ma2 antibody-positive encephalitis associated with a testicular tumor. Antibodies for intracellular antigens are considered not to be pathogenic. Rather, the T-cell response is thought to be responsible. These antibodies are useful markers for the diagnosis of paraneoplastic disorders and in the search for underlying cancer, as neurological symptoms often precede tumor diagnosis. There is a relationship among onco-neural antibodies, clinical features, tumor types, and response to immunotherapy. Here we describe the characteristics of autoimmune encephalitis cases with antibodies against different intracellular antigens, such as Hu, Ma2, CRMP5, or amphiphysin.

  2. The therapy of infantile malignant brain tumors: current status?

    PubMed

    Kalifa, Chantal; Grill, Jacques

    2005-12-01

    Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood [1]. Genetic predisposition to infantile malignant brain tumors are known in Gorlin syndrome for example who present with desmoplastic medulloblastoma in about 5% of the affected patients. In addition, sequelae from tumor and its treatment are more severe at this age [2]. Thus, malignant brain tumors represent a true therapeutic challenge in neuro-oncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group. Since the end of the 80s, noninvasive imaging procedures produce accurate diagnosis of brain tumors and improvement in neurosurgery, neuroanesthesia and perioperative intensive care permit safe tumor resections or at least biopsies. Consequently, the pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications [3]. At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors [4]. Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors

  3. Metastatic Insulinoma Following Resection of Nonsecreting Pancreatic Islet Cell Tumor

    PubMed Central

    Gordon, Ilyssa O.; Van Ha, Thuong G.; Kaplan, Edwin L.; Philipson, Louis H.

    2013-01-01

    A 56-year-old woman presented to our clinic for recurrent hypoglycemia after undergoing resection of an incidentally discovered nonfunctional pancreatic endocrine tumor 6 years ago. She underwent a distal pancreatectomy and splenectomy, after which she developed diabetes and was placed on an insulin pump. Pathology showed a pancreatic endocrine neoplasm with negative islet hormone immunostains. Two years later, computed tomography scan of the abdomen showed multiple liver lesions. Biopsy of a liver lesion showed a well-differentiated neuroendocrine neoplasm, consistent with pancreatic origin. Six years later, she presented to clinic with 1.5 years of recurrent hypoglycemia. Laboratory results showed elevated proinsulin, insulin levels, and c-peptide levels during a hypoglycemic episode. Computed tomography scan of the abdomen redemonstrated multiple liver lesions. Repeated transarterial catheter chemoembolization and microwave thermal ablation controlled hypoglycemia. The unusual features of interest of this case include the transformation of nonfunctioning pancreatic endocrine tumor to a metastatic insulinoma and the occurrence of atrial flutter after octreotide for treatment. PMID:26425568

  4. Reconstruction after resection of malignant parapharyngeal space tumor

    PubMed Central

    Umezawa, Hiroki; Nakamizo, Munenaga; Yokoshima, Kazuhiko; Nara, Shimpei; Ogawa, Rei; Hyakusoku, Hiko

    2014-01-01

    Abstract Primary malignant tumor of the parapharyngeal space (PPS) is rare. After surgical resection, primary closure could be considered if the oropharynx mucosa remains. This report describes two patients who underwent reconstruction by free tissue transfer after the resection of PPS tumors. This report was presented at the 56th annual meeting of the Japanese Society of Plastic and Reconstructive Surgery, 4 April, 2013. PMID:27252950

  5. Collision tumor with inflammatory breast carcinoma and malignant phyllodes tumor: a case report and literature review.

    PubMed

    Shin, Young Duck; Lee, Seul Kee; Kim, Kyu Sun; Park, Mi Ja; Kim, Joo Heon; Yim, Hyun Sun; Choi, Young Jin

    2014-01-08

    There have been some reports of coincidental presentation of breast carcinoma and phyllodes tumor in the same breast. Most of the cases were carcinoma that arose from a phyllodes tumor with a histologically identified transitional area, and they behaved less aggressively than the usually encountered carcinoma. Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement at the same site. The occurrence of these tumors in the breast is extremely rare. Here, we report a case of 45-year-old woman who had both invasive ductal carcinoma as the finding of inflammatory carcinoma and a malignant phyllodes tumor in the same breast. There was no evidence of a transitional area between the phyllodes tumor and the invasive ductal carcinoma. To our knowledge, this is the first report of a collision tumor of inflammatory breast carcinoma coincident with a malignant phyllodes tumor in same breast.

  6. Malignant mammary tumor in female dogs: environmental contaminants

    PubMed Central

    2010-01-01

    Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7%) as having complex carcinoma and three (33.3%) with simple carcinoma. From these tumors, seven (77.8%) presented aggressiveness degree III and two (22.2%) degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits. PMID:20587072

  7. Malignant mammary tumor in female dogs: environmental contaminants.

    PubMed

    Andrade, Fábio He; Figueiroa, Fernanda C; Bersano, Paulo Ro; Bissacot, Denise Z; Rocha, Noeme S

    2010-06-30

    Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7%) as having complex carcinoma and three (33.3%) with simple carcinoma. From these tumors, seven (77.8%) presented aggressiveness degree III and two (22.2%) degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits.

  8. Malignant brainstem tumors in children, excluding diffuse intrinsic pontine gliomas.

    PubMed

    Klimo, Paul; Nesvick, Cody L; Broniscer, Alberto; Orr, Brent A; Choudhri, Asim F

    2016-01-01

    OBJECT Malignant tumors of the brainstem, excluding classic diffuse intrinsic pontine gliomas (DIPGs), are a very rare, heterogeneous group of neoplasms that have been infrequently described in the literature. In this paper, the authors present their experiences with treating these unique cancers. METHODS A retrospective chart review was conducted to identify eligible cases over a 15-year period. All tumors involving the pons were, by consensus, felt not to be DIPGs based on their neuroimaging features. Demographic information, pathological specimens, neuroimaging characteristics, surgical and nonsurgical management plans, and survival data were gathered for analysis. RESULTS Between January 2000 and December 2014, 29 patients were identified. The mean age at diagnosis was 8.4 years (range 2 months to 25 years), and 17 (59%) patients were male. The most common presenting signs and symptoms were cranial neuropathies (n = 24; 83%), hemiparesis (n = 12; 41%), and ataxia or gait disturbance (n = 10; 34%). There were 18 glial and 11 embryonal tumors. Of the glial tumors, 5 were radiation-induced and 1 was a malignant transformation of a previously known low-grade tumor. Surgical intervention consisted of biopsy alone in 12 patients and some degree of resection in another 15 patients. Two tumors were diagnosed postmortem. The median overall survival for all patients was 196 days (range 15 to 3999 days). There are currently 5 (17%) patients who are still alive: 1 with an anaplastic astrocytoma and the remaining with embryonal tumors. CONCLUSIONS In general, malignant non-DIPG tumors of the brainstem carry a poor prognosis. However, maximal cytoreductive surgery may be an option for select patients with focal tumors. Long-term survival is possible in patients with nonmetastatic embryonal tumors after multimodal treatment, most importantly maximal resection.

  9. Esophageal subepithelial lesion diagnosed as malignant gastrointestinal neuroectodermal tumor.

    PubMed

    Kim, Sung Bum; Lee, Si Hyung; Gu, Mi Jin

    2015-05-14

    A 21-year-old male visited our hospital with a complaint of aggravating dysphagia and odynophagia for a few days. Esophagogastroduodenoscopy showed huge bulging mucosa with an intact surface causing luminal narrowing at 35 cm from the incisor teeth. Endoscopic ultrasonography showed an about 35 mm sized irregular margined in-homogenous hypoechoic lesion with an obscure layer of origin. Endoscopic ultrasonography fine needle aspiration revealed spindle cell proliferation without immunoreactivity for CD117, SMA, and cytokeratin. The patient underwent excision of the subepithelial lesion at the distal esophagus. On pathologic examination of the specimen, the tumor was composed of short fascicles of oval to spindle cells with eosinophilic and clear cytoplasm and vesicular nuclei. The tumor cells were positive for S-100 and SOX10 and negative for CD117, SMA, HMB-45, melan-A, cytokeratin, and CD99. The split-apart signal was detected in EWSR1 on FISH, suggesting a malignant gastrointestinal neuroectodermal tumor. At the time of writing, the patient is on radiation therapy at the operated site of esophagus and doing well, with no recurrence for three months. Malignant gastrointestinal neuroectodermal tumor is a rare gastrointestinal tumor with features of clear cell sarcoma, without melanocytic differentiation, and shows a poor prognosis. This is the first reported case of malignant gastrointestinal neuroectodermal tumor arising as subepithelial lesion in the esophagus.

  10. Unexpected pheochromocytoma presenting as a pancreatic tumor: A case report

    PubMed Central

    HUANG, YI-HSUAN; LIAW, WEN-JINN; KUO, CHANG-PO; WU, ZHI-FU; CHERNG, CHEN-HWAN; YU, JYH-CHERNG; HORNG, HUEI-CHI; HUANG, SHUN-TSUNG

    2013-01-01

    A 54-year-old female presented with a large pancreatic tumor of the tail during a regular physical examination. The patient underwent surgical intervention and the surgeon identified that the tumor originated from the retroperitoneal region. Markedly severe hemodynamic fluctuations occurred during the manipulation of the tumor and continued to occur subsequent to the tumor being removed. The vital signs were adequately managed and the surgery was successful without complications. The patient was discharged without any sequelae days later. The pathology report indicated a diagnosis of pheochromocytoma. Unexpected pheochromocytoma may lead to a fatal hypertensive crisis with catastrophic sequelae during surgery. The peri-operative management of pheochromocytoma remains a complicated challenge that requires intensive pre-operative preparation and vigilant peri-operative care. For surgeons and anesthesiologists who may encounter an unexpected hypertensive crisis during abdominal tumor surgery, undiagnosed pheochromocytoma should always be considered. PMID:24137420

  11. Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant Metastasis

    PubMed Central

    Pàez-Ribes, Marta; Allen, Elizabeth; Hudock, James; Takeda, Takaaki; Okuyama, Hiroaki; Viñals, Francesc; Inoue, Masahiro; Bergers, Gabriele; Hanahan, Douglas; Casanovas, Oriol

    2009-01-01

    SUMMARY Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and distant metastasis. Increased invasiveness is also seen by genetic ablation of the Vegf-A gene in both models, substantiating the results of the pharmacological inhibitors. The realization that potent angiogenesis inhibition can alter the natural history of tumors by increasing invasion and metastasis warrants clinical investigation, as the prospect has important implications for the development of enduring antiangiogenic therapies. PMID:19249680

  12. [Malignant peripheral nerve sheath tumor with perineural differentiation (malignant perineurinoma) of the cervix uteri].

    PubMed

    Dolzhikov, A A; Mukhina, T S

    2014-01-01

    The paper describes a case of a malignant peripheral nerve sheath tumor with perineural differentiation and at the rare site of the cervix uteri in a 57-year-old patient. The diagnosis was established on the basis of extensive immunohistochemical examination, by excluding the similar neoplasms and detecting an immunophenotype characteristic of perineural differentiation. There are data available in the literature on the morphological and immunophenotypical characteristics of this tumor.

  13. Using Artificial Neural Networks to Predict Malignancy of Ovarian Tumors

    DTIC Science & Technology

    2007-11-02

    This paper discusses the application of artificial neural networks (ANNs) to preoperative discrimination between benign and malignant ovarian tumors...With the input variables selected by logistic regression analysis, two types of feed-forward neural networks were built: multi-layer perceptrons

  14. TUMOR CONTAMINATION IN THE BIOPSY PATH OF PRIMARY MALIGNANT BONE TUMORS

    PubMed Central

    Oliveira, Marcelo Parente; Lima, Pablo Moura de Andrade; de Mello, Roberto José Vieira

    2015-01-01

    Objective: To study factors possibly associated with tumor contamination in the biopsy path of primary malignant bone tumors. Method: Thirty-five patients who underwent surgical treatment with diagnoses of osteosarcoma, Ewing's tumor and chondrosarcoma were studied retrospectively. The sample was analyzed to characterize the biopsy technique used, histological type of the tumor, neoadjuvant chemotherapy used, local recurrences and tumor contamination in the biopsy path. Results: Among the 35 patients studied, four cases of contamination occurred (11.43%): one from osteosarcoma, two from Ewing's tumor and one from chondrosarcoma. There was no association between the type of tumor and presence of tumor contamination in the biopsy path (p = 0.65). There was also no association between the presence of tumor contamination and the biopsy technique (p = 0.06). On the other hand, there were associations between the presence of tumor contamination and local recurrence (p = 0.01) and between tumor contamination and absence of neoadjuvant chemotherapy (p = 0.02). Conclusion: Tumor contamination in the biopsy path of primary malignant bone tumors was associated with local recurrence. On the other hand, the histological type of the tumor and the type of biopsy did not have an influence on tumor contamination. Neoadjuvant chemotherapy had a protective effect against this complication. Despite these findings, tumor contamination is a complication that should always be taken into consideration, and removal of the biopsy path is recommended in tumor resection surgery. PMID:27047877

  15. Study of grows of spontaneous malignant tumors using LASCA microscopy

    NASA Astrophysics Data System (ADS)

    Golova, Alina; Laskavy, Vladislav; Ulianova, Onega; Polyanina, Tatyana; Bogoutdinov, Nail; Feodorova, Valentina; Ulyanov, Sergey

    2014-01-01

    Methods t-LASCA and s-LASCA has been adopted for diagnostics of malignant tissue on animal models. Investigations of tumors on inbred mice (line BALB/c) after the inoculation of syngeneic myeloma cells (line Sp.2/0-Ag.8) and on inbred mice (line SHK) with spontaneous tumors have been carried out. The efficiency of application of t-LASCA with illumination by wide laser beam for tumor investigations has been proven. It also has been found that method of LASCA with illumination of tissue by strongly focused laser beam is absolutely non-productive.

  16. Study of malignant peripheral nerve sheath tumor in cerebellopontine angle.

    PubMed

    Hong, WenMing; Cheng, HongWei; Wang, XiaoJie; Hu, XiaoPeng; Feng, ChunGuo

    2014-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are very rare soft tissue sarcomas, usually arising from somatic soft tissues or peripheral nerves. Primary MPNST of the cerebellopontine angle is extremely rare, with only a single case reported so far. Here, we report an unusual case of MPNST in cerebellopontine angle in a 25-year-old man presented with dizziness, left facial numbness, and tinnitus. After hospitalization, the tumor was treated with complete surgical excision followed by adjuvant chemotherapy and radiotherapy. Histologically, the tumor showed malignant spindle cells, which were with focal S-100 positivity on immunohistochemistry, and a diagnosis of the MPNST was made. This case is being reported for its rarity and presence in cerebellopontine and illustrated the difficulties in the diagnosis and treatment of MPNST, which to the best of our knowledge, has not been described before in the soft tissue sarcomas.

  17. In vivo magnetic resonance imaging of pancreatic tumors using iron oxide nanoworms targeted with PTR86 peptide.

    PubMed

    Ahmadi, Yasaman; Kostenich, Genady; Oron-Herman, Mor; Wadsak, Wolfgang; Mitterhauser, Markus; Orenstein, Arie; Mirzaei, Siroos; Knoll, Peter

    2017-07-06

    To cut the high mortality rate of malignant disease such as pancreatic cancer, development of newly diagnostic probes for early stage detection of tumor lesions is required. Multimodal imaging nanoprobes allowing targeted and real time functional/anatomical imaging of tumors meet the demands. For this purpose, a MRI/optical dual-modality probe based on biodegradable magnetic iron oxide nanoworms has been developed. The cross-linked surface of nanoworms were anchored to fluorescent dyes and to FITC.PTR86; a novel synthetic peptide with high affinity towards somatostatin receptors. Combination of various in vitro techniques including Prussian blue staining, fluorescent microscopy and fluorescence activated cell sorting (FACS) have been performed to explore the interaction of developed nanoprobe with pancreatic tumor cell lines. Together with in vivo studies in a xenograft mouse model of human pancreatic adenocarcinoma and ex vivo investigations, the results show the efficient imaging and targeting of pancreatic tumors by our newly developed nanosystem using both MRI and optical imaging modalities. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. A Systematic Review of Proinsulin-Secreting Pancreatic Neuroendocrine Tumors.

    PubMed

    Murtha, Timothy D; Lupsa, Beatrice C; Majumdar, Sachin; Jain, Dhanpat; Salem, Ronald R

    2017-08-01

    Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous group of islet cell-derived neoplasms with a propensity toward hormone production. Among PNETs, proinsulin-secreting tumors (proinsulinomas) are exceedingly rare. The objective of this study is to collect and summarize the existing literature to provide a comprehensive evaluation of this uncommon disease. A systematic review was performed to characterize the clinicopathologic features of proinsulinoma. Using the electronic biomedical databases PubMed, Ovid Medline, and Embase, 316 publications were screened for relevance of which 14 were selected. We also present two patients with proinsulinoma treated at Yale New Haven Hospital. Of the 16 patients included in the study, the mean age was 56.8 and there was a 2:1 female predominance. The majority of patients presented with symptomatic hypoglycemia with normal or low insulin levels. Median tumor diameter was 1.2 cm and 80% were located in the body and tail of the pancreas. Following resection, most patients had normalization of hormonal levels without recurrence (75%; 12/16). Proinsulinomas are rare pancreatic neuroendocrine tumors that have the potential to cause hypoglycemia. While insulinomas and proinsulin-secreting tumors have many physiologic parallels, these cases illustrate several key distinctions in their diagnosis and management.

  19. Identification of peptides that bind to irradiated pancreatic tumor cells

    SciTech Connect

    Huang Canhui; Liu, Xiang Y.; Rehemtulla, Alnawaz; Lawrence, Theodore S. . E-mail: tsl@med.umich.edu

    2005-08-01

    Purpose: Peptides targeting tumor vascular cells or tumor cells themselves have the potential to be used as vectors for delivering either DNA in gene therapy or antitumor agents in chemotherapy. We wished to determine if peptides identified by phage display could be used to target irradiated pancreatic cancer cells. Methods and Materials: Irradiated Capan-2 cells were incubated with 5 x 10{sup 12} plaque-forming units of a phage display library. Internalized phage were recovered and absorbed against unirradiated cells. After five such cycles of enrichment, the recovered phage were subjected to DNA sequencing analysis and synthetic peptides made. The binding of both phage and synthetic peptides was evaluated by fluorescence staining and flow cytometry in vitro and in vivo. Results: We identified one 12-mer peptide (PA1) that binds to irradiated Capan-2 pancreatic adenocarcinoma cells but not to unirradiated cells. The binding of peptide was significant after 48 h incubation with cells. In vivo experiments with Capan-2 xenografts in nude mice demonstrated that these small peptides are able to penetrate tumor tissue after intravenous injections and bind specifically to irradiated tumor cells. Conclusion: These data suggest that peptides can be identified that target tumors with radiation-induced cell markers and may be clinically useful.

  20. Autofluorescence of tissue surrounding malignant tumors

    NASA Astrophysics Data System (ADS)

    Lohmann, Wolfgang; Bohle, Rainer M.; Schill, Wolf-Bernhard; Vahrson, H.; Mussmann, J.

    1998-04-01

    In vitro fluorescence measurements on pap smears of ascites, pleura, or Douglas confirmed results obtained previously with different types of tissue: Cancer tissue fluoresces hardly and is surrounded by a 'fluorescence belt.' Investigations of cytological smears (e.g. Pap smears) have revealed the possible participation of granulocytes in this 'immune' reaction. Furthermore, there seems to be obvious differences in the fluorescence response of pap smears between ovarial- carcinomas and peritoneal carcinomas based on ovarial carcinoma. This observation cannot be explained yet. Because of its sensitivity and specificity the fluorescence method can be used as an additional tool for the evaluation of the tumor invasion front. Preferably it might be used for frozen sections of biopsies and surgical excisions.

  1. Fractal analysis of microvascular networks in malignant brain tumors.

    PubMed

    Di Ieva, Antonio

    2012-01-01

    Brain tumors are characterized by a microvascular network which differs from normal brain vascularity. Different tumors show individual angiogenic patterns. Microvascular heterogeneity can also be observed within a neoplastic histotype. It has been shown that quantification of neoplastic microvascular patterns could be used in combination with the histological grade for tumor characterization and to refine clinical prognoses, even if no objective parameters have yet been validated. To overcome the limits of the Euclidean approach, we employ fractal geometry to analyze the geometric complexity underlying the microangioarchitectural networks in brain tumors. We have developed a computer-aided fractal-based analysis for the quantification of the microvascular patterns in histological specimens and ultra-high-field (7-Tesla) magnetic resonance images. We demonstrate that the fractal parameters are valid estimators of microvascular geometrical complexity. Furthermore, our analysis allows us to demonstrate the high geometrical variability underlying the angioarchitecture of glioblastoma multiforme and to differentiate low-grade from malignant tumors in histological specimens and radiological images. Based on the results of this study, we speculate the existence of a gradient in the geometrical complexity of microvascular networks from those in the normal brain to those in malignant brain tumors. Here, we summarize a new methodology for the application of fractal analysis to the study of the microangioarchitecture of brain tumors; we further suggest this approach as a tool for quantifying and categorizing different neoplastic microvascular patterns and as a potential morphometric biomarker for use in clinical practice.

  2. Malignant tumors of the temporal bone - our experience.

    PubMed

    da Silva, Ana Pereira; Breda, Eduardo; Monteiro, Eurico

    2016-01-01

    Malignant tumors of the temporal bone are rare, with an estimated incidence of about 0.8-1.0 per 1,000,000 inhabitants per year. The vast majority of these tumors are squamous cell carcinomas and their treatment is eminently surgical. This study is an attempt at systematizing the forms of clinical presentation, the therapeutic possibilities, and oncological outcomes of patients with malignant tumors of the temporal bone in a tertiary hospital in Portugal. The authors present a retrospective study of temporal bone tumors treated and followed during otorhinolaryngology consultations between 2004 and 2014. A review of the literature is also included. Of the 18 patients included in the study, 16 had a primary tumor of the temporal bone, in most cases with squamous cell carcinoma histology. Of these, 13 patients were treated with curative intent that always included the surgical approach. Disease persistence was observed in one patient and local recurrence in five patients, on average 36.8 months after the initial treatment. The anatomical complexity of the temporal bone and the close associations with vital structures make it difficult to perform tumor resection with margins of safety and thus, tumor relapses are almost always local. A high level of suspicion is crucial for early diagnosis, and stringent and prolonged follow-up after treatment is essential for diagnosis and timely treatment of recurrances. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  3. Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms.

    PubMed

    Honda, Kazufumi; Kobayashi, Michimoto; Okusaka, Takuji; Rinaudo, Jo Ann; Huang, Ying; Marsh, Tracey; Sanada, Mitsuaki; Sasajima, Yoshiyuki; Nakamori, Shoji; Shimahara, Masashi; Ueno, Takaaki; Tsuchida, Akihiko; Sata, Naohiro; Ioka, Tatsuya; Yasunami, Yohichi; Kosuge, Tomoo; Miura, Nami; Kamita, Masahiro; Sakamoto, Takako; Shoji, Hirokazu; Jung, Giman; Srivastava, Sudhir; Yamada, Tesshi

    2015-11-09

    We recently reported that circulating apolipoprotein AII (apoAII) isoforms apoAII-ATQ/AT (C-terminal truncations of the apoAII homo-dimer) decline significantly in pancreatic cancer and thus might serve as plasma biomarkers for the early detection of this disease. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measurement of apoAII-ATQ/AT and their clinical applicability for early detection of pancreatic cancer. Plasma and serum concentrations of apoAII-ATQ/AT were measured in three independent cohorts, which comprised healthy control subjects and patients with pancreatic cancer and gastroenterologic diseases (n = 1156). These cohorts included 151 cases of stage I/II pancreatic cancer. ApoAII-ATQ/AT not only distinguished the early stages of pancreatic cancer from healthy controls but also identified patients at high risk for pancreatic malignancy. AUC values of apoAII-ATQ/AT to detect early stage pancreatic cancer were higher than those of CA19-9 in all independent cohorts. ApoAII-ATQ/AT is a potential biomarker for screening patients for the early stage of pancreatic cancer and identifying patients at risk for pancreatic malignancy (161 words).

  4. Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms

    PubMed Central

    Honda, Kazufumi; Kobayashi, Michimoto; Okusaka, Takuji; Rinaudo, Jo Ann; Huang, Ying; Marsh, Tracey; Sanada, Mitsuaki; Sasajima, Yoshiyuki; Nakamori, Shoji; Shimahara, Masashi; Ueno, Takaaki; Tsuchida, Akihiko; Sata, Naohiro; Ioka, Tatsuya; Yasunami, Yohichi; Kosuge, Tomoo; Miura, Nami; Kamita, Masahiro; Sakamoto, Takako; Shoji, Hirokazu; Jung, Giman; Srivastava, Sudhir; Yamada, Tesshi

    2015-01-01

    We recently reported that circulating apolipoprotein AII (apoAII) isoforms apoAII-ATQ/AT (C-terminal truncations of the apoAII homo-dimer) decline significantly in pancreatic cancer and thus might serve as plasma biomarkers for the early detection of this disease. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measurement of apoAII-ATQ/AT and their clinical applicability for early detection of pancreatic cancer. Plasma and serum concentrations of apoAII-ATQ/AT were measured in three independent cohorts, which comprised healthy control subjects and patients with pancreatic cancer and gastroenterologic diseases (n = 1156). These cohorts included 151 cases of stage I/II pancreatic cancer. ApoAII-ATQ/AT not only distinguished the early stages of pancreatic cancer from healthy controls but also identified patients at high risk for pancreatic malignancy. AUC values of apoAII-ATQ/AT to detect early stage pancreatic cancer were higher than those of CA19–9 in all independent cohorts. ApoAII-ATQ/AT is a potential biomarker for screening patients for the early stage of pancreatic cancer and identifying patients at risk for pancreatic malignancy (161 words). PMID:26549697

  5. No Detectable Hypoxia in Malignant Salivary Gland Tumors: Preliminary Results

    SciTech Connect

    Wijffels, Karien; Hoogsteen, Ilse J.; Lok, Jasper; Rijken, Paulus F.J.W.; Marres, Henri A.M.; Wilde, Peter C.M. de; Kogel, Albert J. van der; Kaanders, Johannes H.A.M.

    2009-04-01

    Purpose: Hypoxia is detected in most solid tumors and is associated with malignant progression and adverse treatment outcomes. However, the oxygenation status of malignant salivary gland tumors has not been previously studied. The aim of this study was to investigate the potential clinical relevance of hypoxia in this tumor type. Methods and Materials: Twelve patients scheduled for surgical resection of a salivary gland tumor were preoperatively injected with the hypoxia marker pimonidazole and the proliferation marker iododeoxyuridine. Tissue samples of the dissected tumor were immunohistochemically stained for blood vessels, pimonidazole, carbonic anhydrase-IX, glucose transporters-1 and -3 (Glut-1, Glut-3), hypoxia-inducible factor-1{alpha}, iododeoxyuridine, and epidermal growth factor receptor. The tissue sections were quantitatively assessed by computerized image analysis. Results: The tissue material from 8 patients was of sufficient quality for quantitative analysis. All tumors were negative for pimonidazole binding, as well as for carbonic anhydrase-IX, Glut-1, Glut-3, and hypoxia-inducible factor-1{alpha}. The vascular density was high, with a median value of 285 mm{sup -2} (range, 209-546). The iododeoxyuridine-labeling index varied from <0.1% to 12.2% (median, 2.2%). Epidermal growth factor receptor expression levels were mostly moderate to high. In one-half of the cases, nuclear expression of epidermal growth factor receptor was observed. Conclusion: The absence of detectable pimonidazole binding, as well as the lack of expression of hypoxia-associated proteins in all tumors, indicates that malignant salivary gland tumors are generally well oxygenated. It is unlikely that hypoxia is a relevant factor for their clinical behavior and treatment responsiveness.

  6. Extracellular vesicles from malignant effusions induce tumor cell migration: inhibitory effect of LMWH tinzaparin.

    PubMed

    Gamperl, Hans; Plattfaut, Corinna; Freund, Annika; Quecke, Tabea; Theophil, Friederike; Gieseler, Frank

    2016-10-01

    Elevated levels of extracellular vesicles (EVs) have been correlated with inflammatory diseases as well as progressive and metastatic cancer. By presenting tissue factor (TF) on their membrane surface, cellular microparticles (MPs) activate both the coagulation system and cell-signaling pathways such as the PAR/ERK pathway. We have shown before that malignant effusions are a rich source of tumor cell-derived EVs. Here, we used EVs from malignant effusions from three different patients after serial low-speed centrifugation steps as recommended by the ISTH (lsEV). Significant migration of human pancreatic carcinoma cells could be induced by lsEVs and was effectively inhibited by pre-incubation with tinzaparin, a low-molecular-weight heparin. Tinzaparin induced tissue factor pathway inhibitor (TFPI) release from tumor cells, and recombinant TFPI inhibited EV-induced tumor cell migration. EVs also induced ERK phosphorylation, whereas inhibitors of PAR2 and ERK suppressed EV-induced tumor cell migration. LsEVs have been characterized by high-resolution flow cytometry and, after elimination of smaller vesicles including exosomes, by further high-speed centrifugation (hsEV). The remaining population consisting primarily of MPs is indeed the main migration-inducing population with tenase activity. Compared to other LMWHs, tinzaparin is suggested to have high potency to induce TFPI release from epithelial cells. The migration-inhibitory effect of TFPI and the interruption of tumor cell migration by inhibitors of PAR2 and ERK suggest that lsEVs induce tumor cell migration by activating the PAR2 signaling pathway. Tinzaparin might inhibit this process at least partly by inducing the release of TFPI from tumor cells, which blocks PAR-activating TF complexes. The clinical relevance of the results is discussed. © 2016 The Authors. Cell Biology International Published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.

  7. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    PubMed

    Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

    2016-07-15

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting.

  8. Boron Neutron Capture Therapy for Malignant Brain Tumors

    PubMed Central

    MIYATAKE, Shin-Ichi; KAWABATA, Shinji; HIRAMATSU, Ryo; KUROIWA, Toshihiko; SUZUKI, Minoru; KONDO, Natsuko; ONO, Koji

    2016-01-01

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

  9. Lipiodol enhanced CT scanning of malignant hepatic tumors.

    PubMed

    Eurvilaichit, C

    2000-04-01

    From August 1984 to March 1991, 41 patients with malignant liver tumors, 30 males and 11 females, aged 30-75 years were treated at Ramathibodi Hospital with injection of mitomycin-C lipiodol emulsion into the tumor via the feeding artery followed by embolization of the feeding artery with gelfoam particles. The patients comprised 30 cases of hepatocellular carcinoma, 4 cases of cholangiocarcinoma and 7 cases of metastatic tumors of which one was from CA stomach, three were from CA breast, and three from CA colon. The vascularity of the tumor was assessed in angiogram obtained prior to treatment and retention pattern of lipiodol in the tumor was evaluated in lipiodol-enhanced CT scan images taken 2-4 weeks following therapy. The results showed that lipiodol CT scan images exhibited four patterns of lipiodol retention in the tumor appearing as opacity as follows (1) homogenous (2) heterogeneous (3) ring-like and (4) none. Lipiodol retention pattern appeared to be somewhat related to vascularity of the tumor. Most of the hypervascular tumors such as hepatocellular carcinoma had homogeneous lipiodol accumulation pattern if the tumor size was less than 5 cm. Metastatic tumors and cholangiocarcinoma showed heterogeneous or ring-like pattern of lipiodol accumulation because they were relatively hypovascular. Hypervascular hepatocellular carcinoma may exhibit heterogeneous or ring-like pattern if they are larger than 5 cms, and have multiple feeding arteries, necrosis or AV shunting. Hepatocellular carcinoma with AV shunting may not show any lipiodol accumulation at all.

  10. Autophagy Is Required for Activation of Pancreatic Stellate Cells, Associated With Pancreatic Cancer Progression and Promotes Growth of Pancreatic Tumors in Mice.

    PubMed

    Endo, Sho; Nakata, Kohei; Ohuchida, Kenoki; Takesue, Shin; Nakayama, Hiromichi; Abe, Toshiya; Koikawa, Kazuhiro; Okumura, Takashi; Sada, Masafumi; Horioka, Kohei; Zheng, Biao; Mizuuchi, Yusuke; Iwamoto, Chika; Murata, Masaharu; Moriyama, Taiki; Miyasaka, Yoshihiro; Ohtsuka, Takao; Mizumoto, Kazuhiro; Oda, Yoshinao; Hashizume, Makoto; Nakamura, Masafumi

    2017-05-01

    Pancreatic stellate cells (PSCs) change from a quiescent to activated state in the tumor environment and secrete extracellular matrix (ECM) molecules and cytokines to increase the aggressiveness of tumors. However, it is not clear how PSCs are activated to produce these factors, or whether this process can be inhibited. PSCs have morphologic and functional similarities to hepatic stellate cells, which undergo autophagy to promote fibrosis and tumor growth. We investigated whether autophagy activates PSCs, which promotes development of the tumor stroma and growth of pancreatic tumors in mice. We used immunofluorescence microscopy and immunohistochemistry to analyze pancreatic tumor specimens from 133 patients who underwent pancreatectomy in Japan from 2000 to 2009. PSCs were cultured from pancreatic tumor tissues or tissues of patients with chronic pancreatitis; these were analyzed by immunofluorescence microscopy, immunoblots, quantitative reverse transcription polymerase chain reaction, and in assays for invasiveness, proliferation, and lipid droplets. Autophagy was inhibited in PSCs by administration of chloroquine or transfection with small interfering RNAs. Proteins were knocked down in immortalized PSCs by expression of small hairpin RNAs. Cells were transplanted into pancreatic tails of nude mice, and tumor growth and metastasis were quantified. Based on immunohistochemical analyses, autophagy was significantly associated with tumor T category (P = .018), histologic grade (P = .001), lymph node metastases (P < .001), stage (P = .009), perilymphatic invasion (P = .001), and perivascular invasion (P = .003). Autophagy of PSCs was associated with shorter survival times of patients with pancreatic cancer. PSC expression of microtubule-associated protein 1 light chain 3, a marker of autophagosomes, was associated with poor outcomes (shorter survival time, disease recurrence) for patients with pancreatic cancer (relative risk of shorter survival time, 1

  11. Characteristics of malignant tumors in 230 husband-wife pairs.

    PubMed

    Liu, Ju; Xu, Zhijian; Zhang, Kai; Li, Huai; Chang, Sheng; Bi, Xiaofeng; Dai, Min

    2014-09-01

    The aim of this study is to obtain a reference point for early detection of tumors in individuals whose spouses were diagnosed with malignant tumors. Data from 230 husband and wife pairs with malignant tumors were collected and analyzed from the family history records of 15,000 people who came to the Department of Cancer Prevention, Cancer Institute/Hospital, Chinese Academy of Medical Sciences for cancer screening between January 2009 and May 2012. The median diagnosis age was 67 years for husbands and 65 years for wives. A total of 214 cases (46.5 %) had digestive system malignancies. Respiratory system cancers were diagnosed in 64 husbands, of whom 20 (31.3 %) had spouses also with respiratory system cancer. Lung cancer ranked first for the females. The total number of lung cancer and commonly seen female-specific cancers (breast, ovarian, uterine, and cervical) was 127 (55.2 %). The difference in age at diagnosis between spouses was less than 10 years in 134 couples (58.3 %), while 77 (33.5 %) couples had an age difference less than 5 years. A family history of malignant tumors in first-degree relatives was documented in 48.3 % of the husbands and 48.7 % of the wives. The occurrence of cancer in both spouses of the couples studied resulted from an interaction between genetic and environmental factors. Nonhereditary factors such as diet, smoking, passive smoking, and air pollution also contributed to the development of cancers. It is recommended that when husband is diagnosed with cancer, the wife should be screened focusing on lung, breast, and gynecological cancers. If the wife was diagnosed with malignant disease, then screening for lung and digestive system cancers should be emphasized in the husband.

  12. Phase II Study of Intraventricular Methotrexate in Children With Recurrent or Progressive Malignant Brain Tumors

    ClinicalTrials.gov

    2017-01-12

    Recurrent Childhood Medulloblastoma; Recurrent Childhood Ependymoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Embryonal Tumor With Abundant Neuropil and True Rosettes; Metastatic Malignant Neoplasm to the Leptomeninges

  13. Tumor Reduction in Primary and Metastatic Pancreatic Cancer Lesions With nab-Paclitaxel and Gemcitabine

    PubMed Central

    Kunzmann, Volker; Ramanathan, Ramesh K.; Goldstein, David; Liu, Helen; Ferrara, Stefano; Lu, Brian; Renschler, Markus F.; Von Hoff, Daniel D.

    2017-01-01

    Objectives Results from the phase 3 Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) led to approval of nab-paclitaxel plus gemcitabine for first-line treatment of metastatic pancreatic cancer. The current analysis evaluated the effects of nab-paclitaxel plus gemcitabine versus gemcitabine on primary pancreatic and metastatic lesions. Methods In this analysis of the previously described MPACT trial, changes in pancreatic and metastatic tumor burden were assessed using independently measured diameters of lesions on computed tomography or magnetic resonance imaging scans. Changes in the sums of longest tumor diameters were summarized using descriptive statistics and were included in a multivariate analysis of overall survival. Results Primary pancreatic lesion measurement was feasible. Reductions in primary pancreatic tumor burden and metastatic burden from baseline to nadir were significantly greater with nab-paclitaxel plus gemcitabine versus gemcitabine. Baseline pancreatic tumor burden was independently predictive of survival. Both regimens elicited linear reductions in primary pancreatic and metastatic tumor burden through time. There was a high within-patient concordance of tumor changes between primary pancreatic lesions and metastatic lesions. Conclusions This analysis of MPACT demonstrated significant tumor shrinkage benefit for nab-paclitaxel plus gemcitabine in both primary pancreatic and metastatic lesions, supporting ongoing evaluation of this regimen in locally advanced disease. PMID:27841795

  14. 24-Hydroxycholesterol participates in pancreatic neuroendocrine tumor development

    PubMed Central

    Soncini, Matias; Corna, Gianfranca; Moresco, Marta; Coltella, Nadia; Restuccia, Umberto; Maggioni, Daniela; Raccosta, Laura; Lin, Chin-Yo; Invernizzi, Francesca; Crocchiolo, Roberto; Doglioni, Claudio; Traversari, Catia; Bachi, Angela; Bernardi, Rosa; Bordignon, Claudio; Gustafsson, Jan-Åke; Russo, Vincenzo

    2016-01-01

    Cells in the tumor microenvironment may be reprogrammed by tumor-derived metabolites. Cholesterol-oxidized products, namely oxysterols, have been shown to favor tumor growth directly by promoting tumor cell growth and indirectly by dampening antitumor immune responses. However, the cellular and molecular mechanisms governing oxysterol generation within tumor microenvironments remain elusive. We recently showed that tumor-derived oxysterols recruit neutrophils endowed with protumoral activities, such as neoangiogenesis. Here, we show that hypoxia inducible factor-1a (HIF-1α) controls the overexpression of the enzyme Cyp46a1, which generates the oxysterol 24-hydroxycholesterol (24S-HC) in a pancreatic neuroendocrine tumor (pNET) model commonly used to study neoangiogenesis. The activation of the HIF-1α–24S-HC axis ultimately leads to the induction of the angiogenic switch through the positioning of proangiogenic neutrophils in proximity to Cyp46a1+ islets. Pharmacologic blockade or genetic inactivation of oxysterols controls pNET tumorigenesis by dampening the 24S-HC–neutrophil axis. Finally, we show that in some human pNET samples Cyp46a1 transcripts are overexpressed, which correlate with the HIF-1α target VEGF and with tumor diameter. This study reveals a layer in the angiogenic switch of pNETs and identifies a therapeutic target for pNET patients. PMID:27671648

  15. Variation of tumoral marker after radiofrequency ablation of pancreatic adenocarcinoma

    PubMed Central

    Barbi, Emilio; Girelli, Roberto; Tinazzi Martini, Paolo; De Robertis, Riccardo; Ciaravino, Valentina; Salvia, Roberto; Butturini, Giovanni; Frigerio, Isabella; Milazzo, Teresa; Crosara, Stefano; Paiella, Salvatore; Pederzoli, Paolo; Bassi, Claudio

    2016-01-01

    Background To evaluate the correlation between variations of CA 19.9 blood levels and the entity of necrosis at CT after radiofrequency ablation (RFA) of unresectable pancreatic adenocarcinoma. Methods In this study, from June 2010 to February 2014, patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure were included. All these patients underwent RFA. CT study was performed 1 week after RFA. The dosage of CA 19.9 levels was performed 1 month after RFA. Features of necrosis at CT, as mean entity, density and necrosis percentages compared to the original lesion, were evaluated and compared by using t-test with CA 19.9 blood levels variations after RFA procedure. Results In this study were included 51 patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure and with CT study and CA 19.9 available for analysis. After the procedure, CA 19.9 blood levels reduced in 24/51 (47%), remained stable in 10/51 (20%) and increased in 17/51 (33%). In patients with CA 19.9 levels reduced, the tumor marker were reduced less than 20% in 4/24 (17%) and more than 20% in 20/24 (83%); instead the tumor marker were reduced less than 30% in 8/24 (33%) and more than 30% in 16/24 (67%). At CT scan necrotic area density difference was not statistically significant. Also there was no statistically significant difference among the mean area, the mean volume and the mean ablation volume in percentage related to the treated tumor among the three different groups of patients divided depending on the CA 19.9 blood levels. But a tendency to a statistically significant difference was found in comparing the mean percentage of ablation volume between two subgroups of patients with a decrease of CA 19.9 levels with less or more than 20% reduction of tumor markers and between two subgroups with less or more than

  16. Malignant Triton Tumor (Malignant Peripheral Nerve Sheath Tumor With Rhabdomyoblastic Differentiation) Occurring in a Vascularized Free Flap Reconstruction Graft.

