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1

Salvage pancreaticoduodenectomy after complete response to chemoradiotherapy for a previously unresectable pancreatic adenosquamous carcinoma: a case report.  

PubMed

Pancreatic cancer is known for its typically late presentation and poor survival rates, with overall 5-year survival of less than 5%. The role of chemotherapy alone or with radiotherapy in the management of locally advanced tumors continues to be an area of debate.We report a case of locally advanced, pancreatic adenosquamous carcinoma that was initially deemed unresectable intraoperatively. Nonetheless, the tumor was resected after radiological response to gemcitabine-capecitabine chemoradiotherapy regimen similar to the Selective Chemoradiation in Advanced LOcalised Pancreatic cancer trial. Histological examination revealed complete pathological response with extensive fibrosis (ypT0 N0). On 12-month follow-up CT, a single liver lesion in the left lateral segment was identified and confirmed to be a metastasis with cytological diagnosis via EUS and FNA. The disease remained stable and confined to the solitary hepatic metastasis after further gemcitabine chemotherapy. Therefore, a further successful resection was performed.The 2 main strategies for the management of locally advanced unresectable pancreatic cancer are chemotherapy induction followed by consolidation chemoradiotherapy or chemotherapy alone, with conflicting published evidence. Evidence for the optimal management of the rare histological type of adenosquamous carcinoma is scant. We present a case of such tumor with a complete pathological response to chemoradiotherapy. The results of future studies in the area are eagerly awaited. PMID:25674740

Elias, Anne; Chatzizacharias, Nikolaos A; Xanthis, Athanasios; Corrie, Pippa; Davies, Susan; Brais, Rebecca J; Jamieson, Neville V; Praseedom, Raaj K; Huguet, Emmanuel; Harper, Simon J F; Jah, Asif

2015-02-01

2

A huge adenosquamous carcinoma of the pancreas with sarcomatoid change: An unusual case report  

PubMed Central

Adenosquamous carcinoma rarely occurs in the pancreas, and is characterized by the presence of cellular components from both duct adenocarcinoma and squamous carcinoma. Here, we describe a rare case of pancreatic adenosquamous carcinoma with sarcomatous change. Immunohistochemistry showed that the sarcomatous lesion lost the epithelial marker and aberrantly expressed of acquired mesenchymal markers, which indicated that this special histological phenotype may be attributed to epithelial-mesenchymal transition. This case also indicated that a routine radical surgery without aggressive treatment strategies was still appropriate for adenosquamous carcinoma of the pancreas with sarcomatoid change. PMID:25473201

Lu, Bao-Chun; Wang, Chen; Yu, Jian-Hua; Shen, Zhi-Hong; Yang, Jian-Hui

2014-01-01

3

Characteristics and Outcomes of Adenosquamous Carcinoma of the Pancreas  

PubMed Central

ABSTRACT BACKGROUND: Adenosquamous carcinoma of the pancreas (ASCAP) is a rare histologic type of pancreatic carcinoma that constitutes 1% to 4% of all pancreatic exocrine malignancies. It has a clinical presentation similar to that of adenocarcinoma of the pancreas (ACP), but may have a worse overall prognosis, with most patients surviving for less than 2 years. METHODS: This was an institutional, retrospective, cohort analysis of 237 patients who underwent resection of pancreatic cancer with curative intent. RESULTS: Of the 237 cases examined, we identified 7 (2.9%) with histologically confirmed ASCAP. Demographics, comorbidities, risk factors, presenting symptoms, survival data, tumor characteristics, and types of treatment for each patient were included in the analysis. Risk factors for development of ASCAP were not conclusive. Although human papilloma virus (HPV) has been implicated in other squamous cell cancers, in our cohort, its involvement in ASCAP was 0%. Presurgical fine-needle aspiration failed to identify the invasive squamous cell component in all cases. In this cohort analysis, overall survival ranged from 3 to 25 months, with 2 patients surviving more than 20 months after surgical resection. With a median follow-up of 2.9 years, our data demonstrate a trend to worse median overall survival for ASCAP than for ACP (8.2 vs. 20.4 months; P = .23), with a limited number of long-term survivors. CONCLUSIONS: Although recommended, adjuvant treatment was inconsistently provided for patients in this ASCAP cohort. Published data show variability in overall survival, but our findings support that surgical resection is one of the few options for control of this rare, poorly understood pancreatic malignancy. Further research is necessary to define risk factors and adjuvant and neoadjuvant treatments, to help improve patient outcomes. PMID:23936547

Simone, Christine G.; Zuluaga Toro, Tania; Chan, Ellie; Feely, Michael M.; Trevino, Jose G.

2013-01-01

4

Primary adenosquamous carcinoma of ampulla of Vater—A rare case report  

PubMed Central

INTRODUCTION Primary adenosquamous carcinoma (ASC) of the ampulla of Vater (AmV) is extremely rare. Carcinoma of the ampulla of Vater tends to manifest early due to biliary outflow obstruction, as opposed to pancreatic neoplasms that often are advanced at the time of diagnosis. Periampullary carcinomas are treated by pancreaticoduodenectomy (PD). Adenosquamous carcinoma carries very dismal prognosis. PRESENTATION OF CASE Here we present a case of 58-year-old male who was presented with abdominal pain, jaundice and anorexia with no history of (h/o) pruritus and clay colored stool. All blood investigations were normal except liver function tests (LFTs). Ultrasonography (USG) of abdomen suggestive of periampullary mass with dilated pancreatico-biliary tree. Endoscopic retrograde cholangiopancreatography (E.R.C.P.) demonstrated large deformed and bulky papilla with ulcerated lesion with infiltration in to duodenum. Exploratory laprotomy proceeds Whipple's pancreaticoduodenectomy done. Histopathology revealed adenocarcinoma of the ampulla of Vater. Immunohistochemistry was confirmatory of adenosquamous carcinoma. DISCUSSION Adenosquamous carcinoma (ASC) is defined as a tumor in which both glandular and squamous elements are histologically malignant. Compared to adenocarcinoma, ASC of the AmV is a rare malignancy. Preoperative diagnosis is difficult because of the lack of defining characteristics in imaging studies and the difficulty in acquiring both malignant components by limited biopsy. Periampullary carcinomas are treated by pancreaticoduodenectomy. CONCLUSION Adenosquamous carcinoma is a very rare form of cancer of the AmV. Pancreaticoduodenectomy is the treatment of choice though early recurrence and distal metastasis may be encountered after surgery. Follow-up should be more frequent to detect possible early recurrence and distal metastasis. PMID:24879329

Kshirsagar, Ashok Y.; Nangare, Nitin R.; Vekariya, Mayank A.; Gupta, Vaibhav; Pednekar, Akshay S.; Wader, J.V.; Mahna, Abhishek

2014-01-01

5

Primary urinary bladder adenosquamous carcinoma complicated with lower limb deep venous thromboses: a case report  

PubMed Central

Primary urinary bladder adenosquamous carcinoma is extremely rare and only a few cases have been reported in English literatures. Its biological behavior remains unclear. Here we reported a 60-year-old male patient with lower limb deep venous thromboses associated with primary urinary bladder adenosquamous carcinoma. A color ultrasonography showed right stock total venous thrombosis and right great saphenous vein thrombosis of lower limb. Contrast-enhanced computed tomography (CT) scan confirmed a 3.17 × 3.33 × 3.84 cm enhancing mass within the urinary bladder along the right lateral and posterior wall. Histopathological examination revealed adenosquamous carcinoma of urinary bladder, with extensive infiltration of the muscle layer. To the best of our knowledge, this is the first report of primary urinary bladder adenosquamous carcinoma complicated with deep venous thromboses in lower limb.

Zhang, Xiu-Ling; Wei, Kang-Lai; Dang, Yi-Wu; Xie, You; Zhong, Teng-Fei; Ma, Yun; Chen, Gang

2014-01-01

6

Adenosquamous proliferation of the breast and low grade adenosquamous carcinoma: a common precursor of an uncommon cancer?  

PubMed

Low grade adenosquamous carcinoma (LGASC) is rare but commonly reported to arise in association with benign proliferative and sclerosing breast lesions which themselves may show associated sclerosing or 'adenosquamous proliferation' (ASP) resembling LGASC, but are often derided as reactive mimics or attributed to earlier biopsy. Among other benign lesions, radial sclerosing lesion (RSL) may be associated with LGASC, yet attention is typically focused on its relationship to more common forms of mammary carcinoma. This study aimed to assess the presence and extent of ASP in the context of RSL in a small cohort of 20 cases and its similarity to LGASC.Twenty consecutive breast excisions that had a principal or incidental diagnosis of RSL were reviewed. RSLs that displayed foci of ASP were further examined with immunohistochemical markers for p63, calponin, cytokeratin 5/6, oestrogen and progesterone receptors.Sixty percent of excisions contained ASP either associated with a RSL or a concurrent papilloma, which morphologically and immunohistochemically were indistinguishable from the neoplastic ducts of LGASC. RSL with and without ASP broadly corresponded to accepted definitions for 'early' and 'late' lesions, respectively. ASP corresponded to the characteristic compact branching ducts of the core or nidus of a RSL.The morphological and immunophenotypic similarity of the ASP found in RSL and papillomata to LGASC warrants serious consideration that they are a potential precursor to LGASC, which may most commonly involute given the rarity of clinically apparent LGASC. Further study including micro-dissection of foci of ASP to compare its molecular genetic profile to that of LGASC is required. PMID:24842378

Wilsher, Mark James

2014-08-01

7

Mixed adenocarcinoma, sarcomatoid carcinoma and adenosquamous carcinoma of the prostate: A case report  

PubMed Central

Adenosquamous carcinoma (ASC) and sarcomatoid carcinoma (SC) of the prostate are rare, but highly aggressive tumors. The occurrence of mixed carcinomas in the prostate is even more rarely reported. The present study reports the case of a 62-year-old male who was diagnosed with prostatic adenocarcinoma accompanied by multiple bone metastases, as shown by a needle biopsy and skeletal computed tomography scan. The patient was treated with hormonal therapy, but thereafter, specimens from a transurethral resection of the prostate (TURP) were found to be composed of three histologically distinct elements: ASC, SC and adenocarcinoma. The level of p53 was evaluated by immunohistochemistry in detail, and it was found that this was significantly increased in the TURP samples compared with the needle biopsy samples. The abnormal level of p53 was likely associated with the prognosis of the patient; the patient succumbed to prostate carcinoma two months after the confirmation of the diagnosis. PMID:25295118

ZHANG, ZHONGFU; WANG, YADONG; ZHAO, QING; LI, GANHONG; ZHAO, XINGQI; LI, JUN; LI, XIANXIN

2014-01-01

8

Fever as a first manifestation of advanced gastric adenosquamous carcinoma: A case report  

PubMed Central

Gastric adenosquamous carcinoma (ASC) is a rare type of gastric cancer. It is a mixed neoplasm, consisting of glandular cells and squamous cells. It is often diagnosed at an advanced stage, thus carrying a poor prognosis. We describe a case of a 73-year-old male, who presented with refractory fever and an intra-abdominal mass on imaging. He underwent a laparoscopic exploration followed by a successful totally laparoscopic total gastrectomy with D2 lymphadenectomy for gastric cancer. Postoperative pathology revealed primary gastric ASC (T4aN0M0). The patient received adjuvant radiotherapy and chemotherapy with S1 and is alive 20 mo after surgery without recurrence. This is the first case of advanced gastric ASC with fever as the initial presentation treated with totally laparoscopic total gastrectomy reported in the English literature. PMID:25110448

Ajoodhea, Harsha; Zhang, Ren-Chao; Xu, Xiao-Wu; Jin, Wei-Wei; Chen, Ke; He, Yong-Tao; Mou, Yi-Ping

2014-01-01

9

International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas.  

PubMed

Time trends in the incidence of cervical adenocarcinoma and adenosquamous cell carcinomas during the period 1973-1991 were examined using data provided by 60 population-based cancer registries from 32 defined populations in 25 countries. Three components of the incidence trend were studied: age, calendar period of diagnosis and birth cohort. Cumulative incidence rates per 1,000 for 2 groups with age ranges 25-49 and 50-74 years were calculated from the model that best described the incidence data. There was a significant increase in the cumulative incidence of cervical adenocarcinomas in women born in the mid-1930s and in successive cohorts thereafter in some populations in the United States (whites and Hispanic women), Australia, New Zealand (non-Maori), England, Scotland, Denmark, Slovenia, Slovakia and Japan (Osaka) and among Chinese women in Singapore, with a general decline in the incidence in women born in earlier periods. In Sweden and Slovenia there is a suggestion of an increasing trend in both age groups. A decrease in incidence in both age groups was apparent in Finland, France and Italy. There were no changes in incidence in 24 registries covering other European, Asian and black populations in the United States. Part of the increase may be attributable to an increasing prevalence of human papillomavirus infection, and part to improvements in screening. PMID:9466653

Vizcaino, A P; Moreno, V; Bosch, F X; Muñoz, N; Barros-Dios, X M; Parkin, D M

1998-02-01

10

Clinical Behaviors and Outcomes for Adenocarcinoma or Adenosquamous Carcinoma of Cervix Treated by Radical Hysterectomy and Adjuvant Radiotherapy or Chemoradiotherapy  

SciTech Connect

Purpose: To compare clinical behaviors and treatment outcomes between patients with squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix treated with radical hysterectomy (RH) and adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods and Materials: A total of 318 Stage IB-IIB cervical cancer patients, 202 (63.5%) with SCC and 116 (36.5%) with AC/ASC, treated by RH and adjuvant RT/CCRT, were included. The indications for RT/CCRT were deep stromal invasion, positive resection margin, parametrial invasion, or lymph node (LN) metastasis. Postoperative CCRT was administered in 65 SCC patients (32%) and 80 AC/ASC patients (69%). Patients with presence of parametrial invasion or LN metastasis were stratified into a high-risk group, and the rest into an intermediate-risk group. The patterns of failure and factors influencing survival were evaluated. Results: The treatment failed in 39 SCC patients (19.3%) and 39 AC/ASC patients (33.6%). The 5-year relapse-free survival rates for SCC and AC/ASC patients were 83.4% and 66.5%, respectively (p = 0.000). Distant metastasis was the major failure pattern in both groups. After multivariate analysis, prognostic factors for local recurrence included younger age, parametrial invasion, AC/ASC histology, and positive resection margin; for distant recurrence they included parametrial invasion, LN metastasis, and AC/ASC histology. Compared with SCC patients, those with AC/ASC had higher local relapse rates for the intermediate-risk group but a higher distant metastasis rate for the high-risk group. Postoperative CCRT tended to improve survival for intermediate-risk but not for high-risk AC/ASC patients. Conclusions: Adenocarcinoma/adenosquamous carcinoma is an independent prognostic factor for cervical cancer patients treated by RH and postoperative RT. Concurrent chemoradiotherapy could improve survival for intermediate-risk, but not necessarily high-risk, AC/ASC patients.

Huang, Yi-Ting; Wang, Chun-Chieh; Tsai, Chien-Sheng [Department of Radiation Oncology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China) [Department of Radiation Oncology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan (China); Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China)] [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China); Lee, Steve P. [Department of Radiation Oncology, University of California, Los Angeles School of Medicine, Los Angeles, CA (United States)] [Department of Radiation Oncology, University of California, Los Angeles School of Medicine, Los Angeles, CA (United States); Hong, Ji-Hong, E-mail: jihong@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China) [Department of Radiation Oncology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan (China)

2012-10-01

11

UCSD scientists find gene mutation for aggressive form of pancreatic cancer  

Cancer.gov

Researchers at the University of California, San Diego School of Medicine have identified a mutated gene common to adenosquamous carcinoma tumors – the first known unique molecular signature for this rare, but particularly virulent, form of pancreatic cancer.

12

Long-Term Outcome and Prognostic Factors for Adenocarcinoma/Adenosquamous Carcinoma of Cervix After Definitive Radiotherapy  

SciTech Connect

Purpose: To study the outcomes of patients with adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix primarily treated with radiotherapy (RT), identify the prognostic factors, and evaluate the efficacy of concurrent chemoradiotherapy (CCRT) or salvage surgery. Methods and Materials: A total of 148 patients with Stage I-IVA AC/ASC of cervix after full-course definitive RT were included. Of the 148 patients, 77% had advanced stage disease. Treatment failure was categorized as either distant or local failure. Local failure was further separated into persistent tumor or local relapse after complete remission. The effectiveness of CCRT with cisplatin and/or paclitaxel was examined, and the surgical salvage rate for local failure was reviewed. Results: The 5-year relapse-free survival rate was 68%, 38%, 49%, 30%, and 0% for those with Stage IB/IIA nonbulky, IB/IIA bulky, IIB, III, and IVA disease, respectively, and appeared inferior to that of those with squamous cell carcinoma of the cervix treated using the same RT protocol. Incomplete tumor regression after RT, a low hemoglobin level, and positive lymph node metastasis were independent poor prognostic factors for relapse-free survival. CCRT with weekly cisplatinum did not improve the outcome for our AC/ASC patients. Salvage surgery rescued 30% of patients with persistent disease. Conclusion: Patients with AC/ASC of the cervix primarily treated with RT had inferior outcomes compared to those with squamous cell carcinoma. Incomplete tumor regression after RT was the most important prognostic factor for local failure. Salvage surgery for patients with persistent tumor should be encouraged for selected patients. Our results did not demonstrate a benefit of CCRT with cisplatin for this disease.

Huang, Yi-Ting; Wang, Chun-Chieh; Tsai, Chien-Sheng [Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan (China); Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Hsueh, Swei [Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Chen, Chien-Kuang [Department of Emergency, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Lee, Steve P. [Department of Radiation Oncology, University of California, Los Angeles, School of Medicine, Los, Angeles, CA (United States); Hong, Ji-Hong, E-mail: jihong@adm.cgmh.org.t [Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan (China)

2011-06-01

13

Papillocystic Variant of Acinar Cell Pancreatic Carcinoma  

PubMed Central

Acinar cell pancreatic carcinoma is a rare solid malignant neoplasm. Recent review of the literature showed occasional cases with papillary or papillocystic growth patterns, ranging from 2 to 5?cm in diameter. We report a large 10?cm pancreatic tumor with papillocystic pathology features involving the pancreatic head. The growth pattern of these tumors could be mistaken for intraductal papillary mucinous tumors or other pancreatic cystic neoplasms. PMID:20204128

Radhi, Jasim; Tse, France; Marcaccio, Michael

2010-01-01

14

Inflammatory pancreatic masses: problems in differentiating focal pancreatitis from carcinoma  

SciTech Connect

The authors studied 19 patients with focal inflammatory masses of the pancreas over an 18-month period. In 13 cases, transhepatic cholangiography and/or endoscopic retrograde cholangiopancreatography were unsuccessful in differentiating pancreatitis from carcinoma. Eighteen patients had a history of alcohol abuse, and 12 had had pancreatitis previously. Pre-existing glandular injury appears to be a prerequisite to formation of focal inflammatory pancreatic masses.

Neff, C.C.; Simeone, J.F.; Wittenberg, J.; Mueller, P.R.; Ferrucci, J.T. Jr.

1984-01-01

15

The ? 6-integrin receptor in pancreatic carcinoma  

Microsoft Academic Search

Background\\/Aims: The ?6-containing integrin was suggested to be involved in the process of tumor invasion and metastasis. Therefore, the aim of the study was to investigate the expression and function of this adhesion receptor in pancreatic carcinoma. Methods: Integrin expression was investigated in pancreatic tissue and tumor cell lines using immunohistochemistry. Radioimmunoprecipitation was used to determine the complex composition of

Rolf J. Weinel; Annette Rosendahl; Elisabeth Pinschmidt; Oliver Kisker; Babette Simon; Sentot Santoso

1995-01-01

16

Pancreatic hepatoid carcinoma: A rare form of pancreatic neoplasm.  

PubMed

Primary pancreatic hepatoid carcinoma (PHC) is extremely rare, resembling hepatocellular carcinoma (HCC) in terms of morphology and immunohistochemical features. Hepatoid carcinoma can present in other organs, most noticeably in the stomach. PHC is present in two forms either a pure form like HCC or admixed with other histologic tumor components characteristic of the underlying primary site (endocrine tumors, ductal, or acinar adenocarcinomas). Here, we report a 69-year-old male patient with distal pancreatic mass incidentally found during a CT scan workup for a pulmonary nodule suspicious for metastatic prostate adenocarcinoma. We described the clinical, cytological, and histological finding and conducted a literature review. Diagn. Cytopathol. 2015;43:251-256. © 2014 Wiley Periodicals, Inc. PMID:24965084

Soofi, Yousef; Kanehira, Kazunori; Abbas, Ali; Aranez, Jose; Bain, Andrew; Ylagan, Lourdes

2015-03-01

17

Isolation of Cancer Stem Like Cells from Human Adenosquamous Carcinoma of the Lung Supports a Monoclonal Origin from a Multipotential Tissue Stem Cell  

PubMed Central

There is increasing evidence that many solid tumors are hierarchically organized with the bulk tumor cells having limited replication potential, but are sustained by a stem-like cell that perpetuates the tumor. These cancer stem cells have been hypothesized to originate from transformation of adult tissue stem cells, or through re-acquisition of stem-like properties by progenitor cells. Adenosquamous carcinoma (ASC) is an aggressive type of lung cancer that contains a mixture of cells with squamous (cytokeratin 5+) and adenocarcinoma (cytokeratin 7+) phenotypes. The origin of these mixtures is unclear as squamous carcinomas are thought to arise from basal cells in the upper respiratory tract while adenocarcinomas are believed to form from stem cells in the bronchial alveolar junction. We have isolated and characterized cancer stem-like populations from ASC through application of selective defined culture medium initially used to grow human lung stem cells. Homogeneous cells selected from ASC tumor specimens were stably expanded in vitro. Primary xenografts and metastatic lesions derived from these cells in NSG mice fully recapitulate both the adenocarcinoma and squamous features of the patient tumor. Interestingly, while the CSLC all co-expressed cytokeratins 5 and 7, most xenograft cells expressed either one, or neither, with <10% remaining double positive. We also demonstrated the potential of the CSLC to differentiate to multi-lineage structures with branching lung morphology expressing bronchial, alveolar and neuroendocrine markers in vitro. Taken together the properties of these ASC-derived CSLC suggests that ASC may arise from a primitive lung stem cell distinct from the bronchial-alveolar or basal stem cells. PMID:24324581

Mather, Jennie P.; Roberts, Penelope E.; Pan, Zhuangyu; Chen, Francine; Hooley, Jeffrey; Young, Peter; Xu, Xiaolin; Smith, Douglas H.; Easton, Ann; Li, Panjing; Bonvini, Ezio; Koenig, Scott; Moore, Paul A.

2013-01-01

18

Adenosquamous Carcinoma of the Prostate  

Microsoft Academic Search

We present an unusual variant of prostatic adenocarcinoma with obvious squamous differentiation. The squamous component is represented by cells that contain vesicular or hyperchromatic nuclei and large acidophilic cytoplasm. We could demonstrate immunohistochemically the presence of prostate specific antigen (PSA) and glial fibrillary acidic protein (GFAP) in these tumour cells. Either in adenocarcinomatous or malignant squamous components, the prostatic epithelial

O. I. Turhan; N. E. Aydin; O. Sariyüce

1999-01-01

19

Photodynamic therapy for pancreatic and biliary tract carcinoma  

NASA Astrophysics Data System (ADS)

Patients with non-resectable pancreatic and biliary tract cancer (cholangiocarcinoma and gallbladder cancer) have a dismal outlook with conventional palliative therapies, with a median survival of 3-9 months and a 5 year survival of less than 3%. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then is associated with a 5-year survival of less than 30%. Although most applications of photodynamic therapy (PDT) in gastroenterology have been on lesions of the luminal gut, there is increasing experimental and clinical evidence for its efficacy in cancers of the pancreas and biliary tract. Our group has carried out the only clinical study of PDT in pancreatic carcinoma reported to date, and showed that PDT is feasible for local debulking of pancreatic cancer. PDT has also been used with palliative intent in patients with unresectable cholangiocarcinoma, with patients treated with stenting plus PDT reporting improvements in cholestasis, quality of life and survival compared with historical or randomized controls treated with stenting alone. Further controlled studies are needed to establish the influence of PDT and chemotherapy on the survival and quality of life of patients with pancreatic and biliary tract carcinoma.

Pereira, Stephen P.

2009-02-01

20

Surgical Excision of Duodenal/Pancreatic Metastatic Renal Cell Carcinoma  

PubMed Central

Renal cell carcinoma (RCC) has a potential to metastasize to almost any site and this may occur many years following nephrectomy. We present six cases with uncommon sites of metastasis: four patients presented with distal pancreatic metastasis and two with duodenal/head of the pancreas metastasis. Time to metastatic disease varied from 1 to 19?years following renal surgery. For patients are alive and two succumbed to their disease. Long-term survival can be achieved with aggressive surgical excision of disease. PMID:25177547

Espinoza, Eduardo; Hassani, Ali; Vaishampayan, Ulka; Shi, Dongping; Pontes, J. Edson; Weaver, Donald W.

2014-01-01

21

Lung metastasis of pancreatic carcinoma is regulated by TGF? signaling.  

PubMed

The molecular regulation of the lung metastasis of pancreatic carcinoma (PCC) is not completely understood. Here, we show that the levels of phosphorylated SMAD3, ZEB1, ZEB2, Snail1, and Snail2 were significantly higher in PCC with lung metastasis than in PCC without lung metastasis. Overexpression of TGF?1 enhanced the invasiveness of PCC cells, while inhibition of TGF?1 decreased the invasiveness of PCC cells, which appeared to be conducted by activated TGF? receptor signaling-induced upregulation of ZEB1, ZEB2, Snail1, and Snail2, suggesting a process of epithelial-mesenchymal transition (EMT). Taken together, our study provides evidence that TGF? receptor signaling-induced EMT may be responsible for the increased PCC invasiveness to enhance its lung metastasis. PMID:25409617

Song, Liqiang; Wang, Ping; Tian, Yu; Chang, De; Li, Kailong; Fan, Yongna; Shen, Jing; Du, Hongzhen; Mi, Ruifang; Bian, Xiaoxia; Tang, Xianchao

2014-11-20

22

Missed curable carcinoma of the pancreas presenting as chronic pancreatitis.  