    PubMed

    Ram, Roopa; Gardner, Jerad; Alapati, Sindhura; Jambhekar, Kedar; Pandey, Tarun; Montgomery, Corey; Nicholas, Richard

    2017-08-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare form of sarcoma arising from Schwann cells or pluripotent cells of the neural crest. Malignant triton tumor (MTT) is a subtype of MPNST with a component of malignant rhabdomyoblasts in addition to malignant Schwann cells. MPNST and MTT are both aggressive malignancies that most commonly arise from large deep neurofibromas in patients with neurofibromatosis type 1 (NF-1). However, sporadic non-NF-1 cases of MTT have also been reported in the literature. We present a case of a 50-year-old African American male with no stigmata of NF-1 who developed a large mass in a free flap on the right calf. The free flap had been placed by plastic surgery 15 years previously following open right tibial and fibular fractures associated with a large soft tissue defect. Biopsy of the enlarging mass, followed by wide surgical excision, confirmed the pathology to be MTT. Although the development of a high-grade soft tissue sarcoma has been previously reported as a late complication of radiation therapy following free flap reconstructions, we believe this is the first reported case of sarcomatous transformation arising in a vascularized, free muscle transfer.

  17. Multi-detector row CT of pancreatic islet cell tumors.

    PubMed

    Horton, Karen M; Hruban, Ralph H; Yeo, Charles; Fishman, Elliot K

    2006-01-01

    Pancreatic islet cell tumors (ICTs) are neuroendocrine neoplasms that produce and secrete hormones to a variable degree. These neoplasms can present a diagnostic challenge, both clinically and radiologically. ICTs can be classified as either syndromic or nonsyndromic on the basis of their clinical manifestations. Multi-detector row computed tomography (CT) plays an important role in the diagnosis and staging of both syndromic and nonsyndromic ICTs. In general, syndromic ICTs are less than 3 cm in size. They are typically hyperenhancing and are usually best seen on CT scans obtained during the arterial phase. Nonsyndromic ICTs tend to be larger than syndromic ICTs at presentation and are more likely to be cystic or necrotic. It is important for the radiologist to be familiar with appropriate CT protocol for the evaluation of patients with suspected pancreatic ICT and to understand the variable CT appearances of these neoplasms. (c) RSNA, 2006.

  18. Pediatric malignant salivary gland tumors: 60 year follow up.

    PubMed

    Cockerill, Cara C; Gross, Brian C; Contag, Stephanie; Rein, Sarah; Moore, Eric J; Olsen, Kerry D; Orvidas, Laura J

    2016-09-01

    To evaluate the presentation, treatments and outcomes in pediatric patients with salivary gland malignancies. Retrospective chart review (1950-2012), Prospective phone interview. Patients ≤18 years old with a salivary gland malignancy treated at our institution were identified. Patients were also contacted by phone for a follow up survey. Fifty-six patients were identified. Tumor origin was 88% parotid (n = 49), 5% (n = 3) submandibular and 7% (n = 4) minor salivary glands. Time from onset of symptoms to diagnosis was over one year (mean = 14.4 years). Fifteen out of 52 patients with major gland malignancy had a locoregional recurrence and local recurrences were almost all after initial enucleation. Two of these patients died of disease (overall disease specific survival = 96%). Three out of 4 patients with minor gland malignancy had a local recurrence and two patients with high grade pathology developed metastases and died of their disease (overall survival = 50%). On long term follow up survey in 13 patients (25%), 100% reported normal facial movement and 54% described symptoms of Frey's syndrome, which is higher than other reported series in children. Recurrence was noted up to 45 years after initial treatment. The majority of malignant pediatric salivary gland tumors are low grade and have excellent survival, especially if found at an early stage. Minor salivary gland malignancies, particularly high grade, have a worse prognosis. Long term mild Frey's syndrome can be expected in approximately half of patients. We advocate a need for long term follow up and increased awareness among providers to diagnose these patients earlier. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Management of Pediatric Malignant Germ Cell Tumors: ICMR Consensus Document.

    PubMed

    Agarwala, Sandeep; Mitra, Aparajita; Bansal, Deepak; Kapoor, Gauri; Vora, Tushar; Prasad, Maya; Chinnaswamy, Girish; Arora, Brijesh; Radhakrishnan, Venkatraman; Laskar, Siddharth; Kaur, Tanvir; Dhaliwal, Rupinder Singh; Rath, G K; Bakhshi, Sameer

    2017-06-01

    With the introduction of cisplatin, the outcome of children with malignant germ cell tumors (MGCT) has improved to nearly 90% 5 year survival. Over the years, through the results of various multinational co-operative trials, the chemotherapy and surgical guidelines for both the gonadal and extra-gonadal MGCTs have been refined to decrease the early and late morbidities and at the same time improve survival. Introduction of risk categorization has further added to this effort. There has been no recommendation on how the children with malignant germ cell tumors should be treated in India. The current manuscript is written with the objective of developing a consensus guideline for practitioners at a National level. Based on extensively reviewed literature and personal experience of the major pediatric oncology centres in India, the ICMR Expert group has made recommendations for management of children with MGCT India.

  20. Leptomeningeal metastasis of an intradural malignant peripheral nerve sheath tumor.

    PubMed

    Stark, Andreas M; Mehdorn, H Maximilian

    2013-08-01

    Malignant peripheral nerve sheath tumors (MPNST) are defined as any malignant tumor arising from or differentiating towards the peripheral nerve sheath. Intradural MPNST metastases are very rare. We report, to our knowledge, the first case of leptomeningeal metastasis of a MPNST to the spine and intracranial space. A 56-year-old woman with primary intradural MPNST of the S1 nerve root developed leptomeningeal metastases as well as brain metastases 19 months after diagnosis. The patient had a history of non-Hodgkins lymphoma for which she had received irradiation to the spine 15 years prior to this presentation. She had no stigmata of neurofibromatosis type 1. Patients with MPNST may also develop leptomeningeal metastases as demonstrated in this patient with intradural post-radiation MPNST.

  1. [Tumor markers in the diagnosis of pancreatic cancer].

    PubMed

    Cappelli, G; Paladini, S; D'Agata, A

    1999-01-01

    The difficulty in an early diagnosis of pancreatic cancer is in the absence of early symptoms due to lower limit of detection of the actual imaging techniques. Clinical symptoms like weight loss, abdominal pain and jaundice indicate an advanced cancer stage. Today 50% of pancreatic tumors are diagnosed in advanced metastatic stage and only 20-30% show resectable cancer. Ultrasound and determination of a mucine like antigen as CA 19-9, CA 50 and CA 195 seem to allow an earlier diagnosis with a higher rate of resective surgery and a prolonged survival for these patients. The mucines are high molecular weight glycoproteins consistent of a backbone protein to which oligosaccarides are attached. The linkage of carbohydrate to the peptide is termed O-glycosidic and involves the hydroxylic groups of serine or threonine with N-acetylglucosamine. Only the backbone proteins are genetically determined (genes MUC). The gangliosides are the same or derivative of Lewis antigen. CA 19-9, CA 50 and CA 195 are assays directed to different epitopes probably present on the same mucinous antigen. These epitopes are not present in different mucines as CA 15-3, CA 125 and TAG 72. Recently other two mucines are emploied CA 242 and CAM 17.1 but they are not better than CA 19-9. The use of a "triplet" of tumor markers as CA 19-9, CA 125 and CEA is the best diagnostic tool for cancer of pancreas in an "integrated" use with ultrasonographic evaluation of the lesion. CA 19-9 permits differential diagnosis from neuroendocrine tumor or pancreatitis, the values of CA 125 and CEA are useful in the evaluation of the stage, resectability and prognosis of pancreatic cancer. The recent use of CA19-9 for the evaluation of radiochemotherapy in preoperative management of the patient is a mode of a well known application of tumor markers in a kinetic evaluation of the tumor for the radicality of therapy, follow-up, recurrence and the effectiveness of the palliative therapy.

  2. [Synchronous tumors of the female genital tract: triple malignant and one benign tumor].

    PubMed

    Dudnyikova, Anna; Vereczkey, Ildikó; Pete, Imre

    2012-03-01

    Synchronous tumors of the female genital tract are rare, accounting for 0.7-1.8% of all cases. Double synchronous tumors are most often mentioned in the literature. Reviewing the English literature on this topic, we have found only one case report of a triple synchronous tumor. The 55-year-old patient mentioned in our case has had advanced diabetes mellitus, and has been treated with corticosteroid therapy for a long time because of chronic obstructive pulmonary disease (COPD). She was examined because of her vulvar tumor. During the diagnostic procedure, cervical and endometrial malignant tumors and a benign ovarian cyst have also been found. This event brings to our attention the fact that we should be prepared to manage synchronous even triple malignant gynecological tumors.

  3. Accumulation of indium-111-labeled granulocytes in malignant tumors

    SciTech Connect

    Schmidt, K.G.; Rasmussen, J.W.; Wedebye, I.M.; Frederiksen, P.B.; Pedersen, N.T.

    1988-04-01

    In a retrospective study of 220 (/sup 111/In)granulocyte scintigrams from 208 patients, 25 patients had malignant neoplasms. Among these, tumor uptake of /sup 111/In activity was observed in ten patients (intense activity in two patients with non-Hodgkin's lymphoma and colonic carcinoma, respectively; moderate uptake in a patient with non-Hodgkin's lymphoma, and in a patient with an ovarian carcinoma; weak activity in three patients with cerebral neoplasms; and activity within otherwise cold metastatic lesions of the liver in three patients). Microscopic investigation following specific granulocyte staining revealed the greatest extent of granulocyte infiltration in the tumors which took up /sup 111/In activity, emphasizing the importance of tumor granulocyte infiltration as the single most important factor underlying tumor accumulation of /sup 111/In activity during (/sup 111/In)granulocyte scintigraphy.

  4. Modular endoprosthetic reconstruction in malignant bone tumors: indications and limits.

    PubMed

    Balke, Maurice; Ahrens, Helmut; Streitbürger, Arne; Gosheger, Georg; Hardes, Jendrik

    2009-01-01

    Modular tumor prostheses are well established today for the reconstruction of osseous defects after resection of malignant bone tumors. Almost every joint and even total bones (e.g., total femur or humerus) can be replaced with promising functional results, dramatically reducing the need for ablative procedures. Although the complication rate with the use of modern modular endoprostheses is constantly decreasing, the need for revision surgery is still significantly higher than in primary joint arthroplasty. In this review we present the modular endoprosthesis system developed in our institution, summarize the postoperative management, and discuss the indications, limits, and complications as well as the functional results.

  5. A rare case of metastasized non-functional pancreatic neuroendocrine tumor with a good long-term survival

    PubMed Central

    Mirică, A; Bădărău, IA; Mirică, R; Păun, S; Păun, DL

    2016-01-01

    Background: Non-functional neuroendocrine tumors of the pancreas (NF-pNETs) are a varied group of extremely rare malignancies. The majority of patients already have liver metastases at the diagnosis moment, thus, treatment options are restricted, and the survival rate is reserved. Case report: We presented the case of 59-year-old patient, diagnosed with non-functional well-differentiated pancreatic neuroendocrine tumor grade II (NET G2) with the presence of chromogranin A, synaptophysin and somatostatin receptor 2, together with liver and bone metastases. Patient underwent a surgical excision of the pancreatic tumor, started long-acting somatostatin analogues (octreotide), interferon therapy for liver metastases and local radiotherapy for bone metastases. After one year, the patient developed diabetes, needing insulin therapy. At approximately three years after the diagnosis, the patient was still living, had a good quality of life, and was free of local recurrence of the tumor or other metastases. Conclusion: Our case report presented a rare case of metastatic non-functional well-differentiated pancreatic neuroendocrine tumor, involving a multidisciplinary therapeutic approach in order to obtain a good long-term survival. PMID:27928440

  6. A rare case of metastasized non-functional pancreatic neuroendocrine tumor with a good long-term survival.

    PubMed

    A, Mirică; Ia, Bădărău; R, Mirică; S, Păun; Dl, Păun

    2016-01-01

    Background: Non-functional neuroendocrine tumors of the pancreas (NF-pNETs) are a varied group of extremely rare malignancies. The majority of patients already have liver metastases at the diagnosis moment, thus, treatment options are restricted, and the survival rate is reserved. Case report: We presented the case of 59-year-old patient, diagnosed with non-functional well-differentiated pancreatic neuroendocrine tumor grade II (NET G2) with the presence of chromogranin A, synaptophysin and somatostatin receptor 2, together with liver and bone metastases. Patient underwent a surgical excision of the pancreatic tumor, started long-acting somatostatin analogues (octreotide), interferon therapy for liver metastases and local radiotherapy for bone metastases. After one year, the patient developed diabetes, needing insulin therapy. At approximately three years after the diagnosis, the patient was still living, had a good quality of life, and was free of local recurrence of the tumor or other metastases. Conclusion: Our case report presented a rare case of metastatic non-functional well-differentiated pancreatic neuroendocrine tumor, involving a multidisciplinary therapeutic approach in order to obtain a good long-term survival.

  7. [Influence of anesthesia procedure on malignant tumor outcome].

    PubMed

    Fukui, K; Werner, C; Pestel, G

    2012-03-01

    Malignant tumors are the second major cause of death in Germany. The essential therapy of operable cancer is surgical removal of primary tumors combined with adjuvant therapy. However, several consequences of surgery may promote metastasis, such as shedding of tumor cells into the circulation, decrease in tumor-induced antiangiogenesis factors, excessive release of growth factors for wound healing and suppression of immunity induced by surgical stress. In the last decade it has become clear that cell-mediated immunity controls the development of metastasis. Various perioperative factors, such as surgical stress, certain anesthetic and analgesic drugs and pain can suppress the patients' immune system perioperatively. On the other hand, by modifications of the anesthesia technique (e.g. regional anesthesia) and perioperative management to minimize immunosuppression, anesthesiologists can play a considerable role for a better outcome in patients having malignant tumors. Sufficient clinical evidence is not yet available to prove or disprove the hypothesis that anesthesia practice can improve cancer prognosis. Despite difficulties in study design, several prospective randomized trials are currently running and the results are awaited to elucidate this topic.

  8. Training stem cells for treatment of malignant brain tumors.

    PubMed

    Li, Shengwen Calvin; Kabeer, Mustafa H; Vu, Long T; Keschrumrus, Vic; Yin, Hong Zhen; Dethlefs, Brent A; Zhong, Jiang F; Weiss, John H; Loudon, William G

    2014-09-26

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.

  9. Unusual aggressive breast cancer: metastatic malignant phyllodes tumor.

    PubMed

    Singer, Adam; Tresley, Jonathan; Velazquez-Vega, Jose; Yepes, Monica

    2013-02-01

    For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

  10. Malignant tumors in two ancient populations: An approach to historical tumor epidemiology.

    PubMed

    Nerlich, Andreas G; Rohrbach, Helmut; Bachmeier, Beatrice; Zink, Albert

    2006-07-01

    The actual increase in the rate of malignant tumors has been ascribed to a higher life expectancy and the influence of various environmental factors. Herein, we present data on the frequency of malignant tumors in paleopathologically well-defined historic populations. Thereby, we looked for malignant growth affecting the skeleton in three study populations of 905 individuals that have been excavated from the necropoles of Thebes-West and Abydos, Upper Egypt covering the time period between 3200 and 500 BC and 2547 individuals that have been buried in a Southern German ossuary dating from between AD 1400 and 1800. The tissue preservation of both the Egyptian and Southern German material was excellent. All available specimens were subjected to a very careful macroscopic examination; isolated findings were also radiologically investigated. In parallel, anthropological data, such as gender and age at death, were recorded. We identified 5 cases of malignant tumors affecting the skeleton in the Egyptian material and 13 cases affecting the skeletal material from Southern Germany. In most instances, multiple osteolytic lesions with slight osteoblastic reaction are strongly suggestive for metastatic carcinoma. Few cases with poorly reactive osteolyses were most compatible with plasmacytoma. Relative tumor frequencies on an age- and sex-adjusted population basis (using a mathematic model of skeletal involvement of malignant tumors in a well-defined English study population from AD 1901 to 1905) indicated that the tumor rates were not statistically different between ancient Egyptian, the historical Southern German and the recent English reference population. These observations indicate that malignant tumors were present in spatially and temporarily different populations over the last 4000 years with an age- and gender-adjusted frequency not different from Western industrial populations of c. 100 years ago. Therefore, we conclude that the current rise in tumor frequencies in

  11. Borderline and malignant phyllodes tumors display similar promoter methylation profiles.

    PubMed

    Kim, Jo-Heon; Choi, Yoo Duk; Lee, Ji Shin; Lee, Jae Hyuk; Nam, Jong Hee; Choi, Chan; Park, Min Ho; Yoon, Jung Han

    2009-12-01

    Mammary phyllodes tumors (PTs) are uncommon fibroepithelial neoplasms. On the basis of histologic criteria, PTs can be divided into benign, borderline, and malignant groups; however, the histologic distinction of PTs is often difficult and arbitrary. In breast cancer, promoter hypermethylation is a common phenomenon, but there are no data available concerning methylation status in PTs. The aim of this study was to assess whether the methylation profiles support the classification of PTs into three subgroups. A multiplex, nested, methylation-specific polymerase chain reaction approach was used to examine promoter methylation of five genes (GSTP1, HIN-1, RAR-beta, RASSF1A, and Twist) in 87 PTs (54 benign, 23 borderline, and 10 malignant). Immunohistochemical staining for GSTP1 was performed using tissue microarray blocks to determine whether GSTP1 promoter hypermethylation correlated with loss of GSTP1 expression. There was a trend of increasing methylation frequency with increasing grade of PTs. The methylation frequency of all genes and the mean number of methylated genes in borderline and malignant PTs were higher than those in benign PTs; however, there were no statistically significant differences between borderline and malignant PTs. GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (p < 0.001). These results suggest that PTs segregate into only two groups on the basis of their methylation profiles: the benign group and the combined borderline/malignant group.

  12. The Occurrence of Gastrointestinal Stromal Tumors and Second Malignancies.

    PubMed

    Giuliani, Jacopo; Bonetti, Andrea

    2015-12-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. GISTs may coexist with different types of cancer, either synchronous or metachronous. The frequency of this association and the spectrum of neoplasms involved have not been sufficiently analyzed; most of publications describe a single case report and rare case series. In the absence of definitive data, it could be interesting to compare the frequency of the occurrence of GIST and second malignancies in literature. A review of all case series that reported the frequency of the occurrence of GIST and synchronous second malignancies were considered. Six retrospective case series were considered, including 440 GIST patients; of these, there were 64 (14.5 %) patients with other synchronous second malignancies. Median age was 67 years, median GIST size was 3.91 cm (range 3.0-4.79 cm), and all cases (100.0 %) were CD117 and CD34 positive. According to the risk categories, 35.2 % of patients had a very low risk, 24.0 % a low risk, 27.6 % an intermediate risk, and 13.2 % a high risk. Regarding the occurrence of GISTs and synchronous second malignancies, we can consider it as more common than it has been considered. Differently, concerning the topic of the incidence of second primary malignancies (SPMs) and metachronous second malignancies in pre-imatinib and after-imatinib era, we can consider it as a clinically relevant topic; according to the present knowledge, the main cause for the increased incidence of SPMs in the imatinib era is explained by the increased survival of patients with metastatic GISTs and therefore more time available to develop SPMs.

  13. Pancreatic tumor cell secreted CCN1/Cyr61 promotes endothelial cell migration and aberrant neovascularization.

    PubMed

    Maity, Gargi; Mehta, Smita; Haque, Inamul; Dhar, Kakali; Sarkar, Sandipto; Banerjee, Sushanta K; Banerjee, Snigdha

    2014-05-16

    The complex signaling networks between cancer cells and adjacent endothelial cells make it challenging to unravel how cancer cells send extracellular messages to promote aberrant vascularization or tumor angiogenesis. Here, in vitro and in vivo models show that pancreatic cancer cell generated unique microenvironments can underlie endothelial cell migration and tumor angiogenesis. Mechanistically, we find that pancreatic cancer cell secreted CCN1/Cyr61 matricellular protein rewires the microenvironment to promote endothelial cell migration and tumor angiogenesis. This event can be overcome by Sonic Hedgehog (SHh) antibody treatment. Collectively, these studies identify a novel CCN1 signaling program in pancreatic cancer cells which activates SHh through autocrine-paracrine circuits to promote endothelial cell migration and tumor angiogenesis and suggests that CCN1 signaling of pancreatic cancer cells is vital for the regulation of tumor angiogenesis. Thus CCN1 signaling could be an ideal target for tumor vascular disruption in pancreatic cancer.

  14. Is "prepectoral edema" a morphologic sign for malignant breast tumors?

    PubMed

    Kaiser, Clemens G; Herold, Michael; Baltzer, Pascal A T; Dietzel, Matthias; Krammer, Julia; Gajda, Mieczyslaw; Camara, Oumar; Schoenberg, Stefan O; Kaiser, Werner A; Wasser, Klaus

    2015-06-01

    A variety of morphologic and kinetic signs of benign or malignant breast lesions contribute to a final diagnosis and differential diagnosis in magnetic resonance (MR) mammography (MRM). As a new sign, prepectoral edema (PE) in patients without any history of previous biopsy, operation, radiation, or chemotherapy was detected during routine breast MR examinations. The purpose of this study was to retrospectively evaluate the role of this morphologic sign in the differential diagnosis of breast lesions. Between January 2005 and October 2006, a total of 1109 consecutive MRM examinations have been performed in our institution. In this study, only patients who would later be biopsied or operated in our own hospital were included. They had no previous operation, biopsy, intervention, chemotherapy, hormone replacement therapy, or previous mastitis. In total, 162 patients with 180 lesions were included, histologically correlated later-on by open biopsy (124 patients and 136 lesions) or core biopsy (38 patients and 44 lesions). The evaluations were performed by four experienced radiologists in consensus. One hundred eighty evaluated lesions included 104 malignant lesions (93 invasive and 11 noninvasive cancers) and 76 benign lesions. PE was detected in 2.6% of benign lesions (2 of 76), in none of the Ductal cacinoma in situ (DCIS) cases (0 of 11), and in 25.8% of malignant lesions (24 of 93; P < .000). PE was found significantly more frequently in presence of malignant tumors >2 cm in diameter (48.5%, 17 of 35 vs. 13.8%, 8 of 58; P < .001). PE was not statistically associated to malignant tumor type, presence or absence of additional DCIS, and number of lesions. This resulted in the following diagnostic parameters for PE as an indicator for malignancy: sensitivity of 19.3%, specificity of 97.3%, positive predictive value (PPV) of 92.3%, negative predictive value of 48%, and accuracy of 57.7%. In case of occurrence, the "PE sign" seems to be a specific indicator for

  15. Feasibility of boron neutron capture therapy for malignant spinal tumors.

    PubMed

    Nakai, Kei; Kumada, Hiroaki; Yamamoto, Tetsuya; Tsurubuchi, Takao; Zaboronok, Alexander; Matsumura, Akira

    2009-07-01

    Treatment of malignant spinal cord tumors is currently ineffective. The characteristics of the spine are its seriality, small volume, and vulnerability: severe QOL impairment can be brought about by small neuronal damage. The present study aimed to investigate the feasibility of BNCT as a tumor-selective charged particle therapy for spinal cord tumors from the viewpoint of protecting the normal spine. A previous report suggested the tolerance dose of the spinal cord was 13.8 Gy-Eq for radiation myelopathy; a dose as high as 11 Gy-Eq demonstrated no spinal cord damage in an experimental animal model. We calculated the tumor dose and the normal spinal cord dose on a virtual model of a spinal cord tumor patient with a JAEA computational dosimetry system (JCDS) treatment planning system. The present study made use of boronophenylalanine (BPA). In these calculations, conditions were set as follows: tumor/normal (T/N) ratio of 3.5, blood boron concentration of 12 ppm, tumor boron concentration of 42 ppm, and relative biological effectiveness (RBE) values for tumor and normal spinal cord of 3.8 and 1.35, respectively. We examined how to optimize neutron irradiation by changing the beam direction and number. In our theoretical example, simple opposed two-field irradiation achieved 28.0 Gy-Eq as a minimum tumor dose and 7.3 Gy-Eq as a maximum normal spinal dose. The BNCT for the spinal cord tumor was therefore feasible when a sufficient T/N ratio could be achieved. The use of F-BPA PET imaging for spinal tumor patients is supported by this study.

  16. [Clinicopathologic features and prognostic factors of malignant phyllodes tumors].

    PubMed

    Jia, Cui; Mei, Fang; Zheng, Jie; You, Jiang-feng; Liu, Jian-ying

    2013-11-01

    To study the clinicopathologic features of malignant phyllodes tumors (PT) by histopathologic analyses, immunohistochemical profiling and DNA content assay, and evaluation of the clinical outcome. Ten patients with malignant PT from 1999 to 2013 who were treated by surgery were enrolled in this study. The morphologic characteristics were studied under light microscope, standard two-step EnVision method of immunohistochemical staining was used to assess the expression of CK5/6, CKpan, 34β E12, desmin, p63, ER-α, PR, Ki-67, CD34, SMA, p53, p16, bcl-2 and CD117 in the tumors. The corresponding paraffin blocks were also used for flow cytometric DNA content assay. These data were correlated with the follow-up results. The median age of onset was 46.5 years old. The mean tumor size was 7.4 cm (2.0-25.0 cm). At the end of the follow-up period (22 to 125 months), there were tumor recurrences in 3/8 patients and the median time of recurrence was 24 months. Metastasis occurred in 3/8 patients who all died of the tumors. PT had heterogeneous histology, with stromal overgrowth with leaf-like projections, periductal stromal overgrowth, and most commonly, diffuse stromal overgrowth with sarcomatous differentiation. The mean positive index of Ki-67 was 11.4%. The stromal tumor cells were positive for CD34, SMA, p53, p16, and bcl-2 in 3/10, 9/10, 6/10, 8/10, and 4/10 cases, respectively. CD117,ER-α and PR were negative. Interpretable DNA histograms were obtained in nine cases with triploidy in two cases. The diagnosis of malignant PT should be considered based on the diversity of growth patterns and heterogeneous histology.Ki-67 and CD34 are valuable diagnostic and prognostic factors in patients with malignant PT. Tumors with diffuse stromal overgrowth, heterologous elements, Ki-67 ≥ 20% or aneuploidy are more likely to metastasize.

  17. A renaissance in therapeutic options for pancreatic neuroendocrine tumors.

    PubMed

    Kunz, Pamela L

    2012-01-01

    The field of pancreatic neuroendocrine tumors (NETs) has seen a remarkable renaissance in recent years with exponential increases in published research, clinical trials, and U.S. Food and Drug Administration (FDA)-approved treatments. Surgical resection remains the foundation for management of locoregional disease. However, for patients with advanced disease, novel therapeutic options have emerged. Two separate randomized placebo-controlled studies have shown prolonged progression-free survival (PFS) with everolimus or sunitinib. Future studies are designed to answer questions about the role of somatostatin analogs as antiproliferative agents, combinations of biologic therapies, and new cytotoxic chemotherapy backbones.

  18. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Jensen, Robert T.

    2013-01-01

    Pancreatic neuroendocrine tumors (pNETs) comprise with gastrointestinal carcinoids, the main groups of gastrointestinal neuroendocrine tumors (GI-NETs). Although these two groups of GI-NETs share many features including histological aspects; over-/ectopic expression of somatostatin receptors; the ability to ectopically secrete hormones/peptides/amines which can result in distinct functional syndromes; similar approaches used for tumor localization and some aspects of treatment, it is now generally agreed they should be considered separate. They differ in their pathogenesis, hormonal syndromes produced, many aspects of biological behavior and most important, in their response to certain anti-tumor treatment (chemotherapy, molecular targeted therapies). In this chapter the clinical features of the different types of pNETs will be considered as well as aspects of their diagnosis and medical treatment of the hormone-excess state. Emphasis will be on controversial areas or recent advances. The other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, because they are covered in other chapters in this volume. PMID:23582916

  19. Chemotherapy and metformin in pancreatic adenocarcinoma and neuroendocrine tumors.

    PubMed

    Burney, Saira; Khawaja, Khadija Irfan; Saif, Muhammad Wasif; Masud, Faisal

    2014-07-28

    Pancreatic cancer, despite being a relatively less commonly occurring cancer is among the deadliest ones, leading to a grave prognosis. Surgery stands as the mainstay of treatment of pancreatic cancer but is an option in less than 15% patients owing to the late presentation of the tumor. Chemotherapy offers an important part of treatment but can adversely affect the quality of life because of devastating side effects and has limited survival benefit. Unavailability of effective and less toxic treatment options for pancreatic cancer has prompted the search for new treatment strategies. One such drug being considered for its potential anti-neoplastic role is the time-tested and widely used oral hypoglycemic drug, metformin. Metformin is proposed to target metabolic pathways involved in tumorigenesis, specifically the AMPK-mTOR complex. Epidemiological evidence is mounting in favor of its role in various cancers both for treatment and prophylaxis. Herein, we aim to summarize the epidemiological data on metformin as a potential anti-cancer drug in various cancers followed by a look at some of the abstracts relating to this topic that were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2014.

  20. Optically Measured Microvascular Blood Flow Contrast of Malignant Breast Tumors

    PubMed Central

    Choe, Regine; Putt, Mary E.; Carlile, Peter M.; Durduran, Turgut; Giammarco, Joseph M.; Busch, David R.; Jung, Ki Won; Czerniecki, Brian J.; Tchou, Julia; Feldman, Michael D.; Mies, Carolyn; Rosen, Mark A.; Schnall, Mitchell D.; DeMichele, Angela; Yodh, Arjun G.

    2014-01-01

    Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS), a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval) tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92–2.63); tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94–2.66), and using normal tissue in the contralateral breast was 2.27 (1.90–2.70). Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography. PMID:24967878

  1. [Age of onset of different malignant tumors in childhood].

    PubMed

    Mejía Aranguré, Juan Manuel; Flores Aguilar, Hilario; Juárez Muñoz, Irina; Vázquez Langle, José; Games Eternod, Juan; Pérez Saldívar, María Luisa; Ortega Alvarez, Manuel Carlos; Rendón Macías, Mario Enrique; Gutiérrez, Arturo Fajardo

    2005-01-01

    To identify the main age of onset of different malignant tumors in childhood and to describe the distribution of the different tumors in each pediatric age group. Descriptive survey was used. We reviewed the files of six Mexico City hospitals from 1980 to 1992. We included 4595 cases divided into 13 types of cancer. Peak age was defined when in that year we encountered a frequency equal to or below 10 % of the cases. Peak ages for hepatic, sympathetic nervous system, germ cell tumors, retinoblastoma and rhabdomyosarcoma were between 2 and 3 years of age. Wilms' tumor appeared between the first and fourth years; central nervous system tumors between 4 and 5 years; acute lymphoblastic leukemia between 2 and 4 years; non-Hodgkin's lymphomas between 3 and 6 years; Hodgkin's disease between 4 and 8 years; bone tumors between 10 and 14 years. In acute myeloid leukemia and carcinomas no age peak was found. Lymphomas present an age peak different from that reported in developed countries. In neonates and infants, the most frequent tumor was retinoblastoma.

  2. Extrathyroidal Calcitonin Secreting Tumors: Pancreatic Neuroendocrine Tumors in Patients With Multinodular Goiter: Two Case Reports.

    PubMed

    Giannetta, Elisa; Gianfrilli, Daniele; Pozza, Carlotta; Lauretta, Rosa; Graziadio, Chiara; Sbardella, Emilia; Baroli, Alberto; Caronna, Roberto; Chirletti, Piero; Lenzi, Andrea; Isidori, Andrea M

    2016-01-01

    Calcitonin is the hallmark of medullary thyroid carcinoma. However, extrathyroidal neuroendocrine tumors can also release calcitonin.We report 2 cases of calcitonin-secreting pancreatic tumors found in asymptomatic patients with thyroid nodules referred to our center within 11 months.Case 1: A man initially referred for thyroid nodule characterization was found to have hypercalcitoninemia (>200 pg/mL) during non-neoplastic fine-needle aspiration.Case 2: A woman evaluated for liver metastasis was found to have hypercalcitoninemia and multinodular goiter.Our research emphasizes that marked hypercalcitoninemia in the presence of thyroid nodules is not necessarily due to medullary thyroid carcinoma; awareness of this could avoid unnecessary thyroidectomy. The lack of specific symptoms related to hypercalcitoninemia may be the reason that the prevalence of calcitonin-secreting pancreatic tumors is underestimated.

  3. Extrathyroidal Calcitonin Secreting Tumors: Pancreatic Neuroendocrine Tumors in Patients With Multinodular Goiter

    PubMed Central

    Giannetta, Elisa; Gianfrilli, Daniele; Pozza, Carlotta; Lauretta, Rosa; Graziadio, Chiara; Sbardella, Emilia; Baroli, Alberto; Caronna, Roberto; Chirletti, Piero; Lenzi, Andrea; Isidori, Andrea M.

    2016-01-01

    Abstract Calcitonin is the hallmark of medullary thyroid carcinoma. However, extrathyroidal neuroendocrine tumors can also release calcitonin. We report 2 cases of calcitonin-secreting pancreatic tumors found in asymptomatic patients with thyroid nodules referred to our center within 11 months. Case 1: A man initially referred for thyroid nodule characterization was found to have hypercalcitoninemia (>200 pg/mL) during non-neoplastic fine-needle aspiration. Case 2: A woman evaluated for liver metastasis was found to have hypercalcitoninemia and multinodular goiter. Our research emphasizes that marked hypercalcitoninemia in the presence of thyroid nodules is not necessarily due to medullary thyroid carcinoma; awareness of this could avoid unnecessary thyroidectomy. The lack of specific symptoms related to hypercalcitoninemia may be the reason that the prevalence of calcitonin-secreting pancreatic tumors is underestimated. PMID:26817871

  4. TANGO is a tumor suppressor of malignant melanoma.

    PubMed

    Arndt, Stephanie; Bosserhoff, Anja K

    2006-12-15

    The TANGO gene was originally identified as a new family member of the melanoma inhibitory activity gene family. The gene codes for a 14 kDa protein of so far unknown function. In our study we revealed that TANGO was downregulated or lost in 9 melanoma cell lines when compared to normal melanocytes and in most of the 8 tumor samples analyzed. The losses were associated with advanced stage of the disease. These results were confirmed in situ by immunohistochemistry on 10 paraffin-embedded sections of human malignant melanoma primary tumors and melanoma skin metastases. A small reduction of TANGO was also seen in different benign and atypical nevi when compared to normal skin. For functional analysis of TANGO we evaluated TANGO re-expressing melanoma cell clones and antisense TANGO cell clones with a complete loss of TANGO. Functional assays with TANGO transfected or treated cell lines revealed that TANGO expression reduces motility, whereas reduction of TANGO enhances migration. Our studies, therefore, indicate that reduction of TANGO expression contributes to tumor progression. These results taken together provide the first indications for a tumor suppressor role of TANGO gene in human malignant melanoma.

  5. CT-guided percutaneous microwave ablation of pulmonary malignant tumors

    PubMed Central

    Ko, Wei-Chun; Lee, Yee-Fan; Chen, Yi-Chang; Chien, Ning; Huang, Yu-Sen; Tseng, Yao-Hui; Lee, Jang-Ming; Hsu, Hsao-Hsun; Chen, Jin-Shing

    2016-01-01

    Background Microwave ablation (MWA) of lung tumors is a new approach for local tumor control. The purpose of this retrospective study was to evaluate the preliminary results of safety and efficacy of MWA with a dynamic frequency range (902–928 MHz) and power (10–32 W) for local tumor control of thoracic malignancies. Methods From December 1, 2013 to February 1, 2016, there were total 32 lung tumors among 15 patients (7 men, 8 women, age range 43–82 years, mean 57.8±11.1 years of age) receiving MWA of thoracic neoplasms, including lung adenocarcinoma (n=5), metastatic colorectal cancer (n=7), invasive thymoma (n=1), metastatic uterine leiomyosarcoma (n=1), and metastatic ampullary carcinoma (n=1). Mean tumor size was 13.5 mm (range, 3.0–32.0 mm). The mean sequential ablation during each MWA was 2.3±1.1 times (range, 1–5 times). The outcomes of ablation were evaluated by follow-up computed tomography (CT) scans and the complications were assessed by medical records and CT scan after ablation. Results The mean follow-up interval of each tumor was 446.8 days (range, 196–902 days). Local tumor recurrence was found in 5 of the 32 tumors resulting in a local control rate 84.4%. No MWA-related mortality was noted. After MWA, the incidence of pneumothorax was 37.5% (12/32). Only one patient with pneumothorax required air evacuation. Third-degree skin burn adjacent to the entry site occurred in one patient and required debridement and closure with flap. Conclusions After appropriate patient selection, MWA with a dynamic frequency range (902–928 MHz) and power (10–32 W) is an effective and safe procedure for local tumor control of recurrent and metastatic lung tumors. PMID:28066666

  6. DNA Copy Number Variations Characterize Benign and Malignant Thyroid Tumors

    PubMed Central

    Liu, Yan; Cope, Leslie; Sun, Wenyue; Wang, Yongchun; Prasad, Nijaguna; Sangenario, Lauren; Talbot, Kristen; Somervell, Helina; Westra, William; Bishop, Justin; Califano, Joseph; Zeiger, Martha

    2013-01-01

    Context: Fine-needle aspiration (FNA) is the best diagnostic tool for preoperative evaluation of thyroid nodules but is often inconclusive as a guide for surgical management. Objective: Our hypothesis was that thyroid tumor subtypes may show characteristic DNA copy number variation (CNV) patterns, which may further improve the preoperative classification. Design: Our study cohorts included benign follicular adenomas (FAs), classic papillary thyroid carcinomas (PTCs), and follicular variant PTCs (FVPTCs), the three subtypes most commonly associated with inconclusive preoperative cytopathology. Setting: Tissue and FNA samples were obtained at an academic tertiary referral center. Patients: Cases were identified that underwent partial or complete thyroidectomy for malignant or indeterminate thyroid lesions between 2000 and 2008 and had adequate snap-frozen tissue. Interventions: Pairs of tumor tissue and matching normal thyroid tissue-derived DNA were compared using 550K single-nucleotide polymorphism arrays. Main Outcome Measure: Statistically significant differences in CNV patterns between tumor subtypes were identified. Results: Segmental amplifications in chromosomes (Ch) 7 and 12 were more common in FAs than in PTCs or FVPTCs. Additionally, a subset of FAs and FVPTCs showed deletions in Ch22. We identified the 5 CNV-associated genes best at discriminating between FAs and PTCs/FVPTCs, which correctly classified 90% of cases. These 5 Ch12 genes were validated by quantitative genomic PCR and gene expression array analyses on the same patient cohort. The 5-gene signature was then successfully validated against an independent test cohort of benign and malignant tumor samples. Finally, we performed a feasibility study on matched FA-derived intraoperative FNA samples and were able to correctly identify FAs harboring the Ch12 amplification signature, whereas FAs without amplification showed a normal Ch12 signature. Conclusions: Thyroid tumor subtypes possess

  7. Malignant bone tumors: therapeutical strategies related to localization.

    PubMed

    Burnei, Gh; Nayef, T E; Hodorogea, D; Georgescu, Ileana; Vlad, C; Gavriliu, St; Drăghic, Isabela

    2010-01-01

    Modular concept of reconstruction in malignant bone tumors in children and adolescents is trying to solve a complex problem in order to replace a certain bone segment of various sizes or joint, fully adjustable and fully aware ofmorpho-functional features related to the child's age. Given the high frequency of malignant bone tumors in children, occupying the third place in osteoarticular pathology, after injuries and malformations, due to the progress made in terms of knowledge and identifying certain factors (genetical, biological, immunological, etc.) and the increasing life expectancy of these sick children, paediatric orthopedics should offer the possibility of reconstruction of the resected segment. One of the basic concerns in this regard is modular endoprosthetic reconstruction of the resected area, adapted to each case and each bone or osteoarticular segment. Amputation is no longer the only option in the modern treatment in children and adolescent bone malignancies, being often replaced with increasing size piece resection and reconstruction with large massive cortical bone grafts or modular endoprosthetic replacement.

  8. Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors.

    PubMed

    Bonnavion, Rémy; Teinturier, Romain; Jaafar, Rami; Ripoche, Doriane; Leteurtre, Emmanuelle; Chen, Yuan-Jia; Rehfeld, Jens F; Lepinasse, Florian; Hervieu, Valérie; Pattou, François; Vantyghem, Marie-Christine; Scoazec, Jean-Yves; Bertolino, Philippe; Zhang, Chang Xian

    2015-10-01

    The cells of origin of pancreatic gastrinomas remain an enigma, since no gastrin-expressing cells are found in the normal adult pancreas. It was proposed that the cellular origin of pancreatic gastrinomas may come from either the pancreatic cells themselves or gastrin-expressing cells which have migrated from the duodenum. In the current study, we further characterized previously described transient pancreatic gastrin-expressing cells using cell lineage tracing in a pan-pancreatic progenitor and a pancreatic endocrine progenitor model. We provide evidence showing that pancreatic gastrin-expressing cells, found from embryonic day 12.5 until postnatal day 7, are derived from pancreatic Ptf1a(+) and neurogenin 3-expressing (Ngn3(+)) progenitors. Importantly, the majority of them coexpress glucagon, with 4% coexpressing insulin, indicating that they are a temporary subpopulation of both alpha and beta cells. Interestingly, Men1 disruption in both Ngn3 progenitors and beta and alpha cells resulted in the development of pancreatic gastrin-expressing tumors, suggesting that the latter developed from islet cells. Finally, we detected gastrin expression using three human cohorts with pancreatic endocrine tumors (pNETs) that have not been diagnosed as gastrinomas (in 9/34 pNETs from 6/14 patients with multiple endocrine neoplasia type 1, in 5/35 sporadic nonfunctioning pNETs, and in 2/20 sporadic insulinomas), consistent with observations made in mouse models. Our work provides insight into the histogenesis of pancreatic gastrin-expressing tumors.

  9. A novel distinguishing system for the diagnosis of malignant pancreatic cystic neoplasm.

    PubMed

    Shen, Xiaoyong; Lu, Di; Xu, Xiao; Wang, Jianguo; Wu, Jian; Yan, Sheng; Zheng, Shu-sen

    2013-11-01

    To explore a simple and reliable non-invasive distinguishing system for the pre-operative evaluation of malignancy in pancreatic cystic neoplasm (PCN). This study first enrolled an observation cohort of 102 consecutive PCN patients. Demographic information, results of laboratory examinations, and computed tomography (CT) presentations were recorded and analyzed to achieve a distinguishing model/system for malignancy. A group of 21 patients was then included to validate the model/system prospectively. Based on the 11 malignancy-related features identified by univariate analysis, a distinguishing model for malignancy in PCN was established by multivariate analysis: PCN malignant score=2.967 × elevated fasting blood glucose (FBG) (≥6.16 mmol/L) ± 4.496 × asymmetrically thickened wall (or mural nodules ≥ 4 mm) ± 1.679 × septum thickening (≥2 mm)-5.134. With the optimal cut-off value selected as -2.8 in reference to the Youden index, the proposed system for malignant PCN was established: septum thickening (>2 mm), asymmetrically thickened wall (or mural nodules>4 mm), or elevated FBG (>6.16 mmol/L, accompanying commonly known malignant signs), the presence of at least one of these 3 features indicated malignancy in PCN. The accuracy, sensitivity and specificity of this system were 81.4%, 95.8% and 76.9%, respectively. MRI was performed on 32 patients, making correct prediction of malignancy explicitly in only 68.8% (22/32). The subsequent prospective validation study showed that the proposed distinguishing system had a predictive accuracy of 85.7% (18/21). Moreover, a higher model score, or aggregation of the features in the proposed system, indicated a higher grade of malignancy (carcinoma) in PCN. Elevated FBG (>6.16 mmol/L), asymmetrically thickened wall (or mural nodules>4 mm) and septum thickening (>2 mm) are of great value in differentiating the malignancy in PCN. The developed distinguishing system is reliable in the diagnosis of malignant PCN

  10. Performance of the Risk of Malignancy Index for Discriminating Malignant Tumors in Women With Adnexal Masses.

    PubMed

    Campos, Camila; Sarian, Luis Otávio; Jales, Rodrigo Menezes; Hartman, Caio; Araújo, Karla Galvão; Pitta, Denise; Yoshida, Adriana; Andrade, Liliana; Derchain, Sophie

    2016-01-01

    We examined the performance of 4 risk of malignancy index (RMI) variants in a medium-resource gynecologic cancer center. A total of 158 women referred for adnexal masses were evaluated before surgery by the 4 RMI variants. Physicians with varied experience in ultrasound assessment of adnexal masses performed ultrasound examinations. We compared the performance of the 4 RMI variants using receiver operating characteristic curve analyses followed by calculation of sensitivity, specificity, and positive and negative likelihood ratios using the pathologic diagnosis of the masses as the reference standard. Among the 158 women with adnexal masses included in this study, 51 (32%) had malignant tumors; 26 (51%) of them were stage I. All RMI variants performed similarly (accuracy range, 74%-83%), regardless of menopausal status. Considering all women included, the positive likelihood ratios of the 4 RMI variants ranged from 3.52 to 4.41. In subset analyses, all RMI variants had decreased sensitivity for stage I malignant tumors and for those of nonepithelial histologic types. The 4 RMI variants performed acceptably in a medium-resource setting where ultrasound examiners were physicians with varied experience. This finding indicates a good tradeoff between performance and feasibility, since ultrasound RMI protocols are of low complexity.

  11. Surgical approaches used in the reconstruction of the eyelids after excision of malignant tumors.

    PubMed

    Gündüz, Kaan; Demirel, Sibel; Günalp, Ilhan; Polat, Burcu

    2006-01-01

    The choice of reconstructive technique for eyelid defects after malignant tumors was based on tumor location and defect size after tumor excision. Treatments included direct closure for defects measuring less than 25%, Tenzel flap for defects measuring 25-50%, lid-sharing procedures for defects measuring more than 50%, skin grafts for tumors affecting the inner canthus advancement flap for outer canthus tumors, and orbital exenteration for malignant tumors demonstrating orbital invasion.

  12. Total Humeral Endoprosthetic Replacement following Excision of Malignant Bone Tumors

    PubMed Central

    Kotwal, Suhel; Moon, Bryan; Lin, Patrick; Satcher, Robert; Lewis, Valerae

    2016-01-01

    Humerus is a common site for malignant tumors. Advances in adjuvant therapies and reconstructive methods provide salvage of the upper limb with improved outcomes. Reports of limb salvage with total humeral replacement in extensive humeral tumors are sparse. We undertook a retrospective study of 20 patients who underwent total humeral endoprosthetic replacement as limb salvage following excision of extensile malignant tumor from 1990 to 2011. With an average followup of 42.9, functional and oncological outcomes were analyzed. Ten patients were still alive at the time of review. Mean estimated blood loss was 1131 mL and duration of surgery was 314 minutes. Deep infection was encountered in one patient requiring debridement while mechanical loosening of ulnar component was identified in one patient. Subluxation of prosthetic humeral head was noted in 3 patients. Mean active shoulder abduction was 12.5° and active flexion was 15°. Incompetence of abduction mechanism was the major determinant of poor active functional outcome. Mean elbow flexion was 103.5° with 30.5° flexion contracture in 10 patients with good and useful hand function. Average MSTS score was 71.5%. Total humeral replacement is a reliable treatment option in restoring mechanical stability and reasonable functional results without compromising patient survival, with low complication rate. PMID:27042158

  13. [Origin of malignant tumors of the upper respiratory and digestive tracts and the ear. 4. Malignant rumors caused by irradiation. B. Special part (author's transl)].

    PubMed

    Leicher, H

    1979-12-01

    The problem of radiation-induced tumors is explained in detail in the following chapters: 1. Malignant tumors in dial painters using luminous paint, 2. Malignant tumors after injection of Thorotrast, 3. Bronchial tumors in Uran-mineworkers, 4. Malignant tumors caused by radium-compresses and radium-moulages, 5. Thyroid cancer caused by irradiation, 6. Leukemia and malignant tumors following the atomic bomb detonation in Hiroshima and Nakasaki, 7. Malignant tumors in Lupus vulgaris, 8. Development of malignant tumors following the irradiation of praecancerous alterations, of benign tumors and other benign changes in head and neck, 9. Radiation induced soft-tissue and bone sarcoma in the skull, 10. Radiation-induced cancers in hypopharynx diverticula, 11. Radiation-induced cancers in the antethoracic skin graft esophagus, 12. Radiation-induced second-tumors, 13. Cancer caused by ultraviolet rays, 14. Increase of hematogenic metastases by irradiation. 15. Malignant tumors caused by irradiation of the fetus in utero.

  14. Pancreatic Neuroendocrine Tumor in the Setting of Dorsal Agenesis of the Pancreas

    PubMed Central

    2016-01-01

    Dorsal agenesis of the pancreas (DAP) is an uncommon embryological abnormality where there is absence of the distal pancreas. DAP is mostly asymptomatic, but common presenting symptoms include diabetes mellitus, abdominal pain, pancreatitis, enlarged pancreatic head, and, in a few cases, polysplenia. MRCP and ERCP are the gold standard imaging techniques to demonstrate the absence of the dorsal pancreatic duct. The literature on the association of pancreatic neoplasia and DAP is limited. We present the case of a pancreatic neuroendocrine tumor in a patient with dorsal agenesis of the pancreas, with a review of the related literature. PMID:27738535

  15. Malignant phyllodes tumor of the breast: treatment and prognosis.

    PubMed

    Mituś, Jerzy; Reinfuss, Marian; Mituś, Jerzy W; Jakubowicz, Jerzy; Blecharz, Pawel; Wysocki, Wojciech M; Skotnicki, Piotr

    2014-01-01

    Surgery remains the mainstay of the treatment in patients with malignant phyllodes tumor of the breast (MPTB); however, the extent of surgery (breast conserving surgery [BCS] versus mastectomy) and the role of adjuvant radiotherapy have been controversial. We report a single institution's experience with MPTB. We discuss controversial therapeutic aspects of this rare tumor. Seventy patients with MPTB treated primarily with surgery were evaluated. The mean age was 50 years (21-76), and the mean size of the tumor was 6 cm. Thirty-four (48.6%) patients were treated with total mastectomy, and 36 (51.4%) were treated with BCS (lumpectomy or wide local excision). Microscopic surgical margins were free of tumor in all cases. In 64 (91.4%) patients, margins were ≥1 cm. Remaining 6 (8.6%) patients treated with BCS margins were <1 cm and subsequently radiotherapy was performed. Among 70 patients, 58 (82.9%) had no evidence of disease (NED) after 5 years. The extent of surgery was not significantly related to the 5-year NED survival rates (82.4% in patients who underwent mastectomy and 83.3% in patients who underwent BCS only or BCS with adjuvant irradiation). The 5-year NED survival rates in BCS (tumor-free margin ≥1 cm) and BCS with irradiation (tumor-free margin <1 cm) groups were identical (83.3%). Our data support the potential use of BCS in patients with MPTB. Mastectomy is indicated only if tumor-free margins cannot be obtained by BCS. Adjuvant radiotherapy may be considered if tumor-free margins are <1 cm.

  16. Composite pheochromocytoma with a malignant peripheral nerve sheath tumor: Case report and review of the literature.

    PubMed

    Namekawa, Takeshi; Utsumi, Takanobu; Imamoto, Takashi; Kawamura, Koji; Oide, Takashi; Tanaka, Tomoaki; Nihei, Naoki; Suzuki, Hiroyoshi; Nakatani, Yukio; Ichikawa, Tomohiko

    2016-07-01

    Adrenal tumors with more than one cellular component are uncommon. Furthermore, an adrenal tumor composed of a pheochromocytoma and a malignant peripheral nerve sheath tumor is extremely rare. A composite pheochromocytoma with malignant peripheral nerve sheath tumor in a 42-year-old man is reported here. After adequate preoperative control, left adrenalectomy was performed simultaneously with resection of the ipsilateral kidney for spontaneous rupture of the left adrenal tumor. Pathological findings demonstrated pheochromocytoma and malignant peripheral nerve sheath tumor in a ruptured adrenal tumor. To date, there have been only four reported cases of composite pheochromocytoma with malignant peripheral nerve sheath tumor, so the present case is only the fifth case in the world. Despite the very poor prognosis of patients with pheochromocytoma and malignant peripheral nerve sheath tumors reported in the literature, the patient remains well without evidence of recurrence or new metastatic lesions at 36 months postoperatively. Copyright © 2012. Published by Elsevier Taiwan.

  17. Simulating ‘structure-function’ patterns of malignant brain tumors

    NASA Astrophysics Data System (ADS)

    Mansury, Yuri; Deisboeck, Thomas S.

    2004-01-01

    Rapid growth and extensive tissue infiltration are characteristics of highly malignant neuroepithelial brain tumors. Very little is known, however, about the existence of structure-function relationships in these types of neoplasm. Therefore, using a previously developed two-dimensional agent-based model, we have investigated the emergent patterns of multiple tumor cells that proliferate and migrate on an adaptive grid lattice, driven by a local-search mechanism and guided by the presence of distinct environmental conditions. Numerical results indicate a strong correlation between the fractal dimensions of the tumor surface and the average velocity of the tumor's spatial expansion. In particular, when the so called ‘beaten-path advantage’ intensifies, i.e., rising ‘mechanical rewards’ for cells to follow each other along preformed pathways, it results in an increase of the tumor system's fractal dimensions leading to a concomitant acceleration of its spatial expansion. Whereas cell migration is the dominant phenotype responsible for the more extensive branching patterns exhibiting higher fractal dimensions, cell proliferation appears to become more active primarily at lower fracticality associated with stronger mechanical confinements. Implications of these results for experimental and clinical cancer research are discussed.

  18. Screening for Pancreatic Cancer

    PubMed Central

    Brand, Randall E.

    2007-01-01

    Despite improvements in the clinical and surgical management of pancreatic cancer, limited strides have been made in the early detection of this highly lethal malignancy. The majority of localized pancreatic tumors are asymptomatic, and the recognized presenting symptoms of pancreatic adenocarcinoma are often vague and heterogeneous in nature. These factors, coupled with the lack of a sensitive and noninvasive screening method, have made population-based screening for pancreatic cancer impossible. Nevertheless, at least two large institutions have performed multimodality-screening protocols for individuals with high risk of pancreatic cancer based on genetic predisposition and strong family history. Abnormalities noted during these screening protocols prompted further investigation or surgery that resulted in the discovery of benign, potentially malignant, and malignant pancreatic lesions. In addition to ductal epithelial pancreatic intraepithelial neoplasia, greater sensitivity has recently been achieved in the identification and characterization of precancerous mucinous pancreatic tumors. Advancements in proteomics and DNA microarray technology may confirm serum-based biomarkers that could be incorporated into future screening algorithms for pancreatic cancer. PMID:21960811

  19. Temperature rise during photoradiation therapy of malignant tumors

    SciTech Connect

    Svaasand, L.O.; Doiron, D.R.; Dougherty, T.J.

    1983-01-01

    This report discusses the optical and thermal distribution during photoradiation therapy of malignant tumors. Emphasis is put on the therapeutic procedure with the light dose delivered through an inserted optical fiber. Theoretical predictions and experimental results indicate that the temperature rise during the procedure may give rise to hyperthermal cell kill. The report discusses the extent of the regions with hyperthermal bioeffects in terms of tissue parameters as optical absorption and scattering, thermal conductivity, specific heat, blood flow, and optical dose parameters as optical power and exposure time. Key words: photoradiation therapy, hematoporphyrin derivative, hyperthermia

  20. Fulminant course in a case of malignant phyllodes tumor

    PubMed Central

    Chang, Young Woo; Kim, Hwan Soo; Kim, Deok Woo

    2017-01-01

    We present the case of a 31-year-old woman with an inflammatory and ulcerative malignant phyllodes tumor in her right breast. A right modified radical mastectomy and transverse rectus abdominis myocutaneous (TRAM) flap were performed. A month after the initial operation, several masses recurred at the superior margin and deep margin of the TRAM flap. Wide excision was performed, but masses recurred at the inferior margin and in both lung fields 2 weeks after the second operation. Six weeks after the second operation, the patient died due to progression of dyspnea and respiratory failure. PMID:28203559

  1. Malignant phyllodes tumor metastasized to the right ventricle: a case report.

    PubMed

    Yoshidaya, Fumi; Hayashi, Naoki; Takahashi, Katsuhito; Suzuki, Koyu; Akiyama, Futoshi; Ishiyama, Mitsutomi; Takahashi, Yuko; Yoshida, Atsushi; Yagata, Hiroshi; Nakamura, Seigo; Tsunoda, Hiroko; Yamauchi, Hideko

    2015-12-01

    Cardiac metastasis of malignant phyllodes tumor is very rare. We herein report a rare case that developed cardiac metastasis from malignant phyllodes tumor. A 38-year-old woman underwent lumpectomy, and the final pathological findings showed the 5-cm malignant phyllodes tumor partially containing 1 cm of squamous cell carcinoma. Four months after the first surgery, a local recurrence of malignant phyllodes tumor and distant metastases to the bone, lung, pulmonary main trunk, and right ventricle were detected. Mass reduction surgery of cardiac metastasis of the malignant phyllodes tumor was performed to avoid sudden death. In immunohistochemical findings, the tumor was suspected to be originated in myoepithelial cells because of the expression of smooth muscle lineage including α-smooth muscle actin and Calponin1 and highly malignant characteristics showing MIB-1 and p53 highly positive with angiogenesis. Further studies are needed to clarify the effective treatment to these tumors.

  2. Therapeutic approach to the malignant tumors of the biliary tract.

    PubMed

    Mihalache, Florentina; Tantău, M; Iancu, C; Bodea, Raluca; Părău, Angela; Acalovschi, Monica

    2010-01-01

    Cholangiocarcinomas (CCA) are malignant tumors that originate in the cholangiocytes, occur at any level of the biliary tract, are very aggressive and have a 5-year survival rate of 7-8%. Their diagnosis is late and difficult, and the prognosis is very poor. The only curative treatment of these tumors is the complete surgical resection. Signs of unresectability can be detected in most patients with CCA when establishing the diagnosis. Thus, only certain palliative measures can be employed in most cases. The ideal palliative method should be minimally invasive, accompanied by few complications, should offer an increased quality of life, require reduced hospitalization and the lowest costs. The palliative treatment of the obstructive jaundice may be achieved by means of surgical bypass, endoscopic insertion of biliary stents, percutaneous stents, transhepatic stents, photodynamic therapy and/or radio-chemotherapy.

  3. Surgical resection and reconstruction for primary malignant sternal tumor.

    PubMed

    Hirai, Shinji; Nobuto, Hiroaki; Yokota, Kazunori; Matsuura, Yosuke; Uegami, Shinnosuke; Sato, Katsutoshi; Mitsui, Norimasa; Sugita, Takashi; Hamanaka, Yoshiharu

    2009-06-01

    We report a very rare and successful surgery for primary malignant tumor of the sternum. A 73-year-old male, previously healthy, was admitted to our hospital because a chest computed tomography scan detected an abnormal shadow that suggested a sternal tumor destroying part of the sternum body. Aspiration needle biopsy demonstrated a primary sternal chondrosarcoma measuring 3 x 4 cm in diameter. The sternum below the second intercostal space was resected along with a 1-cm width of cartilage below the third rib on each side. Sternal reconstruction was performed with Composix mesh, titanium mesh, and Marlex mesh, using a right pectoralis major muscle flap translation. The patient was extubated just after surgery, and the postoperative course was uneventful. This procedure may be useful for repairing the detect after wide sternotomy.

  4. Omental-mesenteric myxoid hamartomas. Infantile lesions simulating malignant tumors.

    PubMed

    Gonzalez-Crussi, F; deMello, D E; Sotelo-Avila, C

    1983-09-01

    Three infants presented with multiple nodular tumors of the omentum and mesentery characterized histologically by plump mesenchymal cells in a myxoid, well-vascularized stroma. Electron microscopy of one tumor revealed reticulated inclusions in dilated cisterna of endoplasmic reticulum. Diagnoses by the original pathologist, or by consultants from referral centers in the United States included liposarcoma, primitive sarcoma, possible leiomyosarcoma, and fibromatosis, but the subsequent evolution of the patients questions the validity of such diagnoses. Two patients received what was deemed ineffective therapy, yet survived with no evidence of disease for over a decade of close follow-up. Another patient received no therapy other than the initial surgery, and has been well for more than a year. Infantile lesions may show deceptive features of immaturity and high cellularity that are apt to be confused with a true malignancy. Omentalmesenteric "myxoid" lesions are probably hamartomatous in origin.

  5. Targeting Focal Adhesion Kinase and Resistance to mTOR Inhibition in Pancreatic Neuroendocrine Tumors

    PubMed Central

    François, Rony A.; Maeng, Kyungah; Nawab, Akbar; Kaye, Frederic J.; Hochwald, Steven N.; Zajac-Kaye, Maria

    2015-01-01

    Background: Focal adhesion kinase (FAK) mediates survival of normal pancreatic islets through activation of AKT. Upon malignant transformation of islet cells into pancreatic neuroendocrine tumors (PanNETs), AKT is frequently overexpressed and mutations in the AKT/mTOR pathway are detected. Because mTOR inhibitors rarely induce PanNET tumor regression, partly because of feedback activation of AKT, novel combination strategies are needed to target FAK/AKT/mTOR signaling. Methods: We characterized the activation of FAK in PanNETs using immunohistochemistry and Western blot analysis and tested the FAK inhibitor PF-04554878 in human PanNET cells in vitro and in vivo (at least three mice per group). In addition, we evaluated the effect of combined FAK and mTOR inhibition on PanNET viability and apoptosis. All statistical tests were two-sided. Results: We found that FAK is overexpressed and hyperphosphorylated in human PanNETs and that PF-04554878 strongly inhibited FAK (Tyr397) autophosphorylation in a dose-dependent manner. We found that PF-04554878 inhibited cell proliferation and clonogenicity and induced apoptosis in PanNET cells. Moreover, oral administration of PF-04554878 statistically significantly reduced tumor growth in a patient-derived xenograft model of PanNET (P = .02) and in a human PanNET xenograft model of peritoneal carcinomatosis (P = .03). Importantly, PF-04554878 synergized with the mTOR inhibitor everolimus by preventing feedback AKT activation. Conclusions: We demonstrate for the first time that FAK is overexpressed in PanNETs and that inhibition of FAK activity induces apoptosis and inhibits PanNET proliferation. We found that the novel FAK inhibitor PF-04554878 synergizes with everolimus, a US Food and Drug Administration–approved agent for PanNETs. Our findings warrant the clinical investigation of combined FAK and mTOR inhibition in PanNETs. PMID:25971297

  6. Evolution and morphology of microenvironment-enhanced malignancy of three-dimensional invasive solid tumors

    NASA Astrophysics Data System (ADS)

    Jiao, Yang; Torquato, Salvatore

    2013-05-01

    The emergence of invasive and metastatic behavior in malignant tumors can often lead to fatal outcomes for patients. The collective malignant tumor behavior resulting from the complex tumor-host interactions and the interactions between the tumor cells is currently poorly understood. In this paper, we employ a cellular automaton (CA) model to investigate microenvironment-enhanced malignant behaviors and morphologies of in vitro avascular invasive solid tumors in three dimensions. Our CA model incorporates a variety of microscopic-scale tumor-host interactions, including the degradation of the extracellular matrix by the malignant cells, nutrient-driven cell migration, pressure buildup due to the deformation of the microenvironment by the growing tumor, and its effect on the local tumor-host interface stability. Moreover, the effects of cell-cell adhesion on tumor growth are explicitly taken into account. Specifically, we find that while strong cell-cell adhesion can suppress the invasive behavior of the tumors growing in soft microenvironments, cancer malignancy can be significantly enhanced by harsh microenvironmental conditions, such as exposure to high pressure levels. We infer from the simulation results a qualitative phase diagram that characterizes the expected malignant behavior of invasive solid tumors in terms of two competing malignancy effects: the rigidity of the microenvironment and cell-cell adhesion. This diagram exhibits phase transitions between noninvasive and invasive behaviors. We also discuss the implications of our results for the diagnosis, prognosis, and treatment of malignant tumors.

  7. Increased incidence of second primary malignancy in patients with carcinoid tumors: case report and literature review.

    PubMed Central

    Rivadeneira, D. E.; Tuckson, W. B.; Naab, T.

    1996-01-01

    There is an increased incidence of second noncarcinoid neoplasms in patients with carcinoid tumors. This article reports a case of a synchronous malignant ileal carcinoid tumor in a patient with an adenocarcinoma of the sigmoid colon. This report illustrates the increased association of carcinoid tumors with other gastrointestinal malignancies. Images Figure 1 Figure 2 Figure 3 PMID:8667441

  8. Tumor malignancy is engaged to prokaryotic homolog toolbox.

    PubMed

    Fernandes, Janaina; Guedes, Patrícia G; Lage, Celso Luiz S; Rodrigues, Juliany Cola F; Lage, Claudia de Alencar S

    2012-04-01

    Cancer cells display high proliferation rates and survival provided by high glycolysis, chemoresistance and radioresistance, metabolic features that appear to be activated with malignancy, and seemed to have arisen as early in evolution as in unicellular/prokaryotic organisms. Based on these assumptions, we hypothesize that aggressive phenotypes found in malignant cells may be related to acquired unicellular behavior, launched within a tumor when viral and prokaryotic homologs are overexpressed performing likely robust functions. The ensemble of these expressed viral and prokaryotic close homologs in the proteome of a tumor tissue gives them advantage over normal cells. To assess the hypothesis validity, sequences of human proteins involved in apoptosis, energetic metabolism, cell mobility and adhesion, chemo- and radio-resistance were aligned to homologs present in other life forms, excluding all eukaryotes, using PSI-BLAST, with further corroboration from data available in the literature. The analysis revealed that selected sequences of proteins involved in apoptosis and tumor suppression (as p53 and pRB) scored non-significant (E-value>0.001) with prokaryotic homologs; on the other hand, human proteins involved in cellular chemo- and radio-resistance scored highly significant with prokaryotic and viral homologs (as catalase, E-value=zero). We inferred that such upregulated and/or functionally activated proteins in aggressive malignant cells represent a toolbox of modern human homologs evolved from a similar key set that have granted survival of ancient prokaryotes against extremely harsh environments. According to what has been discussed along this analysis, high mutation rates usually hit hotspots in important conserved protein domains, allowing uncontrolled expansion of more resistant, death-evading malignant clones. That is the case of point mutations in key viral proteins affording viruses escape to chemotherapy, and human homologs of such retroviral

  9. Antibody against CD44s Inhibits Pancreatic Tumor Initiation and Post-Radiation Recurrence in Mice

    PubMed Central

    Li, Ling; Hao, Xinbao; Qin, Jun; Tang, Wenhua; He, Fengtian; Smith, Amber; Zhang, Min; Simeone, Diane M.; Qiao, Xiaotan T.; Chen, Zhi-Nan; Lawrence, Theodore S.; Xu, Liang

    2014-01-01

    Background & Aims CD44s is a surface marker of tumor-initiating cells (TICs); high tumor levels correlate with metastasis and recurrence, as well as poor outcomes of patients. Monoclonal antibodies against CD44s might eliminate TICs with minimal toxicity. This strategy is unclear for treatment of pancreatic cancer, and little is known about how anti-CD44s affect pancreatic cancer initiation or recurrence after radiotherapy. Methods 192 pairs of human pancreatic adenocarcinoma and adjacent non-tumor pancreatic tissues were collected from patients undergoing surgery. We measured CD44s levels in tissue samples and pancreatic cancer cell lines by immunohistochemistry, real-time PCR and immunoblot; levels were correlated with patient survival times. We studied the effects of anti-CD44s in mice with human pancreatic tumor xenografts, and used flow cytometry to determine effects on TICs. Changes in CD44s signaling were examined by real-time PCR, immunoblot, reporter assay, and in vitro tumorsphere formation assays. Results Levels of CD44s were significantly higher in pancreatic cancer than adjacent non-tumor tissues. Patients whose tumors expressed high levels of CD44s had a median survival of 10 months, compared to 43 months for those with low levels. Anti-CD44s reduced growth, metastasis, and post-radiation recurrence of pancreatic xenograft tumors in mice. The antibody reduced the number of TICs in cultured pancreatic cancer cells and in xenograft tumors, as well as their tumorigenicity. In cultured pancreatic cancer cell lines, anti-CD44s downregulated the stem cell self-renewal genes Nanog, Sox-2, and Rex-1 and inhibited STAT3-mediated cell proliferation and survival signaling. Conclusions The TIC marker CD44s is upregulated in human pancreatic tumors and associated with patient survival time. CD44s is required for initiation, growth, metastasis, and post-radiation recurrence of xenograft tumors in mice. Anti-CD44s eliminated bulk tumor cells as well as TICs from the

  10. Cutis rhomboidalis protects skin from malignant epithelial tumors.

    PubMed

    Bonkevitch, F; Souza, P R M

    2014-06-01

    Cutis rhomboidalis nuchae is a skin alteration which comes from chronic sun exposure and it integrates the solar elastosis group, acquiring a coriaceous aspect, with a yellowish and grooved surface. There is the occurrence of elastic and collagen fibers degeneration found in the dermis caused by ultraviolet radiation [1]. Another group of skin diseases which has solar exposure as a determining factor is the group of actinic keratoses, the non-melanoma malignant epithelial tumors {basal cell carcinoma (CBC) and squamous cell carcinoma (CEC)} [2]. However, the occurrence of actinic keratoses, CBCs or CECs on the area of cutis rhomboidalis is infrequent in dermatology clinical practice. The authors do not know why people with neoplasias and pre neoplastic lesions in some areas with chronic photo damage amendments (face and upper limbs), do not present the same pre and neoplastic lesions in areas with similar appearance of chronic sun damage (nape). The authors seek to understand why the nape is protected for pre and neoplastic lesions. We suggest that cutis rhomboidalis protects skin from malignant epithelial tumors in nuchae.

  11. Modulation of the leptin receptor mediates tumor growth and migration of pancreatic cancer cells.

    PubMed

    Mendonsa, Alisha M; Chalfant, Madeleine C; Gorden, Lee D; VanSaun, Michael N

    2015-01-01

    Obesity has been implicated as a significant risk factor for development of pancreatic cancer. In the setting of obesity, a systemic chronic inflammatory response is characterized by alterations in the production and secretion of a wide variety of growth factors. Leptin is a hormone whose level increases drastically in the serum of obese patients. High fat diet induced obesity in mice leads to an overall increased body weight, pancreatic weight, serum leptin, and pancreatic tissue leptin levels. Here we report the contribution of obesity and leptin to pancreatic cancer growth utilizing an in vivo orthotopic murine pancreatic cancer model, which resulted in increased tumor proliferation with concomitant increased tumor burden in the diet induced obese mice compared to lean mice. Human and murine pancreatic cancer cell lines were found to express the short as well as the long form of the leptin receptor and functionally responded to leptin induced activation through an increased phosphorylation of AKT473. In vitro, leptin stimulation increased cellular migration which was blocked by addition of a PI3K inhibitor. In vivo, depletion of the leptin receptor through shRNA knockdown partially abrogated increased orthotopic tumor growth in obese mice. These findings suggest that leptin contributes to pancreatic tumor growth through activation of the PI3K/AKT pathway, which promotes pancreatic tumor cell migration.

  12. Modulation of the Leptin Receptor Mediates Tumor Growth and Migration of Pancreatic Cancer Cells

    PubMed Central

    Chalfant, Madeleine C.; Gorden, Lee D.

    2015-01-01

    Obesity has been implicated as a significant risk factor for development of pancreatic cancer. In the setting of obesity, a systemic chronic inflammatory response is characterized by alterations in the production and secretion of a wide variety of growth factors. Leptin is a hormone whose level increases drastically in the serum of obese patients. High fat diet induced obesity in mice leads to an overall increased body weight, pancreatic weight, serum leptin, and pancreatic tissue leptin levels. Here we report the contribution of obesity and leptin to pancreatic cancer growth utilizing an in vivo orthotopic murine pancreatic cancer model, which resulted in increased tumor proliferation with concomitant increased tumor burden in the diet induced obese mice compared to lean mice. Human and murine pancreatic cancer cell lines were found to express the short as well as the long form of the leptin receptor and functionally responded to leptin induced activation through an increased phosphorylation of AKT473. In vitro, leptin stimulation increased cellular migration which was blocked by addition of a PI3K inhibitor. In vivo, depletion of the leptin receptor through shRNA knockdown partially abrogated increased orthotopic tumor growth in obese mice. These findings suggest that leptin contributes to pancreatic tumor growth through activation of the PI3K/AKT pathway, which promotes pancreatic tumor cell migration. PMID:25919692

  13. Pancreatic tumors in children and young adults with tuberous sclerosis complex.

    PubMed

    Koc, Gonca; Sugimoto, Sam; Kuperman, Rachel; Kammen, Bamidele F; Karakas, S Pinar

    2017-01-01

    Pancreatic neuroendocrine tumors are not included in the diagnostic criteria for tuberous sclerosis complex, although an association has been described. To investigate the association of pancreatic neuroendocrine tumor in children and young adults with tuberous sclerosis complex and define MRI characteristics of the tumor. We retrospectively evaluated the abdominal MRI scans of 55 children and young adults with tuberous sclerosis complex for the presence of a pancreatic mass. The scans were performed over a period of 7 years to monitor renal pathology. We obtained each patient's clinical history and treatment protocol from the hospital's electronic medical records. A solid pancreatic mass was identified in 5/55 (9%, 95% confidence interval [CI] 3-20%) patients (4 male) with a mean age of 12.6 years. Four of the lesions were located in the pancreatic tail and one in the pancreatic body. All of the lesions were solid, ovoid and well demarcated, with a mean diameter of 3.1 cm. The masses uniformly demonstrated T1 and T2 prolongation, but their diffusion behavior and post-contrast enhancement varied. The two surgically resected lesions were synaptophysin (+) non-functional pancreatic neuroendocrine tumors on pathology. Two of the patients who did not have surgery were treated with everolimus; one of the lesions has shown interval decrease in size and the other has remained stable. Pancreatic tumor is relatively common in children and young adults with tuberous sclerosis complex.

  14. Senescence and pre-malignancy: how do tumors progress?

    PubMed

    Saab, Raya

    2011-12-01

    Cellular senescence is a tumor suppressor response that has been observed both in vitro and in vivo, and features of senescence have been documented in various human premalignant lesions, including melanoma, colon and lung adenoma, prostatic intraepithelial neoplasia, and others. The fact that a subset of these lesions eventually progress to malignant invasive tumors suggests that premalignant cells can either bypass or escape the senescent response. Much work has been done to understand the mechanisms underlying such progression, but it remains unclear whether tumors progress by evasion of senescence induction, or by disruption of senescence maintenance, or whether both mechanisms can occur in human cancer development. This review presents the current evidence for mechanisms of senescence evasion and reversion, and discusses what has been learnt about this process using in vitro and in vivo experimental systems. As we learn more about the key signaling effectors of senescence, the hope is that appropriate targets will be identified for preservation and/or re-induction of senescence in human tumors. Such knowledge may also find application in better estimation of risks of cancer progression in individual premalignant lesions, which will lead to more accurate allocation of appropriate treatment options for such patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. [The importance of ADAM family proteins in malignant tumors].

    PubMed

    Walkiewicz, Katarzyna; Gętek, Monika; Muc-Wierzgoń, Małgorzata; Kokot, Teresa; Nowakowska-Zajdel, Ewa

    2016-02-11

    Increasing numbers of reports about the role of adamalysins (ADAM) in malignant tumors are being published. To date, more than 30 representatives of this group, out of which about 20 occur in humans, have been described. The ADAM family is a homogeneous group of proteins which regulate, from the stage of embryogenesis, a series of processes such as cell migration, adhesion, and cell fusion. Half of them have proteolytic activity and are involved in the degradation of the extracellular matrix and the disintegration of certain protein complexes, thereby regulating the bioavailability of various growth factors. Many of these functions have a direct role in the processes of carcinogenesis and promoting the growth of tumor, which affect some signaling pathways, including those related to insulin-like growth factors (IGF1, IGF2), vascular growth factor (VEGF), tumor necrosis factor α (TNFα) and the EGFR/HER pathway. Another branch of studies is the evaluation of the possibility of using members of ADAM family proteins in the diagnosis, especially in breast, colon and non- small cell lung cancer. The detection of concentrations of adamalysin in serum, urine and pleural aspirates might contribute to the development of methods of early diagnosis of cancer and monitoring the therapy. However, both the role of adamalysins in the development and progression of tumors and their importance as a diagnostic and predictive further research still need to be checked on large groups of patients.

  16. Surgical treatment of rare giant malignant tumors of the scalp: A report of 3 cases with different tumor types

    PubMed Central

    Liu, Xiaoliang; Li, Wenzhong; Yuan, Hepei; Gu, Weihong; Chen, Dawei

    2016-01-01

    The scalp is the most frequent site of occurrence of malignant tumors. As an area that is generally neglected by the patient and not closely monitored during physical examinations, scalp tumors can go unnoticed until they become malignant. The present study reports 3 cases of rare giant malignant tumors of the scalp, namely a peripheral nerve sheath tumor, a fibrous tumor and a malignant proliferating trichilemmal tumor, that were treated at The First Bethune Hospital of Jilin University (Changchun, China). Vascularized free anterolateral thigh flap surgery was performed in 2 of the 3 cases. A local flap repair was applied to the third case. The implanted skin grafts remained viable post-operatively and wound repair was uneventful. No signs of malignancy were detected on the edge of the pathological section upon closer pathological examination. In the follow-up period, no recurrence was detected in any of the cases. PMID:27900013

  17. Malignant triton tumor: Grand Round presentation of a rare aggressive case thoracolumbar spine tumor.

    PubMed

    Ghailane, Soufiane; Fauquier, Sandra; Lepreux, Sébastien; Le Huec, Jean-Charles

    2017-09-18

    We report a rare and aggressive case of malignant triton tumor (MTT) at the thoracolumbar junction with foraminal extension mistreated as schwannoma. A 70-year-old man with a 2-year history of lower back pain and left L4 radiculopathy with no history of neurofibromatosis. Pre-operative MRI suggested a typical schwannoma. Upon complete marginal resection, histological findings revealed a MTT. The patient presented with a local and regional recurrence and died 10 months after surgery. MTTs are a subgroup of malignant peripheral nerve sheath tumors, which develop from Schwann cells of peripheral nerves or within existing neurofibromas, and display rhabdomyoblastic differentiation. Based on the Grand Round case and relevant literature, we present a case of a highly aggressive and fast-growing tumor with a very high local and distant recurrence. There is no consensus treatment plan available and patients usually die shortly after diagnosis.