PubMed Central

We present a case of pancreatic malignancy which presented as chronic pancreatitis. The diagnostic difficulties are discussed. We recommend that when there is any doubt about a diagnosis of chronic pancreatitis with a pancreatic mass, then early resection is appropriate. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9373601

Wharton, S. M.; Rahman, Z.; Johnson, C. D.

1997-01-01

23

Comparative Phenotypic Studies of Duct Epithelial Cell Lines Derived from Normal Human Pancreas and Pancreatic Carcinoma  

PubMed Central

We have investigated the mRNA/protein expression of several tyrosine kinase receptors, growth factors, and p16INK4A cyclin inhibitor in cell lines derived from normal human pancreatic duct epithelium (HPDE) and compared them with those of five pancreatic ductal carcinoma cell lines. Cultured HPDE cells express low levels of epidermal growth factor receptor (EGFR), erbB2, transforming growth factor (TGF)-?, Met/hepatocyte growth factor receptor (HGFR), vascular endothelial growth factor (VEGF), and keratinocyte growth factor (KGF). They also expressed high levels of amphiregulin but did not express EGF and cripto. The expression levels were similar in primary normal HPDE cells and those expressing transfected E6E7 genes of human papilloma virus-16, but their immortalization appeared to enhance the expression of EGFR and Met/HGFR. In comparison, pancreatic carcinoma cell lines commonly demonstrated overexpression of EGFR, erbB2, TGF-?, Met/HGFR, VEGF, and KGF, but they consistently showed marked down-regulation of amphiregulin mRNA expression. In contrast to all carcinoma cell lines that showed deletions of the p16 gene, HPDE cells consistently demonstrated normal p16 genotype and its mRNA expression. This is the first report that compares the phenotypic expression of cultured pancreatic ductal carcinoma cells with epithelial cell lines derived from normal human pancreatic ducts. The findings confirm that malignant transformation of human pancreatic duct cells commonly results in a deregulation of expression of various growth factors and receptors. PMID:9665487

Liu, Ni; Furukawa, Toru; Kobari, Masao; Tsao, Ming-Sound

1998-01-01

24

Pancreatic metastases from renal cell carcinoma: The state of the art  

PubMed Central

Pancreatic metastases are rare, with a reported incidence varying from 1.6% to 11% in autopsy studies of patients with advanced malignancy. In clinical series, the frequency of pancreatic metastases ranges from 2% to 5% of all pancreatic malignant tumors. However, the pancreas is an elective site for metastases from carcinoma of the kidney and this peculiarity has been reported by several studies. The epidemiology, clinical presentation, and treatment of pancreatic metastases from renal cell carcinoma are known from single-institution case reports and literature reviews. There is currently very limited experience with the surgical resection of isolated pancreatic metastasis, and the role of surgery in the management of these patients has not been clearly defined. In fact, for many years pancreatic resections were associated with high rates of morbidity and mortality, and metastatic disease to the pancreas was considered to be a terminal-stage condition. More recently, a significant reduction in the operative risk following major pancreatic surgery has been demonstrated, thus extending the indication for these operations to patients with metastatic disease. PMID:22147975

Ballarin, Roberto; Spaggiari, Mario; Cautero, Nicola; De Ruvo, Nicola; Montalti, Roberto; Longo, Cristina; Pecchi, Anna; Giacobazzi, Patrizia; De Marco, Giuseppina; D’Amico, Giuseppe; Gerunda, Giorgio Enrico; Di Benedetto, Fabrizio

2011-01-01

25

Spontaneous rupture of a pancreatic acinar cell carcinoma presenting as an acute abdomen  

PubMed Central

INTRODUCTION Pancreatic acinar cell carcinoma is a rare malignant pancreatic neoplasm. To the best of our knowledge, there has been no report on spontaneous rupture of acinar cell carcinoma. PRESENTATION OF CASE A 39-year-old Azari male presented with a history of sudden onset, acute epigastric pain of 12-h duration. Eight hours later the patient's general condition rapidly deteriorated, blood pressure was decreased to 90/70 mm/Hg and heart rate was increased to 120 beat/min. Emergent abdominal computed tomography scan showed a well-defined hypo-dense, necrotic mass, measured 12 cm × 12 cm that was originating from the uncinate process of pancreas with marked free peritoneal fluid and extensive haziness of retroperitoneal and mesenteric fat compatible with marked bleeding. Emergent abdominal operation was performed and histopathology revealed acinar cell carcinoma of the pancreas. DISCUSSION Pancreatic acinar cell carcinoma (ACC) usually presents with abdominal pain, nausea and vomiting. To best of our knowledge, no report has been made of spontaneous rupture of ACC. CONCLUSION Pancreatic carcinoma may present as acute abdomen due to rupture of underlying neoplasm. PMID:22543229

Mohammadi, Afshin; Porghasem, Jalal; Esmaeili, Arefeh; Ghasemi-rad, Mohammad

2012-01-01

26

Frequency and spectrum of c-Ki-ras mutations in human sporadic colon carcinoma, carcinomas arising in ulcerative colitis, and pancreatic adenocarcinoma  

SciTech Connect

Sporadic colon carcinomas, carcinomas arising in chronic ulcerative colitis, and pancreatic adenocarcinomas have been analyzed for the presence of c-Ki-ras mutations by a combination of histological enrichment, cell sorting, polymerase chain reaction, and direct sequencing. Although 60% (37/61) of sporadic colon carcinomas contained mutations in codon 12, only 1 of 17 specimens of dysplasia or carcinoma from ulcerative colitis patients contained c-Ki-ras mutations, despite a high frequency of aneuploid tumors. In contrast, a higher percentage (16/20 = 80%) of pancreatic adenocarcinomas contained mutations in c-Ki-ras 2, despite a lower frequency of DNA aneuploidy in these neoplasms. Moreover, the spectrum of mutations differed between sporadic colon carcinoma, where the predominant mutation was a G to A transition, and pancreatic carcinomas, which predominantly contained G to C or T transversions. These results suggest that the etiology of ras mutations is different in these three human neoplasms.

Burmer, G.C.; Rabinovitch, P.S.; Loeb, L.A. (Univ. of Washington School of Medicine, Seattle (United States))

1991-06-01

27

Stage IB2 adenosquamous cervical cancer diagnosed at 19-weeks gestation.  

PubMed

Neoadjuvant chemotherapy (NACT) for advanced cervical cancer in pregnancy has been shown to increase operability and be effective against spread of disease. In all reported cases of advanced disease, residual tumour has been found at surgery following NACT. We present a case of a 27-year old diagnosed with stage IB2 adenosquamous cervical carcinoma at 19-weeks gestation who was treated with NACT. Following caesarean section and radical hysterectomy, histopathology showed no evidence of residual tumour in the cervix and negative pelvic lymph nodes. PMID:25470742

Peculis, Luiza D; Ius, Yvette; Campion, Michael; Friedlander, Michael; Hacker, Neville

2014-12-01

28

The clinical relevance of the tumor marker CA 19-9 in the diagnosing and monitoring of pancreatic carcinoma.  

PubMed

The tumor marker test CA19-9 is based on monoclonal antibody to colonic carcinoma cell lines. In this study, the utility of the tumor marker in the diagnosis of pancreatic carcinoma was evaluated. CA19-9 is strongly expressed in most tissue specimens from pancreatic carcinomas. However, this antigen is also found in normal pancreas and specimens from chronic pancreatitis. CA19-9 is released into the circulation, and was found in increased concentrations (greater than 37 U/ml) in 87% of the patients with pancreatic carcinoma (N = 145), as compared with only 13% in the group of patients with benign diseases (N = 1081) and 29% of those with extrapancreatic malignancies (N = 691). The preoperatively raised CA19-9 concentration in patients with stage I of pancreatic carcinoma decreased after curative resection of the carcinoma to values within normal range. However, in no CA19-9 estimation following a palliative surgical intervention of stage III and IV patients or in cases of inoperable carcinomas was a serum concentration of less than 37 U/ml recorded. The mean survival rate of stage I patients was 29 months, whereas it was only 6 months for stage III, IV and patients with inoperable carcinomas. PMID:2180502

Safi, F; Roscher, R; Beger, H G

1990-01-01

29

Hematoporphyrin derivative uptake and photodynamic therapy in pancreatic carcinoma  

SciTech Connect

Little information is currently available concerning the uptake of porphyrins by pancreatic tumors, or the effect of photodynamic therapy (PDT) on pancreatic cancer. In Syrian golden hamsters (n = 33), the organ distribution of /sup 125/I-labeled dihematoporphyrin ether (DHE) was studied in a pancreatic cancer model. In the same animal model the effect of PDT was studied using a gold vapor laser for energy delivery 3 hr after the injection of DHE (n = 7). DHE was 2.4 times more concentrated in the pancreatic tumor than in the nontumorous pancreas at 3 hr. Simultaneously there was a considerable accumulation of DHE in the surrounding gastrointestinal tract, causing perforation of the duodenum and jejunum with resultant death in four (57%) animals after PDT. Photodynamic therapy caused extensive tumor necrosis without any obvious effect on the nontumor-bearing pancreas. Damage to the surrounding tissue in the hamster indicates that precautions should be taken if PDT is to be used clinically in pancreatic cancer. Intratumoral injection of DHE may give higher drug concentrations with greater specificity for tumor treatment.

Schroder, T.; Chen, I.W.; Sperling, M.; Bell, R.H. Jr.; Brackett, K.; Joffe, S.N.

1988-05-01

30

Everolimus and Octreotide Acetate With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors That Cannot Be Removed by Surgery  

ClinicalTrials.gov

Gastrin-Producing Neuroendocrine Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Pancreatic Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

2015-01-05

31

Advanced pancreatic carcinoma: current treatment and future challenges  

Microsoft Academic Search

Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth leading cause of cancer-related death in North America. Most patients present with locally advanced or metastatic disease that precludes curative resection. These patients have an extremely poor prognosis. In the absence of effective screening methods, considerable efforts have been made during the past decade to identify better

Anastasios Stathis; Malcolm J. Moore

2010-01-01

32

Incidence and pathology of pancreatic carcinoma among atomic bomb survivors, 1950-1982  

SciTech Connect

There is little evidence that pancreatic carcinoma is radiogenic in humans. To further investigate this possibility, all follow-up sources at the Radiation Effects Research Foundation were utilized to identify 378 incident cases of pancreatic cancer which occurred between October 1, 1950 and December 31, 1982 among 91,231 members of the cohort of atomic bomb survivors in Hiroshima and Nagasaki, Japan. An independent pathology review was conducted for all eligible cases, and pathology reports and slides were sought for those having a tissue diagnosis. The incidence of pancreatic carcinoma in this cohort was evaluated with respect to city, sex, age at exposure, time since exposure, radiation dose, and selected pathologic characteristics. Radiation dose effects, as well as spontaneous (background) incidence rates, were estimated using generalized Poisson regression models. Allowing for natural variations in background incidence, a significantly increased risk of pancreatic cancer was found to be associated with atomic bomb radiation exposure (relative risks = 1.3,95% confidence interval = 1.1-1.6). This relationship was much stronger in Nagasaki than Hiroshima, and among males than females. Age at exposure and time since exposure had little effect on radiation risk estimates. The interpretation of these findings in relation to their biologic plausibility is stressed, and the implications of using Radiation Effects Research Foundation incidence data in this regard are discussed.

Davis, S.; Yamamoto, T.

1986-09-01

33

Molecular consequences of SOD2 expression in epigenetically silenced pancreatic carcinoma cell lines  

PubMed Central

Manganese superoxide dismutase (SOD2) is an enzyme that catalyses the dismutation of superoxide in the mitochondria, leading to reduced levels of reactive oxygen species. Reduced expression levels of SOD2 have been shown to result in increased DNA damage and sod2 heterozygous mice have increased incidences of cancer. It has also been shown that SOD2 expression is lost in pancreatic cell lines, with reintroduction of SOD2 resulting in decreased rate of proliferation. The mechanism of decreased SOD2 expression in pancreatic carcinoma has not been previously determined. We demonstrate, through sodium bisulphite sequencing, that the sod2 locus is methylated in some pancreatic cell lines leading to a corresponding decrease in SOD2 expression. Methylation can be reversed by treatment with zebularine, a methyltransferase inhibitor, resulting in restored SOD2 expression. Furthermore, we demonstrate that sensitivity of pancreatic carcinoma cell lines to 2-methoxyestradiol correlates with SOD2 expression and SOD2 modulation can alter the sensitivity of these cells. Using both genomics and proteomics, we also identify molecular consequences of SOD2 expression in MIA-PaCa2 cells, including dephosphorylation of VEGFR2 and the identification of both SOD2-regulated genes and transcription factors with altered binding activity in response to SOD2 expression. PMID:17895890

Hurt, E M; Thomas, S B; Peng, B; Farrar, W L

2007-01-01

34

Well-Differentiated Pancreatic Nonfunctioning Tumors\\/Carcinoma  

Microsoft Academic Search

Nonfunctioning pancreatic neuroendocrine tumors (NET) are defined by their histopathological differentiation. Neuroendocrine cells are characterized by the expression of marker molecules like neuron-specific enolase (NSE), an unspecific cytosolic marker or vesicle proteins like chromogranin A or synaptophysin, indicating large and dense hormone-storing core vesicles and neuropeptides- or small neurotransmitter-storing synaptic vesicles, respectively [1–4]. These proteins define the neuroendocrine origin of

Massimo Falconi; Ursula Plöckinger; Dik J. Kwekkeboom; Riccardo Manfredi; Meike Körner; Larry Kvols; Ulrich F. Pape; Jens Ricke; Peter E. Goretzki; Stefan Wildi; Thomas Steinmüller; Kjell Öberg; Jean-Yves Scoazec

2006-01-01

35

Negative methylation status of Vimentin predicts improved prognosis in pancreatic carcinoma  

PubMed Central

AIM: To determine the existence of a potential relationship between the methylation state of the Vimentin gene and its prognostic value in pancreatic cancer. METHODS: Sixty-four primary tumor specimens and normal tissues were collected consecutively from pancreatic cancer patients during surgery at Hangzhou First People’s Hospital and Affiliated Hospital of the Logistics University of the Chinese People’s Armed Police Force. DNA was extracted from the samples and subsequently quantitative methylation-specific polymerase chain reaction was used to detect the Vimentin methylation status of the samples. All of the patients were followed up to December 2012. ?2 test, Kaplan-Meier survival and Cox regression statistical models were used. RESULTS: Out of 64 pancreatic cancer tissues, 21 were marked as Vimentin methylation-positive, and 43 were marked as Vimentin methylation-negative. The location of pancreatic carcinoma was related to the Vimentin methylation state. The pathological T staging (P < 0.001), adjuvant chemotherapy (P = 0.003) and the Vimentin methylation state (P = 0.037) were independent prognostic factors. CONCLUSION: In our study, Vimentin methylation status can predict the prognosis of pancreatic cancer patients. However, additional experiments and clinical trials are needed to accurately validate this observation. PMID:25278713

Zhou, Yi-Feng; Xu, Wei; Wang, Xia; Sun, Jin-Shan; Xiang, Jing-Jing; Li, Zhao-Shen; Zhang, Xiao-Feng

2014-01-01

36

Comparison of pancreatic acinar cell carcinoma and adenocarcinoma using multidetector-row computed tomography  

PubMed Central

AIM: To distinguish acinar cell carcinoma (ACC) from pancreatic adenocarcinoma (AC) by comparing their computed tomography findings. METHODS: Patients with ACC and AC were identified on the basis of results obtained using surgically resected pancreatectomy specimens. The preoperative computer tomographic images of 6 acinar cell carcinoma patients and 67 pancreatic adenocarcinoma patients in 4 phases (non-contrast, arterial, portal venous, and delayed phase) were compared. The scan delay times were 40, 70, and 120 s for each contrast-enhanced phase. The visual pattern, tomographic attenuation value, and time attenuation curve were assessed and compared between AC and ACC cases using the ?2 test, Wilcoxon signed-rank test, and Mann Whitney U test. RESULTS: The adenocarcinomas tended to be hypodense in all 4 phases. The acinar cell carcinomas also tended to be hypodense in the 3 contrast-enhanced phases, although their computed tomographic attenuation values were higher. Further, 5 of the 6 acinar cell carcinomas (83%) were isodense in the non-contrast phase. The time attenuation curve of the adenocarcinomas showed a gradual increase through the 4 phases, and all adenocarcinomas showed peak enhancement during the delayed phase. The time attenuation curve of the acinar cell carcinomas showed peak enhancement during the portal venous phase in 4 cases and during the arterial phase in 2 cases. None of the 6 acinar cell carcinomas showed peak enhancement during the delayed phase. CONCLUSION: The tumor density in the non-contrast phase and time attenuation curve pattern clearly differ between acinar cell carcinomas and adenocarcinomas, and multidetector-row computed tomography can thus distinguish these tumors. PMID:24039366

Sumiyoshi, Tatsuaki; Shima, Yasuo; Okabayashi, Takehiro; Kozuki, Akihito; Nakamura, Toshio

2013-01-01

37

The investigation of 125I seed implantation as a salvage modality for unresectable pancreatic carcinoma  

PubMed Central

Background To assess the efficacy of intraoperative ultrasound-guided implantation of 125I seeds for the treatment of unresectable pancreatic carcinoma, and analyze the associated prognostic factors. Methods Twenty-eight patients with pancreatic carcinoma who underwent laparotomy and were considered to have unresectable tumors were included in this study. Nine patients were pathologically diagnosed with Stage II disease, and nineteen patients with Stage III disease. Twenty-eight patients received intraoperative ultrasound-guided 125I seed implantation and received a D90 (at least 90% of the tumor volume received the reference dose) ranging from 60 to 163 Gy, with a median of 120 Gy. Seven patients received an additional 35–50 Gy external beam radiotherapy after seed implantation, and ten patients received two to ten cycles of chemotherapy. Overall survival of the patients was calculated and prognostic factors were evaluated. Results Of the patients, 94.1% (16/17) achieved good to medium pain relief. The tumor response rate was 78.6% (22/28), and local control was achieved in 85.7% (24/28) of patients. The 1-, 2- and 3-year survival rates were 30%, 11% and 4%, and the median survival was 10.1 months (95% CI: 9.0-10.9). Analysis using the Cox proportional hazards model suggested that patients younger than 60 years and patients who received a D90 higher than 110 Gy may survive for a longer period. Conclusions I seed implantation provides a safe and effective method to relieve pain, control local tumor growth and, to some extent, prolong the survival of patients with stage II and III pancreatic disease, without additional complications. Age and accumulated dose may be factors predictive of a favorable outcome for patients with unresectable pancreatic carcinoma treated with 125I seeds. These findings need to be validated by conducting further studies with larger cohorts. PMID:24370348

2013-01-01

38

[Obstructive jaundice associated Burkitt's lymphoma mimicking pancreatic carcinoma].  

PubMed

The primary compromise of the pancreas in lymphomas is uncommon. However, in advanced stages of Non-Hodgkin's lymphomas (LNH) the secondary invasion of the pancreas is observed more frequently. Jaundice due to extrahepatic cholestasis as a presentation form is extremely rare, with only few cases described in the literature. The aim is to present a case of an obstructive jaundice as an expression of Burkitt's lymphoma probably due to a diffuse pancreatic infiltration in an adult without immunodeficiency with a rapid response of cholestasis to low dose of hydrocortisone. Skin tumor simultaneously present with jaundice allowed the histologic diagnosis with skin biopsies. After a unique dose of 100 mg hydrocortisone, jaundice improved and cholestatic enzymes decreased, pancreas became smaller and common bile duct diameter became normal at ultrasound and CT scan, also skin tumors turn pale and diminished in size. There are isolated reports of Burkitt's lymphoma cases with associated obstructive jaundice due to pancreatic infiltration or by compression by lymph nodes of the bile ducts, many of them are pediatric cases or immunodepressed HIV patients. In the case presented, surgical resection of the pancreatic infiltration and biliary drainage, either surgical or endoscopic during the same procedure was not necessary for the histopathologic diagnosis of the illness like is described in the literature. The diagnosis was suspected by the rapid decrease of cholestatic features after a single dose of hydrocortisone and the histology was easy done by a skin biopsy. We think the interest in this case is the quick response to low doses of corticoids, which avoided the necessity of surgical procedure for the diagnosis of the biliary tree obstruction, allowing a quick implementation of the specific chemotherapeutic treatment of the lymphoma without any surgical or endoscopic procedures to heal the jaundice. PMID:18254263

Paissan, Andrea; Wachs, Adolfo; Arias, Mariana; Abeldaño, Alejandra; Frider, Bernardo

2007-12-01

39

Secretion of N-ERC/mesothelin and expression of C-ERC/mesothelin in human pancreatic ductal carcinoma.  

PubMed

ERC/mesothelin gene (MSLN) encodes a precursor protein, which is cleaved by proteases to generate N-ERC/mesothelin and C-ERC/mesothelin. N-ERC/mesothelin is a soluble protein, also known as megakaryocyte-potentiating factor, which is released into extracellular space. N-ERC/mesothelin is known to be a serum marker of mesothelioma. We have previously developed an enzyme-linked immunosorbent assay system for N-ERC/mesothelin, which can detect mesothelioma. C-ERC/mesothelin is expressed in normal mesothelial cell, pancreatic cancers, ovarian cancers, mesotheliomas and some other cancers. Pancreatic ductal carcinoma remains a fatal disease because its diagnosis often occurs very late. In this study, we examined ERC/mesothelin expression in human pancreatic cancer cell lines (MIA-PaCa2, PK-1, KP-3, TCC-PAN2, PK-59 and PK-45H) by reverse transcription-polymerase chain reaction and immunoblotting and N-ERC/mesothelin concentration in the supernatant of cultured cancer cells by the ELISA system. We also investigated C-ERC/mesothlein expression in human pancreatic ductal carcinoma tissues by immunostaining using 5B2 anti-mesothelin monoclonal antibody and N-ERC/mesothelin concentration in sera obtained from patients with pancreatic ductal carcinoma via ELISA. In vitro, N-ERC/mesothelin concentration in cell culture medium nearly correlated with the expression level of C-ERC/mesothelin. Although C-ERC/mesothelin was frequently expressed in human pancreatic ductal carcinoma, serum N-ERC/mesothelin concentration of cancer patients was equivalent to healthy controls. N-ERC/mesothelin was not useful as a serum marker of pancreatic ductal carcinoma, but because of frequent expression, C-ERC/mesothelin might be useful as a target of molecular imaging and immunotherapy. PMID:19020717

Inami, Koichi; Kajino, Kazunori; Abe, Masaaki; Hagiwara, Yoshiaki; Maeda, Masahiro; Suyama, Masafumi; Watanabe, Sumio; Hino, Okio

2008-12-01

40

Carcinoma developing in ectopic pancreatic tissue in the stomach: a case report  

PubMed Central

The development of pancreatic tissue outside the confines of the main gland, without anatomic or vascular connections between them, is a congenital abnormality referred to as heterotopic pancreas. A heterotopic pancreas in the gastrointestinal tract is usually discovered incidentally and the risk of its malignant transformation is extremely low. In this study, we describe the first case of endoepithelial carcinoma arising in a gastric heterotopic pancreas of a 56-year old woman in Greece. She presented with epigastric pain, periodic nausea and vomiting. Esophagogastroduodenoscopy revealed an ulcerated lesion in the gastric antrum, biopsies of which showed intense epithelial dysplasia with incipient malignant degeneration. The pathology report of the distal gastrectomy specimen demonstrated a 2 cm in diameter ulcerative mass in the gastric antrum. Microscopically, an endoepithelial (in situ) carcinoma of the gastric antrum was determined, which in places turned into an microinvasive endomucosal adenocarcinoma. It also incidentally demonstrated heterotopic pancreatic ducts, detected within the mucosa to the muscularis propria of the same region of the stomach, in which an endoepithelial (in situ) carcinoma was evolving. The follow-up course was uneventful 6 months postoperatively. PMID:18928565

Papaziogas, Basilios; Koutelidakis, Ioannis; Tsiaousis, Panagiotis; Panagiotopoulou, Konstantina; Paraskevas, George; Argiriadou, Helena; Atmatzidis, Stefanos; Atmatzidis, Konstantinos

2008-01-01

41

Dendritic cells fused with different pancreatic carcinoma cells induce different T-cell responses  

PubMed Central

Background It is unclear whether there are any differences in the induction of cytotoxic T lymphocytes (CTL) and CD4+CD25high regulatory T-cells (Tregs) among dendritic cells (DCs) fused with different pancreatic carcinomas. The aim of this study was to compare the ability to induce cytotoxicity by human DCs fused with different human pancreatic carcinoma cell lines and to elucidate the causes of variable cytotoxicity among cell lines. Methods Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells (PBMCs), were fused with carcinoma cells such as Panc-1, KP-1NL, QGP-1, and KP-3L. The induction of CTL and Tregs, and cytokine profile of PBMCs stimulated by fused DCs were evaluated. Results The cytotoxicity against tumor targets induced by PBMCs cocultured with DCs fused with QGP-1 (DC/QGP-1) was very low, even though PBMCs cocultured with DCs fused with other cell lines induced significant cytotoxicity against the respective tumor target. The factors causing this low cytotoxicity were subsequently investigated. DC/QGP-1 induced a significant expansion of Tregs in cocultured PBMCs compared with DC/KP-3L. The level of interleukin-10 secreted in the supernatants of PBMCs cocultured with DC/QGP-1 was increased significantly compared with that in DC/KP-3L. Downregulation of major histocompatibility complex class I expression and increased secretion of vascular endothelial growth factor were observed with QGP-1, as well as in the other cell lines. Conclusion The present study demonstrated that the cytotoxicity induced by DCs fused with pancreatic cancer cell lines was different between each cell line, and that the reduced cytotoxicity of DC/QGP-1 might be related to the increased secretion of interleukin-10 and the extensive induction of Tregs. PMID:23378772