  18. Malignant neurocristic hamartoma: a tumor distinct from conventional melanoma and malignant blue nevus.

    PubMed

    Linskey, Katy R; Dias-Santagata, Dora; Nazarian, Rosalynn M; Le, Long P; Lam, Quynh; Bellucci, Kirsten S W; Robinson-Bostom, Leslie; Mihm, Martin C; Hoang, Mai P

    2011-10-01

    Neurocristic hamartomas are rare pigmented lesions comprised of melanocytes, Schwann cells, and pigmented dendritic spindle cells that involve the skin and soft tissue. Malignant transformation can rarely arise within neurocristic hamartomas. Up to date, there has been only 1 series of 7 cases of malignant neurocristic hamartomas (MNHs), with 3 cases that developed metastases. We present the histology and clinical course of 3 additional cases of MNH, 2 of which were metastatic. CD117 was strongly positive in all cases with available archival materials--the tumors and background neurocristic hamartoma of 3 cases, and 1 lymph node metastasis; however, KIT sequencing for exons 11, 13, 17, and 18 was negative. Mutational analyses of recurrent mutations of 17 cancer genes, including BRAF and KIT, were also negative. Although our series is small, KIT overexpression in MNH does not seem to correlate with gene mutation. The lack of BRAF, NRAS, GNAQ, and KIT mutations seems to support the notion that MNH may be distinct from conventional melanoma and from other dermal melanomas, such as malignant blue nevi and melanoma arising in congenital nevi.

  19. Genetics of pancreatic neuroendocrine tumors: implications for the clinic

    PubMed Central

    Pea, Antonio; Hruban, Ralph H.; Wood, Laura D.

    2016-01-01

    Pancreatic neuroendocrine tumors (PanNETs) are a common and deadly neoplasm of the pancreas. Although the importance of genetic alterations in PanNETs has been known for many years, recent comprehensive sequencing studies have greatly expanded our knowledge of neuroendocrine tumorigenesis in the pancreas. These studies have identified specific cellular processes that are altered in PanNETs, highlighted alterations with prognostic implications, and pointed to pathways for targeted therapies. In this review, we will discuss the genetic alterations that play a key role in PanNET tumorigenesis, with a specific focus on those alterations with the potential to change the way patients with these neoplasms are diagnosed and treated. PMID:26413978

  20. Somatostatin analog octreotide LAR in gastro-entero-pancreatic tumors.

    PubMed

    Oberg, Kjell

    2009-05-01

    Neuroendocrine tumors (NETs) are considered to be rare but, during the last two decades, their incidence and prevalence has considerably increased in gastro-entero-pancreatic (GEP) NETs. Most GEP-NETs express somatostatin receptors, which could be targets for treatment. The development of somatostatin analogs for treatment of functioning NETs was a revolution in the treatment of these patients and is still a cornerstone for managing hormone-related clinical symptoms. Furthermore, somatostatin analogs have also demonstrated an anti-tumor effect, with stabilization of tumor growth over long periods of time. The development of a long-acting formulation of octreotide long-acting release (LAR) significantly improved the quality of life for patients with functioning NETs in terms of necessitating only monthly injections. The side effects are few and easily manageable. In the future, somatostatin analogs will continue to be a major treatment option for functioning NETs, but will be combined with other biologicals, such as a-interferons, mTOR inhibitors and VEGF inhibitors. A new multireceptor somatostatin analog, SOM230 (pasireotide), as well as chimeric molecules, such as dopastatin (a combination of a somatostatin analogue plus a dopamine agonist), will come into the clinical management of GEP-NETs.

  1. Malignant tumor formation at the site of previously irradiated acanthomatous epulides in four dogs

    SciTech Connect

    Thrall, D.E.; Goldschmidt, M.H.; Biery, D.N.

    1981-01-15

    The radiation response of acanthomatous epulis in 32 dogs was good, with an estimated median survival time of 21 months. Of the 32 patients, 14 have died. In 4 of those 14, malignant tumors developed at the site of the acanthomatous epulis. The tumors were of epithelial origin in 3 patients and of mesenchymal origin in 1 patient. Possibilities explaining the appearance of the malignancies included spontaneous malignant transformation, radiation induction of neoplasms, and radiation induction of malignant transformation. This uncommon complication was not considered contradictory to radiotherapy of acanthomatous epulides, because of their excellent response to irradiation and the long latent period between irradiation and appearance of the malignant tumor.

  2. MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

    PubMed

    Cros, J; Hentic, O; Rebours, V; Zappa, M; Gille, N; Theou-Anton, N; Vernerey, D; Maire, F; Lévy, P; Bedossa, P; Paradis, V; Hammel, P; Ruszniewski, P; Couvelard, A

    2016-08-01

    Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

  3. Computed tomography-guided percutaneous core needle biopsy in pancreatic tumor diagnosis.

    PubMed

    Tyng, Chiang J; Almeida, Maria Fernanda A; Barbosa, Paula N V; Bitencourt, Almir G V; Berg, José Augusto A G; Maciel, Macello S; Coimbra, Felipe J F; Schiavon, Luiz Henrique O; Begnami, Maria Dirlei; Guimarães, Marcos D; Zurstrassen, Charles E; Chojniak, Rubens

    2015-03-28

    To evaluate the techniques, results, and complications related to computed tomography (CT)-guided percutaneous core needle biopsies of solid pancreatic lesions. CT-guided percutaneous biopsies of solid pancreatic lesions performed at a cancer reference center between January 2012 and September 2013 were retrospectively analyzed. Biopsy material was collected with a 16-20 G Tru-Core needle (10-15 cm; Angiotech, Vancouver, CA) using a coaxial system and automatic biopsy gun. When direct access to the lesion was not possible, indirect (transgastric or transhepatic) access or hydrodissection and/or pneumodissection maneuvers were used. Characteristics of the patients, lesions, procedures, and histologic results were recorded using a standardized form. A total of 103 procedures included in the study were performed on patients with a mean age of 64.8 year (range: 39-94 year). The mean size of the pancreatic lesions was 45.5 mm (range: 15-195 mm). Most (75/103, 72.8%) procedures were performed via direct access, though hydrodissection and/or pneumodissection were used in 22.2% (23/103) of cases and indirect transhepatic or transgastric access was used in 4.8% (5/103) of cases. Histologic analysis was performed on all biopsies, and diagnoses were conclusive in 98.1% (101/103) of cases, confirming 3.9% (4/103) of tumors were benign and 94.2% (97/103) were malignant; results were atypical in 1.9% (2/103) of cases, requiring a repeat biopsy to diagnose a neuroendocrine tumor, and surgical resection to confirm a primary adenocarcinoma. Only mild/moderate complications were observed in 9/103 patients (8.7%), and they were more commonly associated with biopsies of lesions located in the head/uncinate process (n = 8), than of those located in the body/tail (n = 1) of the pancreas, but this difference was not significant. CT-guided biopsy of a pancreatic lesion is a safe procedure with a high success rate, and is an excellent option for minimally invasive diagnosis.

  4. Computed tomography-guided percutaneous core needle biopsy in pancreatic tumor diagnosis

    PubMed Central

    Tyng, Chiang J; Almeida, Maria Fernanda A; Barbosa, Paula NV; Bitencourt, Almir GV; Berg, José Augusto AG; Maciel, Macello S; Coimbra, Felipe JF; Schiavon, Luiz Henrique O; Begnami, Maria Dirlei; Guimarães, Marcos D; Zurstrassen, Charles E; Chojniak, Rubens

    2015-01-01

    AIM: To evaluate the techniques, results, and complications related to computed tomography (CT)-guided percutaneous core needle biopsies of solid pancreatic lesions. METHODS: CT-guided percutaneous biopsies of solid pancreatic lesions performed at a cancer reference center between January 2012 and September 2013 were retrospectively analyzed. Biopsy material was collected with a 16-20 G Tru-Core needle (10-15 cm; Angiotech, Vancouver, CA) using a coaxial system and automatic biopsy gun. When direct access to the lesion was not possible, indirect (transgastric or transhepatic) access or hydrodissection and/or pneumodissection maneuvers were used. Characteristics of the patients, lesions, procedures, and histologic results were recorded using a standardized form. RESULTS: A total of 103 procedures included in the study were performed on patients with a mean age of 64.8 year (range: 39-94 year). The mean size of the pancreatic lesions was 45.5 mm (range: 15-195 mm). Most (75/103, 72.8%) procedures were performed via direct access, though hydrodissection and/or pneumodissection were used in 22.2% (23/103) of cases and indirect transhepatic or transgastric access was used in 4.8% (5/103) of cases. Histologic analysis was performed on all biopsies, and diagnoses were conclusive in 98.1% (101/103) of cases, confirming 3.9% (4/103) of tumors were benign and 94.2% (97/103) were malignant; results were atypical in 1.9% (2/103) of cases, requiring a repeat biopsy to diagnose a neuroendocrine tumor, and surgical resection to confirm a primary adenocarcinoma. Only mild/moderate complications were observed in 9/103 patients (8.7%), and they were more commonly associated with biopsies of lesions located in the head/uncinate process (n = 8), than of those located in the body/tail (n = 1) of the pancreas, but this difference was not significant. CONCLUSION: CT-guided biopsy of a pancreatic lesion is a safe procedure with a high success rate, and is an excellent option for minimally

  5. Tasmanian devil facial tumor disease: insights into reduced tumor surveillance from an unusual malignancy.

    PubMed

    O'Neill, Iain D

    2010-10-01

    Tasmanian devil facial tumor disease (DFTD) is a highly aggressive cancer involving the facial tissues that currently presents a serious extinction risk for the Tasmanian devil population. Although the histogenesis is uncertain, an origin from a neural crest cell-lineage is considered likely. Epidemiological, cytogenetic and immunological data all support the premise that DFTD arose from a single tumor clone from an individual diseased animal, and is being transmitted between individual animals as a tumor "allograft" by biting during social interaction. The spread of this cancer throughout the species is believed to be facilitated by a reduced MHC diversity, possibly as a result of an evolutionary bottleneck. The pathogenesis of DFTD has some similarities with certain human cancers, including donor-recipient tumor transmission, which may complicate organ transplantation, and certain forms of malignancy at the maternal/fetal interface. The natural history and pathology of DFTD, and the data describing this highly unusual tumor biology are discussed.

  6. A Pilot Study Treatment of Malignant Tumors Using [18F] Fluorodeoxyglucose (FDG)

    ClinicalTrials.gov

    2017-09-08

    Radiosensitive Stage IV Solid and Hematological Tumors With High FDG Uptake Not Responding to Standard of Care; Lung Cancer, Head and Neck Cancer, Breast Cancer, Gastric Cancer, Pancreatic Cancer, Colon Cancer, Lymphomas, Sarcomas, Etc

  7. Comparison of cytological and histological preparations in the diagnosis of pancreatic malignancies using endoscopic ultrasound-guided fine needle aspiration.

    PubMed

    Jang, Dong Kee; Lee, Sang Hyub; Lee, Jun Kyu; Paik, Woo Hyun; Chung, Kwang Hyun; Lee, Ban Seok; Son, Jun Hyuk; Lee, Jae Woo; Ryu, Ji Kon; Kim, Yong-Tae; Lee, Kyoung-Bun

    2017-08-15

    Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has become a crucial diagnostic technique for pancreatic malignancies. The specimen obtained by EUS-FNA can be prepared for either cytological or histological examinations. This study was to compare diagnostic performance of cytological and histological preparations using EUS-FNA in the same lesions when pancreatic malignancies were suspected. One hundred and eighteen patients who underwent EUS-FNA for suspected pancreatic malignancies were consecutively enrolled. All procedures were conducted by a single echoendoscopist under the same conditions. Four adequate preparations were obtained by 22-gauge needles with 20 to-and-fro movements for each pass. The 4 preparations included 2 cytological and 2 histological specimens. The pathologic reviews of all specimens were conducted independently by a single experienced cytopathologist. Sensitivity, specificity, and accuracy of the 2 preparations were compared. The enrolled patients consisted of 62 males (52.5%), with the mean age of 64.6±10.5 years. Surgery was performed in 23 (19.5%) patients. One hundred and sixteen (98.3%) lesions were classified as malignant, while 2 (1.7%) were benign. Sensitivity of cytology and histology were 87.9% and 81.9%, respectively, with no significant difference (P=0.190). Accuracy was also not significantly different. Cytological preparation was more sensitive when the size of lesion was <3 cm (86.7% vs 68.9%, P=0.033). Our results suggested that the diagnostic performances of cytological and histological preparations are not significantly different for the diagnosis of pancreatic malignancies. However, cytological preparation might be more sensitive for pancreatic lesions <3 cm. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

  8. Pancreatic schwannoma: Report of a case and review of literature.

    PubMed

    Kinhal, Vidyadhar A; Ravishankar, T H S; Melapure, Ashok I; Jayaprakasha, G; Range Gowda, B C; Manjunath

    2010-07-01

    Connective tissue tumors of pancreas are uncommon, among them pancreatic schwannoma is very rare tumor, very few cases were reported in literature. Aggressive resections like whipple's procedure, or distal pancreatectomy are not necessary for pancreatic schwannoma as it rarely goes to malignant change and simple enuclation is sufficient.In our patient pancreatic schwannoma is associated with simple cyst in liver and absence of one kidney. Here, we are presenting a case of pancreatic schwannoma treated by simple enucleation.

  9. Tumor budding is an independent adverse prognostic factor in pancreatic ductal adenocarcinoma.

    PubMed

    O'Connor, Kate; Li-Chang, Hector H; Kalloger, Steven E; Peixoto, Renata D; Webber, Douglas L; Owen, David A; Driman, David K; Kirsch, Richard; Serra, Stefano; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F

    2015-04-01

    Tumor budding is a well-established adverse prognostic factor in colorectal cancer. However, the significance and diagnostic reproducibility of budding in pancreatic carcinoma requires further study. We aimed to assess the prognostic significance of tumor budding in pancreatic ductal adenocarcinoma, determine its relationship with other clinicopathologic features, and assess interobserver variability in its diagnosis. Tumor budding was assessed in 192 archival cases of pancreatic ductal adenocarcinoma using hematoxylin and eosin (H&E) sections; tumor buds were defined as single cells or nonglandular clusters composed of <5 cells. The presence of budding was determined through assessment of all tumor-containing slides, and associations with clinicopathologic features and outcomes were analyzed. Six gastrointestinal pathologists participated in an interobserver variability study of 120 images of consecutive tumor slides stained with H&E and cytokeratin. Budding was present in 168 of 192 cases and was associated with decreased overall survival (P=0.001). On multivariable analysis, tumor budding was prognostically significantly independent of stage, grade, tumor size, nodal status, lymphovascular invasion, and perineural invasion. There was substantial agreement among pathologists in assessing the presence of tumor budding using both H&E (K=0.63) and cytokeratin (K=0.63) stains. The presence of tumor budding is an independent adverse prognostic factor in pancreatic ductal carcinoma. The assessment of budding with H&E is reliable and could be used to better risk stratify patients with pancreatic ductal adenocarcinoma.

  10. A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors.

    PubMed

    Ding, Ning; Cui, Xiao-Xing; Gao, Zhi; Huang, Huarong; Wei, Xingchuan; Du, Zhiyun; Lin, Yong; Shih, Weichung Joe; Rabson, Arnold B; Conney, Allan H; Hu, Chunhong; Zheng, Xi

    2014-06-01

    Because K-Ras mutation and cyclooxygenase-2 (COX-2) overexpression are hallmarks of majority of pancreatic cancer patients, an approach to inhibit the progression and growth of pancreatic cancer using the simultaneous administration of agents that inhibit the function of both targets, should be considered. In the present study, we assessed the effects of atorvastatin (Lipitor), celecoxib (Celebrex) and tipifarnib (Zarnestra) on the growth of human pancreatic cancer. In the in vitro studies, we found that treatment of human pancreatic tumor cells with a combination of atorvastatin, celecoxib and tipifarnib had a stronger inhibitory effect on growth and a stronger stimulatory effect on apoptosis than each drug alone or for any combination of two drugs. We also found that treatment of Panc-1 cells with a combination of all three drugs strongly decreased the levels of phosphorylated Erk1/2 and Akt. In an animal model of xenograft tumors in severe combined immunodeficient (SCID) mice, we found that daily i.p. injections of a combination of atorvastatin, celecoxib and tipifarnib had a stronger inhibitory effect on the growth of the tumors in mice than each drug alone or for any combination of two drugs. The results of our study indicate that a combination of atorvastatin, celecoxib and tipifarnib may be an effective strategy for the treatment of pancreatic cancer.

  11. Molecular Markers for Novel Therapeutic Strategies in Pancreatic Endocrine Tumors

    PubMed Central

    Gilbert, Judith A.; Adhikari, Laura J.; Lloyd, Ricardo V.; Halfdanarson, Thorvardur R.; Muders, Michael H.; Ames, Matthew M.

    2012-01-01

    Objectives Pancreatic endocrine tumors (PETs) share numerous features with gastrointestinal neuroendocrine (carcinoid) tumors. Targets of novel therapeutic strategies previously assessed in carcinoid tumors were analyzed in PETs (44 cases). Methods Activating mutations in EGFR, KIT, and PDGFRA, and non-response mutations in KRAS, were evaluated. Copy number of EGFR and HER-2/neu was quantified by fluorescence in situ hybridization. Expression of EGFR, PDGFRA, VEGFR1, TGFBR1, Hsp90, SSTR2A, SSTR5, IGF1R, mTOR, and MGMT was measured immunohistochemically. Results Elevated EGFR copy number was found in 38% of cases, but no KRAS non-response mutations. VEGFR1, TGFBR1, PDGFRA, SSTR5, SSTR2A, and IGF1R exhibited the highest levels of expression in the largest percentages of PETs. Anticancer drugs BMS-754807 (selective for IGF1R/IR), 17-(allylamino)-17-demethoxygeldanamycin (17-AAG, targeting Hsp90), and axitinib (directed toward VEGFR1–3/PDGFRA-B/KIT) induced growth inhibition of human QGP-1 PET cells with IC50 values (nM) of 273, 723, and 743, respectively. At growth-inhibiting concentrations, BMS-754807 inhibited IGF1R phosphorylation; 17-AAG induced loss of EGFR, IGF1R, and VEGFR2; and axitinib increased p21Waf1/Cip1(CDKN1A) expression without inhibiting VEGFR2 phosphorylation. Conclusions Results encourage further research into multi-drug strategies incorporating inhibitors targeting IGF1R or Hsp90 and into studies of axitinib combined with conventional chemotherapeutics toxic to tumor cells in persistent growth arrest. PMID:23211371

  12. Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

    PubMed Central

    Johnson, Eric D.; Gulbahce, Evin; McNally, Joseph; Buys, Saundra S.

    2016-01-01

    Introduction Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported. PMID:28203179

  13. A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer.

    PubMed

    Mello, Stephano S; Valente, Liz J; Raj, Nitin; Seoane, Jose A; Flowers, Brittany M; McClendon, Jacob; Bieging-Rolett, Kathryn T; Lee, Jonghyeob; Ivanochko, Danton; Kozak, Margaret M; Chang, Daniel T; Longacre, Teri A; Koong, Albert C; Arrowsmith, Cheryl H; Kim, Seung K; Vogel, Hannes; Wood, Laura D; Hruban, Ralph H; Curtis, Christina; Attardi, Laura D

    2017-10-09

    The p53 transcription factor is a critical barrier to pancreatic cancer progression. To unravel mechanisms of p53-mediated tumor suppression, which have remained elusive, we analyzed pancreatic cancer development in mice expressing p53 transcriptional activation domain (TAD) mutants. Surprisingly, the p53(53,54) TAD2 mutant behaves as a "super-tumor suppressor," with an enhanced capacity to both suppress pancreatic cancer and transactivate select p53 target genes, including Ptpn14. Ptpn14 encodes a negative regulator of the Yap oncoprotein and is necessary and sufficient for pancreatic cancer suppression, like p53. We show that p53 deficiency promotes Yap signaling and that PTPN14 and TP53 mutations are mutually exclusive in human cancers. These studies uncover a p53-Ptpn14-Yap pathway that is integral to p53-mediated tumor suppression. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  14. Prediction of survival and tumor recurrence in patients undergoing surgery for pancreatic neuroendocrine neoplasms.

    PubMed

    Kaltenborn, Alexander; Matzke, Svenja; Kleine, Moritz; Krech, Till; Ramackers, Wolf; Vondran, Florian W R; Klempnauer, Jürgen; Bektas, Hüseyin; Schrem, Harald

    2016-02-01

    This study strives to define prognostic models for outcome after surgery for malignant pancreatic neuroendocrine tumors. Forty-one patients were included. Prognostic models for mortality and disease recurrence were developed with multivariate binary logistic regression. The proposed prognostic model for tumor recurrence risk after surgery in percentage (AUROC = 0.774, 95%CI = 0.611-0.937) is: Risk in % = Exp(Y)/(1 + Exp(Y)), with Y = -4.360 + (0.015 × tumor diameter in cm) + (0.010 × preoperative platelet count in thousand/μl) + (1.077 × distant metastases, if yes = 1; if no = 0) + (-0.026 × Ki-67-positive cells in %) + (-1.086 × upper abdominal pain, if yes = 1; if no = 0). The proposed prognostic model for observed 3-year survival probability after surgery in % (AUROC = 0.932, 95%CI = 0.857-0.999) is: Survival probability in % = Exp(Y)/(1 + Exp(Y)), with Y = -12.492 + (0.054 × preoperative platelet count in thousand/μl) + (0.112 × minimal distance of the resection margin from the tumor in mm) + (-1.574 × number of positive lymph nodes) + (2.292 × histological tumor infiltration, if yes = 1; if no = 0) CONCLUSIONS: The platelet count was identified as a relevant risk factor. Proposed prognostic models with good model-fit display properties that indicate potential clinical usefulness. © 2015 Wiley Periodicals, Inc.

  15. Molecular pathogenesis and targeted therapy of sporadic pancreatic neuroendocrine tumors.

    PubMed

    Capurso, Gabriele; Archibugi, Livia; Delle Fave, Gianfranco

    2015-08-01

    Over the past few years, knowledge regarding the molecular pathology of sporadic pancreatic neuroendocrine tumors (PNETs) has increased substantially, and a number of targeted agents have been tested in clinical trials in this tumor type. For some of these agents there is a strong biological rationale. Among them, the mammalian target of rapamycin inhibitor Everolimus and the antiangiogenic agent Sunitinib have both been approved for the treatment of PNETs. However, there is lack of knowledge regarding biomarkers able to predict their efficacy, and mechanisms of resistance. Other angiogenesis inhibitors, such as Pazopanib, inhibitors of Src, Hedgehog or of PI3K might all be useful in association or sequence with approved agents. On the other hand, the clinical significance, and potential for treatment of the most common mutations occurring in sporadic PNETs, in the MEN-1 gene and in ATRX and DAXX, remains uncertain. The present paper reviews the main molecular changes occurring in PNETs and how they might be linked with treatment options.

  16. GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass

    PubMed Central

    Guimarães, Marta; Rodrigues, Pedro; Pereira, Sofia S; Nora, Mário; Gonçalves, Gil; Albrechtsen, Nicolai Wewer; Hartmann, Bolette; Holst, Jens Juul

    2015-01-01

    Summary Post-prandial hypoglycemia is frequently found after bariatric surgery. Although rare, pancreatic neuroendocrine tumors (pNET), which occasionally are mixed hormone secreting, can lead to atypical clinical manifestations, including reactive hypoglycemia. Two years after gastric bypass surgery for the treatment of severe obesity, a 54-year-old female with previous type 2 diabetes, developed post-prandial sweating, fainting and hypoglycemic episodes, which eventually led to the finding by ultrasound of a 1.8-cm solid mass in the pancreatic head. The 72-h fast test and the plasma chromogranin A levels were normal but octreotide scintigraphy showed a single focus of abnormal radiotracer uptake at the site of the nodule. There were no other clinical signs of hormone secreting pNET and gastrointestinal hormone measurements were not performed. The patient underwent surgical enucleation with complete remission of the hypoglycemic episodes. Histopathology revealed a well-differentiated neuroendocrine carcinoma with low-grade malignancy with positive chromogranin A and glucagon immunostaining. An extract of the resected tumor contained a high concentration of glucagon (26.707 pmol/g tissue), in addition to traces of GLP1 (471 pmol/g), insulin (139 pmol/g) and somatostatin (23 pmol/g). This is the first report of a GLP1 and glucagon co-secreting pNET presenting as hypoglycemia after gastric bypass surgery. Although pNET are rare, they should be considered in the differential diagnosis of the clinical approach to the post-bariatric surgery hypoglycemia patient. Learning points pNETs can be multihormonal-secreting, leading to atypical clinical manifestations.Reactive hypoglycemic episodes are frequent after gastric bypass.pNETs should be considered in the differential diagnosis of hypoglycemia after bariatric surgery. PMID:26266036

  17. Teratoma: from spontaneous tumors to the pluripotency/malignancy assay.

    PubMed

    Bulic-Jakus, Floriana; Katusic Bojanac, Ana; Juric-Lekic, Gordana; Vlahovic, Maja; Sincic, Nino

    2016-01-01

    A teratoma is a benign tumor containing a mixture of differentiated tissues and organotypic derivatives of the three germ layers, while a teratocarcinoma also contains embryonal carcinoma cells (EC cells). Experimental teratomas and teratocarcinomas have been derived from early mammalian embryos transplanted into the adult animal (ectopic sites). In the rat, the pluripotency of the transplanted epiblast was demonstrated and a quantifiable restriction of developmental potential persisted after subsequent transplantation of chemically defined cultivated postimplantation embryos. The rat is nonpermissive for teratocarcinoma development and rat pluripotent cell lines have been established only recently. Transplantation of mouse embryos, epiblast, or embryonic stem cells (mESCs) gave rise to teratocarcinomas. The pluripotency of reprogrammed human cells has been tested by a 'gold standard' trilaminar teratoma assay in immunocompromised mice in vivo. Human pluripotent stem cells proposed for use in regenerative medicine such as human embryonic stem cell (hESC), human nuclear-transfer/therapeutic cloning embryonic stem cell (NT-ESC), or human induced pluripotent stem cell (hiPSC) lines, once differentiated in vitro to the desired cell type, should be again tested in a long-term animal teratoma assay to exclude their malignancy. Such an approach led to a recently implemented human therapy with retinal pigmented epithelium. For greater biosafety, the teratoma assay should be standardized and complemented by assessments of mutations/epimutations, RNA/protein expression, and possible immunogenicity of autologous pluripotent cells. Furthermore, the standardized teratoma assay should be directed more to the assessment of EC/malignant cell features than of differentiated tissues, especially after a unique case of human therapy with neural stem cells was found to lead to malignancy. For further resources related to this article, please visit the WIREs website. © 2015 Wiley

  18. Pancreatic Neuroendocrine Tumors: Computed Tomography Enhancement, But Not Histological Grade, Correlates With Tumor Aggression.

    PubMed

    Yano, Motoyo; Misra, Sunil; Carpenter, Danielle H; Salter, Amber; Hildebolt, Charles F

    2017-09-19

    The aims of this study were to assess computed tomography enhancement of pancreatic neuroendocrine tumors (NETs), determine correlation with histological vascularity and fibrosis, and identify a biomarker for tumor aggression. The arterial and venous enhancement of NET was calculated on computed tomography for 56 patients. Tumor size and vascularity/fibrosis were assessed. Tumor aggression was grouped by World Health Organization and Hochwald grade and the presence of metastases. Variables were assessed for correlation. Groups were compared using t test/Wilcoxon rank sum test. Arterial enhancement and dynamic washout (r = 0.35, P = 0.02; r = 0.34, P = 0.02, respectively) correlate with vascularity. There is inverse correlation between vascularity and fibrosis (r = -0.62, P < 0.001), but no correlation between enhancement and fibrosis. Metastatic NET had less arterial (mean, -2 [standard deviationi {SD}, 27.1] Hounsfield unit [HU]; 35.7 [SD, 57.5] HU; P = 0.01) and venous (12.6 [SD, 14.4] HU; 29.2 [SD, 38.3] HU; P = 0.04) enhancement and less washout (8.5 [SD, 18.5] HU; 26.8 [SD, 30] HU, P = 0.02) compared with nonmetastatic NET. These differences were not present when comparing by tumor grade. Arterial hypoenhancement was the only significant predictor of metastases. Aggressive tumors, as determined by metastases, but not histological grade, enhance less than nonmetastatic tumors.

  19. [Primary pancreatic plasmacytoma].

    PubMed

    Sánchez Acevedo, Z; Pomares Rey, B; Alpera Tenza, M R; Andrada Becerra, E

    2014-01-01

    Extramedullary plasmacytomas are uncommon malignant plasma cell tumors that present outside the bone marrow; 80% of extramedullary plasmacytomas are located in the upper respiratory tract, and gastrointestinal plasmacytomas are rare. We present the case of an asymptomatic 65-year-old man in whom a pancreatic mass was found incidentally. The lesion was determined to be a pancreatic plasmacytoma after fine-needle aspiration cytology and surgical resection. No clinical, laboratory, or imaging findings indicative of multiple myeloma or association with other plasmacytomas were found, so the tumor was considered to be a primary pancreatic plasmacytoma.

  20. Phyllodes Tumor of the Breast With Malignant Melanoma Component: A Case Report.

    PubMed

    Vergine, Marco; Guy, Catherine; Taylor, Mark R

    2015-09-01

    Phyllodes tumors of the breast display a wide variation in histological appearance and are classified into benign, borderline, and malignant categories based on a combination of histological parameters. These tumors may include a malignant heterologous component that is believed to originate through a process of multidirectional differentiation from a cancer stem cell. In these cases, the tumor is classified as a malignant phyllodes tumor. Among the heterologous elements that have been described in malignant phyllodes tumors are rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma and angiosarcoma. We present the first case of a phyllodes tumor with a malignant melanoma component in the breast of a 71-year-old lady, discussing the clinical implications of this diagnosis.

  1. Frozen Autograft-Prosthesis Composite Reconstruction in Malignant Bone Tumors.

    PubMed

    Subhadrabandhu, Saran; Takeuchi, Akihiko; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Miwa, Shinji; Tsuchiya, Hiroyuki

    2015-10-01

    Several methods are available using an endoprosthesis or biological reconstruction for malignant bone tumors. Methods that use allograft-prosthesis composites have shown promising results. In 1999, the authors developed a method of reconstruction that uses a tumor-bearing autograft treated with liquid nitrogen. This technique was modified to produce a pedicle frozen autograft to maintain anatomical continuity on one side. In this study, the results of bone reconstructions using frozen autograft-prosthesis composites were retrospectively evaluated. The demographic data, histological records, surgical procedures, functional scores, and complications of 22 patients who had bone sarcoma or metastasis and at least 2 years of follow-up were reviewed. There were 19 patients with primary bone sarcoma and 3 with bone metastasis. Average age was 36 years (range, 9-73 years), and mean follow-up was 63 months (range, 24-176 months). Reconstructions were performed on 10 proximal femurs, 5 distal femurs, 4 proximal tibias, 1 proximal humerus, 1 proximal radius, and 1 hemipelvis. There were 12 pedicle-freezing and 10 free-freezing procedures. Union rate was 90% (9/10), and average union time was 9.5 months. Average Musculoskeletal Tumor Society score was 89.3%. Complications included 1 fracture, 2 infections, 3 soft tissue recurrences, and 1 posterior interosseous nerve palsy. The authors concluded that the frozen autograft-prosthesis composite demonstrated excellent Musculoskeletal Tumor Society scores, a low complication rate, and a good union rate and was superior when used with the pedicle-freezing technique.

  2. Pleomorphic liposarcoma arising in a malignant phyllodes tumor of breast: A rare occurrence.

    PubMed

    Sancheti, Sankalp M; Sawaimoon, Satyakam K; Ahmed, Rosina

    2015-01-01

    Primary malignant phyllodes tumor of the breast accounts for 0.3-1% of all the tumors of breast and only a couple of cases of pleomorphic liposarcoma (PL) arising in a malignant phyllodes (MP) tumor have been reported. A thorough sampling is most essential in phyllodes tumor, not only to detect high grade component of the neoplasm but also to diagnose heterologous elements in the same lesion elsewhere, as it may affect the prognosis adversely and may have a greater metastatic potential.

  3. Metformin with everolimus and octreotide in pancreatic neuroendocrine tumor patients with diabetes.

    PubMed

    Pusceddu, Sara; Buzzoni, Roberto; Vernieri, Claudio; Concas, Laura; Marceglia, Sara; Giacomelli, Luca; Milione, Massimo; Leuzzi, Livia; Femia, Daniela; Formisano, Barbara; Mazzaferro, Vincenzo; de Braud, Filippo

    2016-05-01

    A bidirectional relationship seems to exist between diabetes mellitus and development of pancreatic tumors. Metformin, the most widely used drug in the treatment of Type 2 diabetes mellitus, has recently emerged as a potentially active agent in cancer chemoprevention and treatment. In this article, we discuss the potential correlation between glycemic status, administration of antiglycemic treatments, such as metformin or insulin, and prognosis of pancreatic neuroendocrine tumors patients treated with everolimus and octreotide, on the basis of existing evidence and our experience.

  4. Nicotine enhances the malignant potential of human pancreatic cancer cells via activation of atypical protein kinase C.

    PubMed

    Hanaki, Takehiko; Horikoshi, Yosuke; Nakaso, Kazuhiro; Nakasone, Masato; Kitagawa, Yoshinori; Amisaki, Masataka; Arai, Yosuke; Tokuyasu, Naruo; Sakamoto, Teruhisa; Honjo, Soichiro; Saito, Hiroaki; Ikeguchi, Masahide; Yamashita, Kazunari; Ohno, Shigeo; Matsura, Tatsuya

    2016-11-01

    Pancreatic cancer (PC) is the most lethal malignancy among solid tumors, and the most common risk factor for its development is cigarette smoking. Atypical protein kinase C (aPKC) isozymes function in cell polarity, proliferation, and survival, and have also been implicated in carcinogenesis. However, the involvement of aPKC in PC progression and the effect of nicotine, a major component of cigarette smoke, on the biological activities of aPKC remain to be fully elucidated. We investigated the effects of nicotine on the proliferation, migration and invasion of the human PC cell lines Panc1 and BxPC3. We analyzed aPKC localization and activity by immunohistochemistry and in vitro kinase assays, respectively, to assess their involvement in the regulation of PC progression. Moreover, we examined the effect of nicotine on implanted peritoneal tumors of PC cells in mice. Nicotine enhanced cell proliferation, migration and invasion in Panc1 and BxPC3 cells. In nicotine-treated PC cells, the aPKC was significantly activated. We also found that nicotine induced phosphatidylinositol 3-kinase (PI3K) signal activation, and a specific inhibitor of the nicotine acetylcholine receptor (nAChR) as well as knockdown of nAChR prevented nicotine-mediated Akt phosphorylation and aPKC activation. In a peritoneal dissemination model of PC, nicotine-treated mice had larger tumors and increased numbers of nodules. Immunohistochemistry showed enhanced expression levels of aPKC and phosphorylated Akt in nodules from nicotine-treated mice. Nicotine induces aberrant activation of aPKC via nAChR/PI3K signaling in PC cells, resulting in enhancement of cellular proliferation, migration and invasion. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Immunotherapy with autologous dendritic cells and tumor antigens for children with refractory malignant solid tumors.

    PubMed

    Suminoe, Aiko; Matsuzaki, Akinobu; Hattori, Hiroyoshi; Koga, Yuhki; Hara, Toshiro

    2009-09-01

    Immature DCs were generated from the peripheral blood monocytes from five children with refractory solid tumors (Ewing sarcoma, synovial sarcoma, neuroblastoma) using GM-CSF and IL-4. These DCs were then pulsed with tumor-specific synthetic peptides or tumor lysates in the presence of the immunogenic protein KLH for 12 h. Pulsed DCs were administered subcutaneously every one or two weeks in an outpatient setting without any toxicity. In one patient with Ewing sarcoma, the residual tumor disappeared following autologous PBSCT and DC therapy, and a complete remission has been maintained for 77 months. In two patients with synovial sarcoma or with neuroblastoma, growth of the tumors was temporally suppressed for one and 10 months, respectively, followed by their exacerbation. A DTH response was detected against KLH in all five patients and against the tumor lysate in one patient. In the patients with a possible DC-mediated anti-tumor effect, the number of CD8(+) HLA-DR(+) lymphocytes and INF-gamma(+)CD8(+) lymphocytes increased and an elevation of the NK cell cytotoxic activity was observed during and/or after DC therapy. DC-based immunotherapy may therefore be a feasible, well-tolerated and promising approach in the treatment of children with refractory malignant tumors.

  6. Acycloguanosyl 5'-thymidyltriphosphate, a thymidine analogue prodrug activated by telomerase, reduces pancreatic tumor growth in mice.

    PubMed

    Polvani, Simone; Calamante, Massimo; Foresta, Valeria; Ceni, Elisabetta; Mordini, Alessandro; Quattrone, Alessandro; D'Amico, Massimo; Luchinat, Claudio; Bertini, Ivano; Galli, Andrea

    2011-02-01

    Gemcitabine is the standard of care for metastatic and nonresectable pancreatic tumors. Phase II and III trials have not demonstrated efficacy of recently developed reagents, compared with gemcitabine alone; new chemotherapic agents are needed. Ninety percent of pancreatic tumors have telomerase activity, and expression correlates with tumor stage. We developed a thymidine analogue prodrug, acycloguanosyl 5'-thymidyltriphosphate (ACV-TP-T), that is metabolized by telomerase and releases the active form of acyclovir. We investigated the antitumor efficacy of ACV-TP-T in vitro and in vivo. We evaluated proliferation and apoptosis of human pancreatic cancer cells (PANC-1, MiaPaca2, BxPc3, PL45, and Su.86.86) incubated with ACV-TP-T. The presence of ACV-TP-T and its metabolite inside the cells were analyzed by mass spectrometry. In vivo efficacy was evaluated in nude mice carrying PANC-1 or MiaPaca2 pancreatic xenograft tumors. The prodrug of ACV-TP-T was actively metabolized inside pancreatic cancer cells into the activated form of acyclovir; proliferation was reduced, apoptosis was increased, and the cell cycle was altered in pancreatic cancer incubated with ACV-TP-T, compared with controls. Administration of ACV-TP-T to mice reduced growth, increased apoptosis, and reduced proliferation and vascularization of pancreatic xenograft tumors. ACV-TP-T, a thymidine analogue that is metabolized by telomerase and releases the active form of acyclovir, reduces proliferation and induces apoptosis of human pancreatic cancer cell lines in vitro and pancreatic xenograft tumors in mice. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. En bloc spondylectomy in malignant tumors of the spine.