Andoh, Yoshiaki; Makino, Naohiko; Yamakawa, Mitsunori

2013-01-01

42

Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens: implications for survival  

Microsoft Academic Search

Cytokine shedding by tumor cells into the local microenvironment modulates host immune response, tumor growth, and metastasis.\\u000a The study aimed to verify the hypothesis that the immunological microenvironment of pancreatic carcinoma exists in a prevalently\\u000a immunosuppressive state, influencing survival. We analyzed expression profiles of pro-inflammatory (IL-1?, IL-2, IL-6, IL-8,\\u000a IL-12 p40, IL-18 and IFN-?) and anti-inflammatory (IL-10, IL-11, IL-13 and

Graziella Bellone; Carlo Smirne; Francesco Angelo Mauri; Elena Tonel; Anna Carbone; Alessandra Buffolino; Luca Dughera; Antonio Robecchi; Mario Pirisi; Giorgio Emanuelli

2006-01-01

43

Cytogenetic Findings in Thirty Lung Carcinoma Patients  

Microsoft Academic Search

Primary tissue cultures of human lung tumors were prepared from 30 cases of which 16 were diagnosed as squamous cell carcinoma, six adenocarcinoma, four adenosquamous cell carcinoma, three large cell carcinoma, and one small cell lung carcinoma. Chromosomal abnormalities were observed in 26 cases by cytogenetic studies with a GTG banding technique. Specific chromosome bands frequently involved in structural abnormalities

Sibel Berker-Karaüzüm; Güven Lüleci; Gülay Özbilim; Abdullah Erdo?an; Ak?n Kuzucu; Abid Demircan

1998-01-01

44

APPL proteins modulate DNA repair and radiation survival of pancreatic carcinoma cells by regulating ATM  

PubMed Central

Despite intensive multimodal therapies, the overall survival rate of patients with ductal adenocarcinoma of the pancreas is still poor. The chemo- and radioresistance mechanisms of this tumor entity remain to be determined in order to develop novel treatment strategies. In cancer, endocytosis and membrane trafficking proteins are known to be utilized and they also critically regulate essential cell functions like survival and proliferation. On the basis of these data, we evaluated the role of the endosomal proteins adaptor proteins containing pleckstrin homology domain, phosphotyrosine binding domain and a leucine zipper motif (APPL)1 and 2 for the radioresistance of pancreatic carcinoma cells. Here, we show that APPL2 expression in pancreatic cancer cells is upregulated after irradiation and that depletion of APPL proteins by small interfering RNA (siRNA) significantly reduced radiation survival in parallel to impairing DNA double strand break (DSB) repair. In addition, APPL knockdown diminished radiogenic hyperphosphorylation of ataxia telangiectasia mutated (ATM). Activated ATM and APPL1 were also shown to interact after irradiation, suggesting that APPL has a more direct role in the phosphorylation of ATM. Double targeting of APPL proteins and ATM caused similar radiosensitization and concomitant DSB repair perturbation to that observed after depletion of single proteins, indicating that ATM is the central modulator of APPL-mediated effects on radiosensitivity and DNA repair. These data strongly suggest that endosomal APPL proteins contribute to the DNA damage response. Whether targeting of APPL proteins is beneficial for the survival of patients with pancreatic adenocarcinoma remains to be elucidated. PMID:24763056

Hennig, J; McShane, M P; Cordes, N; Eke, I

2014-01-01

45

CD44v/CD44s expression patterns are associated with the survival of pancreatic carcinoma patients  

PubMed Central

Background and purpose CD44 variants have been associated with tumor invasion and metastasis, but CD44 expression patterns have not been systematically investigated in pancreatic carcinoma. This study systematically investigated whether CD44 expression patterns are involved in pancreatic carcinoma metastasis and prognosis. Methods We applied primers specific for all CD44 variants and CD44s to analyze the expression patterns of CD44 (CD44v2-CD44v10 and CD44s) using quantitative real-time PCR (qRT-PCR). We then further evaluated their roles in pancreatic carcinoma metastasis and prognosis using clinical survival analysis. Results Increased CD44v expression and decreased CD44s expression were found in metastatic pancreatic carcinoma in three different cell lines and in human tumor tissue. Clinical analysis showed that CD44v6+ and CD44v9+ were correlated with lymph node metastasis, liver metastasis and TNM stage. However, CD44s? was associated with liver metastasis, tumor differentiation and TNM stage. Survival analysis showed that patients with CD44v6+/CD44s? or CD44v6+/CD44s? had lower overall survival (OS) rates, although the individual expression of CD44v6, CD44v9 and CD44s was also related to decreased OS rates. Univariate analysis showed that lymph node metastasis; vessel invasion; hepatic metastases; TNM stage; and individual or co-expression of CD44v6, CD44v9 and CD44s were risk factors affecting survival. Multivariate analysis showed that CD44v6+/CD44s? was an independent predictor of survival. Conclusions We found that CD44v6+, CD44v9+ and CD44s? were associated with pancreatic carcinoma metastasis and progression and that CD44v6+/CD44s? was an independent risk factor affecting survival in pancreatic carcinoma. Therefore, the different expression patterns of CD44v/CD44s may determine pancreatic carcinoma prognosis. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1579257224116287. PMID:24708709

2014-01-01

46

Activation of Phosphatidylinositol 3Kinase and Extracellular Signal-Regulated Kinase Is Required for Glial Cell Line-Derived Neurotrophic Factor-Induced Migration and Invasion of Pancreatic Carcinoma Cells  

Microsoft Academic Search

Pancreatic carcinoma cells exhibit a pronounced tendency to invade along and into intra- and extrapancreatic nerves, even at early stages of the disease. The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) has been shown to promote pancreatic cancer cell invasion. Here, we demonstrate that pancreatic carcinoma cell lines, such as PANC-1, expressed the RET and GDNF family receptor receptor

Christine Veit; Felicitas Genze; Andre Menke; Silke Hoeffert; Thomas M. Gress; Peter Gierschik; Klaudia Giehl

2004-01-01

47

Molecular and immunochemical analyses of RB1 and cyclin D1 in human ductal pancreatic carcinomas and cell lines.  

PubMed

Somatic mutations in the retinoblastoma-1 gene (RB1) and loss of RB1 protein function have been implicated in a number of human malignancies, but the role of RB1 gene and protein abnormalities in ductal pancreatic cancer (DPCA) is virtually unknown. We therefore analyzed expression of the RB1 protein immunohistochemically and/or by western blotting in a total of 54 sporadic and eight familial cases of archival and frozen DPCA and in 18 pancreatic carcinoma cell lines by using the antibodies RB-WL-1, 84-B3-1, and PMG3-245. Mutations in the RB1 promotor region and exons 13-21 of the RB1 gene were likewise examined by single-strand conformation polymorphism (SSCP) analyses and DNA sequencing of genomic DNA from 30 microdissected primary pancreatic tumors and the pancreatic carcinoma cell lines. Moreover, amplification and expression of a major regulatory component of RB1 function, cyclin D1, were assessed by southern and immunohistochemical analyses, respectively. The DPCAs were heterogeneous in both the intensity of RB1 nuclear staining and the percentage of immunoreactive cells. The tumors often had areas where RB1 staining was weak or absent adjacent to normal pancreatic tissue; however, only two of 32 archival cases and one of 30 frozen cases of DPCA completely lacked RB1 nuclear staining. Immunohistochemical and western blot analyses of 18 pancreatic carcinoma cell lines demonstrated the absence of RB1 expression in only two cell lines, Capan-1 and QGP-1. Analyses of the RB1 gene and promotor region by SSCP and DNA sequencing largely confirmed the immunochemical findings. Three of 30 primary carcinomas had abnormalities revealed by SSCP analyses. In one case a single base-pair deletion was confirmed in exon 18 and resulted in premature termination and the absence of detectable RB1 protein. A second case had TAC-->TTC missense mutation in exon 13. The third primary carcinoma could not be reliably sequenced because it had a low percentage of epithelial cells. The cyclin D1 gene was not amplified in any of the primary pancreatic tumors or cell lines examined. These immunochemical and molecular analyses of the RB1 tumor suppressor gene and cyclin D1 proto-oncogene in a large series of human pancreatic cancers and cell lines indicate that RB1 and cyclin D1 alterations occur during the development of some human DPCAs. Nevertheless, it is probable that alterations in cell-cycle regulation in DPCAs more frequently involve pathways other than those involving RB1 and cyclin D1. PMID:8599583

Huang, L; Lang, D; Geradts, J; Obara, T; Klein-Szanto, A J; Lynch, H T; Ruggeri, B A

1996-02-01

48

Expansion of anti-mesothelin specific CD4+ and CD8+ T cell responses in patients with pancreatic carcinoma.  

PubMed

We aimed to assess the status of naturally occurring CD4(+) and CD8(+) T cell responses to a tumour associated antigen, Mesothelin, in patients with pancreatic carcinoma and study the effects of elevated IL-10 on Mesothelin-specific T cell responses. For that sake, short term T cell lines were generated from PBMCs of 16 healthy controls, 15 patients with benign pancreatic diseases and 25 patients with pancreatic carcinoma and Mesothelin-specific CD4(+) and CD8(+) T cell responses were analysed using intracellular cytokine assays for IFN-?. Plasma levels of IL-10 and Mesothelin were measured using cytometric bead array and ELISA assay, respectively. The blocking assays were performed to assess the effects of IL-10 on Mesothelin-specific T cell responses. Here, we demonstrate that the plasma levels of Mesothelin and IL-10 are significantly increased in patients with pancreatic carcinoma. Additionally, we found that (a) Mesothelin-specific T cell responses are significantly expanded in cancer patients (p = 0.0053), (b) the multifunctional CD4(+) T cell response is directed toward a broad repertoire of epitopes within the Mesothelin protein. (c) Mesothelin-specific CD4+ T cell response is directly inhibited by elevated IL-10 in cancer patients. These data provides evidence for the use of Mesothelin as an immunogen for tumour-specific T cell response. PMID:24520352

Chen, Yuan; Ayaru, Lakshmana; Mathew, Sanju; Morris, Emma; Pereira, Stephen P; Behboudi, Shahriar

2014-01-01

49

Establishment of a carcinoembryonic antigen-producing cell line from human pancreatic carcinoma.  

PubMed

A human pancreatic carcinoma cell line of islet cell origin (QGP-1) has been established and maintained for over two years. The parent tumor and the cultured cell line produce carcinoembryonic antigen (CEA), and there is no evidence of hormone secretion from the tumor cells. The epithelioid cells, which had migrated from rounded, irregular cell aggregates, grow as a confluent monolayer with piling up of cells in some areas, and have a population doubling time of 3.5 days. The modal chromosome number was 50. Exponentially growing cultures produce 76.3 ng of CEA/10(6) cells after 7 days. CEA production was confirmed by immuno-peroxidase staining. PMID:7227711

Kaku, M; Nishiyama, T; Yagawa, K; Abe, M

1980-10-01

50

[Quality management in surgery: treatment of pancreatic carcinoma--What is evidence-based?].  

PubMed

Summary. The term "evidence-based medicine" (EBM) - an Anglicism in common use in modern medicine - has of the nature of a catchword, the actual meaning of which is not always clear to all who use it. Generally speaking it is taken to mean that decision-making in the areas of diagnosis and treatment is based on data obtained from randomized, preferably double-blind and controlled, studies involving sufficient numbers of cases. This, however, is not always automatically equatable with arriving at a decision at the highest level of confirmed scientific knowledge, including the most recently acquired facts. Taking account of the current literature, the present article attempts an analysis of the following four aspects of surgical treatment of pancreatic carcinoma: the required extent of lymph node dissection, the relevance of multimodal treatment concepts, the significance of pylorus-preserving partial duodenopancreatectomy and the relevance of portal vein resection. PMID:11753801

Hohenberger, W; Schoolmann, S; Kastl, S

2001-11-01

51

Prognostic significance and therapeutic implications of peroxisome proliferator-activated receptor ? overexpression in human pancreatic carcinoma.  

PubMed

Peroxisome proliferator-activated receptor ? (PPAR?) is a ligand-activated nuclear receptor which has been implicated in carcinogenesis and angiogenesis in a wide range of cancers, including pancreatic carcinoma (PC). We aimed to characterize the prognosis and potential therapeutic implications of PPAR? in PC. Real-time RT-PCR and western blotting were used to quantify PPAR? expression in immortalized pancreatic epithelial cells, PC cell lines and freshly isolated matched tumor and non-tumor tissues. PPAR? protein expression was analyzed by immunohistochemistry (IHC) in archived tumor tissues from 101 PC patients. Furthermore, the effect of PPAR? on the cytotoxic action of gemcitabine (Gem) and 5-fluorouracil (5-FU) in PC cell lines was investigated in vitro using RNA interference techniques. Both PPAR? protein and mRNA were expressed at markedly higher levels in all of the PC cell lines and freshly isolated PC tissues, compared to normal immortalized pancreatic epithelial cells and the matched adjacent non-tumor tissues. High levels of PPAR? expression correlated significantly with tumor-node-metastasis (TNM) staging (P<0.001) and poor overall survival (P<0.001), especially in patients with advanced disease who received postoperative chemotherapy. While silencing of PPAR? significantly inhibit the cytotoxic effects of both gemcitabine and 5-fluorouracil in PC cells in vitro. This study suggests that high levels of PPAR? expression are associated with poor overall survival in PC. Additionally, PPAR? promotes chemoresistance in PC cells, indicating that PPAR? may represent a novel therapeutic target for PC. PMID:25333644

Zhang, Yan; Luo, Hui-Yan; Liu, Guang-Lin; Wang, De-Shen; Wang, Zhi-Qiang; Zeng, Zhao-Lei; Xu, Rui-Hua

2015-01-01

52

Application of a genetic algorithm to optimizing radiation therapy treatment plans for pancreatic carcinoma.  

PubMed

The performance of an automated treatment planning algorithm was tested using cases of patients with pancreatic carcinoma; the system implements optimization tools that suggest high-quality plans for consideration by the planner and physician, making best use of the capabilities of a conventional linear accelerator: isocentric setup, shaped fields, and wedges. Ten consecutive patients presenting with pancreatic cancer were first planned using a conventional 3-field protocol to provide a basis for comparison. Each was then planned using an automated optimization technique using a genetic algorithm and a dose-based score function subject to volume-dose constraints. Two sets of optimized plans were created, 1 using only axial beams and the other permitting non-axial beams. The improvement afforded by the optimization was assessed by comparing the score function results and by computing the combined normal tissue complication probability (NTCP) for a constant isocenter dose. In all 10 cases, optimization improved the dose-based score function. In 9 cases, the non-axial plan scored higher than the axial plan. Optimization driven by the dose-based score function improved or equaled the predicted NTCP in 8 axial and 9 nonaxial plans. This study demonstrates progress toward the goal of developing an automated planning tool that can robustly suggest high-quality plans. PMID:10856688

Ezzell, G A; Gaspar, L

2000-01-01

53

Evaluation of the Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy for the Treatment of Advanced Pancreatic Carcinoma  

SciTech Connect

Purpose. To evaluate the effects of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in patients with advanced pancreatic carcinoma. Methods. CTAI was performed in 17 patients with stage IV pancreatic cancer with (n = 11) or without (n = 6) liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The inferior pancreatic artery (IPA) was embolized to achieve delivery of the pancreatic blood supply through only the celiac artery. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. Treatment effects were evaluated based on the primary tumor size, liver metastasis, and survival time and factors such as tumor size, tumor location, and stage of pancreatic carcinoma; the embolized arteries were analyzed with respect to treatment effects and prognosis. Results. A catheter was fixed in the gastroduodenal artery and splenic artery in 10 and 7 patients, respectively. Complete peripancreatic arterial occlusion was successful in 10 patients. CT showed a decrease in tumor size in 6 of 17 (35%) patients and a decrease in liver metastases in 6 of 11 (55%) patients. The survival time ranged from 4 to 18 months (mean {+-} SD, 8.8 {+-} 1.5 months). Complete embolization of arteries surrounding the pancreas was achieved in 10 patients; they manifested superior treatment effects and prognoses (p < 0.05). Conclusion. In patients with advanced pancreatic cancer, long-term CTAI with systemic chemotherapy appeared to be effective not only against the primary tumor but also against liver metastases. Patients with successfully occluded peripancreatic arteries tended to survive longer.

Ikeda, O., E-mail: osamu-3643ik@do9.enjoy.ne.jp; Kusunoki, S.; Kudoh, K. [Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Department of Diagnostic Radiology (Japan); Takamori, H.; Tsuji, T.; Kanemitsu, K. [Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Department of Gastroenterological Surgery (Japan); Yamashita, Y. [Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Department of Diagnostic Radiology (Japan)

2006-06-15

54

Bioengineered Human Arginase I with Enhanced Activity and Stability Controls Hepatocellular and Pancreatic Carcinoma Xenografts1  

PubMed Central

Hepatocellular carcinoma (HCC) and pancreatic carcinoma (PC) cells often have inherent urea cycle defects rendering them auxotrophic for the amino acid l-arginine (l-arg). Most HCC and PC require extracellular sources of l-arg and undergo cell cycle arrest and apoptosis when l-arg is restricted. Systemic, enzyme-mediated depletion of l-arg has been investigated in mouse models and human trials. Non-human enzymes elicit neutralizing antibodies, whereas human arginases display poor pharmacological properties in serum. Co2+ substitution of the Mn2+ metal cofactor in human arginase I (Co-hArgI) was shown to confer more than 10-fold higher catalytic activity (kcat/Km) and 5-fold greater stability. We hypothesized that the Co-hArgI enzyme would decrease tumor burden by systemic elimination of l-arg in a murine model. Co-hArgI was conjugated to 5-kDa PEG (Co-hArgI-PEG) to enhance circulation persistence. It was used as monotherapy for HCC and PC in vitro and in vivo murine xenografts. The mechanism of cell death was also investigated. Weekly treatment of 8 mg/kg Co-hArgI-PEG effectively controlled human HepG2 (HCC) and Panc-1 (PC) tumor xenografts (P = .001 and P = .03, respectively). Both cell lines underwent apoptosis in vitro with significant increased expression of activated caspase-3 (P < .001). Furthermore, there was evidence of autophagy in vitro and in vivo. We have demonstrated that Co-hArgI-PEG is effective at controlling two types of l-arg-dependent carcinomas. Being a nonessential amino acid, arginine deprivation therapy through Co-hArgI-PEG holds promise as a new therapy in the treatment of HCC and PC. PMID:21633669

Glazer, Evan S; Stone, Everett M; Zhu, Cihui; Massey, Katherine L; Hamir, Amir N; Curley, Steven A

2011-01-01

55

Comparison of K-ras oncogene activation in pancreatic duct carcinomas and cholangiocarcinomas induced in hamsters by N-nitrosobis(2-hydroxypropyl)amine.  

PubMed

The presence of K-ras point mutations in pancreatic duct carcinomas and cholangiocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in Syrian hamsters was investigated by single-strand conformation polymorphism analysis of polymerase chain reaction products from frozen fresh materials in order to clarify the K-ras mutation rates in those two carcinomas induced simultaneously by one carcinogen, BHP. In the examined pancreatic duct carcinomas, 10 out of 16 were positive for a mutation in codon 12 while 3 out of 12 cholangiocarcinomas demonstrated mutation of K-ras gene. G-to-A transition was detected in the second position of codon 12 in both pancreatic carcinomas and cholangiocarcinomas. These results suggest that the role of genetic alteration in carcinogenesis may differ with the target organ, even when initiation is with the same carcinogen. PMID:8407562

Tsutsumi, M; Murakami, Y; Kondoh, S; Tsujiuchi, T; Hohnoki, K; Horiguchi, K; Noguchi, O; Kobayashi, E; Okita, S; Sekiya, T

1993-09-01

56

Pylorus-Preserving Versus Pylorus-Resecting Pancreaticoduodenectomy for Periampullary and Pancreatic Carcinoma: A Meta-Analysis  

PubMed Central

Background The aim of this meta-analysis was to compare the long-term survival, mortality, morbidity and the operation-related events in patients with periampullary and pancreatic carcinoma undergoing pylorus-preserving pancreaticoduodenectomy (PPPD) and pylorus-resecting pancreaticoduodenectomy (PRPD). Method A systematic search of literature databases (Cochrane Library, PubMed, EMBASE and Web of Science) was performed to identify studies. Outcome measures comparing PPPD versus PRPD for periampullary and pancreatic carcinoma were long-term survival, mortality, morbidity (overall morbidity, delayed gastric emptying [DGE], pancreatic fistula, wound infection, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage) and operation related events (hospital stays, operating time, intraoperative blood loss and red blood cell transfusions). Results Eight randomized controlled trials (RCTs) including 622 patients were identified and included in the analysis. Among these patients, it revealed no difference in long-term survival between the PPPD and PRPD groups (HR?=?0.23, p?=?0.11). There was a lower rate of DGE (RR?=?2.35, p?=?0.04, 95% CI, 1.06–5.21) with PRPD. Mortality, overall morbidity, pancreatic fistula, wound infection, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage were not significantly different between the groups. PPPDs were performed more quickly than PRPDs (WMD?=?53.25 minutes, p?=?0.01, 95% CI, 12.53–93.97); and there was less estimated intraoperative blood loss (WMD?=?365.21 ml, p?=?0.006, 95% CI, 102.71–627.71) and fewer red blood cell transfusions (WMD?=?0.29 U, p?=?0.003, 95% CI, 0.10–0.48) in patients undergoing PPPD. The hospital stays showed no significant difference. Conclusions PPPD had advantages over PRPD in operating time, intraoperative blood loss and red blood cell transfusions, but had a significantly higher rate of DGE for periampullary and pancreatic carcinoma. PPPD and PRPD had comparable mortality and morbidity including pancreatic fistulas, wound infections, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage. Our conclusions were limited by the available data. Further evaluations of high-quality RCTs are needed. PMID:24603478

Yang, Chong; Wu, He-Shui; Chen, Xing-Lin; Wang, Chun-You; Gou, Shan-Miao; Xiao, Jun; He, Zhi-Qiang; Chen, Qi-Jun; Li, Yong-Feng

2014-01-01

57

Secretion of neurotensin from a human pancreatic islet cell carcinoma cell line (QGP-1N).  

PubMed

Effects of various secretagogues on secretion of neurotensin from a pancreatic islet cell carcinoma cell line (QGP-1N) were examined. Carbachol stimulated secretion of neurotensin concentration-dependently in the range of 10(-6) - 10(-4) M. The neurotensin secretion stimulated with 10(-5) M carbachol was completely inhibited by atropine at 10(-5) M. Phorbol ester and calcium ionophore (A23187) stimulated secretion of neurotensin. The removal of extracellular Ca2+ suppressed the secretion through the stimulation with 10(-5) M carbachol. Fluoride, an activator of guanine nucleotide-binding (G) protein, stimulated secretion of neurotensin. Neurotensin released into culture medium through stimulation with carbachol coeluted with neurotensin 1-13 on a gel-chromatography. Our results suggest that secretion of neurotensin from QGP-1N cells is mainly regulated by acetylcholine through muscarinic receptors coupled to G protein and that an increase in intracellular Ca2+ and protein kinase C play an important role in stimulus-secretion coupling. PMID:8134614

Tateishi, K; Funakoshi, A; Kitayama, N; Matsuoka, Y

1993-12-10

58

Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells  

PubMed Central

Prognosis of pancreatic cancer is extremely poor, suggesting critical needs for additional drugs to improve disease outcome. In this study, we examined efficacy and associated mechanism of a novel agent bitter melon juice (BMJ) against pancreatic carcinoma cells both in culture and nude mice. BMJ anticancer efficacy was analyzed in human pancreatic carcinoma BxPC-3, MiaPaCa-2, AsPC-1 and Capan-2 cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide, cell death enzyme-linked immunosorbent assay and annexin/propidium iodide assays. BMJ effect on apoptosis regulators was assessed by immunoblotting. In vivo BMJ efficacy was evaluated against MiaPaCa-2 tumors in nude mice, and xenograft was analyzed for biomarkers by immunohistochemistry (IHC). Results showed that BMJ (2–5% v/v) decreases cell viability in all four pancreatic carcinoma cell lines by inducing strong apoptotic death. At molecular level, BMJ caused caspases activation, altered expression of Bcl-2 family members and cytochrome-c release into the cytosol. Additionally, BMJ decreased survivin and X-linked inhibitor of apoptosis protein but increased p21, CHOP and phosphorylated mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2 and p38) levels. Importantly, BMJ activated adenosine monophosphate-activated protein kinase (AMPK), a biomarker for cellular energy status, and an AMPK inhibitor (Compound C) reversed BMJ-induced caspase-3 activation suggesting activated AMPK involvement in BMJ-induced apoptosis. In vivo, oral administration of lyophilized BMJ (5mg in 100 µl water/day/mouse) for 6 weeks inhibited MiaPaCa-2 tumor xenograft growth by 60% (P < 0.01) without noticeable toxicity in nude mice. IHC analyses of MiaPaCa-2 xenografts showed that BMJ also inhibits proliferation, induces apoptosis and activates AMPK in vivo. Overall, BMJ exerts strong anticancer efficacy against human pancreatic carcinoma cells, both in vitro and in vivo, suggesting its clinical usefulness. PMID:23475945

Agarwal, Rajesh

2013-01-01

59

CARMA3 is upregulated in human pancreatic carcinoma, and its depletion inhibits tumor proliferation, migration, and invasion.  

PubMed

Elevated CARMA3 expression has been reported to be involved in tumor progression of several cancer types. In the present study, we examined the expression pattern of CARMA3 protein and its biological roles in human pancreatic carcinoma. Using immunohistochemistry, we checked CARMA3 protein expression in 95 pancreatic ductal carcinoma specimens. We found that CARMA3 was overexpressed in 34 of 95 (35.8 %) specimens. A significant association was observed between CARMA3 overexpression with histological grade (p=0.0099) and nodal status (p=0.0126). To further explore its biological roles, we knocked down CARMA3 expression in CAPAN2 cell line using small interfering RNA (siRNA). MTT growth assay, wound healing assay, and Transwell assay showed that CARMA3 depletion inhibited cell proliferation, migration, and invasion. We also showed that CARMA3 depletion inhibited EGF-induced nuclear factor-kappaB (NF-?B) activation and its target genes' expression. The effect of CARMA3 depletion on NF-?B signaling was significantly reduced in Bcl10-depleted cells. In conclusion, CARMA3 is overexpressed in pancreatic cancer and regulates malignant cell growth, invasion, and NF-?B signaling, which was dependent on its association with Bcl10. PMID:24633921

Du, Shiyu; Jia, Liping; Zhang, Yanli; Fang, Long; Zhang, Xiang; Fan, Yanhua

2014-06-01

60

Combination therapy of gemcitabine or oral S-1 with the anti-VEGF monoclonal antibody bevacizumab for pancreatic neuroendocrine carcinoma.  

PubMed

We previously reported that the administration of bevacizumab for pancreatic neuroendocrine tumors inhibited angiogenesis in the host, resulting in tumor growth inhibition. In light of these results, we compared the effect of bevacizumab/gemcitabine/S-1 combination therapy vs. bevacizumab monotherapy. The QGP-1 pancreatic neuroendocrine carcinoma cell line and the BxPC-3 ductal cell carcinoma cell line were transplanted into the subcutaneous tissue of mice, and the mice were treated for 3 weeks with bevacizumab [50 mg/kg intraperitoneally (i.p.) twice weekly], gemcitabine (240 mg/kg i.p. once weekly) and S-1 (10 mg/kg orally five times weekly). The antitumor effect and side effects were evaluated by measuring the tumor volume and weight and by changes in body weight, respectively. The tumor volume became smaller (from the maximum volume) in the group treated with bevacizumab, gemcitabine and S-1 (BGS) and the group treated with bevacizumab and gemcitabine (BG). A significant difference was noted in the tumor weight between the BG group and the group treated with bevacizumab alone. A relatively significant decrease in the body weight was observed in the BGS and BG groups. We conclude that gemcitabine is appropriate as a drug used in combination with bevacizumab for pancreatic neuroendocrine tumors. PMID:22969935

Kasuya, Kazuhiko; Nagakawa, Yuichi; Suzuki, Minako; Suzuki, Yoshiaki; Kyo, Bunso; Suzuki, Satoru; Matsudo, Takaaki; Itoi, Takao; Tsuchida, Akihiko; Aoki, Tatsuya

2012-04-01

61

Combination therapy of gemcitabine or oral S-1 with the anti-VEGF monoclonal antibody bevacizumab for pancreatic neuroendocrine carcinoma  

PubMed Central

We previously reported that the administration of bevacizumab for pancreatic neuroendocrine tumors inhibited angiogenesis in the host, resulting in tumor growth inhibition. In light of these results, we compared the effect of bevacizumab/gemcitabine/S-1 combination therapy vs. bevacizumab monotherapy. The QGP-1 pancreatic neuroendocrine carcinoma cell line and the BxPC-3 ductal cell carcinoma cell line were transplanted into the subcutaneous tissue of mice, and the mice were treated for 3 weeks with bevacizumab [50 mg/kg intraperitoneally (i.p.) twice weekly], gemcitabine (240 mg/kg i.p. once weekly) and S-1 (10 mg/kg orally five times weekly). The antitumor effect and side effects were evaluated by measuring the tumor volume and weight and by changes in body weight, respectively. The tumor volume became smaller (from the maximum volume) in the group treated with bevacizumab, gemcitabine and S-1 (BGS) and the group treated with bevacizumab and gemcitabine (BG). A significant difference was noted in the tumor weight between the BG group and the group treated with bevacizumab alone. A relatively significant decrease in the body weight was observed in the BGS and BG groups. We conclude that gemcitabine is appropriate as a drug used in combination with bevacizumab for pancreatic neuroendocrine tumors. PMID:22969935

KASUYA, KAZUHIKO; NAGAKAWA, YUICHI; SUZUKI, MINAKO; SUZUKI, YOSHIAKI; KYO, BUNSO; SUZUKI, SATORU; MATSUDO, TAKAAKI; ITOI, TAKAO; TSUCHIDA, AKIHIKO; AOKI, TATSUYA

2012-01-01

62

A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis.  

PubMed

Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/?-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of ?-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31(+) vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models. PMID:25450371

Kim, Su Jin; Chang, Suhwan; Lee, Yangsoon; Kim, Na Young; Hwang, Yeonsil; Min, Hye Jin; Yoo, Kyung-Sook; Park, Eun Hye; Kim, Seokho; Chung, Young-Hwa; Park, Young Woo; Koh, Sang Seok

2014-10-18

63

Synergistic combination of valproic acid and oncolytic parvovirus H-1PV as a potential therapy against cervical and pancreatic carcinomas  

PubMed Central

The rat parvovirus H-1PV has oncolytic and tumour-suppressive properties potentially exploitable in cancer therapy. This possibility is being explored and results are encouraging, but it is necessary to improve the oncotoxicity of the virus. Here we show that this can be achieved by co-treating cancer cells with H-1PV and histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA). We demonstrate that these agents act synergistically to kill a range of human cervical carcinoma and pancreatic carcinoma cell lines by inducing oxidative stress, DNA damage and apoptosis. Strikingly, in rat and mouse xenograft models, H-1PV/VPA co-treatment strongly inhibits tumour growth promoting complete tumour remission in all co-treated animals. At the molecular level, we found acetylation of the parvovirus nonstructural protein NS1 at residues K85 and K257 to modulate NS1-mediated transcription and cytotoxicity, both of which are enhanced by VPA treatment. These results warrant clinical evaluation of H-1PV/VPA co-treatment against cervical and pancreatic ductal carcinomas. PMID:24092664

Li, Junwei; Bonifati, Serena; Hristov, Georgi; Marttila, Tiina; Valmary-Degano, Séverine; Stanzel, Sven; Schnölzer, Martina; Mougin, Christiane; Aprahamian, Marc; Grekova, Svitlana P; Raykov, Zahari; Rommelaere, Jean; Marchini, Antonio

2013-01-01

64

Ziv-Aflibercept in Treating and Computed Tomography Perfusion Imaging in Predicting Response in Patients With Pancreatic Neuroendocrine Tumors That Are Metastatic or Cannot Be Removed by Surgery  

ClinicalTrials.gov

Gastrin-Producing Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Pancreatic Neuroendocrine Carcinoma; Somatostatin-Producing Neuroendocrine Tumor

2015-01-13

65

Gene Expression Profiling of Microdissected Pancreatic Ductal Carcinomas Using High-Density DNA Microarrays  

Microsoft Academic Search

Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of malignancy-related death and is the eighth most common cancer with the lowest overall 5-year relative survival rate. To identify new molecular markers and candidates for new therapeutic regimens, we investigated the gene expression profile of microdissected cells from 11 normal pancreatic ducts, 14 samples of PDAC, and 4 well-characterized pancreatic cancer

Robert Grützmann; Christian Pilarsky; Ole Ammerpohl; Jutta Lüttges; Armin Böhme; Bence Sipos; Melanie Foerder; Ingo Alldinger; Beatrix Jahnke; Hans Konrad Schackert; Holger Kalthoff; Bernd Kremer; Günter Klöppel; Hans Detlev Saeger

2004-01-01

66

Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed By the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed By Surgery  

ClinicalTrials.gov

Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary-Mucinous Neoplasm; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer

2015-02-09

67

Targeting pancreatic and ovarian carcinomas using the auristatin-based anti-CD70 antibody–drug conjugate SGN-75  

PubMed Central

Background: CD70 is an ideal target for antibody-based therapies because of its aberrant high expression in renal carcinomas and non-Hodgkin lymphomas and its highly restricted expression in normal tissues. The expression profiling of CD70 in carcinomas has been limited because of the lack of a CD70-specific reagent that works in formalin-fixed paraffin-embedded (FFPE) tissues. Methods: We generated murine monoclonal antibodies (mAbs) specific for CD70 and validated their specificity by western blot analysis and developed a protocol for immunohistochemistry on FFPE tissues. CD70+ tumour cell lines were used for testing the anti-tumour activity of the anti-CD70 antibody–drug conjugate, SGN-75. Results: We report novel detection of CD70 expression in multiple cancers including pancreatic (25%), larynx/pharynx (22%), melanoma (16%), ovarian (15%), lung (10%), and colon (9%). Our results show that pancreatic and ovarian tumour cell lines, which express high levels of endogenous or transfected CD70, are sensitive to the anti-tumour activity of SGN-75 in vitro and in vivo. Conclusion: Development of murine mAbs for robust and extensive screening of FFPE samples coupled with the detection of anti-tumour activity in novel indications provide rationale for expanding the application of SGN-75 for the treatment of multiple CD70 expressing cancers. PMID:20664585

Ryan, M C; Kostner, H; Gordon, K A; Duniho, S; Sutherland, M K; Yu, C; Kim, K M; Nesterova, A; Anderson, M; McEarchern, J A; Law, C-L; Smith, L M

2010-01-01

68

[Carcinoma of the pancreatic remnant developing after pancreaticoduodenectomy for adenocarcinoma of the head of pancreas].  

PubMed

In November 1996 a 44-year-old man with an adenocarcinoma of the pancreatic head (T2 N1 Mx- UICC 1998 Stage III) underwent a Traverso-Longmire pancreaticoduodenectomy. Early reoperation was required owing to postoperative acute pancreatitis and haemorrhage of the pancreatic remnant, after which he received chemo- and radiotherapy. Twenty-nine months later, an increase in the level of CA19.9 was observed with neither clinical nor radiological evidence of cancer recurrence. Forty months later, there was evidence of a new neoplasia of the pancreatic remnant. Since the recurrence involved only the pancreatic remnant with no evidence of metastases and the patient was in good condition and enough time had elapsed since surgical eradication of the primary cancer, we decided to perform an en bloc resection of the pancreatic body and tail and the spleen. Histologically, the tumour proved to be a pancreatic adenocarcinoma (T2). It is difficult to assess whether this cancer of the pancreatic remnant was a recurrence or a second primary cancer because of the long recurrence-free survival period, the absence of neoplastic invasion of the resection margins of the two surgical specimens and the absence of multicentricity both of the portion of the gland removed by the first operation and that removed by the second. PMID:12239765

D'Amato, Alberto; Gentili, Vincenzo; Santella, Sergio; Boschetto, Arianna; Pronio, Annamaria; Montesani, Chiara

2002-01-01

69

Anti-vascular endothelial growth factor antibody single therapy for pancreatic neuroendocrine carcinoma exhibits a marked tumor growth-inhibitory effect.  

PubMed

At present, no effective chemotherapy for pancreatic neuroendocrine carcinoma (PNEC) exists. However, anti-angiogenic therapy is expected to be effective for PNEC, a hypervascular tumor. We treated PNEC and hypovascular pancreatic ductal cell carcinoma (DCC) cell lines with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab, and compared the antitumor effect between the two different types of cell lines. The PNEC cell line QGP-1 and the DCC cell lines BxPC-3 and AsPC-1 were used. We evaluated the ability of the cell lines to proliferate and secrete VEGF in vitro, the antitumor effect of bevacizumab administration in vivo and the side effects of bevacizumab on the pancreas in a caerulein-induced pancreatitis model. Comparison of the QGP-1 and DCC cell lines showed that QGP-1 secreted a higher level of VEGF under a hypoxic environment than the DCC cell line, and bevacizumab exerted the most marked growth-inhibitory effect on QGP-1; the number of intratumoral blood vessels decreased and the percentage of proliferating cells was approximately the same. In the pancreatitis model, bevacizumab administration did not adversely affect the pancreatitis or the associated hypoxic environment. Bevacizumab does not affect the pancreas itself; therefore, its potent inhibitory effect on the growth of pancreatic neuroendocrine tumors alone can be expected. PMID:22977618

Kasuya, Kazuhiko; Nagakawa, Yuichi; Suzuki, Minako; Tanaka, Hiroaki; Ohta, Hiroshi; Itoi, Takao; Tsuchida, Akihiko

2011-11-01

70

Anti-vascular endothelial growth factor antibody single therapy for pancreatic neuroendocrine carcinoma exhibits a marked tumor growth-inhibitory effect  

PubMed Central

At present, no effective chemotherapy for pancreatic neuroendocrine carcinoma (PNEC) exists. However, anti-angiogenic therapy is expected to be effective for PNEC, a hypervascular tumor. We treated PNEC and hypovascular pancreatic ductal cell carcinoma (DCC) cell lines with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab, and compared the antitumor effect between the two different types of cell lines. The PNEC cell line QGP-1 and the DCC cell lines BxPC-3 and AsPC-1 were used. We evaluated the ability of the cell lines to proliferate and secrete VEGF in vitro, the antitumor effect of bevacizumab administration in vivo and the side effects of bevacizumab on the pancreas in a caerulein-induced pancreatitis model. Comparison of the QGP-1 and DCC cell lines showed that QGP-1 secreted a higher level of VEGF under a hypoxic environment than the DCC cell line, and bevacizumab exerted the most marked growth-inhibitory effect on QGP-1; the number of intratumoral blood vessels decreased and the percentage of proliferating cells was approximately the same. In the pancreatitis model, bevacizumab administration did not adversely affect the pancreatitis or the associated hypoxic environment. Bevacizumab does not affect the pancreas itself; therefore, its potent inhibitory effect on the growth of pancreatic neuroendocrine tumors alone can be expected. PMID:22977618

KASUYA, KAZUHIKO; NAGAKAWA, YUICHI; SUZUKI, MINAKO; TANAKA, HIROAKI; OHTA, HIROSHI; ITOI, TAKAO; TSUCHIDA, AKIHIKO

2011-01-01

71

Diagnostic value of combining CA 19-9 and K-ras gene mutation in pancreatic carcinoma: a meta-analysis  

PubMed Central

Aims: To assess diagnostic value of Carbohydrate Antigen 19-9 (CA 19-9), combined CA 19-9 and K-ras mutation in plasma DNA in diagnosing patients with pancreatic carcinoma. Materials and methods: MEDLINE, EMBASE, the Cochrane Library, Sinomed, CNKI and other databases, from established to November, 2013, were searched for initial studies. All the studies published in English or Chinese relating to the diagnostic value of CA 19-9 and K-ras gene mutation for patients with pancreatic cancer were collected. Methodological quality was assessed. The statistic software called “Meta-disc” (version 1.4) was used for data analysis. Results: 10 studies were included in this meta-analysis. The pooled sensitivity estimate for CA 19-9 (78%) was significantly higher than K-ras mutation (65%). While, for the specificity estimate, K-ras mutation (93%) was significantly higher than CA 19-9 (77%). The pooled DOR estimate for K-ras mutation (21.82) was significantly higher than CA 19-9 (18.36). SROC curves for K-ras mutation showed better diagnostic accuracy than CA 19-9. For CA 19-9 measurement, its diagnostic value decreased in differentiating pancreatic cancer for patients with pancreatitis, especially chronic process. Conclusion: CA 19-9 was a high sensitive and K-ras was a high specific method in diagnosing patients with pancreatic cancer. These two modalities probably act different roles during different conditions in diagnosing pancreatic carcinoma. PMID:25419353

Gu, Jiangning; Wang, Di; Huang, Ya; Lu, Yi; Peng, Chenghong

2014-01-01

72

Differentiating autoimmune pancreatitis from pancreatic cancer.  

PubMed

Differential diagnosis between autoimmune pancreatitis (AIP) and pancreatic cancer can be very difficult. The main clinical symptoms in patients with autoimmune pancreatitis are jaundice, weight loss, abdominal pain and new onset of diabetes mellitus. Unfortunately, the same symptoms could be observed in patients with pancreatic carcinoma too. Imaging methods as computed tomography (CT) scan, magnetic resonance imaging (MRI) and endosonography (EUS); together with serological examination (IgG4 and Ca 19-9) play the important role in differentiation autoimmune pancreatitis from pancreatic cancer. Extrapancreatic findings are distinctive in patients with autoimmune pancreatitis. In some cases the pancreatic biopsy is indicated, mainly in patients with focal or multifocal form of autoimmune pancreatitis. Response to steroids (decreased pancreatic or extrapancreatic lesion or damage) is distinctive to AIP. In clinical practice, CT scan seems to be the most reasonable tool for examining the patients with obstructive jaundice with or without present pancreatic mass. Stratification the patients with possible AIP versus pancreatic cancer is important. In patients with AIP it may avoid pancreatic resection, as well as incorrect steroid treatment in patients with pancreatic carcinoma. PMID:25288201

Díte, P; Uvírová, M; Bojková, M; Novotný, I; Dvorácková, J; Kianicka, B; Nechutová, H; Dovrtelová, L; Floreánová, K; Martínek, A

2014-12-01

73

Comparison of Intrahepatic and Pancreatic Perfusion on Fusion Images Using a Combined SPECT/CT System and Assessment of Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy in Advanced Pancreatic Carcinoma  

SciTech Connect

Purpose. The purpose of this study was to compare intrahepatic and pancreatic perfusion on fusion images using a combined single-photon emission computed tomography (SPECT)/CT system and to evaluate the efficacy of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in the treatment of advanced pancreatic carcinoma. Materials and Methods. CTAI was performed in 33 patients (22 men, 11 women; age range, 35-77 years; mean age, 60 years) with stage IV pancreatic cancer with liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. In all patients we obtained fusion images using a combined SPECT/CT system. Pancreatic perfusion on fusion images was classified as perfusion presence or as perfusion absent in the pancreatic cancer. Using WHO criteria we recorded the tumor response after 3 months on multislice helical CT scans. Treatment effects were evaluated based on the pancreatic cancer, liver metastasis, and factors such as intrahepatic and pancreatic perfusion on fusion images. For statistical analysis we used the chi-square test; survival was evaluated by the Kaplan Meier method (log-rank test). Results. On fusion images, pancreatic and intrahepatic perfusion was recorded as hot spot and as homogeneous distribution, respectively, in 18 patients (55%) and as cold spot and heterogeneous distribution, respectively, in 15 (45%). Patients with hot spot in the pancreatic tumor and homogeneous distribution in the liver manifested better treatment results (p < 0.05 and p < 0.01, respectively). Patients with hot spot both in the pancreatic cancer and in the liver survived longer than those with cold spot in the pancreatic cancer and heterogeneous distribution in the liver (median {+-} SD, 16.0 {+-} 3.7 vs. 8.0 {+-} 1.4 months; p < 0.05). Conclusions. We conclude that in patients with advanced pancreatic cancer, CTAI with systemic chemotherapy appeared to be effective and may prolong their survival. The development of a reservoir port system allowing for the homogeneous distribution of anticancer drugs is necessary to improve the prognosis of patients with advanced pancreatic cancer.

Ikeda, Osama, E-mail: osamu-3643ik@do9.enjoy.ne.jp; Tamura, Yoshitaka; Nakasone, Yutaka; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Yamashita, Yasuyuki [Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Department of Diagnostic Radiology (Japan); Takamori, Hiroshi; Kanemitsu, Keiichiro; Baba, Hideo [Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Department of Gastroenterological Surgery (Japan)

2007-09-15

74

Adjuvant Chemoradiotherapy After Pancreatic Resection for Invasive Carcinoma Associated With Intraductal Papillary Mucinous Neoplasm of the Pancreas  

SciTech Connect

Purpose: Intraductal papillary mucinous neoplasms are mucin-producing cystic neoplasms of the pancreas. One-third are associated with invasive carcinoma. We examined the benefit of adjuvant chemoradiotherapy (CRT) for this cohort. Methods and Materials: Patients who had undergone pancreatic resection at Johns Hopkins Hospital between 1999 and 2004 were reviewed. Of these patients, 83 with a resected pancreatic mass were found to have an intraductal papillary mucinous neoplasm with invasive carcinoma, 70 of whom met inclusion criteria for the present analysis. Results: The median age at surgery was 68 years. The median tumor size was 3.3 cm, and invasive carcinoma was present at the margin in 16% of the patients. Of the 70 patients, 50% had metastases to the lymph nodes and 64% had Stage II disease. The median survival was 28.0 months, and 2- and 5-year survival rate was 57% and 45%, respectively. Of the 70 patients, 40 had undergone adjuvant CRT. Those receiving CRT were more likely to have lymph node metastases, perineural invasion, and Stage II-III disease. The 2-year survival rate after surgery with vs. without CRT was 55.8% vs. 59.3%, respectively (p = NS). Patients with lymph node metastases or positive surgical margins benefited significantly from CRT (p = .047 and p = .042, respectively). On multivariate analysis, adjuvant CRT was associated with improved survival, with a relative risk of 0.43 (95% confidence interval, 0.19-0.95; p = .044) after adjusting for major confounders. Conclusion: Adjuvant CRT conferred a 57% decrease in the relative risk of mortality after pancreaticoduodenectomy for intraductal papillary mucinous neoplasms with an associated invasive component after adjusting for major confounders. Patients with lymph node metastases or positive margins appeared to particularly benefit from CRT after definitive surgery.

Swartz, Michael J.; Hsu, Charles C. [Department of Radiation Oncology and Molecular Radiation Sciences, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Pawlik, Timothy M.; Winter, Jordan [Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Hruban, Ralph H.; Guler, Mehmet [Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Schulick, Richard D.; Cameron, John L. [Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Laheru, Daniel A. [Department of Medical Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Wolfgang, Christopher L. [Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States); Herman, Joseph M., E-mail: Jherma15@jhmi.ed [Department of Radiation Oncology and Molecular Radiation Sciences, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD (United States)

2010-03-01

75

Experimental virotherapy of chemoresistant pancreatic carcinoma using infectivity-enhanced fiber-mosaic oncolytic adenovirus  

PubMed Central

Pancreatic cancer is a significant clinical problem and novel therapeutic approaches are desperately needed. Recent advances in conditionally replicative adenovirus-based (CRAd) oncolytic virus design allow the application of CRAd vectors as a therapeutic strategy to efficiently target and eradicate chemoresistant pancreatic cancer cells thereby improving the efficacy of pancreatic cancer treatment. The goal of this study was to construct and validate the efficacy of an infectivity-enhanced, liver-untargeted, tumor-specific CRAd vector. A panel of CRAds has been derived which embody the C-X-C chemokine receptor type 4 promoter for conditional replication, two fiber complex mosaicism for targeting expansion, and hexon hypervariable region 7 (HVR7) modification for liver untargeting. We evaluated CRAds for cancer virotherapy using a human pancreatic tumor xenograft model. Employment of the fiber mosaic approach improved CRAd replication in pancreatic tumor xenografts. Substitution of the HVR7 of the Ad5 hexon for Ad serotype 3 hexon resulted in decreased liver tropism of systemically administrated CRAd. Obtained data demonstrated that employment of complex mosaicism increased efficacy of the combination of oncolytic virotherapy with chemotherapy in a human pancreatic tumor xenograft model. PMID:24903014

Kaliberov, Sergey A.; Kaliberova, Lyudmila N.; Buchsbaum, Donald J.; Curiel, David T.

2014-01-01

76

K-ras gene mutation in early ductal lesions induced in a rapid production model for pancreatic carcinomas in Syrian hamsters.  

PubMed

The presence of K-ras gene mutation was examined in experimentally induced preneoplastic pancreatic ductal lesions. Syrian hamsters received 70 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of choline-deficient diet combined with DL-ethionine and L-methionine and administration of 20 mg/kg BOP. After two augmentation pressure cycles, pancreatic ductal cell hyperplasias appeared and after three cycles, atypical hyperplasias of pancreatic ductal cells and intraductal carcinomas developed. K-ras mutations were detected by single-strand conformation polymorphism analysis of polymerase chain reaction products and nucleotide sequencing. The results showed that K-ras mutation had occurred in one of 9 simple hyperplasias of pancreatic ductal epithelium, in 5 of 9 atypical hyperplasias, and in 4 of 8 intraductal carcinomas. The findings thus suggested that K-ras is activated in association with very early stage malignant transformation of pancreatic ductal cells in hamsters. PMID:8276713

Tsutsumi, M; Kondoh, S; Noguchi, O; Horiguchi, K; Kobayashi, E; Okita, S; Ohashi, K; Honoki, K; Tsujiuchi, T; Konishi, Y

1993-11-01

77

Targeting of Urokinase Plasminogen Activator Receptor in Human Pancreatic Carcinoma Cells Inhibits c-Met- and Insulin-like Growth Factor-I Receptor-Mediated Migration and Invasion and Orthotopic Tumor Growth in Mice  

Microsoft Academic Search

Pancreatic carcinomas express high levels of urokinase-type plasminogen activator (uPA) and its receptor (uPAR), both of which mediate cell migration and invasion. We investigated the hypotheses that (a) insulin-like growth factor-I (IGF-I)- and hepatocyte growth factor (HGF)-mediated migration and invasion of human pancreatic carcinoma cells require uPA and uPAR function and (b) inhibition of uPAR inhibits tumor growth, retroperitoneal invasion,

Todd W. Bauer; Wenbiao Liu; Ernest R. Camp; Anthony Yang; Ray J. Somcio; Corazon D. Bucana; Jennifer Callahan; Graham C. Parry; Douglas B. Evans; Douglas D. Boyd; Andrew P. Mazar; Lee M. Ellis

78

An epithelial cell adhesion molecule- and CD3-bispecific antibody plus activated T-cells can eradicate chemoresistant cancer stem-like pancreatic carcinoma cells in vitro.  