    PubMed

    Liljenqvist, Ulf; Lerner, Thomas; Halm, Henry; Buerger, Horst; Gosheger, Georg; Winkelmann, Winfried

    2008-04-01

    En bloc spondylectomy is a technique that enables wide or marginal resection of malignant lesions of the spine. Both all posterior techniques as well as combined approaches are reported. Aim of the present study was to analyse the results of 21 patients with malignant lesions of the spine, all treated with en bloc excision in a combined posteroanterior (n = 19) or all posterior approach (n = 2). Twenty-one consecutive patients, operated between 1997 and 2005, were included into this retrospective study. Thirteen patients had primary malignant lesions, eight patients had solitary metastases, all located in the thoracolumbar spine. There were 16 single level, three two-level, one three-level and one four-level spondylectomy. The patients were followed clinically and radiographically (including CT studies) with an average follow-up of 4 years. Out of 11 patients with primary Ewing or osteosarcoma seven patients are alive without any evidence of disease. One patient died after 5 years from other causes and three are alive with evidence of disease. Latter had either a poor histologic response to the preoperative chemotherapy (n = 2) or an intralesional resection (n = 1). All three patients with solitary spinal metastases of Ewing or osteosarcoma died of the disease. Five patients with solitary metastases of mainly hypernephroma are alive. In total, six resections were intralesional, mainly due to large intraspinal tumor masses, with two patients having had previous surgery. In the remaining cases, wide (n = 10) or marginal (n = 5) resection was accomplished. There were one pseudarthrosis requiring extension of the fusion and two cases with local recurrences and repeated excisional surgery. At follow-up CT studies, all cages were fused. Health related quality of life analysis (SF-36) revealed only slightly decreased physical component and normal mental component scores compared to normals in those patients with no evidence of disease. En bloc spondylectomy enables wide

  8. En bloc spondylectomy in malignant tumors of the spine

    PubMed Central

    Lerner, Thomas; Halm, Henry; Buerger, Horst; Gosheger, Georg; Winkelmann, Winfried

    2008-01-01

    En bloc spondylectomy is a technique that enables wide or marginal resection of malignant lesions of the spine. Both all posterior techniques as well as combined approaches are reported. Aim of the present study was to analyse the results of 21 patients with malignant lesions of the spine, all treated with en bloc excision in a combined posteroanterior (n = 19) or all posterior approach (n = 2). Twenty-one consecutive patients, operated between 1997 and 2005, were included into this retrospective study. Thirteen patients had primary malignant lesions, eight patients had solitary metastases, all located in the thoracolumbar spine. There were 16 single level, three two-level, one three-level and one four-level spondylectomy. The patients were followed clinically and radiographically (including CT studies) with an average follow-up of 4 years. Out of 11 patients with primary Ewing or osteosarcoma seven patients are alive without any evidence of disease. One patient died after 5 years from other causes and three are alive with evidence of disease. Latter had either a poor histologic response to the preoperative chemotherapy (n = 2) or an intralesional resection (n = 1). All three patients with solitary spinal metastases of Ewing or osteosarcoma died of the disease. Five patients with solitary metastases of mainly hypernephroma are alive. In total, six resections were intralesional, mainly due to large intraspinal tumor masses, with two patients having had previous surgery. In the remaining cases, wide (n = 10) or marginal (n = 5) resection was accomplished. There were one pseudarthrosis requiring extension of the fusion and two cases with local recurrences and repeated excisional surgery. At follow-up CT studies, all cages were fused. Health related quality of life analysis (SF-36) revealed only slightly decreased physical component and normal mental component scores compared to normals in those patients with no evidence of disease. En bloc spondylectomy

  9. Clinical Utility of Circulating Tumor DNA for Molecular Assessment and Precision Medicine in Pancreatic Cancer.

    PubMed

    Takai, Erina; Totoki, Yasushi; Nakamura, Hiromi; Kato, Mamoru; Shibata, Tatsuhiro; Yachida, Shinichi

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect molecular characteristics of tumors, supporting the concept of "liquid biopsy".We determined the mutational status of KRAS in plasma cfDNA using multiplex droplet digital PCR in 259 patients with PDAC, retrospectively. Furthermore, we constructed a novel modified SureSelect-KAPA-Illumina platform and an original panel of 60 genes. We then performed targeted deep sequencing of cfDNA in 48 patients who had ≥1 % mutant allele frequencies of KRAS in plasma cfDNA.Droplet digital PCR detected KRAS mutations in plasma cfDNA in 63 of 107 (58.9 %) patients with inoperable tumors. Importantly, potentially targetable somatic mutations were identified in 14 of 48 patients (29.2 %) examined by cfDNA sequencing.Our two-step approach with plasma cfDNA, combining droplet digital PCR and targeted deep sequencing, is a feasible clinical approach. Assessment of mutations in plasma cfDNA may provide a new diagnostic tool, assisting decisions for optimal therapeutic strategies for PDAC patients.

  10. [Metastasis revealing malignant peritoneum mesothelioma: About the difficulty to identify the primary tumors].

    PubMed

    Bretagne, Charles-Henri; Petitjean, Alain; Felix, Sophie; Bedgedjian, Isabelle; Algros, Marie-Paule; Delabrousse, Eric; Valmary-Degano, Séverine

    2016-04-01

    Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers.

  11. Impact of APE1/Ref-1 Redox Inhibition on Pancreatic Tumor Growth

    PubMed Central

    Fishel, Melissa L.; Jiang, Yanlin; Rajeshkumar, N. V.; Scandura, Glenda; Sinn, Anthony L.; He, Ying; Shen, Changyu; Jones, David R.; Pollok, Karen E.; Ivan, Mircea; Maitra, Anirban; Kelley, Mark R.

    2011-01-01

    Pancreatic cancer is an especially deadly form of cancer with a survival rate <2%. Pancreatic cancers respond poorly to existing chemotherapeutic agents and radiation, and progress for the treatment of pancreatic cancer remains elusive. To address this unmet medical need, a better understanding of critical pathways and molecular mechanisms involved in pancreatic tumor development, progression and resistance to traditional therapy is therefore critical. Reduction-oxidation (redox) signaling systems are emerging as important targets in pancreatic cancer. AP endonuclease1/ Redox effector factor 1 (APE1/Ref-1) is upregulated in human pancreatic cancer cells and modulation of its redox activity blocks the proliferation and migration of pancreatic cancer cells as well as pancreatic cancer-associated endothelial cells (PCECs) in vitro. Modulation of APE1/Ref-1 using a specific inhibitor of APE1/Ref-1’s redox function, E3330 leads to a decrease in transcription factor activity for NFκB, AP-1, and HIF1 in vitro. This study aims to further establish the redox signaling protein APE1/Ref-1 as a molecular target in pancreatic cancer. Here, we show that inhibition of APE1/Ref-1 via E3330 results in tumor growth inhibition in cell lines as well as pancreatic cancer xenograft models in mice. Pharmacokinetic (PK) studies also demonstrate that E3330 attains >10 μM blood concentrations and is detectable in tumor xenografts. Through inhibition of APE1/Ref-1, the activity of NFκB, AP-1, and HIF1α which are key transcriptional regulators involved in survival, invasion and metastasis is blocked. These data indicate that E3330, inhibitor of APE1/Ref-1, has potential in pancreatic cancer and clinical investigation of APE1/Ref-1 molecular target is warranted. PMID:21700832

  12. Resection replantation of the upper limb for aggressive malignant tumors.

    PubMed

    El-Gammal, Tarek Abdalla; El-Sayed, Amr; Kotb, Mohamed Mostafa

    2002-04-01

    Stage IIB malignant tumors of the upper limb have been traditionally treated by amputation or disarticulation. There have been isolated reports on the technique of segmental resection of the tumor-bearing segment complete with the skin, and replanting the distal arm or forearm with or without neurovascular repair. The present paper describes four cases in which a wide resection margin was achieved in all by resecting the affected cylinder of the limb. Functional reconstruction was performed by appropriate tendon transfer. The main vessels and nerves were dealt with according to the findings revealed by preoperative investigations. If they had to be sacrificed, end-to-end suture was performed, but if the main nerves could be spared, it greatly enhanced the functional outcome. Local and systemic recurrences occurred in one case, and systemic recurrence occurred in another case. The other two cases remained disease-free at more than 4 years' follow-up. This operation is as radical as amputation, while the esthetic and functional results are equivalent to those of resection-arthrodesis.

  13. Subacute brain atrophy after radiation therapy for malignant brain tumor

    SciTech Connect

    Asai, A.; Matsutani, M.; Kohno, T.; Nakamura, O.; Tanaka, H.; Fujimaki, T.; Funada, N.; Matsuda, T.; Nagata, K.; Takakura, K.

    1989-05-15

    Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

  14. Current Status of Src Inhibitors in Solid Tumor Malignancies

    PubMed Central

    Puls, Lauren N.; Eadens, Matthew

    2011-01-01

    Summary. Src is believed to play an important role in cancer, and several agents targeting Src are in clinical development. Design. We reviewed Src structure and function and preclinical data supporting its role in the development of cancer via a PubMed search. We conducted an extensive review of Src inhibitors by searching abstracts from major oncology meeting databases in the last 3 years and by comprehensively reviewing ongoing clinical trials on ClinicalTrials.gov. Results. In this manuscript, we briefly review Src structure and function, mechanisms involving Src that lead to the development of cancer, and Src inhibitors and key preclinical data establishing a rationale for clinical application. We then focus on clinical data supporting their use in solid tumor malignancies, a newer arena than their more well-established hematologic applications. Particularly highlighted are clinical trials investigating new biomarkers as well as ongoing studies assessing Src inhibitor activity in biomarker-selected patient populations. We also review newer investigational Src-targeting agents. Conclusions. Src inhibitors have shown little activity in monotherapy trials in unselected solid tumor patient populations. Combination studies and biomarker-driven clinical trials are under way. PMID:21521831

  15. Increased c-kit (CD117) expression in malignant mammary phyllodes tumors.

    PubMed

    Tse, Gary M K; Putti, Thomas C; Lui, Philip C W; Lo, Anthony W I; Scolyer, Richard A; Law, Bonita K B; Karim, Rooshdiya; Lee, C Soon

    2004-07-01

    Mammary phyllodes tumors are uncommon stromal neoplasms, and are divided into benign, borderline and malignant groups basing on histologic criteria. While benign phyllodes tumors may recur, borderline phyllodes tumors show higher propensity to recur locally and rarely metastasize, and malignant phyllodes tumors show even higher chances of local recurrences or distant metastases. c-kit is a proto-oncogene that encodes a tyrosine kinase receptor (CD117) and is a marker for gastrointestinal stromal tumors (GIST). With the advent of therapeutic agent targeted at this receptor for GIST, we investigated 179 phyllodes tumors (101 benign, 50 borderline, 28 malignant) for c-kit expression using immunohistochemistry. The staining was compared to the degree of malignancy, and to the degree of stromal cellularity, mitotic activity, nuclear pleomorphism and stromal overgrowth. The overall positive rate for c-kit was 29% (52/179) and 17% (17/101), 24% (12/50) and 46% (13/28), respectively, for benign, borderline malignant and frank malignant phyllodes and the differences between all categories were significant (chi2=13.844, P=0.001). In mammary phyllodes tumors, there was increasing c-kit expression with increasing degree of malignancy, up to 46% in malignant cases. This provides strong evidence that c-kit receptor mediated tyrosine kinase involvement in the pathogenesis of phyllodes tumors, and the therapeutic agent, STI571, Glivec, may be a potentially useful drug for its management. Copyright 2004 USCAP, Inc.

  16. Liver Transplantation for Malignant Primary Pediatric Hepatic Tumors.

    PubMed

    Khan, Adeel S; Brecklin, Brittany; Vachharajani, Neeta; Subramanian, Vijay; Nadler, Michelle; Stoll, Janice; Turmelle, Yumirle; Lowell, Jeffery A; Chapman, William C; Doyle, Mb Majella

    2017-07-01

    Malignant primary pediatric hepatic tumors (MPPHTs) are rare and account for approximately 1% of all childhood malignancies. In recent years, liver transplantation has emerged as a viable treatment options for select patients with MPPHTs. We performed a single-center retrospective study using a prospective database to compare outcomes of pediatric liver transplant recipients, with and without cancer, between January 2000 and December 2014. One hundred fifty-three children underwent 173 liver transplantations during the study period. Of these, 21 (12%) children received 23 (13.3%) transplants for unresectable MPPHTs: 16 hepatoblastomas (HBs), 3 embryonal cell sarcomas (ECS), and 2 hepatocellular carcinomas (HCCs). There was no significant difference in 1-, 3-, and 10-year patient and graft survival rates between MPPHT and non-MPPHT patients (95.2%, 81.2%, 81.2%, and 95.2%, 72,2%, 72.2% for MPPHT vs 92.7%, 89.8%, 87.6% and 85.4%, 81.1%, 75% for the non-MPPHT group, respectively) (p > 0.05). Rates of 1-, 5-, and 10-year disease-free survival for MPPHT patients were 76%, 76%, and 76%, respectively. Median age at transplantation for MPPHT patients was 3.1 years (range 58 days to 17 years), median listing time was 81 days, and median wait list time was 15 days. Eight (38%) children had 2 tumors or more and 4 of 16 (25%) HB patients had metastatic disease at presentation. All children received neoadjuvant treatment, with radiographic response in 19 of 21 patients. Presence of metastatic HB at presentation, International Society of Pediatric Oncology Epithelial Liver (SIOPEL) high risk status, and persistently elevated alpha fetoprotein levels after neoadjuvant chemotherapy might be risk factors for tumor recurrence and decreased survival. Liver transplantation is an excellent option for select patients with unresectable MPPHTs, with outcomes comparable to those after transplantation for nonmalignant causes. Copyright © 2017 American College of Surgeons. Published by

  17. Characterization of Pancreatic Tumor Motion Using Cine MRI: Surrogates for Tumor Position Should Be Used With Caution

    SciTech Connect

    Feng, Mary Balter, James M.; Normolle, Daniel; Adusumilli, Saroja; Cao Yue; Chenevert, Thomas L.; Ben-Josef, Edgar

    2009-07-01

    Purpose: Our current understanding of intrafraction pancreatic tumor motion due to respiration is limited. In this study, we characterized pancreatic tumor motion and evaluated the application of several radiotherapy motion management strategies. Methods and Materials: Seventeen patients with unresectable pancreatic cancer were enrolled in a prospective internal review board-approved study and imaged during shallow free-breathing using cine MRI on a 3T scanner. Tumor borders were agreed on by a radiation oncologist and an abdominal MRI radiologist. Tumor motion and correlation with the potential surrogates of the diaphragm and abdominal wall were assessed. These data were also used to evaluate planning target volume margin construction, respiratory gating, and four-dimensional treatment planning for pancreatic tumors. Results: Tumor borders moved much more than expected. To provide 99% geometric coverage, margins of 20 mm inferiorly, 10 mm anteriorly, 7 mm superiorly, and 4 mm posteriorly are required. Tumor position correlated poorly with diaphragm and abdominal wall position, with patient-level Pearson correlation coefficients of -0.18-0.43. Sensitivity and specificity of gating with these surrogates was also poor, at 53%-68%, with overall error of 35%-38%, suggesting that the tumor may be underdosed and normal tissues overdosed. Conclusions: Motion of pancreatic tumor borders is highly variable between patients and larger than expected. There is substantial deformation with breathing, and tumor border position does not correlate well with abdominal wall or diaphragmatic position. Current motion management strategies may not account fully for tumor motion and should be used with caution.

  18. Differentiation of solid pancreatic tumors by using dynamic contrast-enhanced MRI

    NASA Astrophysics Data System (ADS)

    Choi, Seung Joon; Kim, Hyung Sik; Park, Hyunjin

    2014-01-01

    Distinguishing among different solid pancreatic tumor types, pancreatic ductal adenocarcinomas, neuroendocrine tumors (NETs), and solid pseudopapillary tumors (SPTs) is important, as the treatment options are vastly different. This study compared characteristics of solid pancreatic tumors by using dynamic contrast enhanced magnetic resonance imaging (MRI). Fifty patients underwent MR imaging of pancreatic masses with a histopathology that was later confirmed as an adenocarcinoma (n = 27), a NET (n = 16), and a SPT (n = 7). For qualitative analysis, two reviewers evaluated the morphologic features of the tumors: locations, margins, shapes, contained products, pancreatic ductal dilatation, and grade of signal intensity (SI). For the quantitative analysis, all phases of the MR images were co-registered using proprietary image registration software; thus, a region of interest (ROI) defined on one phase could be re-applied in other phases. The following four ratios were considered: tumor-to-uninvolved pancreas SI ratio, percent SI change, tumor-touninvolved pancreas enhancement index, and arterial-to-delayed washout rate. The areas under the receiver operating characteristic (ROC) curves were assessed for the four ratios. Adenocarcinomas had ill-defined margins, irregular shapes, and ductal dilatation compared with NETs and SPTs (P < 0.001). The tumor-to-uninvolved pancreas ratio on all dynamic phases was significantly higher for NETs than for both adenocarcinomas and SPTs (P < 0.05). Percentage SI changes of pancreatic tumors on the pancreatic and the portal venous phases were significantly higher for NETs than for both adenocarcinomas and SPTs (P < 0.05). A significant difference between NETs and adenocarcinomas was also found with respect to the tumor-to-uninvolved pancreas enhancement index and arterial-to-delayed washout rate. The percentage SI changes in the pancreatic phase and the arterial-to-delayed washout rate best distinguished between adenocarcinomas and

  19. Ligand stimulation of ErbB4 and a constitutively-active ErbB4 mutant result in different biological responses in human pancreatic tumor cell lines

    SciTech Connect

    Mill, Christopher P.; Gettinger, Kathleen L.; Riese, David J.

    2011-02-15

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Indeed, it has been estimated that 37,000 Americans will die from this disease in 2010. Late diagnosis, chemoresistance, and radioresistance of these tumors are major reasons for poor patient outcome, spurring the search for pancreatic cancer early diagnostic and therapeutic targets. ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases (RTKs), a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3. These RTKs play central roles in many human malignancies by regulating cell proliferation, survival, differentiation, invasiveness, motility, and apoptosis. In this report we demonstrate that human pancreatic tumor cell lines exhibit minimal ErbB4 expression; in contrast, these cell lines exhibit varied and in some cases abundant expression and basal tyrosine phosphorylation of EGFR, ErbB2, and ErbB3. Expression of a constitutively-dimerized and -active ErbB4 mutant inhibits clonogenic proliferation of CaPan-1, HPAC, MIA PaCa-2, and PANC-1 pancreatic tumor cell lines. In contrast, expression of wild-type ErbB4 in pancreatic tumor cell lines potentiates stimulation of anchorage-independent colony formation by the ErbB4 ligand Neuregulin 1{beta}. These results illustrate the multiple roles that ErbB4 may be playing in pancreatic tumorigenesis and tumor progression.

  20. Ligand Stimulation of ErbB4 and A Constitutively-Active ErbB4 Mutant Result in Different Biological Responses In Human Pancreatic Tumor Cell Lines

    PubMed Central

    Mill, Christopher P.; Gettinger, Kathleen L.; Riese, David J.

    2010-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Indeed, it has been estimated that 37,000 Americans will die from this disease in 2010. Late diagnosis, chemoresistance, and radioresistance of these tumors are major reasons for poor patient outcome, spurring the search for pancreatic cancer early diagnostic and therapeutic targets. ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases (RTKs), a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3. These RTKs play central roles in many human malignancies by regulating cell proliferation, survival, differentiation, invasiveness, motility, and apoptosis. In this report we demonstrate that human pancreatic tumor cell lines exhibit minimal ErbB4 expression; in contrast, these cell lines exhibit varied and in some cases abundant expression and basal tyrosine phosphorylation of EGFR, ErbB2, and ErbB3. Expression of a constitutively-dimerized and -active ErbB4 mutant inhibits clonogenic proliferation of CaPan-1, HPAC, MIA PaCa-2, and PANC-1 pancreatic tumor cell lines. In contrast, expression of wild-type ErbB4 in pancreatic tumor cell lines potentiates stimulation of anchorage-independent colony formation by the ErbB4 ligand Neuregulin1β. These results illustrate the multiple roles that ErbB4 may be playing in pancreatic tumorigenesis and tumor progression. PMID:21110957

  1. Mucoepidermoid Carcinoma Associated with Osteosarcoma in a True Malignant Mixed Tumor of the Submandibular Region.

    PubMed

    Marcotullio, Dario; de Vincentiis, Marco; Iannella, Giannicola; Cerbelli, Bruna; Magliulo, Giuseppe

    2015-01-01

    Introduction. True malignant mixed tumor, also known as carcinosarcoma, is a rare tumor of the salivary gland composed of both malignant epithelial and malignant mesenchymal elements. Frequently carcinosarcoma arises in the background of a preexisting pleomorphic adenoma; however, if no evidence of benign mixed tumor is present, the lesion is known as carcinosarcoma "de novo." We reported the first case of true malignant mixed tumor of the submandibular gland composed of high grade mucoepidermoid carcinoma associated with osteosarcoma. Case Presentation. A 69-year-old Caucasian male came to our department complaining of the appearance of an asymptomatic left submandibular neoformation progressively increasing in size over 3 months. We opted for surgical treatment. Histological examination confirmed the diagnosis of carcinosarcoma with the coexistence of high grade mucoepidermoid carcinoma and osteosarcoma. Conclusion. To the best of our knowledge, in the true malignant mixed tumor of the submandibular gland, mucoepidermoid carcinoma associated with osteosarcoma has never been previously reported.

  2. Mucoepidermoid Carcinoma Associated with Osteosarcoma in a True Malignant Mixed Tumor of the Submandibular Region

    PubMed Central

    Marcotullio, Dario; de Vincentiis, Marco; Iannella, Giannicola; Cerbelli, Bruna; Magliulo, Giuseppe

    2015-01-01

    Introduction. True malignant mixed tumor, also known as carcinosarcoma, is a rare tumor of the salivary gland composed of both malignant epithelial and malignant mesenchymal elements. Frequently carcinosarcoma arises in the background of a preexisting pleomorphic adenoma; however, if no evidence of benign mixed tumor is present, the lesion is known as carcinosarcoma “de novo.” We reported the first case of true malignant mixed tumor of the submandibular gland composed of high grade mucoepidermoid carcinoma associated with osteosarcoma. Case Presentation. A 69-year-old Caucasian male came to our department complaining of the appearance of an asymptomatic left submandibular neoformation progressively increasing in size over 3 months. We opted for surgical treatment. Histological examination confirmed the diagnosis of carcinosarcoma with the coexistence of high grade mucoepidermoid carcinoma and osteosarcoma. Conclusion. To the best of our knowledge, in the true malignant mixed tumor of the submandibular gland, mucoepidermoid carcinoma associated with osteosarcoma has never been previously reported. PMID:26600963

  3. Management of germ cell tumors with somatic type malignancy: pathological features, prognostic factors and survival outcomes.

    PubMed

    Rice, Kevin R; Magers, Martin J; Beck, Stephen D W; Cary, K Clint; Einhorn, Lawrence H; Ulbright, Thomas M; Foster, Richard S

    2014-11-01

    Germ cell tumors with somatic type malignancy are rare, occurring in approximately 2.7% to 8.6% of germ cell tumor cases. Prognostic factors and optimal management remain poorly defined. The Indiana University testis cancer database was queried from 1979 to 2011 for patients demonstrating germ cell tumor with somatic type malignancy at orchiectomy or subsequent resection. Patients with transformation to primitive neuroectodermal tumor only were excluded from study due to distinct management. Chart review, pathological review and survival analysis were performed. A total of 121 patients met the study inclusion criteria. The most common somatic type malignancy histologies were sarcoma (59), carcinoma (31) and sarcomatoid yolk sac tumor (17). Of these patients 32 demonstrated somatic type malignancy at germ cell tumor diagnosis. For those with delayed identification, median time from germ cell tumor to somatic type malignancy diagnosis was 33 months. This interval was longest for carcinomas (108 months). At a median followup of 71 months, 5-year cancer specific survival was 64%. Predictors of poorer cancer specific survival included somatic type malignancy diagnosed at late relapse (p = 0.017), referral to Indiana University for reoperative retroperitoneal lymph node dissection (p = 0.026) and grade (p = 0.026). None of these factors maintained prognostic significance on multivariate analysis. Somatic type malignancy histology subtype, stage, risk category and number of resections were not predictive of cancer specific survival. Germ cell tumor with somatic type malignancy is associated with poorer cancer specific survival than traditional germ cell tumor. Established prognostic factors for germ cell tumor lose predictive value in the setting of somatic type malignancy. Aggressive and serial resections are often necessary to optimize cancer specific survival. Tumor grade is an important prognostic factor in sarcomas and sarcomatoid yolk sac tumors. Copyright

  4. Evaluation of tumor markers for the differential diagnosis of benign and malignant ascites.

    PubMed

    Liu, Fang; Kong, Xinjuan; Dou, Qian; Ye, Jin; Xu, Dong; Shang, Haitao; Xu, Keshu; Song, Yuhu

    2014-01-01

    The diagnosis of malignant ascites is a challenging problem in clinical practice, non-invasive techniques should be developed to improve diagnostic accuracy. The diagnostic performances of tumor markers in malignant ascites remained unsettled. Our aim was to evaluate diagnostic performance of tumor markers in differential diagnosis of benign and malignant ascites. A total of 437 patients were enrolled, and the relevant parameters of the patients were analyzed for the differentiation of benign ascites from malignant ascites. At the predetermined cutoff values of tumor makers, tumor markers in ascitic fluid showed better diagnostic performance than those in serum. Combined use of tumor markers and the cytology increased the diagnostic yield of the latter by 37%. In cytologically negative malignant ascites, tumor markers provided assistance in differentiating malignant ascites from benign ascites, and the combination of ascitic tumor markers yielded 86% sensitivity, 97% specificity. Use of a panel of tumor markers exhibited excellent diagnostic performance in diagnosing malignant ascites, which indicated the detection of tumor markers may represent a beneficial adjunct to cytology, thus guiding the selection of patients who might benefit from further invasive procedures.

  5. Pancreatic ducts as an important route of tumor extension for acinar cell carcinoma of the pancreas.

    PubMed

    Ban, Daisuke; Shimada, Kazuaki; Sekine, Shigeki; Sakamoto, Yoshihiro; Kosuge, Tomoo; Kanai, Yae; Hiraoka, Nobuyoshi

    2010-07-01

    Acinar cell carcinoma (ACC) of the pancreas is very rare, which usually grows expansively. Recently, a variant of ACC with predominant growth in the pancreatic ducts has been proposed, and is speculated to have potentially less aggressive behavior. The aim of this study was to investigate how the pancreatic duct system is related to the growth and extension of ACC. We reviewed the detailed gross and histologic features of 13 cases of ACC, of which 7 (54%) showed intraductal polypoid growth (IPG) of the tumor in the large pancreatic ducts with a mean IPG length of 24.8 mm. Tumors with IPG were found to spread characteristically along the pancreatic ducts as extending polypoid projections, filling the ducts and destroying the duct walls, although tumors did not tend to extend beyond the pancreatic parenchyma. Comparison of the clinicopathologic characteristics showed that ACC with IPG had less infiltrative features including lymphatic, venous, and neural invasion, formation of tumor thrombus in the portal vein, nodal metastasis, and invasion beyond the pancreas to the surrounding organs; death in only 1 case (14%) of ACC with IPG was the result of ACC itself. In contrast, ACC without IPG frequently showed more infiltrative growth, and was the cause of death in 50% of patients with this type of tumor. Intraductal dissemination of ACC in pancreatic ducts was proven in 1 case of ACC with IPG. These findings suggest that a significant proportion of ACC shows IPG, which is potentially linked to less aggressive clinicopathologic characteristics.

  6. [Establishment and Management of Multicentral Collection Bio-sample Banks of Malignant Tumors from Digestive System].

    PubMed

    Shen, Si; Shen, Junwei; Zhu, Liang; Wu, Chaoqun; Li, Dongliang; Yu, Hongyu; Qiu, Yuanyuan; Zhou, Yi

    2015-11-01

    To establish and manage of multicentral collection bio-sample banks of malignant tumors from digestive system, the paper designed a multicentral management system, established the standard operation procedures (SOPs) and leaded ten hospitals nationwide to collect tumor samples. The biobank has been established for half a year, and has collected 695 samples from patients with digestive system malignant tumor. The clinical data is full and complete, labeled in a unified way and classified to be managed. The clinical and molecular biology researches were based on the biobank, and obtained achievements. The biobank provides a research platform for malignant tumor of digestive system from different regions and of different types.

  7. Prognostic Value of Somatostatin Receptor Subtypes in Pancreatic Neuroendocrine Tumors.

    PubMed

    Song, Ki Byung; Kim, Song Cheol; Kim, Ji Hun; Seo, Dong-Wan; Hong, Seung-Mo; Park, Kwang-Min; Hwang, Dae Wook; Lee, Jae Hoon; Lee, Young-Joo

    2016-02-01

    Studies on the expression of somatostatin receptor (SSTR) subtypes in pancreatic neuroendocrine tumors (PNETs) are rare. The aim of this study was to determine the expression of the SSTR subtypes via immunohistochemistry analyses and assess the correlation between SSTR subtype expression and prognosis. We examined 199 patients with PNET who underwent surgical resection between January 1995 and December 2010 at the Asan Medical Center. For all cases, medical records, including demographic data, clinical symptoms, radiological findings, postoperative treatment outcomes, and expression of SSTR subtypes, were carefully reviewed. In total, 162 (81.4%) PNETs expressed more than 1 SSTR subtype. Functioning PNET expressed significantly more SSTR subtypes, compared to nonfunctioning PNET. The SSTR2(+) and SSTR5(+) groups had better prognosis than the SSTR2(-) (P = 0.009) and SSTR5(-) groups (P = 0.03), respectively. In the grade 2 PNET of 2010 World Health Organization classification, the SSTR(+) group had better prognosis than SSTR(-) group. The expression of SSTR 2 and 5 were related with good prognosis of PNET. In World Health Organization grade 2 PNET, the SSTR(+) group had better prognosis than SSTR(-) group. The SSTR expression(+) by immunohistochemistry might be related with good prognosis of the patients with surgically resected PNET.

  8. Circulating tumor cells in pancreatic cancer patients: Enrichment and cultivation

    PubMed Central

    Bobek, Vladimir; Gurlich, Robert; Eliasova, Petra; Kolostova, Katarina

    2014-01-01

    AIM: To investigate the feasibility of separation and cultivation of circulating tumor cells (CTCs) in pancreatic cancer (PaC) using a filtration device. METHODS: In total, 24 PaC patients who were candidates for surgical treatment were enrolled into the study. Peripheral blood samples were collected before an indicated surgery. For each patient, approximately 8 mL of venous blood was drawn from the antecubital veins. A new size-based separation MetaCell® technology was used for enrichment and cultivation of CTCs in vitro. (Separated CTCs were cultured on a membrane in FBS enriched RPMI media and observed by inverted microscope. The cultured cells were analyzed by means of histochemistry and immunohistochemistry using the specific antibodies to identify the cell origin. RESULTS: CTCs were detected in 16 patients (66.7%) of the 24 evaluable patients. The CTC positivity did not reflect the disease stage, tumor size, or lymph node involvement. The same percentage of CTC positivity was observed in the metastatic and non-metastatic patients (66.7% vs 66.7%). We report a successful isolation of CTCs in PaC patients capturing proliferating cells. The cells were captured by a capillary action driven size-based filtration approach that enabled cells cultures from the viable CTCs to be unaffected by any antibodies or lysing solutions. The captured cancer cells displayed plasticity which enabled some cells to invade the separating membrane. Further, the cancer cells in the “bottom fraction”, may represent a more invasive CTC-fraction. The CTCs were cultured in vitro for further downstream applications. CONCLUSION: The presented size-based filtration method enables culture of CTCs in vitro for possible downstream applications. PMID:25493031

  9. Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma.

    PubMed

    Zeeberg, Katrine; Cardone, Rosa Angela; Greco, Maria Raffaella; Saccomano, Mara; Nøhr-Nielsen, Asbjørn; Alves, Frauke; Pedersen, Stine Falsig; Reshkin, Stephan Joel

    2016-07-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a very poor prognosis, due to the influence of the tumor stroma, which promotes tumor growth, early invasion and chemoradiation resistance. Efforts to develop models for identifying novel anticancer therapeutic compounds have been hampered by the limited ability of in vitro models to mimic these in vivo tumor-stroma interactions. This has led to the development of various three-dimensional (3D) culture platforms recapitulating the in vivo tumor-stroma crosstalk and designed to better understand basic cancer processes and screen drug action. However, a consensus for different experimental 3D platforms is still missing in PDAC. We compared four PDAC cell lines of different malignancy grown in 2D monolayers to three of the more commonly used 3D techniques (ultralow adhesion concave microwells, Matrigel inclusion and organotypic systems) and to tumors derived from their orthotopic implantation in mice. In these 3D platforms, we observed that cells grow with very different tumor morphologies and the organotypic setting most closely resembles the tumor cytoarchitecture obtained by orthotopically implanting the four cell lines in mice. We then analyzed the molecular and cellular responses of one of these cell lines to epidermal growth factor receptor (EGFR) stimulation with EGF and inhibition with erlotinib and found that only in the 3D platforms, and especially the organotypic, cells: i) responded to EGF by changing the expression of signalling components underlying cell-stroma crosstalk and tissue architecture, growth, invasion and drug resistance (E-cadherin, EGFR, ezrin, β1 integrin, NHERF1 and HIF-1α) similar to those reported in vivo; ii) had stimulated growth and increased erlotinib sensitivity in response to EGF, more faithfully mimicking their known in vivo behaviour. Altogether, these results, indicate the organotypic as the most relevant physiological 3D system to study the

  10. Pancreatic neuroendocrine tumors: correlation between histogram analysis of apparent diffusion coefficient maps and tumor grade.

    PubMed

    Pereira, Jose Antonio Sousa; Rosado, Elsa; Bali, Maria; Metens, Thierry; Chao, Shih-Li

    2015-10-01

    To explore the role of histogram analysis of apparent diffusion coefficient (ADC) MRI maps based on entire tumor volume data in determining pancreatic neuroendocrine tumor (PNT) grade. Retrospective evaluation of 22 patients with PNTs included low-grade (G1; n = 15), intermediate-grade (G2; n = 4), and high-grade (G3; n = 3) tumors. Regions of interest containing the lesion were drawn on every section of the ADC map containing the tumor and summated to obtain histograms for entire tumor volume. Calculated histographic parameters included mean ADC (mADC), 5th percentile ADC, 10th percentile ADC, 25th percentile ADC, 50th percentile ADC, 75th percentile ADC (ADC75), 90th percentile ADC (ADC90) and 95th percentile ADC (ADC95), skewness and kurtosis. Histogram parameters were correlated with tumor grade by repeated measures analysis of variance with Tukey-Kramer post hoc comparisons. The mADC, ADC75, ADC90, and ADC95 were significantly higher in G1 tumors (1283 ± 267; 1404 ± 300; 1495 ± 318; 1562 ± 347 × 10(-6) mm(2)/s) compared to G2 (892 ± 390; 952 ± 381; 1036 ± 384; 1072 ± 374 × 10(-6) mm(2)/s) and to G3 tumors (733 ± 225; 864 ± 284; 1008 ± 288; 1152 ± 192 × 10(-6) mm(2)/s) (p value <0.05). Skewness and kurtosis were significantly different between G1 (0.041 ± 0.466; 2.802 ± 0.679) and G3 (1.01 ± 1.140; 5.963 ± 4.008) tumors (p value <0.05). Tumor volume (mL) was significantly higher on G3 (55 ± 15.7) compared to G1 (1.9 ± 2.7) and G2 (4.5 ± 3.6) tumors (p value <0.05). In this small sample size, we did not detect statistically significant parameters between G2 (n = 4) and G3 (n = 3) tumors. Histographic analysis of ADC maps on the basis of the entire tumor volume can be useful in differentiating histologic grades of PNTs.

  11. Molecular pathology of pancreatic cancer: in quest of tumor suppressor genes.

    PubMed

    Furukawa, Toru; Horii, Akira

    2004-04-01

    To find molecular clues useful for early detection and effective therapy for pancreatic cancer, we first carried out genomic analysis by means of comparative genomic hybridization and micro-satellite analysis. We found very complicated molecular alterations in multiple chromosomal regions, including 1p, 6q, 9p, 12q, 17p, 18q, and 21q for losses and 8q and 20q for gains. These diverse changes are very characteristic of pancreatic cancer, and from this information, we developed a method for detecting the aberrant copy numbers of specific chromosomal regions by fluorescence in situ hybridization in cells collected from pancreatic juice for early diagnosis of pancreatic neoplasms. The regions of losses suggest the existence of tumor suppressor genes (TSGs). We identified DUSP6/MKP-3 at 12q21-q22 as a strong candidate TSG; it showed epigenetic inactivation in some fractions of invasive pancreatic cancer and growth suppression and apoptosis by overexpression in vitro. To determine the pathologic roles of 18q, we introduced a normal copy of chromosome 18 into cultured pancreatic cancer cells. The introduction induced marked suppressions of tumor formation and metastasis formation in vivo. We continue work to more completely understand the complex molecular mechanisms of pancreatic carcinogenesis and to apply the information gained to the clinical treatment of pancreatic cancer.

  12. Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy

    PubMed Central

    Wankhede, Mamta; Bouras, Alexandros; Kaluzova, Milota; Hadjipanayis, Costas G

    2012-01-01

    Magnetic nanoparticles (MNPs) represent a promising nanomaterial for the targeted therapy and imaging of malignant brain tumors. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells. Delivery of nanoparticles to malignant brain tumors represents a formidable challenge due to the presence of the blood–brain barrier and infiltrating cancer cells in the normal brain. Newer strategies permit better delivery of MNPs systemically and by direct convection-enhanced delivery to the brain. Completion of a human clinical trial involving direct injection of MNPs into recurrent malignant brain tumors for thermotherapy has established their feasibility, safety and efficacy in patients. Future translational studies are in progress to understand the promising impact of MNPs in the treatment of malignant brain tumors. PMID:22390560

  13. Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy.

    PubMed

    Wankhede, Mamta; Bouras, Alexandros; Kaluzova, Milota; Hadjipanayis, Costas G

    2012-03-01

    Magnetic nanoparticles (MNPs) represent a promising nanomaterial for the targeted therapy and imaging of malignant brain tumors. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells. Delivery of nanoparticles to malignant brain tumors represents a formidable challenge due to the presence of the blood-brain barrier and infiltrating cancer cells in the normal brain. Newer strategies permit better delivery of MNPs systemically and by direct convection-enhanced delivery to the brain. Completion of a human clinical trial involving direct injection of MNPs into recurrent malignant brain tumors for thermotherapy has established their feasibility, safety and efficacy in patients. Future translational studies are in progress to understand the promising impact of MNPs in the treatment of malignant brain tumors.

  14. Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth

    PubMed Central

    Shukla, Surendra K.; Dasgupta, Aneesha; Mehla, Kamiya; Gunda, Venugopal; Vernucci, Enza; Souchek, Joshua; Goode, Gennifer; King, Ryan; Mishra, Anusha; Rai, Ibha; Nagarajan, Sangeetha; Chaika, Nina V.; Yu, Fang; Singh, Pankaj K.

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic cancer cells. Silibinin treatment diminishes c-MYC expression, a key regulator of cancer metabolism. Furthermore, we observed reduced STAT3 signaling in silibinin-treated cancer cells. Overexpression of constitutively active STAT3 was sufficient to substantially revert the silibinin-induced downregulation of c-MYC and the metabolic phenotype. Our in vivo investigations demonstrate that silibinin reduces tumor growth and proliferation in an orthotopic mouse model of pancreatic cancer and prevents the loss of body weight and muscle. It also improves physical activity including grip strength and latency to fall in tumor-bearing mice. In conclusion, silibinin-induced metabolic reprogramming diminishes cell growth and cachectic properties of pancreatic cancer cells and animal models. PMID:26510913

  15. Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth.

    PubMed

    Shukla, Surendra K; Dasgupta, Aneesha; Mehla, Kamiya; Gunda, Venugopal; Vernucci, Enza; Souchek, Joshua; Goode, Gennifer; King, Ryan; Mishra, Anusha; Rai, Ibha; Nagarajan, Sangeetha; Chaika, Nina V; Yu, Fang; Singh, Pankaj K

    2015-12-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic cancer cells. Silibinin treatment diminishes c-MYC expression, a key regulator of cancer metabolism. Furthermore, we observed reduced STAT3 signaling in silibinin-treated cancer cells. Overexpression of constitutively active STAT3 was sufficient to substantially revert the silibinin-induced downregulation of c-MYC and the metabolic phenotype. Our in vivo investigations demonstrate that silibinin reduces tumor growth and proliferation in an orthotopic mouse model of pancreatic cancer and prevents the loss of body weight and muscle. It also improves physical activity including grip strength and latency to fall in tumor-bearing mice. In conclusion, silibinin-induced metabolic reprogramming diminishes cell growth and cachectic properties of pancreatic cancer cells and animal models.

  16. Acute pancreatitis following granulosa cell tumor removal in a mare

    PubMed Central

    Gomez, Diego E.; Radtke, Catherine L.; Russell, Lauren A.; Lopez, Alfonso; Wichtel, Maureen W.

    2015-01-01

    Acute pancreatitis is a rare disease in horses and is often associated with gastrointestinal disorders. Accurate diagnosis is challenging due to the presence of nonspecific clinical signs. This case represents the first documentation of acute pancreatitis in a horse following surgery of the reproductive tract. PMID:26483579

  17. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib

    PubMed Central

    Wei, Lei; Liu, Song; Conroy, Jeffrey; Wang, Jianmin; Papanicolau-Sengos, Antonios; Glenn, Sean T.; Murakami, Mitsuko; Liu, Lu; Hu, Qiang; Conroy, Jacob; Miles, Kiersten Marie; Nowak, David E.; Liu, Biao; Qin, Maochun; Bshara, Wiam; Omilian, Angela R.; Head, Karen; Bianchi, Michael; Burgher, Blake; Darlak, Christopher; Kane, John; Merzianu, Mihai; Cheney, Richard; Fabiano, Andrew; Salerno, Kilian; Talati, Chetasi; Khushalani, Nikhil I.; Trump, Donald L.; Johnson, Candace S.; Morrison, Carl D.

    2015-01-01

    Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise <2% of all granular cell tumors, are associated with aggressive behavior and poor clinical outcome, and are poorly understood in terms of tumor etiology and systematic treatment. Because of its rarity, the genetic basis of malignant granular cell tumor remains unknown. We performed whole-genome sequencing of one malignant granular cell tumor with metabolic response to pazopanib. This tumor exhibited a very low mutation rate and an overall stable genome with local complex rearrangements. The mutation signature was dominated by C>T transitions, particularly when immediately preceded by a 5′ G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation. PMID:27148567

  18. Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors

    PubMed Central

    Sarin, Hemant

    2009-01-01

    Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous blood-brain tumor barrier of malignant brain tumor microvasculature. Small molecule systemic chemotherapy drugs maintain peak blood concentrations for only minutes, and therefore, do not accumulate to therapeutic concentrations within individual brain tumor cells. The physiologic upper limit of pore size in the blood-brain tumor barrier of malignant brain tumor microvasculature is approximately 12 nanometers. Spherical nanoparticles ranging between 7 nm and 10 nm in diameter maintain peak blood concentrations for several hours and are sufficiently smaller than the 12 nm physiologic upper limit of pore size in the blood-brain tumor barrier to accumulate to therapeutic concentrations within individual brain tumor cells. Therefore, nanoparticles bearing chemotherapy that are within the 7 to 10 nm size range can be used to deliver therapeutic concentrations of small molecule chemotherapy drugs across the blood-brain tumor barrier into individual brain tumor cells. The initial therapeutic efficacy of the Gd-G5-doxorubicin dendrimer, an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range, has been demonstrated in the orthotopic RG-2 rodent malignant glioma model. Herein I discuss this novel strategy to improve the effectiveness of systemic chemotherapy for the treatment of malignant brain tumors and the therapeutic implications thereof. PMID:19723323

  19. [Role of infectious agents in the emergence of malignant tumors].

    PubMed

    Kutikhin, A G; Yuzhalin, A E; Brusina, E B; Briko, N I

    2012-01-01

    According to the data of the International Agency for Research on Cancer (IARC), at least 6 virus species (HPV, EBV, HHV-8/KSHV, HTLV-1, HBV, HCV), 4 helminthes species (Schistosoma haematobium and japonicum, Opisthorchis viverrini, Clonorchis sinensis) and I bacterium species (Helicobacter pylori) have been proved to be capable of causing the development of cancer. The analysis of the data available shows that Merkel cell polyomavirus (MCV), herpes simplex virus (HSV), John Cunningham polyomavirus (JCV), monkey virus 40 (SV40), cytomegalovirus (CMV), xenotropic murine leukemia virus (XMRV), Helicobacter bilis and hepaticus, Campylobacter jejuni, Fusobacterium varium, enteropathogenic Escherichia coli, enterotoxigenic Bacteroides fragilis, Bacteroides vulgatus, Prevotella spp., Streptococcus bovis and anginosus, Treponema denticola, Salmonella typhi, paratyphi and typhimurium, Borrelia burgdorferi, Bartonella spp., Mycobacterium tuberculosis, Chlamydia pneumoniae, trachomatis and psittaci, Neisseria gonorrhoeae, Propionibacterium acnes, Tropheryma whippelii, Schistosoma mansoni, Opistorchis felineus, Strongyloides stercoralis, Taenia solium, Candida spp., Paracoccidioides brasiliensis, Histoplasma capsulatum and Trichomonas vaginalis can also be potential etiological agents of cancer. Apparently, detection of new associations between infectious agents and risk of the development of cancer will facilitate progress in elaboration of prophylaxis measures, early diagnostic methods and, probably, methods of treatment of malignant tumors.

  20. Breast tumor malignancy modelling using evolutionary neural logic networks.

    PubMed

    Tsakonas, Athanasios; Dounias, Georgios; Panagi, Georgia; Panourgias, Evangelia

    2006-01-01

    The present work proposes a computer assisted methodology for the effective modelling of the diagnostic decision for breast tumor malignancy. The suggested approach is based on innovative hybrid computational intelligence algorithms properly applied in related cytological data contained in past medical records. The experimental data used in this study were gathered in the early 1990s in the University of Wisconsin, based in post diagnostic cytological observations performed by expert medical staff. Data were properly encoded in a computer database and accordingly, various alternative modelling techniques were applied on them, in an attempt to form diagnostic models. Previous methods included standard optimisation techniques, as well as artificial intelligence approaches, in a way that a variety of related publications exists in modern literature on the subject. In this report, a hybrid computational intelligence approach is suggested, which effectively combines modern mathematical logic principles, neural computation and genetic programming in an effective manner. The approach proves promising either in terms of diagnostic accuracy and generalization capabilities, or in terms of comprehensibility and practical importance for the related medical staff.

  1. Ipsilateral kidney sparing in treatment of pancreatic malignancies using volumetric-modulated arc therapy avoidance sectors

    SciTech Connect

    Chan, Raymond W. Podgorsak, Matthew B.

    2015-10-01

    Recent research has shown treating pancreatic cancer with volumetric-modulated arc therapy (VMAT) to be superior to either intensity-modulated radiation therapy or 3-dimensional conformal radiotherapy (3D-CRT), with respect to reducing normal tissue toxicity, monitor units, and treatment time. Furthermore, using avoidance sectors with RapidArc planning can further reduce normal tissue dose while maintaining target conformity. This study looks at the methods in reducing dose to the ipsilateral kidney, in pancreatic head cases, while observing dose received by other critical organs using avoidance sectors. Overall, 10 patients were retrospectively analyzed. Each patient had preoperative/unresectable pancreatic tumor and were selected based on the location of the right kidney being situated within the traditional 3D-CRT treatment field. The target planning target volume (286.97 ± 85.17 cm{sup 3}) was prescribed to 50.4 Gy using avoidance sectors of 30°, 40°, and 50° and then compared with VMAT as well as 3D-CRT. Analysis of the data shows that the mean dose to the right kidney was reduced by 11.6%, 15.5%, and 21.9% for avoidance angles of 30°, 40°, and 50°, respectively, over VMAT. The mean dose to the total kidney also decreased by 6.5%, 8.5%, and 11.0% for the same increasing angles. Spinal cord maximum dose, however, increased as a function of angle by 3.7%, 4.8%, and 6.1% compared with VMAT. Employing avoidance sector angles as a complement to VMAT planning can significantly reduce high dose to the ipsilateral kidney while not greatly overdosing other critical organs.

  2. SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

    SciTech Connect

    Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den

    2014-06-01

    Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

  3. Prognostic significance of ATM and cyclin B1 in pancreatic neuroendocrine tumor.

    PubMed

    Shin, Jae Uk; Lee, Chang Hoon; Lee, Kyu Taek; Lee, Jong Kyun; Lee, Kwang Hyuck; Kim, Kwang Min; Kim, Kyoung-Mee; Park, Sang-Mo; Rhee, Jong Chul

    2012-10-01

    Ataxia telangiectasia mutated kinase (ATM) and cyclin B1 are involved in cell cycle control. The prognostic significance of both molecules has not yet been investigated in pancreatic neuroendocrine tumors. The aim of this study was to evaluate the clinical and prognostic significance of ATM and cyclin B1 in patients with pancreatic neuroendocrine tumors. A total of 107 pancreatic neuroendocrine tumor specimens that were surgically resected were immunohistochemically investigated using the tissue microarray technique. Clinicopathologic results and survival were evaluated retrospectively. High expression of ATM and cyclin B1 was related to well-differentiated endocrine tumors of the World Health Organization (WHO) classification, but not related to TNM stages. The high ATM expression group (ATM ≥ 4) had a significantly smaller tumor size, lower recurrence rate, more number of functioning tumor, and well differentiation of WHO classification. The high cyclin B1 expression group (cyclin B1 ≥ 5) was related to smaller tumor size, less vascular invasion, less recurrence rate, and less death rate. However, cyclin B1 was the only significant factor for survival following multivariate analysis (p = 0.008; OR, 0.54; 95 % CI, 0.35-0.85). The current results suggested that expression of ATM and cyclin B1 may be useful markers to identify patients with poor prognosis who may benefit from close follow-up and aggressive therapy in pancreatic neuroendocrine tumors.

  4. Double germline mutations in APC and BRCA2 in an individual with a pancreatic tumor.

    PubMed

    Goehringer, Caroline; Sutter, Christian; Kloor, Matthias; Gebert, Johannes; Slater, Emily P; Keller, Monika; Treiber, Irmgard; Ganschow, Petra; Kadmon, Martina; Moog, Ute

    2017-04-01

    We report on three brothers affected by pancreatic tumors, all due to different causes, including mutations associated with two different cancer predisposition syndromes in the same individual. In the index patient a germline mutation both in the APC and BRCA2 gene was identified while one affected brother showed the BRCA2 mutation only and another brother is supposed to have developed pancreatic cancer due to multiple non-genetic risk factors. We outline the impact of a double germline mutation in two tumor predisposition genes in one individual and proven heterogeneity of multiple cases of pancreatic tumors in one family. With the growing implementation of next generation sequence based panel testing for multiple genes involved in tumor predisposition syndromes, relevant variants in two (or more) genes will be found more frequently. This family illustrates the importance of family studies, especially when using gene panel tests.

  5. A Rare Malignant Peripheral Nerve Sheath Tumor of the Maxilla Mimicking a Periapical Lesion

    PubMed Central

    Álvares, Pamella; Silva, Luciano; Pereira dos Santos Neto, Alexandrino; Rodrigues, Cleomar Donizeth; Caubi, Antônio; Silveira, Marcia; Sayão, Sandra; Sobral, Ana Paula

    2016-01-01

    Malignant peripheral nerve sheath tumor is a malignant neoplasm that is rarely found in the oral cavity. About 50% of this tumor occurs in patients with neurofibromatosis type I and comprises approximately 10% of all soft tissue sarcomas of head and neck region. Intraosseous malignant peripheral nerve sheath tumor of the maxilla is rare. This article is the first to address malignant peripheral nerve sheath tumor of the maxilla presenting as a periapical radiolucency on nonvital endodontically treated teeth in the English medical literature. Surgical approaches to malignant soft tissue tumor vary based on the extent of the disease, age of the patient, and pathological findings. A rare case of intraosseous malignant peripheral nerve sheath tumor is reported in a 16-year-old woman. The patient presented clinically with a pain involving the upper left incisors region and with defined unilocular periapical radiolucency lesion involved between the upper left incisors. An incisional biopsy was made. Histological and immunohistochemical examination were positive for S-100 protein and glial fibrillary acidic protein showed that the lesion was an intraosseous malignant peripheral nerve sheath tumor of the maxilla. Nine years after the surgery, no regional recurrence was observed. PMID:27994888

  6. Challenges in detecting pre-malignant pancreatic lesions during acute pancreatitis using a serum microRNA assay: a study based on KrasG12D transgenic mice

    PubMed Central

    Hong, Xiafei; Zhang, Jie; Wu, Qiao; Wang, Wenze; Ye, Adam Yongxin; Song, Wei; Dai, Hongmei; Wang, Xianze; Wu, Fan; You, Lei; Wu, Wenming; Zhao, Yupei

    2016-01-01

    Caerulein-induced acute pancreatitis accelerates the progression of pancreatic intraepithelial neoplasia (PanIN) lesions in a pancreas-specific KrasG12D mouse model. The purpose of this study was to explore whether serum microRNAs (miRNAs) can serve as sensitive biomarkers to detect occult PanIN in the setting of acute pancreatitis. Serum miRNA profiles were quantified by an array-based method and normalized by both Variance Stabilization Normalization (VSN) and invariant methods. Individual miRNAs were validated by TaqMan real-time PCR with synthetic spike-in C. elegans miRNAs as external controls. Serum miRNA profiles distinguished KrasG12D mice with pancreatitis from wild-type mice without pancreatitis, but failed to differentiate KrasG12D mice with pancreatitis from wild-type mice with pancreatitis. Most individual miRNAs that increased in KrasG12D mice with pancreatitis were not significantly different between KrasG12D mice without pancreatitis and wild-type mice without pancreatitis. Mechanistically, Gene Set Enrichment Analysis (GSEA) of the mRNA array data and immunohistochemical assays showed that caerulein-induced acute pancreatitis involved acinar cell loss and immune cell infiltration, which might contribute to serum miRNA profile changes. This study highlighted the challenges in using sensitive serum miRNA biomarker screening for the early detection of pancreatic malignancies during acute pancreatitis. PMID:27009811

  7. [Spectrum and case fatality of inpatients with malignant tumors from 1995 to 2014 in Shenzhen city].

    PubMed

    Wang, X B; Hong, L C; Wei, Y Z; Fu, X; Bao, X Q; Zhang, J; Hu, G; Wu, S H; Cheng, J Q

    2017-06-10

    Objective: To analyze the epidemiological features, spectrum and case fatality of malignant tumor patients in Shenzhen city, to provide evidence for the development of prevention and treatment strategies on malignant tumor in Shenzhen. Methods: All the hospitalized malignant tumor patients including deaths, were monitored from 1995 to 2014 in Shenzhen, and data was analyzed by SPSS 20.0 software. Results: There were 160 988 inpatients of malignant tumors between 1995 and 2014 in Shenzhen. The top three hospitalized tumors were lung (13.64%), liver (11.13%) and breast (7.86%) cancers. Numbers of the malignant tumor inpatients had been rapidly increasing during the past 20 years, 12.3 times in 2014 higher than in 1995. The total number of deaths due to malignant tumors was 19 460. Deaths of the top three malignant tumors were lung (24.40%), liver (19.84%) and colorectal (8.63%) cancers and the number of deaths was increasing, 12.5 times higher in 2014 than in 1995. The overall case fatality rate was 12.09%. The annual percent change (APC) of malignant tumors case fatality rate was 9.7%(95%CI: 2.0%-18.0%), during 1995-2003, with an increasing trend (t=2.72, P<0.05). The APC of case fatality rate during 2003-2014 was -3.4%(95%CI: -7.6%-1.1%), but the decreasing trend (t=-1.63, P>0.05) was not statistically significant. The top three major malignant tumors related to case fatality rate were lung cancer (21.62%), liver cancer (21.39%), and esophageal cancer (16.50%). The case fatality rates of leukemia and liver cancer had decreased during the past 20 years. The case fatality rates of cancers in lung, esophagus, stomach, breast, colorectal and nasopharyngeal, had all increased. The number of male patients was significantly exceeding the females (χ(2)=41.691, P<0.01), with sex ratio as 1.65∶1. From age 35 and on, the number of deaths due to malignant tumors increased significantly, with the peak after 60 years of age. Conclusions: The number of malignant tumor

  8. APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-05-02

    Metastatic Malignant Neoplasm in the Brain; Metastatic Solid Neoplasm; Recurrent Colorectal Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Solid Neoplasm; Stage IV Colorectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer; Unresectable Solid Neoplasm

  9. Procedure for quantitative determination of effectiveness of photoinduced destruction of malignant tumors

    NASA Astrophysics Data System (ADS)

    Bizyuk, S. A.; Istomin, Yu. P.; Dzhagarov, B. M.

    2006-07-01

    We have developed a procedure for analysis of the functional status of blood vessels in tumor tissues using computer-assisted color scanning of tumor slices and also for a quantitative assessment of the effectiveness of photoinduced destruction of tumor tissues in animal experiments. Its major advantage is direct determination of the size of the tumor necrosis zone. The procedure has been tested in an experiment on three strains of malignant tumors with different morphologies.

  10. A Subset of Malignant Phyllodes Tumors Express p63 and p40

    PubMed Central

    Cimino-Mathews, Ashley; Sharma, Rajni; Illei, Peter B.; Vang, Russell; Argani, Pedram

    2015-01-01

    Breast phyllodes tumors are rare fibroepithelial neoplasms of variable grade, and one key differential of malignant phyllodes on core biopsy is sarcomatoid carcinoma. p63 is reported to be sensitive and specific for sarcomatoid carcinoma, with rare expression in phyllodes in limited series. The p63 deltaNp63 isoform, p40, is postulated to be more specific for squamous differentiation but has not previously been evaluated in breast phyllodes or sarcomatoid carcinoma. Tissue microarrays containing 34 unambiguous phyllodes tumors (10 benign, 10 borderline, 14 malignant), 13 sarcomatoid carcinomas, and 10 fibroadenomas were labeled by immunohistochemistry for p63, p40, CD34, and cytokeratins AE1/AE3, 34betaE12, and CK8/18. No borderline phyllodes tumor, benign phyllodes tumor, or fibroadenoma labeled with p63, p40, or cytokeratin. However, p63 labeled 57% malignant phyllodes tumors and 62% sarcomatoid carcinomas, and p40 labeled 29% malignant phyllodes (focal) and 46% sarcomatoid carcinomas. Among established markers, cytokeratins labeled 21% malignant phyllodes tumors (focal) and 100% sarcomatoid carcinomas. CD34 labeled 57% malignant phyllodes tumors and no sarcomatoid carcinomas. Focal p63, p40, and cytokeratin labeling can be seen in malignant phyllodes tumors but not in lowergrade fibroepithelial lesions, and immunoreactivity with these markers alone is not diagnostic of sarcomatoid carcinoma on core needle biopsy. In the differential diagnosis of malignant phyllodes, p40 is a more specific but less sensitive marker of sarcomatoid carcinoma than p63. These results are consistent with the sarcoma literature in which p63 labeling has been increasingly reported and suggest caution in classifying malignant spindle cell tumors of the breast on core biopsy. PMID:25046342

  11. Small Cell Carcinoma of the Ovary (Hypercalcemic Type): Malignant Rhabdoid Tumor

    PubMed Central

    Kascak, Peter; Zamecnik, Michal; Bystricky, Branislav

    2016-01-01

    We present a rare case of malignant rhabdoid tumor (ovarian small cell carcinoma of hypercalcemic type) in a 24-year-old female with fulminant course. Clinically, hypercalcemia was not found at the time of primary diagnosis. However, it appeared later during the course of tumor progression. Histologically, the tumor showed classical features of small cell carcinoma of hypercalcemic type. Therapy included radical surgery with adjuvant chemotherapy. Despite this intensive therapy, the disease recurred and the patient died 10 months after the diagnosis. We discuss the diagnosis and therapy of this tumor, as well as its recent classification as malignant rhabdoid tumor. PMID:27462229

  12. Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer

    PubMed Central

    Takai, Erina; Totoki, Yasushi; Nakamura, Hiromi; Morizane, Chigusa; Nara, Satoshi; Hama, Natsuko; Suzuki, Masami; Furukawa, Eisaku; Kato, Mamoru; Hayashi, Hideyuki; Kohno, Takashi; Ueno, Hideki; Shimada, Kazuaki; Okusaka, Takuji; Nakagama, Hitoshi; Shibata, Tatsuhiro; Yachida, Shinichi

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect and monitor molecular characteristics of tumors. In the present study, we determined the mutational status of KRAS in plasma cfDNA using multiplex picoliter-droplet digital PCR in 259 patients with PDAC. We constructed a novel modified SureSelect-KAPA-Illumina platform and an original panel of 60 genes. We then performed targeted deep sequencing of cfDNA and matched germline DNA samples in 48 patients who had ≥1% mutant allele frequencies of KRAS in plasma cfDNA. Importantly, potentially targetable somatic mutations were identified in 14 of 48 patients (29.2%) examined by targeted deep sequencing of cfDNA. We also analyzed somatic copy number alterations based on the targeted sequencing data using our in-house algorithm, and potentially targetable amplifications were detected. Assessment of mutations and copy number alterations in plasma cfDNA may provide a prognostic and diagnostic tool to assist decisions regarding optimal therapeutic strategies for PDAC patients. PMID:26669280

  13. Nutritional status among pediatric cancer patients: a comparison between hematological malignancies and solid tumors.

    PubMed

    Tah, Pei Chien; Nik Shanita, Safii; Poh, Bee Koon

    2012-10-01

    This study aimed to compare the nutritional status of pediatric patients with hematological malignancies and solid tumors. A total of 74 pediatric cancer patients were assessed for anthropometric status, biochemical profiles, and dietary intake. The prevalence of undernutrition was higher among patients with solid tumors as reflected in their lower dietary intakes of energy and nutrients compared with patients with hematological malignancies. Adequate dietary intake is important for pediatric cancer patients, but nurses need to pay more attention to the diets of patients with solid tumors as compared with those with hematological malignancies. © 2012, Wiley Periodicals, Inc.

  14. Inhibition of HIF-1α by PX-478 enhances the anti-tumor effect of gemcitabine by inducing immunogenic cell death in pancreatic ductal adenocarcinoma

    PubMed Central

    Jia, Li; Chen, Jing; Xin, Wen; Yan, Fan; Li, Jing; Wang, Xiuchao; Gao, Song; Qian, Dong; Huang, Chongbiao; Hao, Jihui

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the worst prognoses among all the malignancies. Now, gemcitabine (Gem) is the first line chemotherapeutic drug for advanced pancreatic cancer. However, Gem is usually ineffective to the PDAC because of high degree of drug resistance. Hypoxia and immune suppressive milieu are the best-described hallmarks of PDAC; therefore, we investigated the impact of hypoxia inducible factor-1 (HIF-1) inhibitor, PX-478, in combination with Gem on the induction of immunogenic cell death (ICD). We verified that combined treatment with Gem/PX-478 significantly enhanced the anti-tumor effect and increased proportion of tumor infiltrating T-lymphocytes in Panc02-bearing immune-competent but not in immune-deficient mice. Vaccination using Panc02 cell line treated with single agent or in combination showed significant anti-tumor effects. Pancreatic cell lines treated with Gem and PX-478 can induce an increase in eIF2α phosphorylation was correlated with down-regulation of HIF-1α and elicited exposure of CRT and release of HMGB1 and ATP. Only co-treated cells induced DC maturation/phagocytosis and IFN-γ secretion by cytotoxic T lymphocytes. Altogether, combined treatment with Gem/PX-478 showed significantly inhibition on tumor growth and anti-tumor immunization. We propose that inhibition HIF-1α elicits Gem-induced immune response and eliminates PDAC cells by inducing ICD. PMID:25544770

  15. Pancreatic tumor detection using hypericin-based fluorescence spectroscopy and cytology

    NASA Astrophysics Data System (ADS)

    Lavu, Harish; Geary, Kevin; Fetterman, Harold R.; Saxton, Romaine E.

    2005-04-01

    Hypericin is a novel, highly fluorescent photosensitizer that exhibits selective tumor cell uptake properties and is particularly resistant to photobleaching. In this study, we have characterized hypericin uptake in human pancreatic tumor cells with relation to incubation time, cell number, and drug concentration. Ex vivo hypericin based fluorescence spectroscopy was performed to detect the presence of MIA PaCa-2 pancreatic tumor cells in the peritoneal cavity of BALB/c nude mice, as well as to quantify gross tumor burden. Hypericin based cytology of peritoneal lavage samples, using both one and two photon laser confocal microscopy, demonstrated more than a two-fold increase in fluorescence emission of pancreatic tumor cells as compared to control samples. In vitro treatment of pancreatic cancer cells with hypericin based photodynamic therapy showed tumor cell cytotoxicity in a drug dose, incident laser power, and time dependent manner. For these experiments, a continuous wavelength solid-state laser source (532 nm) was operated at power levels in the range of 100-400 mW. Potential applications of hypericin in tumor diagnosis, staging, and therapy will be presented.

  16. Diagnostic value of Thallium-201 scintigraphy in differentiating malignant bone tumors from benign bone lesions.

    PubMed

    Inai, Ryota; Shinya, Takayoshi; Tada, Akihiro; Sato, Shuhei; Fujiwara, Tomohiro; Takeda, Ken; Kunisada, Toshiyuki; Yanai, Hiroyuki; Ozaki, Toshifumi; Kanazawa, Susumu

    2015-10-01

    This retrospective study aims to evaluate the diagnostic capacity of thallium-201 (201Tl) scintigraphy for differentiating malignant bone tumors from benign bone lesions. Between January 2006 and December 2012, 279 patients with bone lesions (51 malignant and 228 benign) underwent 201Tl scintigraphy before treatment. To evaluate 201Tl uptake, we investigated tumor-to-background contrast (TBC) as well as TBC washout rate (WR). The differences of TBC on early and delayed images and WR were estimated by the Mann-Whitney U test. Receiver operating characteristic (ROC) analyses were used to determine the cut-off TBC values for differentiating malignant bone tumors from benign bone lesions. There were statistically significant differences in median TBC between malignant tumors and benign lesions. These differences occurred for early imaging (1.57 vs. 0.09, p < 0.001) as well as for delayed imaging (0.83 vs. 0.07, p < 0.001). However, there was no statistical difference in WR between malignant tumors and benign lesions (44 vs. 43 %, NS). The chosen TBC cut-off value was 0.68 for early imaging and 0.38 for delayed imaging. Using these cut-off values, the prediction of malignancy had a 77 % sensitivity, 74 % specificity, and 75 % accuracy for early imaging and an 80 % sensitivity, 76 % specificity, and 77 % accuracy for delayed imaging. 201Tl scintigraphy may have the ability to distinguish malignant bone tumors from benign bone lesions.

  17. Role of diffusion-weighted imaging in differentiating benign and malignant pediatric abdominal tumors.

    PubMed

    Gawande, Rakhee S; Gonzalez, Gabriel; Messing, Solomon; Khurana, Aman; Daldrup-Link, Heike E

    2013-07-01

    Solid malignant tumors are more highly cellular than benign lesions and hence have a restricted diffusion of water molecules. To evaluate whether diffusion-weighted MR imaging (DWI) can differentiate between benign and malignant pediatric abdominal tumors. We retrospectively analyzed DWI scans of 68 consecutive children with 39 benign and 34 malignant abdominal masses. To calculate the apparent diffusion coefficient (ADC) maps and ADC values, we used 1.5-T sequences at TR/TE/b-value of 5,250-7,500/54-64/b = 0, 500 and 3-T sequences at 3,500-4,000/66-73/b = 0, 500, 800. ADC values were compared between benign and malignant and between data derived at 1.5 tesla (T) and at 3 tesla magnetic field strength, using the Mann-Whitney-Wilcoxon test, ANOVA and a receiver operating curve (ROC) analysis. There was no significant difference in ADC values obtained at 1.5 T and 3 T (P = 0.962). Mean ADC values (× 10(-3) mm(2)/s) were 1.07 for solid malignant tumors, 1.6 for solid benign tumors, 2.9 for necrotic portions of malignant tumors and 3.1 for cystic benign lesions. The differences between malignant and benign solid tumors were statistically significant (P = 0.000025). ROC analysis revealed an optimal cut-off ADC value for differentiating malignant and benign solid tumors as 1.29 with excellent inter-observer reliability (alpha score 0.88). DWI scans and ADC values can contribute to distinguishing between benign and malignant pediatric abdominal tumors.

  18. Molecular beacon imaging of tumor marker gene expression in pancreatic cancer cells.

    PubMed

    Yang, Lily; Cao, Zehong; Lin, Yiming; Wood, William C; Staley, Charles A

    2005-05-01

    We have developed a fluorescence imaging-based approach to detect expression of tumor marker genes in pancreatic cancer cells using molecular beacons (MBs). MBs are short hairpin oligonucleotide probes that bind to specific oligonucleotide sequences and produce fluorescent signals. MBs targeting transcripts of two tumor marker genes, mutant K-ras and survivin, were synthesized and their specificity in detection of the expression of those genes in pancreatic cancer cells was examined. We found that K-ras MBs differentially bind to mutant K-ras mRNAs, resulting in strong fluorescent signals in pancreatic cancer cells with specific mutant K-ras genes but not in normal cells or cancer cells expressing either wild type or a different mutation of the K-ras gene. Additionally, MBs targeting survivin mRNA produced a bright fluorescent signal specifically in pancreatic cancer cells. We also demonstrated that MBs labeled with different fluorophores could detect survivin and mutant K-ras mRNAs simultaneously in single cancer cells. Furthermore, we showed that survivin and K-ras MBs have a high specificity in identifying cancer cells on frozen sections of pancreatic cancer tissues. In conclusion, molecular beacon-based imaging of expression of tumor marker genes has potential for the development of novel approaches for the detection of pancreatic cancer cells.

  19. [Endocrine tumors of the gastrointestinal and pancreatic systems. Multiple endocrine adenoma from another viewpoint].

    PubMed

    Klempa, I; Helmstädter, V; Feurle, G; Röttger, P

    1980-05-01

    The 24 endocrine pancreatic tumors and 14 carcinoids were examined immunohistochemically for cholecystokinin, insulin, gastrin, GIP, glucagon, sercretin, VIP, motilin, neurotensin, pancreatic polypeptide (PP), somatostatin, and ACTH. In 12 tumors of the pancreas more than one peptide-containing cell type was observed. The clinical symptoms showed hypersecretion of only one of the hormones, however. The midgut carcinoids (jejunum, appendix) represented the classical view of the carcinoid as an argentaffin cell tumor secreting 5-hydroxytryptamine. Tumors originating in the foregut (bronchus, stomach, duodenum) and hindgut carcinoids (rectum) were nonargentaffine, containing and secreting various polypeptide hormones. We conclude that light microscopic immunohistochemical methods are useful in distinguishing endocrine from nonendocrine tumors and multihormonal syndromes (MEA) in the classification of predominant hormone-secreting tumors.

  20. Hypercalcitoninemia in a sporadic asymptomatic neuroendocrine tumor of the pancreatic tail.

    PubMed

    Machens, A; Haedecke, J; Hinze, R; Thomusch, O; Schneyer, U; Dralle, H

    2000-01-01

    Asymptomatic neuroendocrine tumors of the gastroenteropancreatic tract represent a significant challenge in terms of postoperative monitoring. A case report of a calcitonin-secreting asymptomatic neuroendocrine tumor of the pancreatic tail is presented. Hypercalcitoninemia was noted in the 76-year-old Caucasian man who had a recurrent neuroendocrine tumor of the pancreatic tail. Upon pentagastrin stimulation, basal calcitonin increased only moderately from 82.3 (<10) to 100.9 and 125 pg/ml after 2 and 5 min, respectively. Surgical removal of the neuroendocrine tumor resulted in postoperative normalization of both basal and stimulated serum calcitonin levels. On immunohistochemistry, the neuroendocrine tumor was positive for calcitonin. Routine measurements of serum calcitonin might be a highly sensitive adjunct capable of identifying a subset of neuroendocrine tumors in which calcitonin monitoring may aid in the early detection of postoperative recurrence. Copyright 2000 S. Karger AG, Basel.

  1. Diagnostic value of metabolic heterogeneity as a reliable parameter for differentiating malignant parotid gland tumors.

    PubMed

    Kim, Bum Soo; Kim, Seong-Jang; Pak, Kyoungjune

    2016-06-01

    Exact classifying between malignant and benign tumors in the parotid gland is important because the cancer has relatively poor prognosis. There have been several studies that F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) can differentiate between malignant and benign parotid gland tumors. However, the role of FDG PET is still controversial because many benign parotid gland tumors, such as Warthin's tumor and pleomorphic adenoma, show high FDG uptake. We hypothesized that metabolic heterogeneity would differentiate malignant parotid tumors because tumoral heterogeneity is an important characteristic in the malignancies. From January 2010 to April 2015, we retrospectively reviewed the 46 patients who showed FDG uptake at the parotid gland. To differentiate malignant parotid gland tumors, we obtained maximum SUV and mean SUV. Metabolic tumor volume and total lesion glycolysis were measured as metabolic volumetric parameters. We also included heterogeneity parameters of FDG PET such as heterogeneity factor (HF) and the coefficient of variation for all patients. There was significant difference of HF between malignant (-0.30 ± 0.25; range -0.937 to -0.084) and benign parotid gland tumors (-0.06 ± 0.05; range -0.291 to -0.012; p < 0.0001). In receiver operating characteristic analysis, when ≤-0.084 was used as the cut-off value for HF, the sensitivity and specificity were 100 % (95 % CI 81.5-100) and 89.2 % (95 % CI 71.8-97.7), respectively. HF showed the highest area under the curve of 0.947 among the parameters. In logistic regression analysis, the HF was the most powerful factor for differentiation of the parotid gland tumors (p = 0.002). Our results suggest that HF can be utilized as a reliable and non-invasive method for differentiation of malignant and benign parotid gland tumors.

  2. Harmonic Motion Imaging for Abdominal Tumor Detection and High-intensity Focused Ultrasound Ablation Monitoring: A Feasibility Study in a Transgenic Mouse Model of Pancreatic Cancer

    PubMed Central

    Chen, Hong; Hou, Gary Y.; Han, Yang; Payen, Thomas; Palermo, Carmine F.; Olive, Kenneth P.; Konofagou, Elisa E.

    2015-01-01

    Harmonic motion imaging (HMI) is a radiation force-based elasticity imaging technique that tracks oscillatory tissue displacements induced by sinusoidal ultrasonic radiation force to assess relative tissue stiffness. The objective of this study was to evaluate the feasibility of HMI in pancreatic tumor detection and high-intensity focused ultrasound (HIFU) treatment monitoring. The HMI system consisted of a focused ultrasound transducer, which generated sinusoidal radiation force to induce oscillatory tissue motion at 50 Hz, and a diagnostic ultrasound transducer, which detected the axial tissue displacements based on acquired radiofrequency signals using a 1D cross-correlation algorithm. For pancreatic tumor detection, HMI images were generated for pancreatic tumors in transgenic mice and normal pancreases in wild-type mice. The obtained HMI images showed a high contrast between normal and malignant pancreases with an average peak-to-peak HMI displacement ratio of 3.2. Histological analysis showed that no tissue damage was associated with HMI when it was used for the sole purpose of elasticity imaging. For pancreatic tumor ablation monitoring, the focused ultrasound transducer was operated with a higher acoustic power and longer pulse length than that used in tumor detection to simultaneously induce HIFU thermal ablation and oscillatory tissue displacements, allowing HMI monitoring without interrupting tumor ablation. HMI monitoring of HIFU ablation found significant decreases in the peak-to-peak HMI displacements before and after HIFU ablation with a reduction rate ranging from 15.8% to 57.0%. The formation of thermal lesions after HIFU exposure was confirmed by histological analysis. This study demonstrated the feasibility of HMI in abdominal tumor detection and HIFU ablation monitoring. PMID:26415128

  3. Harmonic motion imaging for abdominal tumor detection and high-intensity focused ultrasound ablation monitoring: an in vivo feasibility study in a transgenic mouse model of pancreatic cancer.

    PubMed

    Chen, Hong; Hou, Gary Y; Han, Yang; Payen, Thomas; Palermo, Carmine F; Olive, Kenneth P; Konofagou, Elisa E

    2015-09-01

    Harmonic motion imaging (HMI) is a radiationforce- based elasticity imaging technique that tracks oscillatory tissue displacements induced by sinusoidal ultrasonic radiation force to assess the resulting oscillatory displacement denoting the underlying tissue stiffness. The objective of this study was to evaluate the feasibility of HMI in pancreatic tumor detection and high-intensity focused ultrasound (HIFU) treatment monitoring. The HMI system consisted of a focused ultrasound transducer, which generated sinusoidal radiation force to induce oscillatory tissue motion at 50 Hz, and a diagnostic ultrasound transducer, which detected the axial tissue displacements based on acquired radio-frequency signals using a 1-D cross-correlation algorithm. For pancreatic tumor detection, HMI images were generated for pancreatic tumors in transgenic mice and normal pancreases in wild-type mice. The obtained HMI images showed a high contrast between normal and malignant pancreases with an average peak-to-peak HMI displacement ratio of 3.2. Histological analysis showed that no tissue damage was associated with HMI when it was used for the sole purpose of elasticity imaging. For pancreatic tumor ablation monitoring, the focused ultrasound transducer was operated at a higher acoustic power and longer pulse length than that used in tumor detection to simultaneously induce HIFU thermal ablation and oscillatory tissue displacements, allowing HMI monitoring without interrupting tumor ablation. HMI monitoring of HIFU ablation found significant decreases in the peak-to-peak HMI displacements before and after HIFU ablation with a reduction rate ranging from 15.8% to 57.0%. The formation of thermal lesions after HIFU exposure was confirmed by histological analysis. This study demonstrated the feasibility of HMI in abdominal tumor detection and HIFU ablation monitoring.

  4. Malignant tumors associated with ovarian mature teratoma: A single institution experience.

    PubMed

    Trabzonlu, Levent; Durmaz, Guray; Vural, Cigdem; Muezzinoglu, Bahar; Corakci, Aydin

    2017-05-01

    The aims of this study are to present demographical features of cases diagnosed with malignant tumor associated with ovarian mature teratoma and to analyze histopathological features and clinical follow up of these tumors. Single-institution retrospective charts were reviewed to identify all cases of ovarian mature teratoma diagnosed from 1998 to 2015. Clinicopathological parameters that were analyzed include age, tumor size, tumor stage, histological type, laterality, IOC diagnosis and whether or not patient has received adjuvant chemotherapy. A total of 218 ovarian mature teratoma cases were identified during the study period. Of the 218 ovarian mature teratoma specimens, eight (3.7%) exhibited malignant tumors. The average age for cases of malignancy associated with ovarian mature teratoma was 44.6 years. The average size of tumors was 10.36cm. On final pathology, histological types of tumors were as follows: two cases each of squamous cell carcinoma and papillary thyroid carcinoma; one case each of mucinous adenocarcinoma, metastatic adenocarcinoma, sebaceous carcinoma and oligodendroglioma. Only one patient with Stage IIB tumor died of disease. One patient was alive with metastatic disease two months after initial diagnosis. Mean and median follow-up times were 64.1 and 49 months, respectively. An ovarian mass that has characteristics of a teratoma in a postmenopausal patient should alert for malignancy -regardless of tumor size. IOC is a valuable tool for the detection of malignancy and should be requested to determine the modality of surgical approach. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice.