PubMed

Cancer stem-like properties of various types of cancer, including pancreatic cancer, one of the most aggressive types, correlate with metastasis, invasion, and therapeutic resistance. More importantly, chemoresistance in cancer stem-like cells (CSLCs) is a critical problem for eradication of pancreatic cancer. Several cell surface markers, such as CD44 and epithelial cell adhesion molecule (EpCAM), are molecular targets on CSLCs of pancreatic carcinoma. In this study, we investigated whether catumaxomab, a clinical-grade bi-specific antibody that binds to both EpCAM on tumor cells and CD3 on T-cells, combined with activated T-cells can eliminate chemoresistant pancreatic CSLCs in vitro. Firstly, we established a CSLC line (MU-PK1) from human pancreatic carcinoma cells derived from a patient with chemoresistant and disseminated pancreatic cancer. These CSLCs were almost completely resistant to gemcitabine-mediated cytotoxicity up to a concentration of 10 ?g/ml. The cells expressed high levels of CSLC markers (CD44 and EpCAM) and had significantly higher capacities for sphere formation, invasion, and aldehyde dehydrogenase-1 expression, which are associated with cancer stemness properties. We found that pre-treatment with catumaxomab and subsequent addition of interleukin-2/OKT3 activated autologous T-cells eliminated CSLCs during a short incubation period. Moreover, when MU-PK1 cells were cultured under hypoxic conditions, the CSLCs became more aggressive. However, the combination of cytokine-activated killer T-cells with catumaxomab successfully lysed almost all these cells. In conclusion, catumaxomab combined with activated T-cells may be a potent therapeutic modality to eradicate chemoresistant pancreatic CSLCs. PMID:25075094

Umebayashi, Masayo; Kiyota, Akifumi; Koya, Norihiro; Tanaka, Hiroto; Onishi, Hideya; Katano, Mitsuo; Morisaki, Takashi

2014-08-01

79

Interferon ? inhibits growth of human pancreatic carcinoma cells via caspase-1 dependent induction of apoptosis  

PubMed Central

BACKGROUND AND AIMS—The poor prognosis of pancreatic cancer is partly due to resistance to a broad spectrum of apoptotic stimuli. To identify intact proapoptotic pathways of potential clinical relevance, we characterised the effects of interferon ? (IFN-?) on growth and survival in human pancreatic cancer cells.?METHODS—IFN-? receptor expression and signal transduction were examined by reverse transcriptase-polymerase chain reaction (RT-PCR), immunoprecipitation, western blot analysis, and transactivation assays. Effects on cell growth and survival were evaluated in terms of cell numbers, colony formation, cell cycle analysis, DNA fragmentation, and poly(ADP ribose) polymerase (PARP) cleavage.?RESULTS—All four pancreatic cancer cell lines examined expressed functional IFN-? receptors and downstream effectors, including the putative tumour suppressor interferon regulatory factor 1 (IRF-1). IFN-? treatment profoundly inhibited anchorage dependent and independent growth of pancreatic cancer cells. Cell cycle analyses revealed subdiploid cells suggesting apoptosis, which was confirmed by demonstration of DNA fragmentation and PARP cleavage. Time and dose dependency of apoptosis induction and growth inhibition correlated closely, identifying apoptosis as the main, if not exclusive, mechanism responsible for growth inhibition. Apoptosis was preceded by upregulation of procaspase-1 and accompanied by proteolytic activation. Furthermore, the caspase inhibitor z-vad-fmk completely prevented IFN-? mediated apoptosis.?CONCLUSIONS—These results identify an intact proapoptotic pathway in pancreatic cancer cells and suggest that IRF-1 and/or procaspase-1 may represent potential therapeutic targets to be further explored.???Keywords: interferon ?; apoptosis; caspase-1;interferon regulatory factor; pancreatic cancer PMID:11454803

Detjen, K; Farwig, K; Welzel, M; Wiedenmann, B; Rosewicz, S

2001-01-01

80

RhoC Interacts with Integrin ?5?1 and Enhances Its Trafficking in Migrating Pancreatic Carcinoma Cells  

PubMed Central

Human pancreatic ductal adenocarcinoma (PDAC) is characterized by early systemic dissemination. Although RhoC has been implicated in cancer cell migration, the relevant underlying molecular mechanisms remain unknown. RhoC has been implicated in the enhancement of cancer cell migration and invasion, with actions which are distinct from RhoA (84% homology), and are possibly attributed to the divergent C-terminus domain. Here, we confirm that RhoC significantly enhances the migratory and invasive properties of pancreatic carcinoma cells. In addition, we show that RhoC over-expression decreases cancer cell adhesion and, in turn, accelerates cellular body movement and focal adhesion turnover, especially, on fibronectin-coated surfaces. Whilst RhoC over-expression did not alter integrin expression patterns, we show that it enhanced integrin ?5?1 internalization and re-cycling (trafficking), an effect that was dependent specifically on the C-terminus (180-193 amino acids) of RhoC protein. We also report that RhoC and integrin ?5?1 co-localize within the peri-nuclear region of pancreatic tumor cells, and by masking the CAAX motif at the C-terminal of RhoC protein, we were able to abolish this interaction in vitro and in vivo. Co-localization of integrin ?5?1 and RhoC was demonstrable in invading cancer cells in 3D-organotypic cultures, and further mimicked in vivo analyses of, spontaneous human, (two distinct sources: operated patients and rapid autopsy programme) and transgenic murine (LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre), pancreatic cancers. In both cases, co-localization of integrin ?5?1 and RhoC correlated with poor differentiation status and metastatic potential. We propose that RhoC facilitates tumor cell invasion and promotes subsequent metastasis, in part, by enhancing integrin ?5?1 trafficking. Thus, RhoC may serve as a biomarker and a therapeutic target. PMID:24312560

Davies, Derek; Yu, Yongwei; Frese, Kristopher; Froeling, Fieke E. M.; Woolf, Adam K.; Feakins, Roger M.; Naito, Yoshiki; Iacobuzio-Donahue, Christine; Tuveson, David A.; Hart, Ian R.; Kocher, Hemant M.

2013-01-01

81

[Value and limitations of neoplasm markers in the diagnosis of pancreatic carcinoma].  

PubMed

In the last decades several markers of pancreatic neoplasia have been proposed to obtain a diagnosis as earlier as possible. Prerequisites of a good tumor marker are high sensitivity and specificity. Among the various substances, serum determination of pancreatic enzymes has been found of no utility in early diagnosis of pancreatic cancer, due to its lack in sensitivity and specificity. Similar results with ribonuclease and deoxyribonuclease. Oncofetal antigens (CEA and POA) have been initially considered promising indices; however, further studies showed their limits. In particular CEA is greatly influenced by the presence of hepatic metastases; therefore, serum levels are detectable only in advanced stages. TPA is characterized by a high sensitivity, but lacks in specificity and its use is now avoided. A real progress in the field of tumor markers has been made in the last years with the monoclonal antibody technique: among them CA 19-9 showed a good sensitivity and a satisfactory specificity as regards the diagnosis of pancreatic cancer. However, it cannot be considered as absolute aid, since it is influenced by several factors, as tumor spread, jaundice and liver dysfunction. PMID:2047559

Fabris, C; Basso, D; Meggiato, T; Del Favero, G; Fogar, P; Panozzo, M P; Ferrara, C; Scalon, P; Naccarato, R

1991-03-01

82

The Role of Antioxidant Enzymes in the Growth of Pancreatic Carcinoma  

Microsoft Academic Search

Adenocarcinoma of the pancreas is the fourth leading cause of cancer death in the United States. Because of the poor therapeutic responsiveness of pancreatic cancer to surgery, chemotherapy, and radiation therapy, survival beyond five years is rare with median survival less than six months. K-ras mutations have been identified in up to 95% of pancre- atic cancers, implying their critical

Nazee Jabbari; Joseph J. Cullen

2007-01-01

83

[A case of intraductal papillary mucinous carcinoma found with acute obstructive suppurative pancreatic ductitis and liver abscess, and associated with a pancreatobiliary fistula].  

PubMed

We report a rare case of intraductal papillary mucinous carcinoma (IPMC) with acute obstructive suppurative pancreatic ductitis (AOSPD), liver abscess, and pancreatobiliary fistula formation. A man in his sixties was admitted to our hospital with a chief complain of high grade fever and anorexia. CT and MRI revealed a multilocular cystic lesion in the pancreatic head, fistula formation between the common bile duct and this cystic lesion, and multiple liver abscess. We performed endoscopic nasopancreatic drainage for the AOSPD, endoscopic biliary drainage for the biliary flow obstruction, and percutaneous transhepatic drainage for the liver abscess. Klebsiella pneumoniae was detected in the culture of pancreatic juice and liver abscess, but not in the bile and blood culture. These culture studies revealed that the liver abscess was caused by AOSPD. The patient underwent pancreaticoduodenectomy for the IPMC. The pathological diagnosis was IPMC. PMID:23831662

Nishie, Hirotada; Okumura, Fumihiro; Fukusada, Shigeki; Inoue, Tadahisa; Kachi, Kenta; Anbe, Kaiki; Natsume, Makoto; Nishi, Yuji; Yoshimura, Norihiro; Mizushima, Takashi; Sano, Hitoshi; Kajikawa, Masaki; Harada, Akio; Naitoh, Itaru; Hayashi, Kazuki; Nakazawa, Takahiro

2013-07-01

84

Activation of PyMT in beta cells induces irreversible hyperplasia, but oncogene-dependent acinar cell carcinomas when activated in pancreatic progenitors.  

PubMed

It is unclear whether the cellular origin of various forms of pancreatic cancer involves transformation or transdifferentiation of different target cells or whether tumors arise from common precursors, with tumor types determined by the specific genetic alterations. Previous studies suggested that pancreatic ductal carcinomas might be induced by polyoma middle T antigen (PyMT) expressed in non-ductal cells. To ask whether PyMT transforms and transdifferentiates endocrine cells toward exocrine tumor phenotypes, we generated transgenic mice that carry tetracycline-inducible PyMT and a linked luciferase reporter. Induction of PyMT in beta cells causes beta-cell hyperplastic lesions that do not progress to malignant neoplasms. When PyMT is de-induced, beta cell proliferation and growth cease; however, regression does not occur, suggesting that continued production of PyMT is not required to maintain the viable expanded beta cell population. In contrast, induction of PyMT in early pancreatic progenitor cells under the control of Pdx1 produces acinar cell carcinomas and beta-cell hyperplasia. The survival of acinar tumor cells is dependent on continued expression of PyMT. Our findings indicate that PyMT can induce exocrine tumors from pancreatic progenitor cells, but cells in the beta cell lineage are not transdifferentiated toward exocrine cell types by PyMT; instead, they undergo oncogene-dependent hyperplastic growth, but do not require PyMT for survival. PMID:19812721

Du, Yi-Chieh Nancy; Klimstra, David S; Varmus, Harold

2009-01-01

85

Effects of a Non Thermal Plasma Treatment Alone or in Combination with Gemcitabine in a MIA PaCa2-luc Orthotopic Pancreatic Carcinoma Model  

PubMed Central

Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun) was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties. PMID:23300736

Brullé, Laura; Vandamme, Marc; Riès, Delphine; Martel, Eric; Robert, Eric; Lerondel, Stéphanie; Trichet, Valérie; Richard, Serge; Pouvesle, Jean-Michel; Le Pape, Alain

2012-01-01

86

Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma  

ClinicalTrials.gov

Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Gastrointestinal Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Gastrointestinal Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Gastrointestinal Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

2015-01-13

87

Intraoperative Radiation Therapy in Resected Pancreatic Carcinoma: Long-Term Analysis  

SciTech Connect

Purpose: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT + IORT). Methods and Materials: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative 'flash' RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. Results: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p = 0.019). Conclusions: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT ({approx}50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT + external RT)

Valentini, Vincenzo [Department of Radiotherapy, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Morganti, Alessio G. [Department of Radiotherapy, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Department of Radiotherapy, 'John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso (Italy); Macchia, Gabriella [Department of Radiotherapy, 'John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso (Italy)], E-mail: gmacchia@rm.unicatt.it; Mantini, Giovanna; Mattiucci, Gian C. [Department of Radiotherapy, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Brizi, M. Gabriella [Department of Radiology, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Alfieri, Sergio; Bossola, Maurizio; Pacelli, Fabio [Department of Surgery, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Sofo, Luigi [Department of Surgery, 'John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso (Italy); Doglietto, Giovanbattista [Department of Surgery, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy); Cellini, Numa [Department of Radiotherapy, Policlinico Universitario 'A. Gemelli', Catholic University, Rome (Italy)

2008-03-15

88

KRAS mutant allele-specific imbalance is associated with worse prognosis in pancreatic cancer and progression to undifferentiated carcinoma of the pancreas.  

PubMed

KRAS codon 12 mutations are present in about 90% of ductal adenocarcinomas and in undifferentiated carcinomas of the pancreas. The role of KRAS copy number changes and resulting KRAS mutant allele-specific imbalance (MASI) in ductal adenocarcinoma (n=94), and its progression into undifferentiated carcinoma of the pancreas (n=25) was studied by direct sequencing and KRAS fluorescence in situ hybridization (FISH). Semi-quantitative evaluation of sequencing electropherograms showed KRAS MASI (ie, mutant allele peak higher than or equal to the wild-type allele peak) in 22 (18.4%) cases. KRAS FISH (performed on 45 cases) revealed a trend for more frequent KRAS amplification among cases with KRAS MASI (7/20, 35% vs 3/25, 12%, P=0.08). KRAS amplification by FISH was seen only in undifferentiated carcinomas (10/24, 42% vs 0/21 pancreatic ductal adenocarcinoma, 0%, P=0.0007). In 6 of 11 cases with both undifferentiated and well-differentiated components, transition to undifferentiated carcinoma was associated with an increase in KRAS copy number, due to amplification and/or chromosome 12 hyperploidy. Pancreatic carcinomas with KRAS MASI (compared to those without MASI) were predominantly undifferentiated (16/22, 73% vs 9/97, 9%, P<0.001), more likely to present at clinical stage IV (5/22, 23% vs 7/97, 7%, P=0.009), and were associated with shorter overall survival (9 months, 95% confidence interval, 5-13, vs 22 months, 95% confidence interval, 17-27; P=0.015) and shorter disease-free survival (5 months, 95% confidence interval, 2-8 vs 13 months, 95% confidence interval, 10-16; P=0.02). Our findings suggest that in a subset of ductal adenocarcinomas, KRAS MASI correlates with the progression to undifferentiated carcinoma of the pancreas. PMID:23599154

Krasinskas, Alyssa M; Moser, A James; Saka, Burcu; Adsay, N Volkan; Chiosea, Simion I

2013-10-01

89

KRAS mutant allele-specific imbalance is associated with worse prognosis in pancreatic cancer and progression to undifferentiated carcinoma of the pancreas  

PubMed Central

KRAS codon 12 mutations are present in about 90% of ductal adenocarcinomas and in undifferentiated carcinomas of the pancreas. The role of KRAS copy number changes and resulting KRAS mutant allele-specific imbalance (MASI) in ductal adenocarcinoma (n=94), and its progression into undifferentiated carcinoma of the pancreas (n=25) was studied by direct sequencing and KRAS fluorescence in situ hybridization (FISH). Semi-quantitative evaluation of sequencing electropherograms showed KRAS MASI (ie, mutant allele peak higher than or equal to the wild-type allele peak) in 22 (18.4%) cases. KRAS FISH (performed on 45 cases) revealed a trend for more frequent KRAS amplification among cases with KRAS MASI (7/20, 35% vs 3/25, 12%, P=0.08). KRAS amplification by FISH was seen only in undifferentiated carcinomas (10/24, 42% vs 0/21 pancreatic ductal adenocarcinoma, 0%, P=0.0007). In 6 of 11 cases with both undifferentiated and well-differentiated components, transition to undifferentiated carcinoma was associated with an increase in KRAS copy number, due to amplification and/or chromosome 12 hyperploidy. Pancreatic carcinomas with KRAS MASI (compared to those without MASI) were predominantly undifferentiated (16/22, 73% vs 9/97, 9%, P<0.001), more likely to present at clinical stage IV (5/22, 23% vs 7/97, 7%, P=0.009), and were associated with shorter overall survival (9 months, 95% confidence interval, 5–13, vs 22 months, 95% confidence interval, 17–27; P=0.015) and shorter disease-free survival (5 months, 95% confidence interval, 2–8 vs 13 months, 95% confidence interval, 10–16; P=0.02). Our findings suggest that in a subset of ductal adenocarcinomas, KRAS MASI correlates with the progression to undifferentiated carcinoma of the pancreas. PMID:23599154

Krasinskas, Alyssa M; Moser, A James; Saka, Burcu; Adsay, N Volkan; Chiosea, Simion I

2014-01-01

90

Hypomethylating therapy in an aggressive stroma-rich model of pancreatic carcinoma  

PubMed Central

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that resists current treatments. To test epigenetic therapy against this cancer, we used the DNA demethylating drug 5-aza-2?-deoxycytidine (DAC) in an aggressive mouse model of stromal rich PDAC (KPC-Brca1 mice). In untreated tumors, we found globally decreased 5-methyl-cytosine (5mC) in malignant epithelial cells and in cancer-associated myofibroblasts (CAFs), along with increased amounts of 5-hydroxymethyl-cytosine (5HmC) in CAFs, in progression from pancreatic intraepithelial neoplasia (PanIN) to PDAC. DAC further reduced DNA methylation and slowed PDAC progression, markedly extending survival in an early treatment protocol and significantly though transiently inhibiting tumor growth when initiated later, without adverse side effects. Escaping tumors contained areas of sarcomatoid transformation with disappearance of CAFs. Mixing-allografting experiments and proliferation indices showed that DAC efficacy was due to inhibition of both the malignant epithelial cells and the CAFs. Expression profiling and immunohistochemistry highlighted DAC-induction of STAT1 in the tumors, and DAC plus gamma-interferon produced an additive anti-proliferative effect on PDAC cells. DAC induced strong expression of the testis antigen DAZL in CAFs. These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy. PMID:23204224

Shakya, Reena; Gonda, Tamas; Quante, Michael; Salas, Martha; Kim, Samuel; Brooks, Jenna; Hirsch, Steffen; Davies, Justine; Cullo, Angelica; Olive, Kenneth; Wang, Timothy C.; Szabolcs, Matthias; Tycko, Benjamin; Ludwig, Thomas

2012-01-01

91

A somatostatin-secreting cell line established from a human pancreatic islet cell carcinoma (somatostatinoma): release experiment and immunohistochemical study.  

PubMed

Production and secretion of somatostatin (SRIF) were studied using a carcinoembryonic antigen (CEA)-producing cell line (QGP-1) established from a human pancreatic islet cell carcinoma. High concentrations of SRIF (274 +/- 51 ng/mg of protein, mean +/- SD, n = 5) and CEA (3083 +/- 347 ng/mg of protein, mean +/- SD, n = 5) were present in QGP-1 cells, and the basal secretion rates of SRIF and CEA by the cells (n = 5) were 46.4 +/- 4.8 and 1690 +/- 78 pg/10(5) cells/h, respectively. Immunohistochemical studies revealed the presence of SRIF in xenografts of QGP-1 cells and colocalization of SRIF and CEA. Secretion of SRIF by QGP-1 cells was stimulated in the presence of high K+ (50 mmol) and theophylline (10 mmol), but arginine (10 mmol) and glucose (300 mg/dl) had no effect on the SRIF secretion. The QGP-1 cell line may be useful for studying the regulation mechanism of SRIF secretion. PMID:1971195

Iguchi, H; Hayashi, I; Kono, A

1990-06-15

92

In vivo therapeutic synergism of anti-EGFR and anti-HER2 monoclonal antibodies against pancreatic carcinomas  

E-print Network

contributed equally to this work. Running title: Anti-HER antibodies in pancreatic cancer Key words: EGFR, HER2, monoclonal antibodies, therapeutic synergism, pancreatic cancer Abbreviations: EGFR, EGF receptor The incidence of pancreatic cancer has steadily increased over the past four decades, and its prognosis is still

Boyer, Edmond

93

Overexpression of p53 protein during pancreatitis.  

PubMed Central

Overexpression of p53 correlates with neoplasia in many cytological specimens. To test the specificity of overexpressed p53 as a tumour marker for the detection of pancreatic cancer, we analysed cytological specimens of pancreatic juice samples from patients with pancreatitis or pancreatic carcinoma (n = 42) for p53 protein overexpression. p53 protein overexpression was found in 59% of patients with pancreatitis and 67% of patients with pancreatic carcinoma. Thus, the assessment of p53 protein overexpression is not useful in the diagnosis of pancreatic cancer. Overexpressed p53 during pancreatitis appears to be wild-type p53. Overexpression of p53 may result from DNA damage occurring during chronic inflammation. It is well established that p53 can induce apoptosis upon DNA damage. Consequently, we found apoptotic cell death in five out of five tested cytological preparations from patients with pancreatitis as well as in one out of one pancreatic carcinoma specimen. Images Figure 1 Figure 2 PMID:9166944

Maacke, H.; Kessler, A.; Schmiegel, W.; Roeder, C.; Vogel, I.; Deppert, W.; Kalthoff, H.

1997-01-01

94

Optical characterization of lesions and identification of surgical margins in pancreatic metastasis from renal cell carcinoma by using two-photon excited fluorescence microscopy  

NASA Astrophysics Data System (ADS)

Two-photon excited fluorescence (TPEF) microscopy has become a powerful instrument for imaging unstained tissue samples in biomedical research. The purpose of this study was to determine whether TPEF imaging of histological sections without hematoxylin-eosin (H-E) stain can be used to characterize lesions and identify surgical margins in pancreatic metastasis from renal cell carcinoma (RCC). The specimens of a pancreatic metastasis from RCC, as well as a primary RCC from a patient, were examined by TPEF microscopy and compared with their corresponding H-E stained histopathological results. The results showed that high-resolution TPEF imaging of unstained histological sections of pancreatic metastasis from RCC can reveal that the typical morphology of the tissue and cells in cancer tissues is different from the normal pancreas. It also clearly presented histopathological features of the collagenous capsule, which is an important boundary symbol to identify normal and cancerous tissue and to instruct surgical operation. It indicated the feasibility of using TPEF microscopy to make an optical diagnosis of lesions and identify the surgical margins in pancreatic metastasis from RCC.

Chen, Jing; Hong, Zhipeng; Chen, Hong; Chen, Youting; Xu, Yahao; Zhu, Xiaoqin; Zhuo, Shuangmu; Shi, Zheng; Chen, Jianxin

2014-11-01

95

Conditional deletion of p53 and Rb in the renin-expressing compartment of the pancreas leads to a highly penetrant metastatic pancreatic neuroendocrine carcinoma.  

PubMed

Efforts to model human pancreatic neuroendocrine tumors (PanNETs) in animals have been moderately successful, with minimal evidence for glucagonomas or metastatic spread. The renin gene, although classically associated with expression in the kidney, is also expressed in many other extrarenal tissues including the pancreas. To induce tumorigenesis within rennin-specific tissues, floxed alleles of p53 and Rb were selectively abrogated using Cre-recombinase driven by the renin promoter. The primary neoplasm generated is a highly metastatic islet cell carcinoma of the pancreas. Lineage tracing identifies descendants of renin-expressing cells as pancreatic alpha cells despite a lack of active renin expression in the mature pancreas. Both primary and metastatic tumors express high levels of glucagon; furthermore, an increased level of glucagon is found in the serum, identifying the pancreatic cancer as a functional glucagonoma. This new model is highly penetrant and exhibits robust frequency of metastases to the lymph nodes and the liver, mimicking human disease, and provides a useful platform for better understanding pancreatic endocrine differentiation and development, as well as islet cell carcinogenesis. The use of fluorescent reporters for lineage tracing of the cells contributing to disease initiation and progression provides an unique opportunity to dissect the timeline of disease, examining mechanisms of the metastatic process, as well as recovering primary and metastatic cells for identifying cooperating mutations that are necessary for progression of disease. PMID:24292676

Glenn, S T; Jones, C A; Sexton, S; LeVea, C M; Caraker, S M; Hajduczok, G; Gross, K W

2014-12-11

96

Long-term survival following pancreatectomy and s-1 chemotherapy for pancreatic acinar cell carcinoma with peritoneal dissemination: a case report and literature review.  

PubMed

Current case is the third report of S-1 chemotherapy against acinar cell carcinoma (ACC) of pancreas, and our patient has achieved the longest reported recurrence-free survival, longer than 6 years, despite the presence of disseminated nodules at laparotomy.A 77-year-old man presented with abdominal discomfort. Computed tomography showed a low-density tumor in the pancreas tail and the patient was referred for surgery. A 3-cm sized pancreatic tumor, with localized disseminated nodules, was detected on laparotomy. Distal pancreatectomy with concomitant resection of disseminated nodules was performed, and histopathological examination revealed an ACC. Oral S-1 chemotherapy was administered postsurgery, and the patient showed no sign of recurrence during 73 months of follow-up. This is the first report of long-term survivor of pancreatic ACC with peritoneal dissemination, following pancreatectomy and S-1 chemotherapy.Current case suggests a beneficial effect of S-1 chemotherapy in cases of ACC. PMID:25569665

Sumiyoshi, Tatsuaki; Shima, Yasuo; Okabayashi, Takehiro; Kozuki, Akihito; Iwata, Jun; Saisaka, Yuichi; Tokumaru, Teppei; Nakamura, Toshio; Morita, Sojiro

2015-01-01

97

Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma.  

PubMed

Background Pancreatic cancer is the fourth leading cause of cancer death for men and the fifth for women. The standard treatment for resectable tumours consists of a classic Whipple (CW) operation or a pylorus-preserving pancreaticoduodenectomy (PPW). It is unclear which of these procedures is more favourable in terms of survival, mortality, complications and quality of life.Objectives The objective of this systematic review is to compare the effectiveness of CW and PPW techniques for surgical treatment of cancer of the pancreatic head and the periampullary region.Search methods We conducted searches on 28 March 2006, 11 January 2011 and 9 January 2014 to identify all randomised controlled trials (RCTs),while applying no language restrictions. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects(DARE) from The Cochrane Library (2013, Issue 4); MEDLINE (1946 to January 2014); and EMBASE (1980 to January 2014). We also searched abstracts from Digestive Disease Week and United European Gastroenterology Week (1995 to 2010). We identified no additional studies upon updating the systematic review in 2014.Selection criteria We considered RCTs comparing CW versus PPW to be eligible if they included study participants with periampullary or pancreatic carcinoma. Data collection and analysis Two review authors independently extracted data from the included studies. We used a random-effects model for pooling data. We compared binary outcomes using odds ratios (ORs), pooled continuous outcomes using mean differences (MDs) and used hazard ratios (HRs) for meta-analysis of survival. Two review authors independently evaluated the methodological quality and risk of bias of included studies according to the standards of The Cochrane Collaboration.Main results We included six RCTs with a total of 465 participants. Our critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. In-hospital mortality (OR 0.49, 95% confidence interval (CI) 0.17 to 1.40; P value 0.18), overall survival (HR 0.84, 95% CI 0.61 to 1.16; P value 0.29) and morbidity showed no significant differences. However, we noted that operating time (MD -68.26 minutes, 95% CI -105.70 to -30.83; P value 0.0004) and intraoperative blood loss (MD -0.76 mL, 95%CI -0.96 to -0.56; P value < 0.00001) were significantly reduced in the PPW group. All significant results are associated with low quality of evidence as determined on the basis of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria.Authors' conclusions No evidence suggests relevant differences in mortality, morbidity and survival between the two operations. Given obvious clinical and methodological heterogeneity, future research must be undertaken to perform high-quality randomised controlled trials of complex surgical interventions on the basis of well-defined outcome parameters. PMID:25387229

Diener, Markus K; Fitzmaurice, Christina; Schwarzer, Guido; Seiler, Christoph M; Hüttner, Felix J; Antes, Gerd; Knaebel, Hanns-Peter; Büchler, Markus W

2014-01-01

98

The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer.  

PubMed Central

Heparan sulfate proteoglycans (HSPGs) play diverse roles in cell recognition, growth, and adhesion. In vitro studies suggest that cell-surface HSPGs act as coreceptors for heparin-binding mitogenic growth factors. Here we show that the glycosylphosphatidylinositol- (GPI-) anchored HSPG glypican-1 is strongly expressed in human pancreatic cancer, both by the cancer cells and the adjacent fibroblasts, whereas expression of glypican-1 is low in the normal pancreas and in chronic pancreatitis. Treatment of two pancreatic cancer cell lines, which express glypican-1, with the enzyme phosphoinositide-specific phospholipase-C (PI-PLC) abrogated their mitogenic responses to two heparin-binding growth factors that are commonly overexpressed in pancreatic cancer: fibroblast growth factor 2 (FGF2) and heparin-binding EGF-like growth factor (HB-EGF). PI-PLC did not alter the response to the non-heparin-binding growth factors EGF and IGF-1. Stable expression of a form of glypican-1 engineered to possess a transmembrane domain instead of a GPI anchor conferred resistance to the inhibitory effects of PI-PLC on growth factor responsiveness. Furthermore, transfection of a glypican-1 antisense construct attenuated glypican-1 protein levels and the mitogenic response to FGF2 and HB-EGF. We propose that glypican-1 plays an essential role in the responses of pancreatic cancer cells to certain mitogenic stimuli, that it is relatively unique in relation to other HSPGs, and that its expression by pancreatic cancer cells may be of importance in the pathobiology of this disorder. PMID:9802880

Kleeff, J; Ishiwata, T; Kumbasar, A; Friess, H; Büchler, M W; Lander, A D; Korc, M

1998-01-01

99

N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis.  

PubMed

The cell metabolome comprises abundant information that may be predictive of cell functions in response to epigenetic or genetic changes at different stages of cell proliferation and metastasis. An unbiased ultra-performance liquid chromatography-mass spectrometry-based metabolomics study revealed a significantly altered metabolome for human pancreatic carcinoma PANC-1 cells with gain-of-function non-coding microRNA-1291 (miR-1291), which led to a lower migration and invasion capacity as well as suppressed tumorigenesis in a xenograft tumor mouse model. A number of metabolites, including N-methylnicotinamide, involved in nicotinamide metabolism, and l-carnitine, isobutyryl-carnitine and isovaleryl-carnitine, involved in fatty acid metabolism, were elevated in miR-1291-expressing PANC-1. Notably, N-methylnicotinamide was elevated to the greatest extent, and this was associated with a sharp increase in nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1 cells. In addition, expression of NNMT mRNA was inversely correlated with pancreatic tumor size in the xenograft mouse model. These results indicate that miR-1291-altered PANC-1 cell function is associated with the increase in N-methylnicotinamide level and NNMT expression, and in turn NNMT may be indicative of the extent of pancreatic carcinogenesis. PMID:25115443

Bi, Hui-Chang; Pan, Yu-Zhuo; Qiu, Jing-Xin; Krausz, Kristopher W; Li, Fei; Johnson, Caroline H; Jiang, Chang-Tao; Gonzalez, Frank J; Yu, Ai-Ming

2014-10-01

100

Tumor-to-Tumor Metastasis: Lung Carcinoma Metastasizing to Thyroid Neoplasms  

PubMed Central

Tumor-to-tumor metastasis is extremely rare in the thyroid glands, and only seven cases of lung carcinoma metastasizing to thyroid tumors have been reported in the literature. We report another two cases of lung carcinoma metastasizing to thyroid neoplasms and review of the literature. The first case was a 64-year-old man presenting with neck mass, hoarseness, and easy choking for 2 months. Image studies showed several nodular lesions within bilateral thyroid glands. A histological examination after radical thyroidectomy revealed lung small cell carcinoma metastasizing to a thyroid follicular adenoma. The second case was a 71-year-old woman with a history of lung adenosquamous carcinoma. The PET/CT scan showed left lower lung cancer and a hypermetabolic area in the right thyroid lobe, highly suspicious for malignancy. Radical thyroidectomy and left lung lobectomy were performed, and the thyroid gland revealed lung adenosquamous carcinoma metastasizing to a papillary thyroid carcinoma.

Wey, Shiuan-Li; Chang, Kuo-Ming

2015-01-01

101

Antigen-loaded Dendritic Cell Migration: MR Imaging in a Pancreatic Carcinoma Model.  

PubMed

Purpose To test the following hypotheses in a murine model of pancreatic cancer: (a) Vaccination with antigen-loaded iron-labeled dendritic cells reduces T2-weighted signal intensity at magnetic resonance (MR) imaging within peripheral draining lymph nodes ( LN lymph node s) and (b) such signal intensity reductions are associated with tumor size changes after dendritic cell vaccination. Materials and Methods The institutional animal care and use committee approved this study. Panc02 cells were implanted into the flanks of 27 C57BL/6 mice bilaterally. After tumors reached 10 mm, cell viability was evaluated, and iron-labeled dendritic cell vaccines were injected into the left hind footpad. The mice were randomly separated into the following three groups (n = 9 in each): Group 1 was injected with 1 million iron-labeled dendritic cells; group 2, with 2 million cells; and control mice, with 200 mL of phosphate-buffered saline. T1- and T2-weighted MR imaging of labeled dendritic cell migration to draining LN lymph node s was performed before cell injection and 6 and 24 hours after injection. The signal-to-noise ratio ( SNR signal-to-noise ratio ) of the draining LN lymph node s was measured. One-way analysis of variance ( ANOVA analysis of variance ) was used to compare Prussian blue-positive dendritic cell measurements in LN lymph node s. Repeated-measures ANOVA analysis of variance was used to compare in vivo T2-weighted SNR signal-to-noise ratio LN lymph node measurements between groups over the observation time points. Results Trypan blue assays showed no significant difference in mean viability indexes (unlabeled vs labeled dendritic cells, 4.32% ± 0.69 [standard deviation] vs 4.83% ± 0.76; P = .385). Thirty-five days after injection, the mean left and right flank tumor sizes, respectively, were 112.7 mm(2) ± 16.4 and 109 mm(2) ± 24.3 for the 1-million dendritic cell group, 92.2 mm(2) ± 9.9 and 90.4 mm(2) ± 12.8 for the 2-million dendritic cell group, and 193.7 mm(2) ± 20.9 and 189.4 mm(2) ± 17.8 for the control group (P = .0001 for control group vs 1-million cell group; P = .00007 for control group vs 2-million cell group). There was a correlation between postinjection T2-weighted SNR signal-to-noise ratio decreases in the left popliteal LN lymph node 24 hours after injection and size changes at follow-up for tumors in both flanks (R = 0.81 and R = 0.76 for left and right tumors, respectively). Conclusion MR imaging approaches can be used for quantitative measurement of accumulated iron-labeled dendritic cell-based vaccines in draining LN lymph node s. The amount of dendritic cell-based vaccine in draining LN lymph node s correlates well with observed protective effects. © RSNA, 2014 Online supplemental material is available for this article. PMID:25222066

Zhang, Zhuoli; Li, Weiguo; Procissi, Daniele; Li, Kangan; Sheu, Alexander Y; Gordon, Andrew C; Guo, Yang; Khazaie, Khashayarsha; Huan, Yi; Han, Guohong; Larson, Andrew C

2015-01-01

102

Mass-forming pancreatitis: Value of contrast-enhanced ultrasonography  

Microsoft Academic Search

AIM: To assess the utility of contrast-enhanced ultrasonography (CEUS) with a second-generation contrast medium in the differential diagnosis between mass-forming pancreatitis and pancreatic carcinoma. METHODS: From our radio-pathology database, we retrieved all the patients affected by mass-forming pancreatitis or pancreatic carcinoma who underwent CEUS. We evaluated the results of CEUS in the study of the 173 pancreatic masses considering the

D'Onofrio M; Zamboni G; Tognolini A; Malagò R; Faccioli N; Luca Frulloni; Roberto Pozzi Mucelli

103

Elderly patients with pancreatic cancer.  

PubMed

Pancreatic cancer marked significant increase of incidence during the last decades in the elderly population. Despite the certain increase of incidence there are no international guidelines for elderly patients who are suffering from pancreatic cancer. During the ASCO Annual Meeting 2014, two abstracts focusing on elderly patients suffering from different histological types of pancreatic cancer were presented. The first retrospective study (Abstract #4119) showed the benefit of the systemic treatment on overall survival for elderly patients with stage IV pancreatic adenocarcinoma. The second retrospective study (Abstract #4112) demonstrates the positive effect of somatostatin analogue (octreotide-LAR) treatment on overall survival for elderly patients with neuroendocrine pancreatic carcinoma. PMID:25076333

Kougioumtzopoulou, Andromachi S; Syrigos, Kostas N; Saif, Muhammad Wasif

2014-07-01

104

Pancreatic Arteriovenous Malformation  

PubMed Central

An unusual case of pancreatic arteriovenous malformation (P-AVM) combined with esophageal cancer is reported. A 59-year-old man was admitted with upper abdominal pain. Contrast-enhanced computed tomography showed numerous strongly enhanced abnormal vessels and a hypovascular lesion in the area of the pancreatic tail. Angiographic study of the celiac artery confirmed racemose vascular networks in the tail of the pancreas. Endoscopic retrograde pancreatography revealed narrowing and displacement of the main pancreatic duct in the tail of the pancreas. Screening esophagoscopy showed a 0-IIa+IIc type tumor in the lower thoracic esophagus. Histological examination of esophagoscopic biopsies showed squamous cell carcinoma. Based on these findings, P-AVM or pancreatic cancer and esophageal cancer were diagnosed. Video-assisted thoracoscopic esophagectomy and distal pancreatectomy were performed. Histological examination of the resected pancreas revealed abundant abnormal vessels with intravascular thrombi. In addition, rupture of a dilated pancreatic duct with pancreatic stones and both severe atrophy and fibrosis of the pancreatic parenchyma were observed. The final diagnoses were P-AVM consequent to severe chronic pancreatitis and esophageal carcinoma. The patient's postoperative course was relatively good. PMID:24574946

Yamabuki, Takumi; Ohara, Masanori; Kimura, Noriko; Okamura, Kunishige; Kuroda, Aki; Takahashi, Ryo; Komuro, Kazuteru; Iwashiro, Nozomu

2014-01-01

105

Identification of prohibitin 1 as a potential prognostic biomarker in human pancreatic carcinoma using modified aqueous two-phase partition system combined with 2D-MALDI-TOF-TOF-MS/MS.  

PubMed

Membrane proteins are an important source of potential targets for anticancer drugs or biomarkers for early diagnosis. In this study, we used a modified aqueous two-phase partition system combined with two-dimensional (2D) matrix-assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry (MS, 2D-MALDI-TOF-TOF-MS/MS) analysis to isolate and identify membrane proteins in PANC-1 pancreatic cancer cells. Using this method, we identified 55 proteins, of which 31 (56.4 %) were membrane proteins, which, according to gene ontology annotation, are associated with various cellular processes including cell signal transduction, differentiation, and apoptosis. Immunohistochemical analysis showed that the expression level of one of the identified mitochondria membrane proteins, prohibitin 1 (PHB1), is correlated with pancreatic carcinoma differentiation; PHB1 is expressed at a higher level in normal pancreatic tissue than in well-differentiated carcinoma tissue. Further studies showed that PHB1 plays a proapoptotic role in human pancreatic cancer cells, which suggests that PHB1 has antitumorigenic properties. In conclusion, we have provided a modified method for isolating and identifying membrane proteins and demonstrated that PHB1 may be a promising biomarker for early diagnosis and therapy of pancreatic (and potentially other) cancers. PMID:25344214

Zhong, Ning; Cui, Yazhou; Zhou, Xiaoyan; Li, Tianliang; Han, Jinxiang

2014-10-25

106

A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. The Gastrointestinal Tumor Study Group.  

PubMed

One hundred six patients with histologically confirmed pancreatic carcinoma were randomized to one of three radiation treatment programs: 1) radiation therapy alone to 6000 rads; 2) 6000 rads plus 6-FU; or, 3) 4000 rads plus 5-FU. Patient survival was the primary study parameter. Both 4000 rads plus 5-FU (p less than .02) and 6000 rads plus 5-FU (p less than .01) were associated with a significantly longer patient survival than 6000 rads alone. Respective median survivals were 36 weeks, 40 weeks, and 20 weeks. The survival difference between 4000 rads plus 5-FU and 6000 rads plus 5-FU was not statistically significant at the time point selected. PMID:426553

1979-02-01

107

Experimental Therapies Of Human Pancreatic Carcinoma Transplanted To Nude Mice - A Study On Photodynamic Therapy And Local Interstitial Hyperthermia Using Low Power Nd:YAG Laser  

NASA Astrophysics Data System (ADS)

We have used photodynamic therapy (PDT) and local interstitial hyperthermia with low power Nd:YAG laser in nude mice in an attempt to study their therapeutic effects for further investigation. Pieces of solid tumor of human pancreatic carcinoma were subcutaneously transplanted in the backs of 28 nude mice which are 5-weeks old female. The fllowing experimental therapies were begun 5-6 weeks after the transplantation. 1) PDT:Argon dye laser was irradiated into a tumor with 300-400 mW in 72 hours after hematoporphyrine derivative (HpD) in a dose of 3 mg/kg was intravenously injected. Histological changes detected after 7 days were coagulated necrosis and fibrosis in the tissues ranging from 30 to 50% area ratio. 2) Local Interstitial Hyperthermia: The Frosted Probe for interstitial irradiation was punctured under controlling temperature near the margin of the tumor at 42°-43°C with 3W for 10-20 minutes. This therapy caused a marked amount of necrosis in the pancreatic tumors after 7 days. For mechanism, it seems that it is based on the effect of both thermal effect and direct effect of low power Nd:YAG laser energy on cancer cells, and the other is a damage of tumor vessels secondarily caused by this therapy in vivo.

Tajiri, Hisao; Saito, Daizo; Oguro, Yanao; Daikuzono, Norio; Joffe, Stephen N.

1987-03-01

108

Pancreatic tuberculosis with obstructive jaundice—a case report  

Microsoft Academic Search

Isolated pancreatic tuberculosis (TB) is very rare and its treatment somewhat controversial. We report a case of pancreatic TB diagnosed as pancreatic carcinoma. An 82-yr-old man presented with right upper abdominal pain and obstructive jaundice, without fever or weight loss. Ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography showed a mass lesion in the pancreatic head, which caused stricturing of the

Chien-Hua Chen; Chi-Chieh Yang; Yung-Hsiang Yeh; Jyh-Chung Yang; Der-Aur Chou

1999-01-01

109

Sann-Joong-Kuey-Jian-Tang decreases the protein expression of mammalian target of rapamycin but increases microtubule associated protein II light chain 3 expression to inhibit human BxPC?3 pancreatic carcinoma cells.  

PubMed

Sann?Joong?Kuey?Jian?Tang (SJKJT), a Traditional Chinese Medicinal prescription, has been used for the treatment of lymphadenopathy and solid tumors, and has shown therapeutic potential in a number of human malignant tumor cell lines, such as Hep?G2 hepatocellular carcinoma cells. Previous mechanistic studies demonstrated that SJKJT inhibited the proliferation of BxPC?3 pancreatic carcinoma cells through the extrinsic and intrinsic apoptotic pathways in vitro. SJKJT was also shown to be cytotoxic to colo 205 colon cancer cells by inducing autophagy in vitro. The present study therefore investigated molecular mechanisms of autophagy in human BxPC?3 pancreatic cancer cells treated with SJKJT. The cytotoxic effects of SJKJT on BxPC?3 human pancreatic carcinoma cells were evaluated using an MTT assay. Furthermore, the expression of autophagy?associated proteins, including mammalian target of rapamycin (mTOR), beclin?1, autophagocytosis?associated protein (Atg)3, Atg7, Atg5?Atg12 and microtubule?associated protein II light chain 3 (LC3?II), was assessed using western blot analysis. The results demonstrated that BxPC?3 cells treated with SJKJT exhibited decreased expression levels of mTOR and increased expression of LC3?II protein. In addition, the expression of the beclin?1, Atg3, Atg7 and Atg5?Atg12 proteins was increased during the first 24 h, but decreased from 48 to 72 h. The results showed that SJKJT inhibited the proliferation of human BxPC?3 pancreatic cancer cells in vitro. A possible underlying molecular mechanism may be the induction of autophagy. Further investigation into the therapeutic potential of SJKJT in human pancreatic cancer is required. PMID:25516264

Su, Chin-Cheng

2015-04-01

110

[Autoimmune pancreatitis is a differential diagnosis to pancreatic cancer.  

PubMed

Autoimmune pancreatitis is a rare benign inflammatory disease, treated with steroids. It consists of two clinical and histological distinct types, type 1 and type 2. Type 1 is part of an IgG4-related multiorgan disease, while type 2 is pancreas-specific. We here present a case of each type illustrating the difficult diagnostic process and how it can be misinterpreted as pancreatic carcinoma or cholangiocarcinoma. Though autoimmune pancreatitis is rare it should be considered as a differential diagnosis to pancreatic cancer. PMID:25354007

Rode, Anne A; Bremholm, Lasse

2014-10-27

111

PANCREATIC CANCER 14. PANCREATIC CANCER  

E-print Network

PANCREATIC CANCER 125 14. PANCREATIC CANCER 14.1. SUMMARY Pancreatic cancer was the eleventh most increase of approximately 4% per annum. The risk of developing pancreatic cancer up to the age of 74 was 1 their pancreatic cancer diagnosis. Table 14.1 Summary information for pancreatic cancer in Ireland, 1995

Paxton, Anthony T.

112

Treatment of Advanced Pancreatic Carcinoma with 90Y-Clivatuzumab Tetraxetan: A Phase I Single-Dose Escalation Trial  

PubMed Central

Purpose Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of 90Y-clivatuzumab tetraxetan (90Y-labeled hPAM4) in patients with advanced pancreatic cancer. Experimental Design Twenty-one patients (4 stage III; 17 stage IV) received 111In-hPAM4 for imaging and serum sampling before 90Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). Results 111In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before 90Y-hPAM4; otherwise, 20 patients received 90Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m2 (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with 90Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m2 encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m2 as the maximal tolerated 90Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%–52% tumor diameter shrinkage). Conclusion 90Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated 90Y dose, and is a potential new therapeutic for advanced pancreatic cancer. PMID:21527562

Gulec, Seza A.; Cohen, Steven J.; Pennington, Kenneth L.; Zuckier, Lionel S.; Hauke, Ralph J.; Horne, Heather; Wegener, William A.; Teoh, Nick; Gold, David V.; Sharkey, Robert M.; Goldenberg, David M.

2014-01-01

113

Antiproliferative and pro-apoptotic effects of quercetin on human pancreatic carcinoma cell lines EPP85-181P and EPP85-181RDB.  

PubMed

Polyphenols are present in several edible plants and for many years induce high interest mainly due to their antioxidative and anti-inflammatory influence. At present, numerous studies are conducted on antineoplastic effects of the compounds. One of most effective biopolyphenols involves the flavonol quercetin. Our studies aimed at evaluation of antiproliferative and pro-apoptotic effects of quercetin alone and in combinations with daunorubicin on cells of human pancreatic carcinoma lines. The experiments were conducted on two cell lines, sensitive to daunorubicin EPP85-181P line, and its resistant variant EPP85-181RDB. Effect of studied substances on cell proliferation was detected using sulphorhodamine B (SRB) protein staining method. Apoptotic damage was estimated using comet and TUNEL techniques. Our data demonstrated that quercetin exerted cytotoxic action on cells of the both neoplastic cell lines in concentration-dependent manner. In the case of EPP85-181RDB cell line, quercetin seemed to sensitize resistant cells to daunorubicin. In parallel, the effect of both substances on the sensitive cell line was synergistic. Results of the studies confirmed that quercetin may probably break resistance of neoplastic cells to chemotherapy. On the other side, studied flavonol augmented action of cytostatic drug in case of sensitive tumour cells what suggest, that it might allow to decrease dosage of cytostatic drugs and reduce negative side effects of the treatment. PMID:20675278

Borska, Sylwia; Drag-Zalesinska, Malgorzata; Wysocka, Teresa; Sopel, Miroslaw; Dumanska, Malgorzata; Zabel, Maciej; Dziegiel, Piotr

2010-01-01

114

Neuroendocrine pancreatic carcinoma after initial diagnosis of acute postpartal coeliac disease in a 37-year old woman - fatal coincidence or result of a neglected disease?  

PubMed

An acute presentation after pregnancy of coeliac disease (CD) in the puerperium is a rare condition which has been described mostly in primigravidae in patients highly suspicious of latent CD. We report the case of a 37-year-old woman who was referred to our Hospital because of refractory watery diarrhea and malnutrition syndrome. Endoscopy of the upper gastrointestinal tract revealed the classic visual features of CD and in addition, some duodenal ulcers negative for Helicobacter pylori, which seems to be another clinical feature in patients with CD. The diagnosis of acute onset of fulminant postpartal CD (Marsh score stage 3c) was confirmed histologically. Remarkably, simultaneous well-differentiated neuroendocrine non-functioning pancreatic neuroendocrine carcinoma (PNET) was diagnosed on radiological abdominal imaging which was performed since serum gastrin was remarkably high, treated by distal pancreatectomy and splenectomy. This report is, to our knowledge, the first description of the two entities, CD and PNET occurring together. Since results of antral histological studies showed diffuse hyperplasia of G-cells, probably in response to hypergastrinaemia, enterochromaffin cell carcinogenesis might have served as a possible link between both diseases. PMID:24778059

Gundling, Felix; Nerlich, Andreas; Heitland, Wolf; Schepp, Wolfgang

2014-05-01

115

Identification of Hepatocarcinoma-Intestine-Pancreas\\/Pancreatitis-associated Protein I as a Biomarker for Pancreatic Ductal Adenocarcinoma by Protein Biochip Technology1  

Microsoft Academic Search

New biomarkers of pancreatic adenocarcinoma are needed to improve the early detection of this deadly disease. We performed surface enhanced laser desorption ionization (SELDI) mass spectrometry using ProteinChip technology (Ciphergen Biosystems, Fremont, CA) to screen for differen- tially expressed proteins in pancreatic juice. Pancreatic juice samples obtained from patients undergoing pancreatectomy for pancreatic adeno- carcinoma were compared with juice samples

Christophe Rosty; Laurence Christa; Scott Kuzdzal; William M. Baldwin; Marianna L. Zahurak; Francoise Carnot; Daniel W. Chan; Marcia Canto; Keith D. Lillemoe; John L. Cameron; Charles J. Yeo; Ralph H. Hruban; Michael Goggins

2002-01-01

116

Current topics on precursors to pancreatic cancer.  