    PubMed

    Jiang, Shu-Heng; Li, Jun; Dong, Fang-Yuan; Yang, Jian-Yu; Liu, De-Jun; Yang, Xiao-Mei; Wang, Ya-Hui; Yang, Min-Wei; Fu, Xue-Liang; Zhang, Xiao-Xin; Li, Qing; Pang, Xiu-Feng; Huo, Yan-Miao; Li, Jiao; Zhang, Jun-Feng; Lee, Ho-Young; Lee, Su-Jae; Qin, Wen-Xin; Gu, Jian-Ren; Sun, Yong-Wei; Zhang, Zhi-Gang

    2017-07-01

    Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras(G12D/+)/Trp53(R172H/+)/Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses. In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels

  6. Capacity of tumor necrosis factor to augment lymphocyte-mediated tumor cell lysis of malignant mesothelioma

    SciTech Connect

    Bowman, R.V.; Manning, L.S.; Davis, M.R.; Robinson, B.W. )

    1991-01-01

    Recombinant human tumor necrosis factor (rHuTNF) was evaluated both for direct anti-tumor action against human malignant mesothelioma and for its capacity to augment the generation and lytic phases of lymphocyte-mediated cytotoxicity against this tumor. rHuTNF was directly toxic by MTT assay to one of two mesothelioma cell lines evaluated, but had no effect on susceptibility to subsequent lymphocyte-mediated lysis of either line. TNF alone was incapable of generating anti-mesothelioma lymphokine-activated killer cell (LAK) activity. Furthermore, it did not augment the degree or LAK activity produced by submaximal interleukin-2 (IL-2) concentrations nor did it augment lysis of mesothelioma cells by natural killer (NK) or LAK effector cells during the 4-hr 51chromium release cytolytic reaction. The studies also suggest that mesothelioma targets are less responsive to TNF plus submaximal IL-2 concentrations than the standard LAK sensitive target Daudi, raising the possibility that intermediate LAK sensitive tumors such as mesothelioma may require separate and specific evaluation in immunomodulation studies. This in vitro study indicates that use of low-dose rHuTNF and IL-2 is unlikely to be an effective substitute for high-dose IL-2 in generation and maintenance of LAK activity in adoptive immunotherapy for mesothelioma.

  7. [Predictors of malignancy in the management of parotid tumors: about 76 cases].

    PubMed

    Bouaity, Brahim; Darouassi, Youssef; Chihani, Mehdi; Touati, Mohamed Mliha; Ammar, Haddou

    2016-01-01

    Salivary gland tumor pathology is complex and poses a diagnostic and therapeutic problem. A good analysis of predictive factors for malignancy in parotid tumors seems currently necessary for better therapeutic planning. The aim of this study was to investigate the predictive factors for malignancy in parotid tumors through a retrospective study of 76 cases of parotid tumor treated in a service of Otorhinolaryngology and Cervico Facial Surgery of Avicenne military hospital of Marrakech between January 2000 and December 2012. The study involved 40 women and 36 men. The average age was 44 years for benign tumours whereas it was 50 years for malignant tumours. The median of consultation time was 24 months for benign tumors and 16 month for malignant tumours. Swelling in the area of the parotid was always a patient detecting sign. Malignancy is clinically suspected based on pain, facial paralysis, surface structure and deeper structure fixity and on the presence of adenopathy. MRI has become the methodology of choice for evaluating parotid tumors due to its good diagnostic value in the assessment of benignity and malignancy. Fine needle aspiration biopsy has no value unless it is positive. Explorative parotidectomy with extemporaneous anatomopathological examination remains the key to positive diagnosis. Parotid benign tumors represent the most frequent entity (80%) and pleomorphic adenoma remains the predominant histologic type (61%). With regard to malignant tumors, they are rare, mainly dominated by mucoepidermoid carcinomas (6,5%). Surgical treatment is the first choice and it is often associated with lymph node dissection and radiation therapy for malignant tumors. Facial paralysis is the most common complication of parotid surgery.

  8. Giant malignant insulinoma

    PubMed Central

    Karavias, Dimitrios; Habeos, Ioannis; Maroulis, Ioannis; Kalogeropoulou, Christina; Tsamandas, Athanasios; Chaveles, Ioannis

    2015-01-01

    Insulinomas are the most common pancreatic neuroendocrine tumors. Most insulinomas are benign, small, intrapancreatic solid tumors and only large tumors have a tendency for malignancy. Most patients present with symptoms of hypoglycemia that are relieved with the administration of glucose. We herein present the case of a 75-year-old woman who presented with an acute hypoglycemic episode. Subsequent laboratory and radiological studies established the diagnosis of a 17-cm malignant insulinoma, with local invasion to the left kidney, lymph node metastasis, and hepatic metastases. Patient symptoms, diagnostic and imaging work-up and surgical management of both the primary and the metastatic disease are reviewed. PMID:25960993

  9. [Malignant phyllode tumor of the breast with features of intraductal carcinoma].

    PubMed

    Alò, P L; Andreano, T; Monaco, S; Sebastiani, V; Eleuteri Serpieri, D; Di Tondo, U

    2001-04-01

    Malignant phyllode tumor is a rare biphasic breast tumor consisting of a malignant mesenchymal component and an epithelial component that is usually benign. We report an unusual case of a malignant phyllode tumor of the breast with neoplastic features of both the epithelial and stromal components. The patient was a 39-year-old woman with family history for breast carcinoma. Grossly, the excised tumor was a 9 x 7 x 5.5 cm gray lobulated mass with infiltrative margins and necrotic-hemorrhagic areas. Histologically the tumor consisted mainly of neoplastic mesenchyme with non invasive comedo, cribriform and micropapillary features of the ducts. Three months after the excision of the neoplastic mass, the patient developed an infiltrating ductal carcinoma of the opposite breast. Hereditary and bilateral tumors are commonly associated with germline mutations. Tissue from both neoplasms however did not express either BRCA1 or BRCA2 mutations.

  10. My Treatment Approach: Pancreatic Cysts.

    PubMed

    Basar, Omer; Brugge, William R

    2017-09-07

    Our treatment approach for either symptomatic or incidentally found pancreatic cysts continues to improve. The true incidence of pancreatic cysts is not known, and pancreatic cystic neoplasms, especially intraductal papillary mucinous neoplasms, are currently most commonly diagnosed and resected. This is a result of increasing awareness, widespread availability of imaging, and better understanding of the nature of pancreatic cysts as well. Recent studies on molecular analysis and devices such as microbiopsy forceps help us better define and select the treatment approach to alleviate symptoms and to prevent malignant tumors while avoiding unnecessary surgery. Published by Elsevier Inc.

  11. Amenorrhea as a rare drug-related adverse event associated with everolimus for pancreatic neuroendocrine tumors.

    PubMed

    Kawaguchi, Yoshiaki; Maruno, Atsuko; Kawashima, Yohei; Ito, Hiroyuki; Ogawa, Masami; Mine, Tetsuya

    2014-11-14

    The patient was an asymptomatic 43-year-old woman. Abdominal ultrasonography and enhanced computed tomography showed a tumor lesion accompanied by multiple cystic changes in the liver and the pancreatic tail. Endoscopic ultrasound-fine needle aspiration was performed on the pancreatic tumor lesion and revealed pancreatic neuroendocrine tumor (PNET). As it was unresectable due to multiple liver metastases, the decision was made to initiate treatment with everolimus and transcatheter arterial chemoembolization. The patient ceased menstruating after the start of everolimus administration. When the administration was discontinued due to interstitial lung disease, menstruation resumed, but then again stopped with everolimus resumption. An association between everolimus and amenorrhea was highly suspected. Amenorrhea occurred as a rare adverse event of everolimus. As the younger women might be included in PNETs patients, we should put this adverse event into consideration.

  12. [Diagnostic difficulties in the laryngeal malignant peripheral nerve sheath tumor (MPNST)].

    PubMed

    Pabiszczak, Maciej; Woźniak, Aldona; Wierzbicka, Małgorzata; Leszczyńska, Małgorzata; Szyfter, Witold

    2004-01-01

    The malignant tumor deriving from the peripheral nerve sheet, previously described as malignant Schwannoma or neurosarcoma is extremely rare as malignancy localized in the larynx. The half of cases has been developing on the basis of neurofibromatosis in von Recklinghausen disease type I or seldom, type II. The high grade of malignancy end tendency to reccurences and distant metastases is typical for this tumors. The case of 64 year old man with larynx neurosarcoma was presented. The diagnostic difficulties were caused by clinical presentation of the smooth tumor covered by unchanged mucosa and typical histological features of the tumor. The final histological assessment was complemented by positive immunohistochemical reaction (antigens against protein S-100, NSE and PG 9.5).

  13. Unique metabolic features of pancreatic cancer stroma: relevance to the tumor compartment, prognosis, and invasive potential

    PubMed Central

    Knudsen, Erik S.; Balaji, Uthra; Freinkman, Elizaveta; McCue, Peter; Witkiewicz, Agnieszka K.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The aggressiveness and therapeutic recalcitrance of this malignancy has been attributed to multiple factors including the influence of an active desmoplastic stroma. How the stromal microenvironment of PDAC contributes to the fatal nature of this disease is not well defined. In the analysis of clinical specimens, we observed diverse expression of the hypoxic marker carbonic anhydrase IX and the lactate transporter MCT4 in the stromal compartment. These stromal features were associated with the epithelial to mesenchymal phenotype in PDAC tumor cells, and with shorter patient survival. Cultured cancer-associated fibroblasts (CAFs) derived from primary PDAC exhibited a high basal level of hypoxia inducible factor 1a (HIF1α) that was both required and sufficient to modulate the expression of MCT4. This event was associated with increased transcription and protein synthesis of HIF1α in CAFs relative to PDAC cell lines, while surprisingly the protein turnover rate was equivalent. CAFs utilized glucose predominantly for glycolytic intermediates, whereas glutamine was the preferred metabolite for the TCA cycle. Unlike PDAC cell lines, CAFs were resistant to glucose withdrawal but sensitive to glutamine depletion. Consistent with the lack of reliance on glucose, CAFs could survive the acute depletion of MCT4. In co-culture and xenograft studies CAFs stimulated the invasive potential and metastatic spread of PDAC cell lines through a mechanism dependent on HIF1α and MCT4. Together, these data indicate that stromal metabolic features influence PDAC tumor cells to promote invasiveness and metastatic potential and associate with poor outcome in patients with PDAC. PMID:27623078

  14. Laser immunotherapy for metastatic pancreatic cancer (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Zhou, Feifan

    2017-02-01

    Pancreatic cancer is an extremely malignant disease with high mortality rate. Currently there is no effective therapeutic strategy for highly metastatic pancreatic cancers. Laser immunotherapy (LIT) is a combination therapeutic approach of targeted phototherapy and immunotherapy, which could destroy treated primary tumors with elimination of untreated metastases. LIT affords a remarkable efficacy in suppressing tumor growth in pancreatic tumors in mice, and results in complete tumor regression in many cases. LIT could synergize targeted phototherapy and immunological effects of immunoadjuvant, which represent a promising treatment modality to induce systemic antitumor response through a local intervention, paving the way for the treatment of highly metastatic pancreatic cancers.

  15. Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients

    SciTech Connect

    Rock, M.G.; Sim, F.H.; Unni, K.K.; Witrak, G.A.; Frassica, F.J.; Schray, M.F.; Beabout, J.W.; Dahlin, D.C.

    1986-09-01

    Twenty-six patients who had a malignant giant-cell tumor of bone--a sarcoma either juxtaposed to a zone of typical benign giant-cell tumor or occurring at the site of a previously documented benign giant-cell tumor--have been seen at the Mayo Clinic. Of the twenty-six tumors, nineteen were secondary to a previous attempt at local control of a benign giant-cell tumor. All but one of these nineteen patients with a secondary tumor had received therapeutic irradiation four to thirty-nine years earlier. The nature and duration of the symptoms and the sites of predilection of the malignant giant-cell tumors were the same as for benign giant-cell tumor. Fibrosarcoma occurred three times as frequently as osteosarcoma. The best results of treatment of the secondary sarcoma were obtained with early ablation.

  16. Intra-tumoral heterogeneity of gemcitabine delivery and mass transport in human pancreatic cancer

    NASA Astrophysics Data System (ADS)

    Koay, Eugene J.; Baio, Flavio E.; Ondari, Alexander; Truty, Mark J.; Cristini, Vittorio; Thomas, Ryan M.; Chen, Rong; Chatterjee, Deyali; Kang, Ya'an; Zhang, Joy; Court, Laurence; Bhosale, Priya R.; Tamm, Eric P.; Qayyum, Aliya; Crane, Christopher H.; Javle, Milind; Katz, Matthew H.; Gottumukkala, Vijaya N.; Rozner, Marc A.; Shen, Haifa; Lee, Jeffrey E.; Wang, Huamin; Chen, Yuling; Plunkett, William; Abbruzzese, James L.; Wolff, Robert A.; Maitra, Anirban; Ferrari, Mauro; Varadhachary, Gauri R.; Fleming, Jason B.

    2014-12-01

    There is substantial heterogeneity in the clinical behavior of pancreatic cancer and in its response to therapy. Some of this variation may be due to differences in delivery of cytotoxic therapies between patients and within individual tumors. Indeed, in 12 patients with resectable pancreatic cancer, we previously demonstrated wide inter-patient variability in the delivery of gemcitabine as well as in the mass transport properties of tumors as measured by computed tomography (CT) scans. However, the variability of drug delivery and transport properties within pancreatic tumors is currently unknown. Here, we analyzed regional measurements of gemcitabine DNA incorporation in the tumors of the same 12 patients to understand the degree of intra-tumoral heterogeneity of drug delivery. We also developed a volumetric segmentation approach to measure mass transport properties from the CT scans of these patients and tested inter-observer agreement with this new methodology. Our results demonstrate significant heterogeneity of gemcitabine delivery within individual pancreatic tumors and across the patient cohort, with gemcitabine DNA incorporation in the inner portion of the tumors ranging from 38 to 74% of the total. Similarly, the CT-derived mass transport properties of the tumors had a high degree of heterogeneity, ranging from minimal difference to almost 200% difference between inner and outer portions of the tumor. Our quantitative method to derive transport properties from CT scans demonstrated less than 5% difference in gemcitabine prediction at the average CT-derived transport value across observers. These data illustrate significant inter-patient and intra-tumoral heterogeneity in the delivery of gemcitabine, and highlight how this variability can be reproducibly accounted for using principles of mass transport. With further validation as a biophysical marker, transport properties of tumors may be useful in patient selection for therapy and prediction of

  17. Intra-tumoral heterogeneity of gemcitabine delivery and mass transport in human pancreatic cancer

    PubMed Central

    Koay, Eugene J.; Baio, Flavio E.; Ondari, Alexander; Truty, Mark J.; Cristini, Vittorio; Thomas, Ryan M.; Chen, Rong; Chatterjee, Deyali; Kang, Ya’an; Zhang, Joy; Court, Laurence; Bhosale, Priya R.; Tamm, Eric P.; Qayyum, Aliya; Crane, Christopher H.; Javle, Milind; Katz, Matthew H.; Gottumukkala, Vijaya N.; Rozner, Marc A.; Shen, Haifa; Lee, Jeffrey E.; Wang, Huamin; Chen, Yuling; Plunkett, William; Abbruzzese, James L.; Wolff, Robert A.; Maitra, Anirban; Ferrari, Mauro; Varadhachary, Gauri R.; Fleming, Jason B.

    2014-01-01

    There is substantial heterogeneity in the clinical behavior of pancreatic cancer and in its response to therapy. Some of this variation may be due to differences in delivery of cytotoxic therapies between patients and within individual tumors. Indeed, in 12 patients with resectable pancreatic cancer, we previously demonstrated wide inter-patient variability in the delivery of gemcitabine as well as in the mass transport properties of tumors as measured by computed tomography (CT) scans. However, the variability of drug delivery and transport properties within pancreatic tumors is currently unknown. Here, we analyzed regional measurements of gemcitabine DNA incorporation in the tumors of the same 12 patients to understand the degree of intra-tumoral heterogeneity of drug delivery. We also developed a volumetric segmentation approach to measure mass transport properties from the CT scans of these patients and tested inter-observer agreement with this new methodology. Our results demonstrate significant heterogeneity of gemcitabine delivery within individual pancreatic tumors and across the patient cohort, with gemcitabine DNA incorporation in the inner portion of the tumors ranging from 38 to 74% of the total. Similarly, the CT-derived mass transport properties of the tumors had a high degree of heterogeneity, ranging from minimal difference to almost 200% difference between inner and outer portions of the tumor. Our quantitative method to derive transport properties from CT scans demonstrated less than 5% difference in gemcitabine prediction at the average CT-derived transport value across observers. These data illustrate significant inter-patient and intra-tumoral heterogeneity in the delivery of gemcitabine, and highlight how this variability can be reproducibly accounted for using principles of mass transport. With further validation as a biophysical marker, transport properties of tumors may be useful in patient selection for therapy and prediction of

  18. Increased epidermal growth factor receptor (EGFR) expression in malignant mammary phyllodes tumors.

    PubMed

    Tse, Gary M K; Lui, Philip C W; Vong, Joaquim S L; Lau, Kin-Mang; Putti, Thomas C; Karim, Rooshdiya; Scolyer, Richard A; Lee, C-Soon; Yu, Alex M C; Ng, David C H; Tse, Agnes K Y; Tan, Puay-Hoon

    2009-04-01

    Mammary phyllodes tumors are uncommon stromal-epithelial neoplasms, and are divided into benign, borderline malignant and frankly malignant groups on the basis of their histological features. Accumulating evidence shows that epidermal growth factor receptor (EGFR) is involved in the pathogenesis and progression of many malignancies. This study investigated 453 phyllodes tumors (296 benign, 98 borderline, 59 malignant) for EGFR expression using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for gene amplification. The staining was correlated to tumor margin status, degree of malignancy, stromal cellularity, mitotic activity, nuclear pleomorphism and stromal overgrowth. Cases with strong positive IHC staining were selected for FISH. The overall positive rate for EGFR was 16.2% (48/296), 30.6% (30/98) and 56% (33/59) for benign, borderline malignant and frankly malignant phyllodes tumors, respectively. FISH demonstrated egfr gene amplification in 8% of immunohistochemically positive cases. The results of this study provide strong evidence that EGFR overexpression is involved in the pathogenesis of phyllodes tumors, although gene amplification may not be the major underlying mechanism for overexpression.

  19. Autofluorescence of seborrheic keratosis (warts) and of tissue surrounding malignant tumors

    NASA Astrophysics Data System (ADS)

    Lohmann, Wolfgang; Schill, Wolf-Bernhard; Bohle, Rainer M.; Dreyer, Thomas

    1997-12-01

    Autofluorescence measurements on human tissue have revealed a decrease in intensity in malignant tumors and an increase in the healthy region adjacent to the tumor. This latter event might serve as a protective wall against the invasive tumor cells. The composition of this wall is still unknown. Antioxidants such as NADH might be involved. In the case of seborrheic keratosis (wart), the intensity is increased in the pigmented spots. Care must be taken, therefore, when warts are attached to malignant tumors. The resulting value is, then, not indicative for the condition of the system.

  20. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast

    PubMed Central

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P.; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-01

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast. PMID:26625196

  1. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast.

    PubMed

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-12

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast.

  2. Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

    DTIC Science & Technology

    2016-04-01

    notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does...ABSTRACT The most common cause of death in Neurofibromatosis Type 1 (NF1) patients is malignant peripheral nerve sheath tumor (MPNST). MPNSTs are...expectancy by ten to twenty years. Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death in NF1 patients and typically arise

  3. Role of CD44 in Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

    DTIC Science & Technology

    2002-09-01

    Malignant peripheral nerve sheath tumors ( MPNSTs ) are aggressive malignancies that arise within peripheral nerves. These tumors occur with increased...and abnormal expression of the epidermal growth factor receptor (EGFR). We previously found that MPNSTs express increased levels of the CD44 family...kinase activity (and not increased Ras-GTP) contributes to MPNST cell invasion. We further find that EGFR contributes at least part of the elevated Src

  4. Unusual liver locations of growing teratoma syndrome in ovarian malignant germ cell tumors.

    PubMed

    Lorusso, Domenica; Malaguti, Paola; Trivellizzi, Ilaria Nausica; Scambia, Giovanni

    2011-01-01

    ► Growing teratoma syndrome (GTS) with unusual liver locations are described after fertility preserving surgery and chemotherapy treatment for mixed malignant ovarian germ cell tumors (MGCT). ► It's a rare syndrome of mixed malignant ovarian germ cell tumors and in both cases enlarged and growing liver masses appeared during cisplatin-etoposide-bleomicin (BEP) chemotherapy. ► Radiological exams (CT scan and MRI) were suggestive for secondary metastasis and serum markers became negative during chemotherapy.

  5. Induction of malignant peripheral nerve sheath tumors in European hamsters with 1,1-dimethylhydrazine (UDMH).

    PubMed

    Ernst, H; Rittinghausen, S; Wahnschaffe, U; Mohr, U

    1987-06-01

    A rate of up to 43% of malignant peripheral nerve sheath tumors (PNST) was induced in European hamsters (EH) after weekly s.c. administration of 1,1-dimethylhydrazine (UDMH). The overall neoplastic response in the treated EH was also elevated as compared to the untreated controls. Histologically, the malignant PNST were neurofibrosarcomas and melanotic as well as unpigmented schwannomas. The occurrence of melanotic schwannomas is briefly discussed with regard to the histogenesis of this rare tumor type.

  6. TLR7 and TLR8 expression increases tumor cell proliferation and promotes chemoresistance in human pancreatic cancer

    PubMed Central

    GRIMMIG, TANJA; MATTHES, NIELS; HOELAND, KATHARINA; TRIPATHI, SUDIPTA; CHANDRAKER, ANIL; GRIMM, MARTIN; MOENCH, ROMANA; MOLL, EVA-MARIA; FRIESS, HELMUT; TSAUR, IGOR; BLAHETA, ROMAN A.; GERMER, CRISTOPH T.; WAAGA-GASSER, ANA MARIA; GASSER, MARTIN

    2015-01-01

    Chronic inflammation as an important epigenetic and environmental factor for putative tumorigenesis and tumor progression may be associated with specific activation of Toll-like receptors (TLR). Recently, carcinogenesis has been suggested to be dependent on TLR7 signaling. In the present study, we determined the role of both TLR7 and TLR8 expression and signaling in tumor cell proliferation and chemoresistance in pancreatic cancer. Expression of TLR7/TLR8 in UICC stage I–IV pancreatic cancer, chronic pancreatitis, normal pancreatic tissue and human pancreatic (PANC1) cancer cell line was examined. For in vitro/in vivo studies TLR7/TLR8 overexpressing PANC1 cell lines were generated and analyzed for effects of (un-)stimulated TLR expression on tumor cell proliferation and chemoresistance. TLR expression was increased in pancreatic cancer, with stage-dependent upregulation in advanced tumors, compared to earlier stages and chronic pancreatitis. Stimulation of TLR7/TLR8 overexpressing PANC1 cells resulted in elevated NF-κB and COX-2 expression, increased cancer cell proliferation and reduced chemosensitivity. More importantly, TLR7/TLR8 expression increased tumor growth in vivo. Our data demonstrate a stage-dependent upregulation of both TLR7 and TLR8 expression in pancreatic cancer. Functional analysis in human pancreatic cancer cells point to a significant role of both TLRs in chronic inflammation-mediated TLR7/TLR8 signaling leading to tumor cell proliferation and chemoresistance. PMID:26134824

  7. Targeting inhibitors of the tumor suppressor PP2A for the treatment of pancreatic cancer.

    PubMed

    Farrell, Amy S; Allen-Petersen, Brittany; Daniel, Colin J; Wang, Xiaoyan; Wang, Zhiping; Rodriguez, Sarah; Impey, Soren; Oddo, Jessica; Vitek, Michael P; Lopez, Charles; Christensen, Dale J; Sheppard, Brett; Sears, Rosalie C

    2014-06-01

    Pancreatic cancer is a deadly disease that is usually diagnosed in the advanced stages when few effective therapies are available. Given the aggressive clinical course of this disease and lack of good treatment options, the development of new therapeutic agents for the treatment of pancreatic cancer is of the upmost importance. Several pathways that have shown to contribute to pancreatic cancer progression are negatively regulated by the tumor suppressor protein phosphatase 2A (PP2A). Here, the endogenous inhibitors of PP2A, SET (also known as I2PP2A) and cancerous inhibitor of PP2A (CIP2A), were shown to be overexpressed in human pancreatic cancer, contributing to decreased PP2A activity and overexpression and stabilization of the oncoprotein c-Myc, a key PP2A target. Knockdown of SET or CIP2A increases PP2A activity, increases c-Myc degradation, and decreases the tumorigenic potential of pancreatic cancer cell lines both in vitro and in vivo. Moreover, treatment with a novel SET inhibitor, OP449, pharmacologically recapitulates the phenotypes and significantly reduces proliferation and tumorigenic potential of several pancreatic cancer cell lines, with an accompanying attenuation of cell growth and survival signaling. Furthermore, primary cells from patients with pancreatic cancer were sensitive to OP449 treatment, indicating that PP2A-regulated pathways are highly relevant to this deadly disease. The PP2A inhibitors SET and CIP2A are overexpressed in human pancreatic cancer and are important for pancreatic cancer cell growth and transformation; thus, antagonizing SET and/or CIP2A may be an innovative approach for the treatment of human pancreatic cancer. ©2014 American Association for Cancer Research.

  8. The rare malignancy of the hepatobiliary system: ampullary carcinoid tumor.

    PubMed

    Ozsoy, Mustafa; Ozsoy, Yucel; Canda, Aras Emre; Nalbant, Olcay Ak; Haskaraca, Fatih

    2011-01-01

    Introduction. Carcinoid tumors are low-grade tumors originating from endoderm and mostly involving the gastrointestinal system. However; they may be seen in any site within the gastrointestinal system. Case Presentation. A 69-year-old female patient. The results of blood tests were observed to be consistent with obstructive jaundice. A mass appearance was not encountered on tomographic examination. Papilla that was tumor-like macroscopically was seen in the second part of the duodenum in diagnostic endoscopy. Pylorus-preserving pancreaticoduodenectomy surgical procedure was applied. On pathological examination of the mass, a tumoral mass was detected in ampulla vateri localization, 1.5 × 1 × 0.8 cm in size, which, in immunohistochemical staining, was evaluated as a neuroendocrine tumor. Also, Metastasis was observed. Conclusion. The rarest type of carcinoid tumor is ampullary located carcinoid tumor, and tumor size is not a reliable indicator for tumor aggressivity in ampullary carcinoid tumors.

  9. Resection of postoperative liver metastasis from pancreatic neuroendocrine tumors: report of one case

    PubMed Central

    Chen, Xiao; Ren, Hu; Chi, Yihebali; He, Shun; Huang, Zhen; Hu, Xuhui

    2016-01-01

    Pancreatic neuroendocrine tumor (pNET) is a rare type of pancreatic tumors. The incidence of pNET shows a gradually increasing trend in recent years. Except insulinoma, majority of pNET are metastatic when diagnosis. And liver is the most common organ of distant metastases. Liver metastases are the main determinant for long-term survival and quality of life of patients with pNET. A case of liver metastases of pNET of a 44-year-old female patient is presented in this study. Then we have a brief discussion of the diagnosis and multidisciplinary treatment of advanced pNET. PMID:28138614

  10. Ultrasonic Nakagami imaging: a strategy to visualize the scatterer properties of benign and malignant breast tumors.

    PubMed

    Tsui, Po-Hsiang; Yeh, Chih-Kuang; Liao, Yin-Yin; Chang, Chien-Cheng; Kuo, Wen-Hung; Chang, King-Jen; Chen, Chiung-Nien

    2010-02-01

    Previous studies have demonstrated the usefulness of the Nakagami parameter in characterizing breast tumors by ultrasound. However, physicians or radiologists may need imaging tools in a clinical setting to visually identify the properties of breast tumors. This study proposed the ultrasonic Nakagami image to visualize the scatterer properties of breast tumors and then explored its clinical performance in classifying benign and malignant tumors. Raw data of ultrasonic backscattered signals were collected from 100 patients (50 benign and 50 malignant cases) using a commercial ultrasound scanner with a 7.5 MHz linear array transducer. The backscattered signals were used to form the B-scan and the Nakagami images of breast tumors. For each tumor, the average Nakagami parameter was calculated from the pixel values in the region-of-interest in the Nakagami image. The receiver operating characteristic (ROC) curve was used to evaluate the clinical performance of the Nakagami image. The results showed that the Nakagami image shadings in benign tumors were different from those in malignant cases. The average Nakagami parameters for benign and malignant tumors were 0.69 +/- 0.12 and 0.55 +/- 0.12, respectively. This means that the backscattered signals received from malignant tumors tend to be more pre-Rayleigh distributed than those from benign tumors, corresponding to a more complex scatterer arrangement or composition. The ROC analysis showed that the area under the ROC curve was 0.81 +/- 0.04 and the diagnostic accuracy was 82%, sensitivity was 92% and specificity was 72%. The results showed that the Nakagami image is useful to distinguishing between benign and malignant breast tumors. 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  11. Aberrant expression of miR-9 in benign and malignant breast tumors.

    PubMed

    Hasanzadeh, Aisan; Mesrian Tanha, Hamzeh; Ghaedi, Kamran; Madani, Mahboobeh

    2016-10-01

    MicroRNAs (miRNAs) are involved in the progression of breast cancer (BC). miR-9 has been reported to be correlated with either favorable or unfavorable events in BC. This study was aimed to evaluate the expression level of miR-9 in human breast tissues, including benign and malignant tumor samples and also healthy tissue. The expression level of miR-9 was analyzed in 10 normal breast tissues, 30 malignant, and 30 benign breast tumor tissue samples using RT-PCR and qPCR. In addition, bioinformatics assessment upon miR-9 functionality in BC cells was performed. The miR-9 expression level was downregulated in tumor tissues, including benign and malignant compared to the healthy tissue was observed (P value, < 0.0001; fold change, -1.37). In addition, miR-9 expression level was reduced in benign tumors compared with malignant tumors (P value, < 0.0001; fold change, -1.35). Moreover, according to the AUCs (area under curve) of receiver operating characteristic (ROC) curves, miR-9 showed significant capability for distinguishing benign from healthy, malignant from healthy, benign from malignant, and tumor from health tissues. Furthermore, pathways in cancer, p53 signaling pathway, and focal adhesion were manifested by computational analysis as miR-9 related signaling pathways which have logical association with experimental observations. In conclusion, downregulation of miR-9 in benign tumors vs healthy tissue and its overexpression in malignant tumors vs benign tumors suggest paradoxical functionality for this miRNA. Our results shed additional information on controversial expression pattern of miR-9 depending on different progression level of BC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Metastases of pancreatic neuroendocrine tumor to the liver as extremely rare indication for liver transplantation in children. Case report and review of the literature.

    PubMed

    Ismail, Hor; Broniszczak, Dorota; Markiewicz-Kijewska, Małgorzata; Ciopiński, Mateusz; Teisseyre, Joanna; Kluge, Przemysław; Dembowska-Bagińska, Bożenna; Kościesza, Andrzej; Socha, Piotr; Kaliciński, Piotr

    2016-09-01

    Neuroendocrine tumors (NET) are extremely rare in children (0.75 cases per 100,000 children and adolescents a year) and the majority of these tumors are benign or present low grade of malignancy. According to the American registry Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, less than 2% of all neuroendocrine tumors in children occur in the pancreas, making it a rare site for these tumors. The majority of them are found in children over 10years of age, especially those with malignant potential. Treatment of NET consists of different methods: surgery, somatostatin analogues and chemotherapy. Radical surgical resection remains the standard of treatment; however, it is not always feasible because of distant metastases. The authors present a case report of pancreatic NET with multiple metastases to the liver. The patient was treated with pancreatic resection and liver transplantation for liver metastases. Prior to liver transplantation, the patient was treated with somatostatin analogues, sunitinib and chemotherapy. Management of liver metastases with liver transplantation is discussed.

  13. Targeting Inhibitors of the Tumor Suppressor PP2A for the Treatment of Pancreatic Cancer

    PubMed Central

    Farrell, Amy S.; Allen-Petersen, Brittany; Daniel, Colin J.; Wang, Xiaoyan; Wang, Zhiping; Rodriguez, Sarah; Impey, Soren; Oddo, Jessica; Vitek, Michael P.; Lopez, Charles; Christensen, Dale J.; Sheppard, Brett; Sears, Rosalie C.

    2014-01-01

    Pancreatic cancer is a deadly disease that is usually diagnosed in the advanced stages when few effective therapies are available. Given the aggressive clinical course of this disease and lack of good treatment options, the development of new therapeutic agents for the treatment of pancreatic cancer is of the upmost importance. Several pathways shown to contribute to pancreatic cancer progression are negatively regulated by the tumor suppressor, protein phosphatase 2A (PP2A). Here, the endogenous inhibitors of PP2A, SET (also known as I2PP2A) and Cancerous Inhibitor of PP2A (CIP2A), were shown to be overexpressed in human pancreatic cancer, contributing to decreased PP2A activity, and overexpression and stabilization of the oncoprotein c-Myc, a key PP2A target. Knockdown of SET or CIP2A increases PP2A activity, increases c-Myc degradation, and decreases the tumorigenic potential of pancreatic cancer cell lines both in vitro and in vivo. Moreover, treatment with a novel SET inhibitor, OP449, pharmacologically recapitulates the phenotypes and significantly reduces proliferation and tumorigenic potential of several pancreatic cancer cell lines, with an accompanying attenuation of cell growth and survival signaling. Furthermore, primary cells from pancreatic cancer patients were sensitive to OP449 treatment, indicating that PP2A regulated pathways are highly relevant to this deadly disease. PMID:24667985

  14. Malignant phyllodes tumor of the breast with liposarcomatous differentiation and intraductal hyperplasia.

    PubMed

    Ayadi-Kaddour, Aïda; Zeddini, Abdelfatteh; Braham, Emna; Ismail, Olfa; Mlika, Mona; Guelmami, Karim; El Mezni, Faouzi

    2015-01-01

    Phyllodes tumor of the breast is a biphasic fibroepithelial neoplasm. 10 to 20% of phyllodes tumor show malignant transformation, often in the form of stroma, which usually shows fibrosarcomatous differentiation and rarely heterologous sarcomatous elements. Liposarcomatous differentiation is not common among phyllodes tumors. The correct diagnosis of heterologous liposarcomatous differentiation in a malignant PT requires identification of the biphasic component of the tumor. We reported a case of malignant phyllodes tumor which initially transformed into liposarcoma, in addition to a very rare intraductal hyperplasia and flat epithelial atypia. The patient was a 75-year-old woman, with a lump in the left breast without axillary lymphadenopathy. She also have a positive family history of breast carcinoma. She underwent surgery and still alive and disease free after one year.

  15. B-mode and contrast-enhancement characteristics of small nonincidental neuroendocrine pancreatic tumors

    PubMed Central

    Braden, Barbara; Jenssen, Christian; D’Onofrio, Mirko; Hocke, Michael; Will, Uwe; Möller, Kathleen; Ignee, Andre; Dong, Yi; Cui, Xin-Wu; Săftoiu, Adrian; Dietrich, Christoph F.

    2017-01-01

    Background and Objectives: Imaging of the pancreas for detection of neuroendocrine tumors is indicated as surveillance in multiple endocrine neoplasia type 1 (MEN1) or if typical clinical symptoms combined with hormone production raise the suspicion of a neuroendocrine tumor. Endoscopic ultrasound (EUS) is considered the best imaging modality to detect small pancreatic tumors. However, little is known about how small pancreatic neuroendocrine tumors (pNETs) present on EUS. Patients and Methods: In this multicenter study, we retrospectively analyzed the endosonographic characteristics of small pNETs which had been detected due to typical biochemistry and clinical symptoms or during surveillance of MEN 1. Only small pancreatic tumors ≤15 mm with histological confirmation as pNET were included. B-mode and contrast-enhanced ultrasound- and EUS patterns were analyzed. Results: Among 32 patients with histologically proven small pNETs, 7 patients had known MEN1. Among the pNETs, 20 were insulinoma, 2 gastrinoma, 3 glucagonoma, 6 nonfunctional in MEN1, and one PPoma. 94% of the pNET appeared hypoechogenic, only 1 isoechogenic and 1 hyperechogenic. After contrast injection, 90% of the pNETS showed hyperenhancement compared to the surrounding pancreatic parenchyma. Conclusion: The high spatial resolution of EUS allows detection and even cytological confirmation of pNET <7 mm diameter. Hypoechogenicity in B-mode and hyperenhancement after injection of contrast agents are endosonographic characteristics of small pNET and present in >90% of pNETs. PMID:28218201

  16. Bone Windows for Distinguishing Malignant from Benign Primary Bone Tumors on FDG PET/CT

    PubMed Central

    Costelloe, Colleen M.; Chuang, Hubert H.; Chasen, Beth A.; Pan, Tinsu; Fox, Patricia S.; Bassett, Roland L.; Madewell, John E.

    2013-01-01

    Objective. The default window setting on PET/CT workstations is soft tissue. This study investigates whether bone windowing and hybrid FDG PET/CT can help differentiate between malignant and benign primary bone tumors. Materials and methods. A database review included 98 patients with malignant (n=64) or benign primary bone (n=34) tumors. The reference standard was biopsy for malignancies and biopsy or >1 year imaging follow-up of benign tumors. Three radiologists and/or nuclear medicine physicians blinded to diagnosis and other imaging viewed the lesions on CT with bone windows (CT-BW) without and then with PET (PET/CT-BW), and separate PET-only images for malignancy or benignity. Three weeks later the tumors were viewed on CT with soft tissue windows (CT-STW) without and then with PET (PET/CT-STW). Results. Mean sensitivity and specificity for identifying malignancies included: CT-BW: 96%, 90%; CT-STW: 90%, 90%; PET/CT-BW: 95%, 85%, PET/CT-STW: 95%, 86% and PET-only: 96%, 75%, respectively. CT-BW demonstrated higher specificity than PET-only and PET/CT-BW (p=0.0005 and p=0.0103, respectively) and trended toward higher sensitivity than CT-STW (p=0.0759). Malignant primary bone tumors were more avid than benign lesions overall (p<0.0001) but the avidity of benign aggressive lesions (giant cell tumors and Langerhans Cell Histiocytosis) trended higher than the malignancies (p=0.08). Conclusion. Bone windows provided high specificity for distinguishing between malignant and benign primary bone tumors and are recommended when viewing FDG PET/CT. PMID:23983816

  17. Bone Windows for Distinguishing Malignant from Benign Primary Bone Tumors on FDG PET/CT.

    PubMed

    Costelloe, Colleen M; Chuang, Hubert H; Chasen, Beth A; Pan, Tinsu; Fox, Patricia S; Bassett, Roland L; Madewell, John E

    2013-01-01

    Objective. The default window setting on PET/CT workstations is soft tissue. This study investigates whether bone windowing and hybrid FDG PET/CT can help differentiate between malignant and benign primary bone tumors. Materials and methods. A database review included 98 patients with malignant (n=64) or benign primary bone (n=34) tumors. The reference standard was biopsy for malignancies and biopsy or >1 year imaging follow-up of benign tumors. Three radiologists and/or nuclear medicine physicians blinded to diagnosis and other imaging viewed the lesions on CT with bone windows (CT-BW) without and then with PET (PET/CT-BW), and separate PET-only images for malignancy or benignity. Three weeks later the tumors were viewed on CT with soft tissue windows (CT-STW) without and then with PET (PET/CT-STW). Results. Mean sensitivity and specificity for identifying malignancies included: CT-BW: 96%, 90%; CT-STW: 90%, 90%; PET/CT-BW: 95%, 85%, PET/CT-STW: 95%, 86% and PET-only: 96%, 75%, respectively. CT-BW demonstrated higher specificity than PET-only and PET/CT-BW (p=0.0005 and p=0.0103, respectively) and trended toward higher sensitivity than CT-STW (p=0.0759). Malignant primary bone tumors were more avid than benign lesions overall (p<0.0001) but the avidity of benign aggressive lesions (giant cell tumors and Langerhans Cell Histiocytosis) trended higher than the malignancies (p=0.08). Conclusion. Bone windows provided high specificity for distinguishing between malignant and benign primary bone tumors and are recommended when viewing FDG PET/CT.