PubMed

Prognosis of invasive pancreatic ductal adenocarcinoma is bleak and the vast majority of patients with pancreatic cancer die of their disease. The detection and treatment of the non-invasive precursor lesions of pancreatic cancer offer the opportunity to cure this devastating disease and therefore great efforts are being made to identify the precursors to pancreatic cancer. Several distinct precursor lesions have been identified. Mucinous cystic neoplasms (MCNs), intraductal papillary mucinous neoplasms (IPMNs), and pancreatic intraepithelial neoplasias (PanINs) all harbor varying degrees of dysplasia and stepwise accumulation of genetic alterations, suggesting progression of these lesions from benign toward malignant neoplasms. MCNs have a characteristic ovarian-type stroma. About one-third of MCNs are associated with invasive carcinoma of ductal phenotype. IPMNs are recently established clinical entity with characteristic features of mucin hypersecretion and duct dilatation. Some IPMNs are associated with invasive carcinoma and IPMNs are recognized precursors to pancreatic cancer. PanINs are microscopic proliferative lesions arising from any parts of the pancreatic duct system. Low grade PanINs are commonly found in pancreatic ducts of elder individuals, while high grade PanINs, previously called carcinoma in situ/severe ductal dysplasia, may eventually give rise to invasive pancreatic cancer. Appropriate clinical managements are requisite for patients with MCNs, IPMNs and PanINs. Further investigation of these precursor lesions is expected to reduce the mortality from pancreatic cancer. PMID:17357272

Takaori, K; Hruban, R H; Maitra, A; Tanigawa, N

2006-01-01

117

Developments in the pathology of penile squamous cell carcinomas.  

PubMed

Most penile cancers are squamous cell carcinoma (SCC) originating in the epithelium covering glans, coronal sulcus, and foreskin. Several histologic subtypes have been described, each with distinctive clinicopathologic and outcome features. The most common subtype is the usual SCC, representing one half to two thirds of penile carcinomas. Penile verruciform tumors encompass verrucous, warty (condylomatous), and papillary, not otherwise specified, carcinomas. As a group, verruciform tumors are low grade, with low metastatic and mortality rates. In contrast, basaloid and sarcomatoid carcinomas are among the most aggressive penile tumors. Other SCC variants, such as carcinoma cuniculatum and pseudohyperplastic, adenosquamous and acantholytic carcinomas, are rare. The most relevant clinicopathologic and outcome features are outlined for each of these SCC subtypes, and an algorithm that might aid the pathologist in the histologic classification is presented. In addition, recommendations for handling penile cancer specimens, frozen section specimens, and pathology reports are provided. PMID:20691888

Chaux, Alcides; Velazquez, Elsa F; Algaba, Ferran; Ayala, Gustavo; Cubilla, Antonio L

2010-08-01

118

Clinical Features and Differential Diagnoses in Laryngeal Mucoepidermoid Carcinoma  

PubMed Central

Mucoepidermoid carcinoma is the most common malignant tumor of salivary glands. However, it is a rare entity in larynx. Laryngeal cases are frequently misdiagnosed with other malignancies and they are under-reported. So, recognizing the clinical and histological features of this tumor is essential. Laryngeal mucoepidermoid carcinoma can arise in supraglottis, glottis and subglottis. Generally, it presents as a submucosal mass; therefore, progressive symptoms without any identifiable lesion in laryngoscopy must be well considered. The prognosis is somehow dependent on the histological features. In high-grade tumors, recurrence is more common and radical surgery with radiotherapy is recommended. In this paper, we provide a thorough literature review on mucoepidermoid carcinoma in the larynx. The most important distinguishing features of mucoepidermoid carcinoma and its two major differential diagnoses (squamous cell carcinoma and adenosquamous carcinoma) are clearly stated and pitfalls in true diagnosis of this tumor are discussed. PMID:22262946

Mokhtari, Sepideh; Mokhtari, Saeedeh

2012-01-01

119

A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer  

SciTech Connect

Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp [Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba (Japan)] [Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba (Japan); Ioka, Tatsuya [Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan)] [Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)] [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Yonemoto, Naohiro [Department of Epidemiology and Biostatistics, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo (Japan)] [Department of Epidemiology and Biostatistics, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo (Japan); Nagase, Michitaka [Department of Clinical Oncology, Jichi Medical University, Tochigi (Japan)] [Department of Clinical Oncology, Jichi Medical University, Tochigi (Japan); Yamao, Kenji [Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya (Japan)] [Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya (Japan); Miyakawa, Hiroyuki [Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo (Japan)] [Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo (Japan); Ishii, Hiroshi [Hepatobiliary and Pancreatic Division, Cancer Institute Hospital, Tokyo (Japan)] [Hepatobiliary and Pancreatic Division, Cancer Institute Hospital, Tokyo (Japan); Furuse, Junji [Department of Internal Medicine, Medical Oncology School of Medicine, Kyorin University, Tokyo (Japan)] [Department of Internal Medicine, Medical Oncology School of Medicine, Kyorin University, Tokyo (Japan); Sato, Keiko [Kyoto Unit Center, Japan Environment and Children's Study, Kyoto University Graduate School of Medicine, Kyoto (Japan)] [Kyoto Unit Center, Japan Environment and Children's Study, Kyoto University Graduate School of Medicine, Kyoto (Japan); Sato, Tosiya [Department of Biostatistics, Kyoto University School of Public Health, Kyoto (Japan)] [Department of Biostatistics, Kyoto University School of Public Health, Kyoto (Japan); Okusaka, Takuji [Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo (Japan)] [Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo (Japan)

2013-01-01

120

Mutations of K-ras but not p53 genes in biliary duct and pancreatic duct carcinomas induced in hamsters by cholecystoduodenostomy with dissection of the common duct followed by N-nitrosobis(2-oxopropyl)amine.  

PubMed

An experimental model for the induction of extrahepatic biliary duct carcinomas in hamsters given cholecystoduodenostomy with dissection of the extrahepatic duct at the distal end of the common duct (CDDB) followed by N-nitrosobis(2-oxopropyl)amine (BOP) has been reported [Tajima et al. (1994) Jpn. J. Cancer Res., 85, 780-788]. The CDDB procedure greatly accelerates cell turnover in the biliary epithelium. In the present experiment, mutations of K-ras and p53 genes in the induced lesions were investigated by the reverse transcriptase-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) method followed by direct sequencing. Mutations of K-ras, involving a G to A transition in second position of codon 12 of K-ras exon 1, were detected in six out of eight (75%) extrahepatic bile duct carcinomas and six out of eleven (54.5%) pancreatic duct carcinomas. However, no mutations of p53 were observed in either tumor type. The results indicate an association between anomalous pancreaticobiliary junction and development of biliary carcinomas that may be pertinent to the human situation, and indicate that conditions of the model predispose to mutations occurring in K-ras but not p53. PMID:9310259

Majima, T; Tsujiuchi, T; Tsutsumi, M; Tsunoda, T; Konishi, Y

1997-09-16

121

Rising incidence of pancreatic carcinoma in middle-aged and older women-time trends 1961-90 in the city of Malmö, Sweden  

Microsoft Academic Search

The city of Malmö (population 230 000), situated in the south of Sweden, is in an area which has the highest incidence of pancreatic cancer in the country. The present study was designed to assess time trends of the incidence of pancreatic cancer 1961-90. The 1314 incident cases, 651 men and 663 women, were retrieved from the Regional Tumour Register

M Hedberg; H Anderson; A Borgström; L Janzon; SA Larsson

1996-01-01

122

Sann-Joong-Kuey-Jian-Tang decreases the protein expression of Mcl?1 and TCTP and increases that of TNF-? and Bax in BxPC?3 pancreatic carcinoma cells.  

PubMed

Sann-Joong-Kuey-Jian-Tang (SJKJT), a traditional Chinese medicinal prescription, has been used for the treatment of lymphadenopathy and solid tumors, and has shown therapeutic potential in several human malignant tumor cell lines. However, the efficacy and molecular mechanisms of action of SJKJT in human pancreatic cancer have not yet been elucidated. In the present study, we evaluated the cytotoxic effects of SJKJT on BxPC-3 human pancreatic carcinoma cells by MTT assay. The protein expression levels of myeloid cell leukemia 1 protein (Mcl-1), translationally controlled tumor protein (TCTP), tumor necrosis factor-? (TNF??), caspase-8, caspase-3, Bax and Bcl-2 family in the BxPC-3 cells were measured by western blot analysis. The cell cycle was analyzed by flow cytometry. The protein expression of caspase-3 was also detected by immunocytochemistry (ICC). The results revealed that SJKJT inhibited the proliferation of BxPC-3 cells in a time- and dose-dependent manner. The protein expression levels of TNF-?, caspase-8, caspase-3 and Bax increased in the BxPC-3 cells treated with SJKJT; however, the levels of Mcl-1, TCTP and Bcl-xL decreased. The results also demonstrated that SJKJT increased the percentage of BxPC-3 cells in the sub-G1 phase. In addition, ICC staining indicated that the protein expression of caspase-3 was upregulated in the BxPC-3 cells treated with SJKJT. These findings indicate that SJKJT inhibits the proliferation of BxPC-3 cells through the extrinsic and intrinsic pathway, inducing apoptosis in vitro. Our study, using BxPC-3 human pancreatic cancer cells, demonstrates that SJKJT has potential as a chemotherapeutic agent for the treatment of pancreatic cancer. Further sutdies are warranted to fully elucidate its mechanisms of action. PMID:23652631

Chien, Su-Yu; Kuo, Shou-Jen; Chen, Dar-Ren; Su, Chin-Cheng

2013-07-01

123

Small Molecule Inhibitor YM155-Mediated Activation of Death Receptor 5 Is Crucial for Chemotherapy-Induced Apoptosis in Pancreatic Carcinoma.  

PubMed

Despite much effort, pancreatic cancer survival rates are still dismally low. Novel therapeutics may hold the key to improving survival. YM155 is a small molecule inhibitor that has shown antitumor activity in a number of cancers by reducing the expression of survivin. The aim of our study is to understand the mechanisms by which YM155 functions in pancreatic cancer cells. We established the antitumor effect of YM155 with in vitro studies in cultured cells, and in vivo studies using a mouse xenograft model. Our data demonstrated that YM155 reduced the expression of survivin; however, downregulation of survivin itself is insufficient to induce apoptosis in pancreatic cancer cells. We showed for the first time that treatment with YM155 increased death receptor 5 (DR5) expression in pancreatic cancer cells. We found that YM155 induced apoptosis by broad-spectrum inhibition of IAP family member proteins (e.g., CIAP1/2 and FLIP) and induced proapoptotic Bak protein upregulation and activation; the antitumor effect of YM155 treatment with either the DR5 agonist lexatumumab or gemcitabine on pancreatic cancer cells was synergistic. Our data also revealed that YM155 inhibits tumor growth in vivo, without apparent toxicity to the noncancerous human pancreatic ductal epithelial cell line. Together, these findings suggest that YM155 could be a novel therapeutic agent for pancreatic cancer. Mol Cancer Ther; 14(1); 80-89. ©2014 AACR. PMID:25344582

Zhao, Xiangxuan; Puszyk, William M; Lu, Zaiming; Ostrov, David A; George, Thomas J; Robertson, Keith D; Liu, Chen

2015-01-01

124

Histological variants of prostatic carcinoma and their significance.  

PubMed

The vast majority of prostatic cancers are acinar adenocarcinomas. Histological variants of prostatic carcinoma have been variably defined. One approach is to consider two groups of variants. The first group comprises histological variants of acinar adenocarcinoma and the second group non-acinar carcinoma variants or types. Variants of usual acinar adenocarcinoma defined in 2004 by the World Health Organization (WHO) include atrophic, pseudohyperplastic, foamy, colloid, signet ring, oncocytic and lymphoepithelioma-like carcinomas. The second group of non-acinar carcinoma histological variants or types of prostatic carcinoma accounts for about 5-10% of carcinomas that originate in the prostate. These include sarcomatoid carcinoma, ductal adenocarcinoma, urothelial carcinoma, squamous and adenosquamous carcinoma, basal cell carcinoma, and neuroendocrine tumours, specifically small-cell carcinoma. Recently characterized variants not present in the 2004 WHO classification, including microcystic adenocarcinoma, prostatic intraepithelial neoplasia-like adenocarcinoma, large-cell neuroendocrine carcinoma, and pleomorphic giant cell carcinoma, are also described. The aims of this review are to present the essential histomorphological diagnostic attributes of these variants, and to emphasize the clinical signficance of the variants, when different from usual acinar adenocarcinoma, including clinical presentation and outcome. PMID:22212078

Humphrey, Peter A

2012-01-01

125

Pancreatic carcinogenesis: apoptosis and angiogenesis.  

PubMed

Apoptosis and angiogenesis are critical biologic processes that are altered during carcinogenesis. Both apoptosis and angiogenesis may play an important role in pancreatic carcinogenesis. Despite numerous advances in the diagnosis and treatment of pancreatic cancer, its prognosis remains dismal and a new therapeutic approach is much needed. Recent research has revealed that apoptosis and angiogenesis are closely interrelated. Several reports show that a tumor suppresser gene that is expressed in pancreatic carcinoma and related to malignant potential can induce apoptosis and also inhibit angiogenesis. At present, it is generally accepted that tumor growth in cancers, including pancreatic cancer, depends on angiogenesis. We have identified 2 new angiogenesis inhibitors from a conditioned medium of human pancreatic carcinoma cell line (BxPC-3): antiangiogenic antithrombin III (aaAT-III) and vitamin D binding protein-macrophage activating factor (DBP-maf). These molecules were able to regress tumors in severe combined immunodeficiency disease (SCID) mice, demonstrating potent inhibition of endothelial cell proliferation. Moreover, the angiogenesis inhibitors induced tumor dormancy in the animal model. These results suggest that antiangiogenic therapy using angiogenesis inhibitors may become a new strategy for treatment of pancreatic cancer in the near future. PMID:15084979

Onizuka, Shinya; Kawakami, Shunsuke; Taniguchi, Ken; Fujioka, Hikaru; Miyashita, Kosei

2004-04-01

126

Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells  

E-print Network

chemo- radiation followed by maintenance erlotinib for locally advanced pan- creatic cancer:chemo- therapy produced a relative increase of 25% in 1-year sur- vival in patients with pancreatic cancer (

2007-01-01

127

Tumour markers in pancreatic cancer.  

PubMed

Patients with pancreatic cancer usually lack signs and symptoms in the early course of the disease. Even when malignancy is suspected, differential diagnosis between benign and malignant pancreatic disorders may be difficult with current methods. An increasing interest has been focused on the utility of immunological tumour markers. CEA has been widely used since the early seventies, but the results in diagnosis of pancreatic cancer have been disappointing. Tumour marker tests for CA 19-9 and CA 50 are based on monoclonal antibodies to colonic carcinoma cell lines. CA 19-9 and CA 50 are strongly expressed in most tissue specimens from pancreatic carcinomas, but are also found in normal pancreas and benign pancreatic diseases. The CA 19-9 and CA 50 antigens are shed or released into the circulation, and are found in increased concentrations in 70-80% of patients with pancreatic cancer. Also 50-65% of patients with small resectable carcinomas have elevated CA 19-9 and CA 50 levels, although very high serum concentrations usually indicate advanced disease. Slightly elevated serum CA 19-9 and CA 50 levels are seen in some patients with benign pancreatic diseases, more often in acute than in chronic pancreatitis. Elevated values are often observed in patients with benign obstruction of the common bile duct, particularly in patients with cholangitis. In patients with jaundice of hepatocellular origin, the CA 19-9 and CA 50 levels are lower than in extrahepatic cholestasis. CA 19-9 and CA 50 have better diagnostic accuracy for pancreatic cancer than CEA, CA 125, DU-PAN-2, TPA and PSTI/TATI. However, the sensitivities and specificities of CA 19-9 and CA 50 are too low for screening of an asymptomatic population. Nevertheless, CA 19-9 and CA 50 have in our experience shown to be useful complements to other diagnostic methods in symptomatic patients with suspicion of pancreatic cancer. Combinations of different markers improve the sensitivity only slightly compared to the use of CA 19-9 or CA 50 alone. Follow-up using CA 19-9 and CA 50 is a simple and sensitive way of monitoring the postoperative course of patients with pancreatic cancer, and may give a lead time of several months for a recurrence compared to conventional methods. PMID:2667448

Haglund, C; Kuusela, P; Roberts, P J

1989-01-01

128

What Is Pancreatic Cancer?  

MedlinePLUS

... How many people get pancreatic cancer? What is pancreatic cancer? To understand pancreatic cancer, it helps to know ... about these tumors, see our document Pancreatic Cancer . Pancreatic cancers Both the exocrine and endocrine cells of the ...

129

Pancreatic Ductal Adenocarcinoma  

Cancer.gov

Home Cancers Selected for Study Pancreatic Ductal Adenocarcinoma Pancreatic Ductal Adenocarcinoma Last Updated: May 15, 2013 What is pancreatic cancer?Pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer, making up more than

130

Targeting the Cancer-Stroma Interaction: A Potential Approach for Pancreatic Cancer Treatment  

PubMed Central

Recent studies have demonstrated that the interaction between the cancer and the stroma, play a key role in the development of pancreatic cancer. The desmoplasia, which consists of fibroblasts, pancreatic stellate cells, lymphatic and vascular endothelial cells, immune cells, pathologic increased nerves, and the extracellular matrix (ECM), creates a complex tumor microenvironment that promotes pancreatic cancer development, invasion, metastasis, and resistance to chemotherapy. Thus, the potential approach for targeting the components of this desmoplastic reaction or the pancreatic tumor microenvironment might represent a novel therapeutic approach to advanced pancreatic carcinoma. Novel therapies that target on the pancreatic tumor microenvironment should become one of the more effective treatments for pancreatic cancer. PMID:22372501

Li, Xuqi; Ma, Qingyong; Xu, Qinhong; Duan, Wanxing; Lei, Jianjun; Wu, Erxi

2012-01-01

131

Acute pancreatitis.  

PubMed

Acute pancreatitis is most commonly caused by gallstones or chronic alcohol use, and accounts for more than 200,000 hospital admissions annually. Using the Atlanta criteria, acute pancreatitis is diagnosed when a patient presents with two of three findings, including abdominal pain suggestive of pancreatitis, serum amylase and/or lipase levels at least three times the normal level, and characteristic findings on imaging. It is important to distinguish mild from severe disease because severe pancreatitis has a mortality rate of up to 30%. Contrast-enhanced computed tomography is considered the diagnostic standard for radiologic evaluation of acute pancreatitis because of its success in predicting disease severity and prognosis. The BALI and computed tomography severity index scores also can aid in determining disease severity and predicting the likelihood of complications. Treatment begins with pain control, hydration, and bowel rest. In the first 48 to 72 hours of treatment, monitoring is required to prevent morbidity and mortality associated with worsening pancreatitis. When prolonged bowel rest is indicated, enteral nutrition is associated with lower rates of complications, including death, multiorgan failure, local complications, and systemic infections, than parenteral nutrition. In severe cases involving greater than 30% necrosis, antibiotic prophylaxis with imipenem/cilastatin decreases the risk of pancreatic infection. In gallstone-associated pancreatitis, early cholecystectomy and endoscopic retrograde cholangiopancreatography with sphincterotomy can decrease length of hospital stay and complication rates. A multidisciplinary approach to care is essential in cases involving pancreatic necrosis. PMID:25368923

Quinlan, Jeff D

2014-11-01

132

Plumbagin, Isolated from Plumbago zeylanica, Induces Cell Death through Apoptosis in Human Pancreatic Cancer Cells  

Microsoft Academic Search

Background and Aims: Pancreatic cancer is one of the most resistant malignancies. Several studies have indicated that plumbagin isolated from Plumbago zeylanica possesses anticancer activity. However, its antitumor effects against pancreatic cancer have not been explored. Methods: We investigated the effect of plumbagin on the growth of human pancreatic carcinoma cells and its possible underlying mechanisms. Results: Plumbagin inhibited the

Chien-An Chen; Hen-Hong Chang; Chung-Yu Kao; Tung-Hu Tsai; Yu-Jen Chen

2009-01-01

133

Local Staging of Pancreatic Cancer: Criteria for Unresectability of Major Vessels as Revealed by Pancreatic-Phase, Thin-Section Helical CT  

Microsoft Academic Search

OBJECTIVE. This study was conducted to determine the criteria for unresectability of major peripancreatic vessels in patients with pancreatic carcinoma as revealed by optimally enhanced. pancreatic-phase thin-section helical CT. SUBJECTS AND METHODS. Twenty-five patients with pancreatic adenocarcinoma who underwent local dissection during curative or palliative surgery also underwent preoperative pancreatic-phase thin-section helical CT (40- to 70-sec delay. 2.5- to 3-mm

David S. K. Lu; Howard A. Reber; Robert M. KraSny; Barbara M. Kadell; Jim Sayre

134

Prognostic significance of angiogenesis in human pancreatic cancer  

Microsoft Academic Search

To evaluate whether angiogenic factors are of clinical relevance to actual human pancreatic cancers, we studied the intratumoral microvessel density (IMD), and PD-ECGF, VEGF protein expression in 40 pancreatic cancers using immunohistochemistry. We also investigated PD-ECGF and VEGF gene expression using reverse transcriptase-PCR (RT-PCR). Of the 40 pancreatic cancers studied, 30 carcinomas (75.0%) were evaluated to be PD-ECGF-positive and 10

N Ikeda; M Adachi; T Taki; C Huang; H Hashida; A Takabayashi; M Sho; Y Nakajima; H Kanehiro; M Hisanaga; H Nakano; M Miyake

1999-01-01

135

Evaluation of a New Modification of Pancreaticogastrostomy after Pancreaticoduodenectomy: Anastomosis of the Pancreatic Duct to the Gastric Mucosa with Invagination of the Pancreatic Remnant End into the Posterior Gastric Wall for Patients with Cancer Head of Pancreas and Periampullary Carcinoma in terms of Postoperative Pancreatic Fistula Formation  

PubMed Central

Background/Objectives. Postoperative pancreatic fistula (POPF) remains the main problem after pancreaticoduodenectomy and determines to a large extent the final outcome. We describe a new modification of pancreaticogastrostomy which combines duct to mucosa anastomosis with suturing the pancreatic capsule to posterior gastric wall and then invaginating the pancreatic remnant into the posterior gastric wall. This study was designed to assess the results of this new modification of pancreaticogastrostomy. Methods. The newly modified pancreaticogastrostomy was applied to 37 consecutive patients after pancreaticoduodenectomy for periampullary cancer (64.86%) or cancer head of the pancreas (35.14%). Eighteen patients (48.65%) had a soft pancreatic remnant, 13 patients (35.14%) had firm pancreatic remnant, and 6 patients (16.22%) had intermediate texture of pancreatic remnant. Rate of mortality, early postoperative complications, and hospital stay were also reported. Results. Operative mortality was zero and morbidity was 29.73%. Only three patients (8.11%) developed pancreatic leaks; they were treated conservatively. Eight patients (16.1%) had delayed gastric emptying, one patient (2.70%) had minor hemorrhage, one patient (2.70%) had biliary leak, and four patients (10.81%) had superficial wound infection. Conclusions. The new modified pancreatogastrostomy seems safe and reliable with low rate of POPF. However, further prospective controlled trials are essential to support these results. PMID:25302117

Abd El Maksoud, Walid

2014-01-01

136

A novel adhesion factor produced by hamster pancreatic cancer cell line is effective on normal and carcinoma cell lines of different species  

Microsoft Academic Search

Summary  An adhesion factor, produced by the hamster pancreatic cancer cell line PC-1.0, was tested for its efficiency in promoting\\u000a the in vitro adhesion of normal and tumor cells (pancreas, lung, kidney, colon, breast, skin, prostate, neuroblast, melanocyte)\\u000a derived from human, monkey, bovine, hamster, and rat sources. Using a modification of the dimethylthyazol diphenyl tetrazolium\\u000a (MTT) assay, the factor was found

Ilia A. Toshkov; William G. Chaney; David M. Colcher; Michael A. Hollingsworth; Troitza K. Bratanova; Fulvio Perini; Parviz M. Pour

1995-01-01

137

Inhibition of pancreatic carcinoma by homo- and heterocombinations of antibodies against EGF-receptor and its kin HER2/ErbB-2  

PubMed Central

Due to intrinsic aggressiveness and lack of effective therapies, prognosis of pancreatic cancer remains dismal. Because the only molecular targeted drug approved for pancreatic ductal adenocarcinoma is a kinase inhibitor specific to the epidermal growth factor receptor (EGFR), and this receptor collaborates with another kinase, called HER2 (human EGF-receptor 2), we assumed that agents targeting EGFR and/or HER2 would effectively retard pancreatic ductal adenocarcinoma. Accordingly, two immunological strategies were tested in animal models: (i) two antibodies able to engage distinct epitopes of either EGFR or HER2 were separately combined, and (ii) pairs of one antibody to EGFR and another to HER2. Unlike the respective single monoclonal antibodies, which induced weak effects, both types of antibody combinations synergized in animals in terms of tumor inhibition. Immunological cooperation may not depend on receptor density, antigenic sites, or the presence of a mutant RAS protein. Nevertheless, both types of antibody combinations enhanced receptor degradation. Future efforts will examine the feasibility of each strategy and the potential of combining them to achieve sustained tumor inhibition. PMID:24003140

Maron, Ruth; Schechter, Bilha; Mancini, Maicol; Mahlknecht, Georg; Yarden, Yosef; Sela, Michael

2013-01-01

138

Inhibition of pancreatic carcinoma by homo- and heterocombinations of antibodies against EGF-receptor and its kin HER2/ErbB-2.  