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

    PubMed

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

    2013-01-01

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

  19. Intraductal Delivery of Adenoviruses Targets Pancreatic Tumors in Transgenic Ela-myc Mice and Orthotopic Xenografts

    PubMed Central

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

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p<0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors. PMID:23328228

  20. Circulating tumor DNA as a liquid biopsy target for detection of pancreatic cancer.

    PubMed

    Takai, Erina; Yachida, Shinichi

    2016-10-14

    Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The "liquid biopsy" addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA (ctDNA) could provide diagnostic information. In this review, we provide an overview of the current status of blood-based tests for diagnosis of pancreatic cancer and the potential utility of ctDNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ctDNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer.

  1. Circulating tumor DNA as a liquid biopsy target for detection of pancreatic cancer

    PubMed Central

    Takai, Erina; Yachida, Shinichi

    2016-01-01

    Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The “liquid biopsy” addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA (ctDNA) could provide diagnostic information. In this review, we provide an overview of the current status of blood-based tests for diagnosis of pancreatic cancer and the potential utility of ctDNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ctDNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer. PMID:27784960

  2. In vivo tumor transfection with superantigen plus cytokine genes induces tumor regression and prolongs survival in dogs with malignant melanoma.

    PubMed

    Dow, S W; Elmslie, R E; Willson, A P; Roche, L; Gorman, C; Potter, T A

    1998-06-01

    In vivo transfection of established tumors with immunostimulatory genes can elicit antitumor immunity. Therefore, we evaluated the safety and efficacy of intratumoral injections of a bacterial superantigen with a cytokine gene in dogs with malignant melanoma, a spontaneous and highly malignant canine tumor. 26 dogs with melanoma were treated with lipid-complexed plasmid DNA encoding staphylococcal enterotoxin B and either GM-CSF or IL-2. Dogs were evaluated for treatment-associated toxicity, tumor responses, immunologic responses, and survival times. The overall response rate (complete or partial remissions) for all 26 dogs was 46% (12 of 26), and was highest in patients with smaller tumors. Toxicity was minimal or absent in all dogs. Injected tumors developed marked infiltrates of CD4+ and CD8+ T cells and macrophages, and tumor regression was associated with development of high levels of antitumor cytotoxic T lymphocyte activity in peripheral blood lymphocytes. Survival times for animals with stage III melanomas treated by intratumoral gene therapy were prolonged significantly compared with animals treated with surgical tumor excision only. Thus, local tumor transfection with superantigen and cytokine genes was capable of inducing both local and systemic antitumor immunity in an outbred animal with a spontaneously developing malignant tumor.

  3. In vivo tumor transfection with superantigen plus cytokine genes induces tumor regression and prolongs survival in dogs with malignant melanoma.

    PubMed Central

    Dow, S W; Elmslie, R E; Willson, A P; Roche, L; Gorman, C; Potter, T A

    1998-01-01

    In vivo transfection of established tumors with immunostimulatory genes can elicit antitumor immunity. Therefore, we evaluated the safety and efficacy of intratumoral injections of a bacterial superantigen with a cytokine gene in dogs with malignant melanoma, a spontaneous and highly malignant canine tumor. 26 dogs with melanoma were treated with lipid-complexed plasmid DNA encoding staphylococcal enterotoxin B and either GM-CSF or IL-2. Dogs were evaluated for treatment-associated toxicity, tumor responses, immunologic responses, and survival times. The overall response rate (complete or partial remissions) for all 26 dogs was 46% (12 of 26), and was highest in patients with smaller tumors. Toxicity was minimal or absent in all dogs. Injected tumors developed marked infiltrates of CD4+ and CD8+ T cells and macrophages, and tumor regression was associated with development of high levels of antitumor cytotoxic T lymphocyte activity in peripheral blood lymphocytes. Survival times for animals with stage III melanomas treated by intratumoral gene therapy were prolonged significantly compared with animals treated with surgical tumor excision only. Thus, local tumor transfection with superantigen and cytokine genes was capable of inducing both local and systemic antitumor immunity in an outbred animal with a spontaneously developing malignant tumor. PMID:9616212

  4. Retroperitoneal Malignant Mesenchymoma: A Case of Mesenchymal Mixed Tumor with Osteosarcoma, Leiomyosarcoma, Liposarcoma and Fibrosarcoma

    PubMed Central

    Choi, Jung Eun; Yoo, Won Jong; Chung, Myung Hee; Sung, Mi Sook; Lee, Hae Giu; Park, Il Young; Kim, Jeana

    2002-01-01

    Malignant mesenchymoma is an interesting but very rare tumor in which malignant differentiation has occurred twice or more. We report a case of retroperitoneal malignant mesenchymoma consisting of osteosarcoma, leiomyosarcoma, liposarcoma and fibrosarcoma. Abdominal CT showed a large retroperitoneal mass with two separate and distinct parts, namely an area of prominent calcification and one of clearly enhancing solid components. The mass contained histologically distinct tumorous components with no histologic admixure at the interfaces. The densely calcified nodule corresponded to osteosarcoma, and the non-calcified clearly enhancing nodules to leiomyosarcoma, liposarcoma and fibrosarcoma. PMID:12514345

  5. [Electrochemical analysis in differential diagnosis of benign and malignant oral maxillofacial tumors].

    PubMed

    Zhang, C Y

    1993-05-01

    A bioelectrochemical-sensor device was designed according to the principles of galvanic cell reaction. Modified bioelectrochemically, the device was used to measure the current of samples from benign and malignant tumor tissues. Statistical analysis and clinical test showed that the current values (426 microA) of the malignant tissue were higher than those (216 microA) of the benign tissue. The sensitivity and specificity were 95% and 90% respectively. This method provided important information about benignancy or malignancy of the tumor and its involvement and metastasis.

  6. [Malignant tumors of the female genitalia in childhood--yesterday, today and tomorrow].

    PubMed

    Horejsí, J; Rob, L

    2003-02-01

    Genital tumors in children and adolescents represent 1.5 to 2.0% of al malignancies in these age groups. Organ incidence differs from that in adult women. In children and in young adolescents non-epithelial gynaecological tumors predominate, while carcinomas are rare and their incidence rises with the age of girls. Malignant tumors of the external genital are very rare (sarcomas of the soft tissues). Malignancies of vagina are represented by the embryogenic rabdomyosarcoma, yolk sack tumor and tumor of pale cells or vaginal adenocarcinoma. All these tumors are highly malignant. Cytostatics are used as the basic therapy and only later the less radical surgery is recommended. Radiotherapy is used in chemoresistant tumors. Vaginal bleeding of the premenarcheal girl is an early symptom and requires immediate examination, including vaginoscopy. Tumors of uterus in childhood do not occur and they are rare in postmenarcheal girls. Ovarian tumors represent about 1.5% of all tumors in childhood and adolescence and about 95% of all gynaecologic tumors. They differ in types from those of adults: Epithelial tumors (carcinomas) do not occur in childhood, germinal and gonadal stromal tumors are typical in this age. Mature differentiated teratomas are usually benign and the less differentiated they are, the worse biological effect they have (not mature or mixed teratomas). It seems that nowadays the proportion of immature and mixed teratomas has been rising. Dysgerminom occurs more frequently in Y-chromosome karyotypes. It has malignant progression with early propagation along lymph vessels into the lymph nodes. Beside ovarectomy, also lymphadenectomy at the affected side is performed and the treatment proceeds with chemotherapy. For the prognostic reasons, immunological examinations, DNA ploidity identification and other tests are recommended. Gonadal stromal tumors are always unilateral, malignant, and frequently hormonally active, but they usually have a good prognosis. In

  7. Infrared absorption spectra of human malignant tumor tissues

    NASA Astrophysics Data System (ADS)

    Skornyakov, I. V.; Tolstorozhev, G. B.; Butra, V. A.

    2008-05-01

    We used infrared spectroscopy methods to study the molecular structure of tissues from human organs removed during surgery. The IR spectra of the surgical material from breast, thyroid, and lung are compared with data from histological examination. We show that in malignant neoplasms, a change occurs in the hydrogen bonds of protein macromolecules found in the tissue of the studied organs. We identify the spectral signs of malignant pathology.

  8. Secondary malignant giant cell tumor of bone due to malignant transformation 40 years after surgery without radiation therapy, presenting as fever of unknown origin: a case report.

    PubMed

    Takesako, Hisataka; Osaka, Eiji; Yoshida, Yukihiro; Sugitani, Masahiko; Tokuhashi, Yasuaki

    2016-03-08

    Malignant transformation of giant cell tumors of bones, that is, secondary malignant giant cell tumor of bone, is rare. The most common symptoms are local pain and swelling. There are no prior reports of giant cell tumor of bone with fever of unknown origin at the onset. Here we present a case of a secondary malignant giant cell tumor of bone due to malignant transformation 40 years after surgery without radiation therapy, presenting as fever of unknown origin. A 75-year-old Asian man presented with a 3-week history of continuous pyrexia and left knee pain and swelling. He had been diagnosed at age 35 years with a giant cell tumor of bone of his left distal femur and underwent bone curettage and avascular fibula grafting at that time. Postoperative radiation therapy was not performed. He remained recurrence-free for 40 years after surgery. At age 75, histopathological findings suggested a secondary malignant giant cell tumor of bone. The tumor specimen expressed tumor necrosis factor-α. Neoplastic fever was suspected, and a naproxen test was conducted. His pyrexia showed immediate resolution. Surgery was performed under a diagnosis of a secondary malignant giant cell tumor of bone with neoplastic fever. His pyrexia and inflammatory activities diminished postoperatively. This is the first reported case, to the best of our knowledge, of the detection of a secondary malignant giant cell tumor of bone based on fever of unknown origin after long-term (40 years) follow-up. After curettage and bone grafting, giant cell tumor of bone may transform to malignancies within a few years or even decades after surgery. Therefore, meticulous follow-up is essential. The fever might be attributable to the tumor releasing inflammatory cytokines. Not only pain and swelling but also continuous pyrexia may suggest the diagnosis of a secondary malignant giant cell tumor of bone.

  9. Malignant Seminoma With Metastasis, Sertoli Cell Tumor, and Pheochromocytoma in a Spotted Dolphin (Stenella frontalis) and Malignant Seminoma With Metastasis in a Bottlenose Dolphin (Tursiops truncatus)

    DTIC Science & Technology

    2005-01-01

    2005 0pen Literature 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Malignant Seminoma with Metastasis, Sertoli Cell Tumor, and Pheochromocytoma In a...Spotted Dolphin (Stenella frontalis) and Malignant Seminoma with Metastasis in 5b. GRANT NUMBER a Bottlenose Dolphin (Tursiops truncatus) 5c. PROGRAM...reprint. 15. SUBJECT TERMS Atlantic bottlenose dolphin, cetacean, neoplasm, pheochromocytoma, seminoma , Sertoli cell tumor, spotted dolphin, Stenella

  10. Growth hormone-releasing hormone (GRH)-producing pancreatic tumor with no evidence of multiple endocrine neoplasia type 1.

    PubMed

    Kawa, S; Ueno, T; Iijima, A; Midorikawa, T; Fujimori, Y; Tokoo, M; Oguchi, H; Kiyosawa, K; Imai, Y; Kaneko, G; Kuroda, T; Hashizume, K; Osamura, R Y; Katakami, H

    1997-07-01

    The characteristic features of a 48-year-old male presenting with isolated acromegaly caused by a GRH-producing pancreatic endocrine tumor bearing no relation to MEN1 was reported. The clinical features, laboratory findings, and sellar enlargement were improved after removal of the pancreatic tumor. The resected pancreatic tumor showed positive GRH immunoreactivity and contained abundant GRH mRNA. This tumor is extremely rare and to date only 10 cases have been reported. In the management of acromegaly, the measurement of GRH is recommended and the search for an ectopic source will prevent unnecessary and potentially ineffective pituitary surgery.

  11. Tumor vessel destruction resulting from high-intensity focused ultrasound in patients with solid malignancies.

    PubMed

    Wu, Feng; Chen, Wen-Zhi; Bai, Jin; Zou, Jian-Zhong; Wang, Zhi-Long; Zhu, Hui; Wang, Zhi-Biao

    2002-04-01

    The purpose of this study was to explore the sequential imaging and histologic alterations of tumor blood vessels in the patient with solid malignancies after extracorporeal treatment of high-intensity focused ultrasound (HIFU). A total of 164 patients underwent extracorporeal HIFU ablation of malignant solid tumors. After HIFU treatment, enhanced magnetic resonance imaging (MRI), color Doppler ultrasound (US) imaging, dynamic radionuclide scanning, digital subtraction angiography, and histologic study were performed to monitor the response of tumor vessels to HIFU ablation. Compared with tumor images in the patients before HIFU, clinical images showed an abrupt interruption, followed by the cessation of blood flow within the tumor vessels after HIFU treatment. The histologic examination indicated that not only the treated tumor cells showed coagulative necrosis, but also small tumor vessels were severely damaged by the HIFU treatment. The results strongly imply that the damaged tumor vessels might play a critical role in secondary tumor cell death, and then indirectly strengthen the destructive force of focused US beams on tumor tissue. It is concluded that tumor vessel damage can be induced by HIFU, which may be a promising strategy in the treatment of patients with solid malignancies.

  12. A tumor vessel-targeting fusion protein elicits a chemotherapeutic bystander effect in pancreatic ductal adenocarcinoma

    PubMed Central

    Chen, Chun-Te; Chen, Yi-Chun; Du, Yi; Han, Zhenbo; Ying, Haoqiang; Bouchard, Richard R; Hsu, Jennifer L; Hsu, Jung-Mao; Mitcham, Trevor M; Chen, Mei-Kuang; Sun, Hui-Lung; Chang, Shih-Shin; Li, Donghui; Chang, Ping; DePinho, Ronald A; Hung, Mien-Chie

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease characterized by a prominent desmoplastic stroma that may constrain tumor progression but also limit the access of therapeutic drugs. In this study, we explored a tumor-targeting strategy that enlists an engineered anti-angiogenic protein consisting of endostatin and cytosine deaminase linked to uracil phosphoribosyltransferase (EndoCD). This protein selectively binds to tumor vessels to compromise tumor angiogenesis and converts the non-toxic 5-fluorocytosine (5-FC) to the cytotoxic 5-fluorouracil to produce a chemotherapeutic bystander effect at the pancreatic tumor site. We found that resveratrol increased the protein stability of EndoCD through suppression of chymotrypsin-like proteinase activity and synergistically enhances EndoCD-mediated 5-FC-induced cell killing. In various PDAC mouse models, the EndoCD/5-FC/resveratrol regimen decreased intratumoral vascular density and stroma formation and enhances apoptosis in tumors cells as well as in surrounding endothelial, pancreatic stellate, and immune cells, leading to reduced tumor growth and extended survival. Thus, the EndoCD/5-FC/resveratrol combination may be an effective treatment option for PDAC. PMID:28401019

  13. Tumor-like microenvironment in oral lichen planus: evidence of malignant transformation?

    PubMed

    Peng, Qiao; Zhang, Jing; Ye, Xiaojing; Zhou, Gang

    2017-06-01

    Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory autoimmune disease affecting 0.1% to 4% of the world population. The WHO has already recognized it as an oral potentially malignant disorder. However, the reasons for the malignant transformation of OLP are far from being elucidated clearly. The purpose of this review is to clarify how the tumor-like microenvironment in OLP mediates its potentially malignant transformation. Areas covered: We review published articles on the microenvironment characteristics of tumors, the pathogenesis of OLP, and clinical studies of OLP. The main sources of literature derive from MEDLINE/Pubmed and Thomson Reuter's Web of Science. Expert commentary: The tumor-like microenvironment, including hypoxic, inflammatory, immune and acid microenvironment, greatly contributes to carcinogenesis of OLP patients. In order to effectively monitor the malignant transformation of OLP, future studies should focus on long-term follow-up and select important detection biomarkers.

  14. The descriptive epidemiology of malignant cystosarcoma phyllodes tumors of the breast.

    PubMed

    Bernstein, L; Deapen, D; Ross, R K

    1993-05-15

    Malignant cystosarcoma phyllodes tumors of the breast are rare fibroepithelial tumors. The epidemiologic features of these malignancies in a defined population have not previously been described. Incidence data were collected from 1972-1989 by the Cancer Surveillance Program, the population-based cancer registry for Los Angeles County. The average annual age-adjusted incidence rate of malignant cystosarcoma phyllodes is 2.1 per 1 million women. Latina whites have a higher risk of this cancer than other racial-ethnic groups. The age-incidence curve shows that risk of cystosarcoma phyllodes peaks in the 45-49-year-old age group, but the age patterns vary by race-ethnicity, with Asian and Latina patients significantly younger, on average, than non-Latina white patients. The incidence rates of malignant cystosarcoma phyllodes were substantially higher in the 1980s than in the 1970s, particularly among Latina whites and Asians. For Latina whites, birthplace is a significant predictor of risk. Women born in Mexico and Central and South America are at threefold to fourfold greater risk of malignant cystosarcoma phyllodes tumors than Latina whites born in the United States. The epidemiology of malignant cystosarcoma phyllodes tumors of the breast is strikingly different from that of the more common histologic types of breast cancer. The high risk in Latina immigrants may offer an important clue as to the cause of this rare tumor.

  15. Agenesis of the dorsal pancreas and its association with pancreatic tumors.

    PubMed

    Sakpal, Sujit Vijay; Sexcius, Lucretia; Babel, Nitin; Chamberlain, Ronald Scott

    2009-05-01

    Morphogenesis of the pancreas is a complex process; nevertheless, congenital anomalies are rare. At embryogenesis, the pancreas develops from the endoderm-lined dorsal and ventral buds of the duodenum. The ventral bud gives rise to the lower head and uncinate process of the pancreas; whereas, the dorsal bud gives rise to the upper head, isthmus, body, and tail of the pancreas. Rarely, developmental failure of the dorsal pancreatic bud at embryogenesis results in the agenesis of the dorsal pancreas--neck, body, and tail. Even rarer is the association of pancreatic tumors with agenesis of the dorsal pancreas. In addition to citing our case, we provide a comprehensive review on agenesis of the dorsal pancreas and its association with pancreatic tumors.

  16. MRI-based tumor motion characterization and gating schemes for radiation therapy of pancreatic cancer.

    PubMed

    Heerkens, Hanne D; van Vulpen, Marco; van den Berg, Cornelis A T; Tijssen, Rob H N; Crijns, Sjoerd P M; Molenaar, Izaak Q; van Santvoort, Hjalmar C; Reerink, Onne; Meijer, Gert J

    2014-05-01

    To characterize pancreatic tumor motion and to develop a gating scheme for radiotherapy in pancreatic cancer. Two cine MRIs of 60s each were performed in fifteen pancreatic cancer patients, one in sagittal direction and one in coronal direction. A Minimum Output Sum of Squared Error (MOSSE) adaptive correlation filter was used to quantify tumor motion in craniocaudal, lateral and anteroposterior directions. To develop a gating scheme, stability of the breathing phases was examined and a gating window assessment was created, incorporating tumor motion, treatment time and motion margins. The largest tumor motion was found in craniocaudal direction, with an average peak-to-peak amplitude of 15mm (range 6-34mm). Amplitude of the tumor in the anteroposterior direction was on average 5mm (range 1-13mm). The least motion was seen in lateral direction (average 3mm, range 2-5mm). The end exhale position was the most stable position in the breathing cycle and tumors spent more time closer to the end exhale position than to the end inhale position. On average, a margin of 25% of the maximum craniocaudal breathing amplitude was needed to achieve full target coverage with a duty cycle of 50%. When reducing the duty cycle to 50%, a margin of 5mm was sufficient to cover the target in 11 out of 15 patients. Gated delivery for radiotherapy of pancreatic cancer is best performed around the end exhale position as this is the most stable position in the breathing cycle. Considerable margin reduction can be established at moderate duty cycles, yielding acceptable treatment efficiency. However, motion patterns and amplitude do substantially differ between individual patients. Therefore, individual treatment strategies should be considered for radiotherapy in pancreatic cancer. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Malignant perivascular epithelioid cell tumor of the kidney with rare pulmonary and ileum metastases

    PubMed Central

    Shi, Huijuan; Cao, Qinghua; Li, Hui; Zhen, Tiantian; Lai, Yingrong; Han, Anjia

    2014-01-01

    Aims: To report one case of malignant perivascular epithelioid cell tumor (PEComa) of the kidney with rare pulmonary and ileum metastases and analyze its clinicopathological features. Methods: We analyzed the clinicopathological features of one case of malignant PEComa of the kidney with pulmonary and ileum metastases. Immunohistochemistry staining was performed. Results: The patient was a 48-year-old man with a renal mass approximately 14 cm × 11 cm × 8 cm in size. Microscopically, the tumor was mainly composed of polygonal epithelioid cells with dense eosinophilic cytoplasm and round nuclei with small nucleoli. Focal tumor cells showed pleomorphism with multinucleated giant cells and prominent nucleoli. The tumor cells nests were surrounded by thick-walled irregular blood vessels. Focal fat cells were found within the tumor. Hemorrhage and coagulative necrosis were also present. The tumor cells were positive for vimentin, HMB45, and Melan-A, and focally positive for SMA and S-100 protein. After 5 years and 5.6 years of nephrectomy, the tumor metastasized to the right lung and ileum, respectively. Conclusion: We first reported one case of malignant PEComa of the kidney with pulmonary and ileum metastases. Metastatic PEComa of the lung and ileum should differentiate from primary carcinoma, metastatic carcinoma, malignant melanoma, and gastrointestinal stromal tumor. PMID:25337291

  18. Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors

    ClinicalTrials.gov

    2016-11-01

    High-grade Salivary Gland Mucoepidermoid Carcinoma; Low-grade Salivary Gland Mucoepidermoid Carcinoma; Recurrent Salivary Gland Cancer; Salivary Gland Acinic Cell Tumor; Salivary Gland Adenocarcinoma; Salivary Gland Adenoid Cystic Carcinoma; Salivary Gland Anaplastic Carcinoma; Salivary Gland Malignant Mixed Cell Type Tumor; Salivary Gland Poorly Differentiated Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IV Salivary Gland Cancer

  19. Overcoming the stromal barrier for targeted delivery of HPMA copolymers to pancreatic tumors.

    PubMed

    Buckway, Brandon; Wang, Yongjian; Ray, Abhijit; Ghandehari, Hamidreza

    2013-11-01

    Delivery of macromolecules to pancreatic cancer is inhibited by a dense extracellular matrix composed of hyaluronic acid, smooth muscle actin and collagen fibers. Hyaluronic acid causes a high intratumoral fluidic pressure which prevents diffusion and penetration into the pancreatic tumor. This study involves the breaking down of hyaluronic acid by treating CAPAN-1 xenograft tumors in athymic nu/nu mice with targeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers radiolabeled with (111)In for single photon emission computerized tomography (SPECT) imaging. Two targeting strategies were investigated including αvβ3 integrin and HER2 receptors. HPMA copolymers were targeted to these receptors by conjugating short peptide ligands cRGDfK and KCCYSL to the side chains of the copolymer. Results demonstrate that tumor targeting can be achieved in vivo after treatment with hyaluronidase. This approach shows promise for enhanced delivery of polymer-peptide conjugates to solid tumors.

  20. Role of tumor endothelium in CD4+ CD25+ regulatory T cell infiltration of human pancreatic carcinoma.

    PubMed

    Nummer, Daniel; Suri-Payer, Elisabeth; Schmitz-Winnenthal, Hubertus; Bonertz, Andreas; Galindo, Luis; Antolovich, Dalibor; Koch, Moritz; Büchler, Markus; Weitz, Jürgen; Schirrmacher, Volker; Beckhove, Philipp

    2007-08-01

    Regulatory T (Treg) cells have been detected in human carcinomas and may play a role in preventing the rejection of malignant cells. We quantified Treg cells and the expression of the addressins and the respective ligands that attract them in blood and in human pancreatic tumors and adjacent nonmalignant tissues from 47 patients. The capacity of Treg cells to adhere to and transmigrate through autologous endothelial cells was tested in vitro using spheroid adhesion assays and in vivo using a xenotransplant NOD/SCID model and in the presence and absence of antibodies to addressins. All statistical tests were two-sided. More Treg cells infiltrated pancreatic carcinomas than adjacent nonmalignant pancreatic tissues (120 cells per mm2 versus 80 cells per mm2, difference = 40 cells per mm2, 95% confidence interval [CI] = 21.2 cells per mm2 to 52.1 cells per mm2; P<.001). In contrast to conventional CD4+ T cells, more blood-derived Treg cells adhered to (1.0% versus 5.2%, difference = 4.2%, 95% CI = 2.7% to 5.6%; P<.001) and transmigrated through (3332 cells versus 4976 cells, difference = 1644 cells, 95% CI = 708 cells to 2580 cells; P = .008) autologous tumor-derived endothelial cells in vitro and in vivo (458 cells versus 605 cells, difference = 147 cells, 95% CI = 50.8 to 237.2 cells; P = .04). Tumor-derived endothelial cells expressed higher levels of addressins--including mucosal adressin cell adhesion molecule-1 (MAdCAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD62-E, and CD166--than endothelial cells from normal tissue. Experiments using antibodies to addressins showed that transmigration was mediated by interactions of addressins, including MAdCAM-1, VCAM-1, CD62-E, and CD166 with their respective ligands, beta7 integrin, CD62L, and CD166, which were expressed specifically on Treg cells. Tumor-induced expression of addressins on the surface of endothelial cells allows a selective transmigration of Treg cells from peripheral blood to tumor tissues.

  1. Recurrent malignant juxtaglomerular cell tumor: A rare cause of malignant hypertension in a child

    PubMed Central

    Shera, Altaf H.; Baba, Aejaz A.; Bakshi, Iftikhar H.; Lone, Iqbal A.

    2011-01-01

    A juxtaglomerular cell tumor or reninoma is a very rare renin-secreting tumor of the kidney and can be an unusual cause of secondary hypertension. We report a case of recurrence of this uncommon tumor at the hilum of left kidney in an 8-year-old male child. PMID:22121315

  2. Pharmacokinetically Guided Everolimus in Patients With Breast Cancer, Pancreatic Neuroendocrine Tumors, or Kidney Cancer

    ClinicalTrials.gov

    2016-12-09

    Estrogen Receptor-positive Breast Cancer; Gastrinoma; Glucagonoma; HER2-negative Breast Cancer; Insulinoma; Mucositis; Oral Complications; Pancreatic Polypeptide Tumor; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Islet Cell Carcinoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Renal Cell Cancer

  3. Modulating malignant epithelial tumor cell adhesion, migration and mechanics with nanorod surfaces.

    PubMed

    Lee, Jiyeon; Chu, Byung Hwan; Sen, Shamik; Gupte, Anand; Chancellor, T J; Chang, Chih-Yang; Ren, Fan; Kumar, Sanjay; Lele, Tanmay P

    2011-02-01

    The failure of tumor stents used for palliative therapy is due in part to the adhesion of tumor cells to the stent surface. It is therefore desirable to develop approaches to weaken the adhesion of malignant tumor cells to surfaces. We have previously developed SiO₂ coated nanorods that resist the adhesion of normal endothelial cells and fibroblasts. The adhesion mechanisms in malignant tumor cells are significantly altered from normal cells; therefore, it is unclear if nanorods can similarly resist tumor cell adhesion. In this study, we show that the morphology of tumor epithelial cells cultured on nanorods is rounded compared to flat surfaces and associated with decreased cellular stiffness and non-muscle myosin II phosphorylation. Tumor cell viability and proliferation was unchanged on nanorods. Adherent cell numbers were significantly decreased while single tumor cell motility was increased on nanorods compared to flat surfaces. Together, these results suggest that nanorods can be used to weaken malignant tumor cell adhesion, and therefore potentially improve tumor stent performance.

  4. Primary pulmonary glomus tumor of uncertain malignant potential: A case report with literature review focusing on current concepts of malignancy grade estimation.

    PubMed

    Oide, Takashi; Yasufuku, Kazuhiro; Shibuya, Kiyoshi; Yoshino, Ichiro; Nakatani, Yukio; Hiroshima, Kenzo

    2016-01-01

    We report a 38-year-old woman with a left lung tumor presenting as obstructive pneumonia. Bronchoscopic examination revealed a polypoid tumor filling the left main bronchus. The tumor was partially resected by a snaring procedure for diagnostic purposes. Microscopic examination revealed a submucosal tumor located underneath normal bronchial epithelium. The tumor was composed of sheets of uniform oval to cuboidal cells encompassing numerous blood vessels. Immunohistochemically, the tumor cells exhibited smooth muscle markers, but were negative for neuroendocrine markers. The diagnosis of primary pulmonary glomus tumor was therefore made. Subsequent bronchoscopic intervention allowed us to pin-point the origin of the tumor: superior segmental B(6a/b). She underwent a left lower lobe superior segmental resection successfully. Glomus tumors are relatively rare soft tissue tumors, and those of bronchopulmonary origin are exceedingly rare clinical condition. Among primary lung tumors, the carcinoid tumor is a mimic of the glomus tumor, and differentiating these tumors is known to be difficult, especially using small biopsy samples. In the present case, a large tissue sample obtained by bronchoscopic snaring was quite useful for the correct preoperative diagnosis. Because of the disease rarity, malignancy grade estimation of visceral glomus tumors has not been clearly addressed. Recently, the histopathological diagnostic criteria for malignant glomus tumors was defined in the WHO classification of soft tissue and bone tumors 4th edition. Here we also reviewed the literature on primary bronchopulmonary glomus tumors with special attention to the current concept of malignancy grade estimation.

  5. Malignant Triton tumor: a rare cause of sciatic pain and foot drop.

    PubMed

    Gomes, Maribel R; Sousa, Alexandre M P; Couto, Roberto J A; Oliveira, Marco M B; Moura, João L M; Vilela, Carlos A

    2017-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are very rare and are frequently localized in the buttocks, thigh, arm, or paraspinal region; one variant is the malignant Triton tumor, with rhabdomyosarcomatous differentiation. The authors present a challenging differential diagnosis of a sciatic pain and foot drop in a woman with history of lumbar disk herniation, which was found to be caused by a Triton tumor of the sciatic nerve. She underwent surgical excision, followed by radiation and chemotherapy. Malignant Triton tumor cases have rarely been described and reported in the literature. The recommended treatment is radical excision followed by high-dose radiotherapy and chemotherapy. The prognosis, although poor, depends on the location, grade, and completeness of surgical margins.

  6. Removal of a malignant cystic brain tumor utilizing pyoktanin blue and fibrin glue: Technical note

    PubMed Central

    Hayashi, Nobuhide; Sasaki, Takahiro; Tomura, Nagatsuki; Okada, Hideo; Kuwata, Toshikazu

    2017-01-01

    Background: The leakage of cystic fluid during metastatic cystic brain tumor resection may cause tumor dissemination. When the cyst wall is thin, excision without removing the wall is often difficult. Methods: We were able to perform an en bloc resection of a cystic malignant brain tumor after aspirating the cystic fluid, injecting pyoktanin blue into the cyst to stain the cyst walls, and solidifying the empty cyst cavity by filling it with fibrin glue. Results: Pyoktanin blue readily stained the thin cystic walls and enabled visualization of mural damage. Solidification of the tumor made it easier to grasp and facilitated the dissection of tumor margins. Conclusions: This method has the potential to become a useful technique for the resection of malignant cystic brain tumors. PMID:28303204

  7. Comparison of clinical characteristics between benign borderline and malignant phyllodes tumors of the breast.

    PubMed

    Wang, Hui; Wang, Xiang; Wang, Cheng-Feng

    2014-01-01

    Phyllodes tumors of the breast are rare fibroepithelial lesions, so relatively little is known about this disease entity. The present study was designed to identify differences in clinical features between benign borderline and malignant phyllodes tumors. Data from 246 women with phyllodes tumors of the breast treated in Cancer Hospital Chinese Academy of Medical Sciences between 2002 and 2012 were collected and analyzed, including age at presentation, age at treatment, course, size of primary tumor, location, histological type, type of surgery and treatment, local recurrence, distant metastasis, fibroadenoma history, disease-free survival and number of mitosis per 10hpf. There are 125 (55%) benign, 55 (24%) borderline and 47 (21%) malignant tumors. In univariate analysis, average age at presentation, average age at treatment, size of primary tumor, ulceration or not, type of primary surgery, distant metastasis and number of mitosis per 10 hpf turned out to be statistically different among the three PT types (p=0.014, 0.018, <0.000, 0.003, <0.000, 0.001 and <0.000, respectively), while recurrence and disease-free survival (DFS) demonstrated trends for statistical significance (P =0.055 and 0.060, respectively). Multivariate analysis revealed distant metastasis and excision were significantly different in benign, borderline and malignant phyllodes tumors of the breast (p=0.041 and 0.018, OR=0.061 and 0.051). At the same time, size of primary tumor with p=0.052 tended to be different between groups (OR=1.127). However, age at treatment, ulceration and DFS showed no statistically significant variation (p=0.400, 0.286 and 0.413, respectively). Benign borderline and malignant phyllode tumors have different distant metastasis risk, different primary tumor size and different surgical procedures, and malignant PTs are more likely to be bigger and to metastasize.

  8. Circulating Tumor Cells in the Diagnosis and Management of Pancreatic Cancer

    PubMed Central

    Cen, Putao; Ni, Xiaoling; Yang, Jingxuan; Graham, David Y.; Li, Min

    2012-01-01

    Pancreatic cancers are typically resistant to chemo and radiation therapy and are predisposed to distant metastases. Circulating tumor cells (CTCs) are tumor cells disseminated from primary and metastatic sites and can be isolated from peripheral blood. CTC may overcome the limitation of the current available tumor markers, CA19-9. As a surrogate for ‘real-time biopsy’, CTCs allow recurrent assessment of a tumor’s biological activity. We review the current methodologies for CTCs extraction and characterization including antibody-based immunological assays, PCR-based assays, and novel technologies based on the physical or biological characteristics of CTCs. CTCs also provide an accessible link to the existence of epithelial to mesenchymal transition, tumor stem cell markers, and ongoing clonal mutations and epigenetic changes in the tumor. We also explore the potential of using CTC profiling in diagnosis, selection of neoadjuvant and adjuvant therapy, detection of recurrent disease, examination of pharmacodynamic biomarkers, as well as in gene therapy and immunotherapy for pancreatic cancer. Ongoing CTC characterization not only has the potential to represent all cells shed from primary pancreatic tumor and each metastatic site, but also allows dynamic sampling at multiple time points during the clinical course to identify the subpopulations of CTCs and the specific molecules driving metastasis and chemo resistance. We predict that CTC genotyping and phenotyping will play an increasing role in personalized therapy and in identification of novel therapeutic targets as well as monitoring the course and status of the disease. PMID:22683404

  9. Pancreatic Tumor Growth Prediction with Multiplicative Growth and Image-Derived Motion.

    PubMed

    Wong, Ken C L; Summers, Ronald M; Kebebew, Electron; Yao, Jianhua

    2015-01-01

    Pancreatic neuroendocrine tumors are abnormal growths of hormone-producing cells in the pancreas. Different from the brain in the skull, the pancreas in the abdomen can be largely deformed by the body posture and the surrounding organs. In consequence, both tumor growth and pancreatic motion attribute to the tumor shape difference observable from images. As images at different time points are used to personalize the tumor growth model, the prediction accuracy may be reduced if such motion is ignored. Therefore, we incorporate the image-derived pancreatic motion to tumor growth personalization. For realistic mechanical interactions, the multiplicative growth decomposition is used with a hyperelastic constitutive law to model tumor mass effect, which allows growth modeling without compromising the mechanical accuracy. With also the FDG-PET and contrast-enhanced CT images, the functional, structural, and motion data are combined for a more patient-specific model. Experiments on synthetic and clinical data show the importance of image-derived motion on estimating physiologically plausible mechanical properties and the promising performance of our framework. From six patient data sets, the recall, precision, Dice coefficient, relative volume difference, and average surface distance were 89.8 ± 3.5%, 85.6 ± 7.5%, 87.4 ± 3.6%, 9.7 ± 7.2%, and 0.6 ± 0.2 mm, respectively.

  10. Serum Carbohydrate Antigen 19-9 in Differential Diagnosis of Benign and Malignant Pancreatic Cystic Neoplasms: A Meta-Analysis

    PubMed Central

    Cao, Shaobo; Hu, Ya; Gao, Xiang; Liao, Quan; Zhao, Yupei

    2016-01-01

    Background Using serum carbohydrate antigen 19–9 (CA 19–9) in discriminating between benign and malignant pancreatic disease remains controversial. We aim to evaluate the diagnostic value of serum CA 19–9 in predicting malignant pancreatic cystic lesions. Methods Eligible studies were identified through searching MEDLINE and EMBASE prior to March 2016. Studies were assessed for quality using the Quality Assessment for Studies of Diagnostic Accuracy, 2nd version (QUADAS-2). Pooled sensitivity and specificity with 95% confidence interval (CI) were calculated using random-effects models. Summary receiver operator characteristic (SROC) curves and the area under curve (AUC) were performed. Results A total of thirteen studies including 1437 patients were enrolled in this meta-analysis. The pooled sensitivity and specificity were 0.47(95% CI: 0.35–0.59), and 0.88(95% CI: 0.86–0.91), respectively, and the AUC was 0.87(95% CI, 0.84–0.90). Meta-regression analysis showed that sample size, region and reference standards were not the main sources of heterogeneity. Conclusions Serum CA 19–9 has satisfying pooled specificity while poor pooled sensitivity for discriminating benign from malignant PCNs. It deserves to be widely used as complementary to other clinical diagnostic methods. PMID:27835676

  11. Malignant nerve-sheath neoplasms in neurofibromatosis: distinction from benign tumors by using imaging techniques

    SciTech Connect

    Levine, E.; Huntrakoon, M.; Wetzel, L.H.

    1987-11-01

    Malignant peripheral nerve-sheath neoplasms frequently complicate neurofibromatosis causing pain, enlarging masses, or neurologic deficits. However, similar findings sometimes also occur with benign nerve neoplasms. Our study was done retrospectively to determine if imaging techniques can differentiate malignant from benign nerve tumors in neurofibromatosis. Eight patients with symptomatic neoplasms (three benign, five malignant) were studied by CT in eight, MR in six, and /sup 67/Ga-citrate scintigraphy in seven. Uptake of /sup 67/Ga occurred in all five malignant lesions but not in two benign neoplasms studied. On CT or MR, all eight lesions, including three benign neoplasms, showed inhomogeneities. Of five lesions with irregular, infiltrative margins on CT or MR, four were malignant and one was benign. Of three lesions with smooth margins, one was malignant and two were benign. One malignant neoplasm caused irregular bone destruction. Accordingly, CT and MR could not generally distinguish malignant from benign lesions with certainty. However, both CT and MR provided structural delineation to help surgical planning for both types of lesion. /sup 67/Ga scintigraphy appears promising as a screening technique to identify lesions with malignant degeneration in patients with neurofibromatosis. Any area of abnormal radiogallium uptake suggests malignancy warranting further evaluation by CT or MR. Biopsy of any questionable lesion is essential.

  12. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2017-01-17

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

  13. Male Malignant Phyllodes Breast Tumor After Prophylactic Breast Radiotherapy and Bicalutamide Treatment: A Case Report.

    PubMed

    Karihtala, Peeter; Rissanen, Tarja; Tuominen, Hannu

    2016-07-01

    Phyllodes tumor in male breast is an exceptionally rare neoplasm with only few published case reports. Herein, we present a case of malignant phyllodes tumor in male breast nine years after prophylactic breast 10 Gy radiotherapy and after nine year bicalutamide treatment. The imaging findings of the tumor and pathological correlation are also presented. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.