PubMed

Due to intrinsic aggressiveness and lack of effective therapies, prognosis of pancreatic cancer remains dismal. Because the only molecular targeted drug approved for pancreatic ductal adenocarcinoma is a kinase inhibitor specific to the epidermal growth factor receptor (EGFR), and this receptor collaborates with another kinase, called HER2 (human EGF-receptor 2), we assumed that agents targeting EGFR and/or HER2 would effectively retard pancreatic ductal adenocarcinoma. Accordingly, two immunological strategies were tested in animal models: (i) two antibodies able to engage distinct epitopes of either EGFR or HER2 were separately combined, and (ii) pairs of one antibody to EGFR and another to HER2. Unlike the respective single monoclonal antibodies, which induced weak effects, both types of antibody combinations synergized in animals in terms of tumor inhibition. Immunological cooperation may not depend on receptor density, antigenic sites, or the presence of a mutant RAS protein. Nevertheless, both types of antibody combinations enhanced receptor degradation. Future efforts will examine the feasibility of each strategy and the potential of combining them to achieve sustained tumor inhibition. PMID:24003140

Maron, Ruth; Schechter, Bilha; Mancini, Maicol; Mahlknecht, Georg; Yarden, Yosef; Sela, Michael

2013-09-17

139

Radiological intervention in pancreatic cancer.  

PubMed

Pancreatic carcinoma is increasing in its incidence, and despite advances in surgical treatment and chemotherapy, its prognosis remains extremely poor. Realistic therapy is targeted primarily at the relief of obstruction of the biliary tract and the duodenum, as well as the relief of pain. This paper discusses the indications and techniques for palliation and illustrates the critical team approach between radiologist, endoscopist and surgeon. PMID:9442121

Martin, D F; England, R E; Tweedle, D E

1998-01-01

140

Thalidomide in Treating Patients With Recurrent or Persistent Endometrial Cancer  

ClinicalTrials.gov

Endometrial Adenoacanthoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma

2013-01-23

141

Clinicopathologic Characteristics of 29 Invasive Carcinomas Arising in 178 Pancreatic Mucinous Cystic Neoplasms With Ovarian-type Stroma: Implications for Management and Prognosis.  

PubMed

Information on the clinicopathologic characteristics of invasive carcinomas arising from mucinous cystic neoplasms (MCNs) is limited, because in many early studies they were lumped and analyzed together with noninvasive MCNs. Even more importantly, many of the largest prior studies did not require ovarian-type stroma (OTS) for diagnosis. We analyzed 178 MCNs, all strictly defined by the presence of OTS, 98% of which occurred in perimenopausal women (mean age, 47 y) and arose in the distal pancreas. Twenty-nine (16%) patients had associated invasive carcinoma, and all were female with a mean age of 53. Invasion was far more common in tumors with grossly visible intracystic papillary nodule formation ?1.0 cm (79.3% vs. 8.7%, P=0.000) as well as in larger tumors (mean cyst size: 9.4 vs. 5.4 cm, P=0.006); only 4/29 (14%) invasive carcinomas occurred in tumors that were <5 cm; however, none were <3 cm. Increased serum CA19-9 level (>37 U/L) was also more common in the invasive tumors (64% vs. 23%, P=0.011). Most invasive carcinomas (79%) were of tubular type, and the remainder (5 cases) were mostly undifferentiated carcinoma (2, with osteoclast-like giant cells), except for 1 with papillary features. Interestingly, there were no colloid carcinomas; 2 patients had nodal metastasis at the time of diagnosis, and both died of disease at 10 and 35 months, respectively. While noninvasive MCNs had an excellent prognosis (100% at 5 y), tumors with invasion often had an aggressive clinical course with 3- and 5-year survival rates of 44% and 26%, respectively (P=0.000). The pT2 (>2 cm) invasive tumors had a worse prognosis than pT1 (?2 cm) tumors (P=0.000), albeit 3 patients with T1a (<0.5 cm) disease also died of disease. In conclusion, invasive carcinomas are seen in 16% of MCNs and are mostly of tubular (pancreatobiliary) type; colloid carcinoma is not seen in MCNs. Serum CA19-9 is often higher in invasive carcinomas, and invasion is typically seen in OTS-depleted areas with lower progesterone receptor expression. Invasion is not seen in small tumors (<3 cm) and those lacking intracystic papillary (mural) nodules of ?1 cm, thus making the current branch-duct intraductal papillary mucinous neoplasm management protocols also applicable to MCNs. PMID:25517958

Jang, Kee-Taek; Park, Sang Mo; Basturk, Olca; Bagci, Pelin; Bandyopadhyay, Sudeshna; Stelow, Edward B; Walters, Dustin M; Choi, Dong Wook; Choi, Seoung Ho; Heo, Jin Seok; Sarmiento, Juan M; Reid, Michelle D; Adsay, Volkan

2015-02-01

142

Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis  

Microsoft Academic Search

Hedgehog signalling-an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer-may also be an important mediator in human pancreatic carcinoma. Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx-Shh mice (in which Shh

Sarah P. Thayer; Marina Pasca di Magliano; Patrick W. Heiser; Corinne M. Nielsen; Drucilla J. Roberts; Gregory Y. Lauwers; Yan Ping Qi; Stephan Gysin; Carlos Fernández-del Castillo; Vijay Yajnik; Bozena Antoniu; Martin McMahon; Andrew L. Warshaw; Matthias Hebrok

2003-01-01

143

Pancreatic Cancer  

MedlinePLUS

... sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for ... therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. NIH: National Cancer Institute

144

Pancreatic Carcinogenesis  

PubMed Central

Pancreatic cancer is an almost universally lethal disease. Research over the last two decades has shown that pancreatic cancer is fundamentally a genetic disease, caused by inherited germline and acquired somatic mutations in cancer-associated genes. Multiple alterations in genes that are important in pancreatic cancer progression have been identified, including tumor suppressor genes, oncogenes, and genome maintenance genes. Furthermore, the identification of noninvasive precursor lesions of pancreatic adenocarcinoma has led to the formulation of a multi-step progression model of pancreatic cancer and the subsequent identification of early and late genetic alterations culminating in invasive cancer. In addition, an increased understanding of the molecular basis of the disease has facilitated the identification of new drug targets enabling rational drug design. The elucidation of genetic alterations in combination with the development of high-throughput sensitive techniques should lead to the discovery of effective biomarkers for early detection of this malignancy. This review focuses mainly on the current knowledge about the molecular insights of the pathogenesis of pancreatic ductal adenocarcinoma. PMID:18382097

Koorstra, Jan-Bart M.; Hustinx, Steven R.; Offerhaus, G. Johan A.; Maitra, Anirban

2008-01-01

145

Evaluation of Four-Dimensional Computed Tomography-Based Intensity-Modulated and Respiratory-Gated Radiotherapy Techniques for Pancreatic Carcinoma  

SciTech Connect

Purpose: To compare conformal radiotherapy (CRT), intensity-modulated radiotherapy (IMRT), and respiration-gated radiotherapy (RGRT) planning techniques for pancreatic cancer. All target volumes were determined using four-dimensional computed tomography scans (4D CT). Methods and Materials: The pancreatic tumor and enlarged regional lymph nodes were contoured on all 10 phases of a planning 4D CT scan for 10 patients, and the planning target volumes (PTV{sub allphases}) were generated. Three consecutive respiratory phases for RGRT delivery in both inspiration and expiration were identified, and the corresponding PTVs (PTV{sub inspiration} and PTV{sub expiration}) and organ at risk volumes created. Treatment plans using CRT and IMRT, with and without RGRT, were created for each PTV. Results: Compared with the CRT plans, IMRT significantly reduced the mean volume of right kidney exposed to 20 Gy from 27.7% {+-} 17.7% to 16.0% {+-} 18.2% (standard deviation) (p < 0.01), but this was not achieved for the left kidney (11.1% {+-} 14.2% to 5.7% {+-} 6.5%; p = 0.1). The IMRT plans also reduced the mean gastric, hepatic, and small bowel doses (p < 0.01). No additional reductions in the dose to the kidneys or other organs at risk were seen when RGRT plans were combined with either CRT or IMRT, and the findings for RGRT in end-expiration and end-inspiration were similar. Conclusion: 4D CT-based IMRT plans for pancreatic tumors significantly reduced the radiation doses to the right kidney, liver, stomach, and small bowel compared with CRT plans. The additional dosimetric benefits from RGRT appear limited in this setting.

Geld, Ylanga G. van der; Triest, Baukelien van; Verbakel, Wilko; Soernsen de Koste, John R. van; Senan, Suresh; Slotman, Ben J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Lagerwaard, Frank J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)], E-mail: FJ.Lagerwaard@vumc.nl

2008-11-15

146

Modulation of tumor-associated antigen expression on human pancreatic and prostate carcinoma cells in vitro by alpha- and gamma-interferons.  

PubMed

Interferons (IFNs) are known to have antiviral effects and have been shown to enhance the expression of tumor-associated antigens (TAA) on different target cells. In our current study, we investigated the potential of IFN-alpha or IFN-gamma to enhance the expression of the TAAs recognized by monoclonal antibodies (MAbs) 19-9, B72.3, 17-1A, and BR55-2 on pancreatic cancer cell lines and the potential of IFN-gamma to modulate the expression of a single TAA, BR55-2, on nonpancreatic cancer cell lines. Expression of these TAAs, percentage of positive cells and mean fluorescence intensity, was measured by flow cytometry. In these studies, we provide evidence that one prostate (DU 145) and two pancreatic (HPAF and BxPC-3) cancer cell lines that moderately express BR55-2 can be upregulated by IFN-gamma treatment, with optimal enhancement occurring between 48 and 72 h with 1,000 IU/ml. Cell lines that highly expressed BR55-2 could not be further upregulated by the doses of IFNs tested during the various periods used. IFN-alpha or IFN-gamma treatments did not significantly change the levels of TAA expression on pancreatic cancer cell lines that bound MAbs 17-1A or 19-9. Cell lines that did not bind MAbs 17-1A, 19-9, B72.3, or BR55-2 before IFN treatments could not be induced to express these antigens after treatment. Although antigen expression does not ensure detectable therapeutic benefit, increased antigen expression on tumor tissues may augment the efficacy of MAbs bearing radionuclides, toxins, or effector cells to the tumor site. In each of these situations, the use of IFNs to enhance TAA expression, particularly IFN-gamma, may merit consideration. PMID:8770771

Sivinski, C L; Lindner, D J; Borden, E C; Tempero, M A

1995-10-01

147

Hepatic Arterial Therapy with Drug-Eluting Beads in the Management of Metastatic Pancreatic Carcinoma to the Liver: A Multi-Institutional Registry  

PubMed Central

Introduction. There has been limited reporting on the use of hepatic-directed therapy in liver dominant hepatic metastases arising from pancreatic cancer. Methods. An IRB-approved prospective multi-institutional treatment registry of 885 patients undergoing 1458 treatments for primary or secondary cancers in the liver was evaluated from January 2007 to January 2011. Results. Ten patients underwent a total of 17 treatment sessions with drug-eluting beads (DEBs). Six patients received concurrent chemotherapy while undergoing DEB with no severe adverse events. After a median followup of 16 months, the 6- and 12-month response rates were 80% and 75%, respectively, with a median overall survival of 9.3 months. Conclusion. Hepatic arterial therapy with DEB can be safely and effectively used in selected patients with liver predominant metastatic disease from pancreatic cancer. This therapy should be considered in combination with systemic chemotherapy as a possible second therapy given the limited response rates of second-line chemotherapy. PMID:22481917

Kotoyan, Raffi; Metzger, Tiffany; Tatum, Cliff; Robbins, Ken; Martin, Robert C. G.

2012-01-01

148

Prospective evaluation of squamous cell carcinoma and carcinoembryonic antigen as prognostic factors in patients with cervical cancer.  

PubMed

Carcinoembryonic antigen (CEA) and squamous cell carcinoma(SCC) serum levels were prospectively determined in 159 untreated patients diagnosed with carcinoma of the uterine cervix from 1991 to 2001. The histological analysis showed epidermoid cancer in 117 patients, adenocarcinoma in 26 patients, adenosquamous carcinoma in 12 patients and other histological types in the remaining 4 patients. Tumor marker sensitivity was related to the histological type with abnormal SCC (>2 ng/ml) in 51.3% of squamous tumors in contrast to the 7.1% found in other histologies. By contrast, CEA sensitivity was not related to histology with abnormal values (>5 ng/ml) in 25% of squamous tumors, 19% of adenocarcinomas, 33% of adenosquamous carcinomas and 25% of other histologies. CEA and SCC serum levels were clearly related to tumor stage, parametrial invasion, tumor size and nodal involvement. Elevated pretreatment CEA indicates parametrial invasion with a probability of 82%. Likewise, pretreatment CEA and SCC serum levels were of prognostic value, with a shorter disease-free survival and overall survival in patients with abnormal levels. All patients with adenocarcinomas and abnormal CEA had relapse during follow-up. Multivariate analysis indicated that parametrial invasion, age, tumor size and SCC were independent prognostic factors. In conclusion, CEA and SCC are useful tumor markers in carcinomas of the uterine cervix, with a clear relationship with well-known prognostic factors (parametrial invasion, nodal involvement), and are of prognostic value. PMID:14610320

Molina, Rafael; Filella, Xavier; Lejarcegui, Jose A; Pahisa, Jaime; Torné, Aurelio; Rovirosa, Angels; Mellado, Begoña; Ordi, Jaume; Puig-Tintore, Luis M; Alicarte, Julian; Biete, Alberto; Iglesias, Javier

2003-01-01

149

Autoimmune Pancreatitis.  

PubMed

Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult to treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells, and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes. PMID:24040625

Ketwaroo, Gyanprakash A; Sheth, Sunil

2013-04-01

150

Autoimmune pancreatitis  

PubMed Central

Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult-to-treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes. PMID:24040625

Ketwaroo, Gyanprakash A.; Sheth, Sunil

2013-01-01

151

Autoimmune pancreatitis.  

PubMed

Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult-to-treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes. PMID:24759664

Ketwaroo, Gyanprakash A; Sheth, Sunil

2013-07-01

152

Autoimmune pancreatitis: an illustrated guide to diagnosis.  

PubMed

Autoimmune pancreatitis (AIP) remains one of the rarer forms of pancreatitis but has become increasingly well recognized and widely diagnosed as it is an important differential, particularly due to the dramatic response to appropriate therapy. It is now best considered as part of a multisystem disease and the notion of "IgG4-related systemic sclerosing disease" has become widely recognized as the number of extra-pancreatic associations of AIP grows. More recently AIP has been classified into two subtypes: lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP) with distinct geographical, age and sex distributions for the two subtypes, in addition to different pathological characteristics. The role of imaging is crucial in AIP and should be considered in conjunction with clinical, serological, and histopathological findings to make the diagnosis. Radiologists are uniquely placed to raise the possibility of AIP and aid the exclusion of significant differentials to allow the initiation of appropriate management and avoidance of unnecessary intervention. Radiological investigation may reveal a number of characteristic imaging findings in AIP but appearances can vary considerably and the focal form of AIP may appear as a pancreatic mass, imitating pancreatic carcinoma. This review will illustrate typical and atypical appearances of AIP on all imaging modes. Emphasis will be placed on the imaging features that are likely to prove useful in discriminating AIP from other causes prior to histopathological confirmation. In addition, examples of relevant differential diagnoses are discussed and illustrated. PMID:23177083

Proctor, R D; Rofe, C J; Bryant, T J C; Hacking, C N; Stedman, B

2013-04-01

153

Autoimmune pancreatitis mimicking pancreatic tumor  

PubMed Central

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

Dede, Kristóf; Salamon, Ferenc; Taller, András; Tekn?s, Dániel; Bursics, Attila

2012-01-01

154

Mucoepidermoid carcinoma of the cervix: another tumor with the t(11;19)-associated CRTC1-MAML2 gene fusion.  

PubMed

Mucoepidermoid carcinoma (MEC) of the uterine cervix is a controversial entity. By strict morphologic criteria, the tumor has features identical to those of salivary gland MEC and is characterized by nests composed of 3 cell types (epidermoid, intermediate, and mucin producing) in the absence of overt glandular differentiation. Nonetheless, the entity is not recognized in the current World Health Organization classification of cervical tumors. Given the morphologic similarity between MEC of the cervix and MEC of the salivary glands, we sought to determine if MEC of the cervix harbors the t(11;19)(q21;p13) characteristic of MEC of the major and minor salivary glands, a rearrangement that results in fusion of the cyclic adenosine 3',5' monophosphate coactivator CRTC1 to the Notch coactivator MAML2. We identified 7 cervical tumors from our departmental files and performed reverse transcription-polymerase chain reaction and fluorescence in situ hybridization-based molecular analysis for rearrangements of CRTC1 and MAML2; 14 conventional cervical adenosquamous carcinomas were used as controls. Analysis of the cervical MECs demonstrated a CRTC1-MAML2 fusion in 1 case, rearrangements of CRTC1 in 4 cases, and aberrations of MAML2 in 5 cases (rearrangements in 2 cases, amplification in 3 cases). All MEC showed aberrations of at least 1 of the loci, whereas none of the cervical adenosquamous carcinomas harbored rearrangements or amplification of either locus. Our results demonstrate that cervical tumors defined as MEC by strict morphologic criteria harbor genetic aberrations involving the genes characteristically rearranged in MEC of the salivary glands, and suggest that cervical MEC is an entity distinct from conventional cervical adenosquamous carcinoma. The development of drug therapy targeted to the genes rearranged in MEC underscores the importance of correct classification of cervical MEC because the diagnosis may hold therapeutic implications different from other cervical malignancies. PMID:19092631

Lennerz, Jochen K M; Perry, Arie; Mills, Jason C; Huettner, Phyllis C; Pfeifer, John D

2009-06-01

155

[Pancreatic cytosteatonecrosis].  

PubMed

If cutaneous panniculitis, made of dermo-hypodermic nodules, is the most constant manifestation of pancreatic cytosteatonecrosis, articular and bony localizations are quite frequent and sometimes the first manifestation of the disease. Articular lesions: monoarthritis, oligo-arthritis and mostly polyarthritis, often assume a very inflammatory picture; the synovial fluid is oily or puriform, and has a high content of polynuclear cells or macrophages with a foamy cytoplasm, lipid droplets, triglycerides, non-esterified fatty acids, and pancreatic enzymes; the most typical synovial lesion is a cytosteatonecrosis with adipocytes showing a huge lipidic vacuole. The bony lesions are mostly osteolytic, microgeodic lesions, or more extended ones, pseudo-tumoral without soft tissue invasion: more rarely, there is a periosteal thickening, bony infarctions, or epiphyseal osteonecrosis; these lesions do not always demonstrate a hyperfixation on scintigrams. The physiopathology of these various lesions is usually linked to a diffusion of pancreatic lipases, but other enzymes or enzymatic inhibitors also intervene, as well as a cytotoxic and local inflammatory activity of the fatty acids themselves. Surgical treatment of the pancreatic lesions, when possible, is the only treatment that is truly effective. PMID:3563379

Brégeon, C; Sentenac, P; Queinnec, J Y; Renier, J C

1987-02-01

156

Pancreatic panniculitis.  

PubMed

We describe a rare case of a patient with pancreatic adenocarcinoma who presented initially with a rash on her lower legs. Skin biopsy showed lobular panniculitis and characteristic "ghost" adipocytes consistent with pancreatitic panniculitis. This clinical case is an interesting example where a seemingly innocuous skin condition heralds an underlying malignant disease process. PMID:25612121

Yang, Sam Shiyao; Soon, Gwyneth Shook Ting; Aw, Derrick Chen-Wee

2015-01-01

157

Pancreatic Cancer Stage 4  

MedlinePLUS

... My Pictures Browse Search Quick Search Image Details Pancreatic Cancer Stage 4 View/Download: Small: 533x576 View Download Add to My Pictures Title: Pancreatic Cancer Stage 4 Description: Stage IV pancreatic cancer; drawing ...

158

Is Pancreatic Cancer Hereditary?  

MedlinePLUS

... Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? Cancer of the pancreas is a genetic ... found in cigarette smoke. The genetics of hereditary pancreatic cancer is a focus of research at Johns Hopkins. ...

159

Pancreatic Cancer Stage 3  

MedlinePLUS

... My Pictures Browse Search Quick Search Image Details Pancreatic Cancer Stage 3 View/Download: Small: 720x576 View Download Add to My Pictures Title: Pancreatic Cancer Stage 3 Description: Stage III pancreatic cancer; drawing ...

160

Pancreatic Cancer: Surgery  

MedlinePLUS

... Topic Ablation or embolization treatments for pancreatic cancer Surgery for pancreatic cancer There are 2 general types ... and risks of such surgery carefully. Potentially curative surgery Fewer than 1 in 5 pancreatic cancers appear ...

161

Pancreatic enzyme replacement therapy during pancreatic insufficiency.  

PubMed

Pancreatic stimulation and therefore digestion is a tightly controlled and hormonally mediated process. Any alterations affecting any of the systematic steps for successful digestion and absorption to occur will impair appropriate pancreatic enzymatic secretion, entry into the bowel lumen, functionality once inside the lumen, and thus appropriate mixing with foods and nutrients. Many causes of pancreatic insufficiency may require the initiation of pancreatic enzyme therapy, including but not limited to cystic fibrosis, pancreatic cancer, acute and chronic pancreatitis, and pancreatic surgery. This purpose of this article is to help clarify the conditions that cause pancreatic insufficiency, how to determine if the patient is malabsorbing, and the best use of pancreatic enzyme replacement therapy for treatment in these conditions. The first step in determining if pancreatic enzyme therapy is appropriate is to determine if the patient is malabsorbing specifically due to pancreatic exocrine insufficiency. An overview of the methods used to determine pancreatic insufficiency is provided, as well as appropriate treatment methods. Recent Food and Drug Administration regulations require a more thorough process, including randomized controlled trials to prove the safety and efficacy of pancreatic enzymes, to approve them for use. The studies used to verify efficacy also are examined. Last, dosing guidelines and some unconventional ways to administer pancreatic enzymes, such as during enteral feedings, are reviewed. PMID:24687867

Berry, Amy J

2014-06-01

162

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

PubMed

Chronic pancreatitis is progressive and irreversible, leading to digestive and absorptive disorders by destruction of the exocrine pancreas and to diabetes mellitus by destruction of the endocrine pancreas. When complications such as pancreatolithiasis and pseudocyst occur, elevated pancreatic ductal pressure exacerbates pain and induces other complications, worsening the patient's general condition. Combined treatment with extracorporeal shock-wave lithotripsy and endoscopic lithotripsy is a useful, minimally invasive, first-line treatment approach that can preserve pancreatic exocrine function. Pancreatic duct stenosis elevates intraductal pressure and favor both pancreatolithiasis and pseudocyst formation, making effective treatment vitally important. Endoscopic treatment of benign pancreatic duct stenosis stenting frequently decreases pain in chronic pancreatitis. Importantly, stenosis of the main pancreatic duct increases risk of stone recurrence after treatment of pancreatolithiasis. Recently, good results were reported in treating pancreatic duct stricture with a fully covered self-expandable metallic stent, which shows promise for preventing stone recurrence after lithotripsy in patients with pancreatic stricture. Chronic pancreatitis has many complications including pancreatic carcinoma, pancreatic atrophy, and loss of exocrine and endocrine function, as well as frequent recurrence of stones after treatment of pancreatolithiasis. As early treatment of chronic pancreatitis is essential, the new concept of early chronic pancreatitis, including characteristics findings in endoscopic ultrasonograms, is presented. PMID:24251715

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

2013-12-01

163

Production and secretion of chromogranin A and pancreastatin by the human pancreatic carcinoma cell line QGP-1N on stimulation with carbachol.  

PubMed

Chromogranin A (CGA) is thought to be a precursor of pancreastatin (PST). Carbachol (Cch) stimulated the secretion of CGA and PST from QGP-1N cells derived from a human pancreatic islet cell tumor. Atropine inhibited the secretion of both. Sodium fluoride, phorbol ester, and calcium ionophore also stimulated the secretion of both. Cch (10(-5) M) stimulated inositol 1,4,5-trisphosphate production in QGP-1N cells. Stimulation with Cch increased the total amount of PST in the cells and the medium 1.7-fold and decreased the amount of CGA in the cells and medium. QGP-1N cells were labelled with [35S]methionine, and then CGA and PST in the cells and medium were immunoprecipitated with specific antisera, and separated by electrophoresis in polyacrylamide gel. Stimulation with Cch resulted in an increase in the intensity of PST-immunoreactive bands and a decrease in those of CGA-immunoreactive bands. Cch did not increase the cellular level of CGA messenger RNA. These results suggested that (1) the secretion of CGA and PST from QGP-1N cells is regulated mainly through muscarinic receptors coupled with activation of polyphosphoinositide breakdown by a G protein, with intracellular calcium ion and protein kinase C playing a role in the stimulus-secretion coupling and that (2) Cch may induce the secretion of PST and CGA and processing from CGA to PST. PMID:7800852

Kitayama, N; Tateishi, K; Funakoshi, A; Kono, A; Matsuoka, Y

1994-08-01

164

Cutaneous squamous cell carcinoma with mucinous metaplasia on the sole associated with high-risk human papillomavirus type 18.  

PubMed

A case of superficially invasive cutaneous squamous cell carcinoma (SCC) of the sole containing numerous mucin-producing vacuolated cells resembling "signet-ring" cells is reported. The 2 cellular components of the tumor, both squamous and mucinous, were atypical with pleomorphic nuclei, and expressed the same immunophenotype, consistent in weak and focal positivity for cytokeratin 5/6 and epithelial membrane antigen (EMA) and weak cytoplasmic and nuclear positivity for p16. Real-time PCR genotyping demonstrated the presence of high-risk human papillomavirus (HPV) type 18. We diagnose our case as "cutaneous SCC with mucinous metaplasia" and discuss the differential diagnoses with other skin tumors exhibiting mucin-containing cells, in particular with adenosquamous carcinoma and mucoepidermoid carcinoma. Although HPV 18 is not uncommon in cervico-vaginal pathology, where is often associated with mucinous adenocarcinoma or adenosquamous carcinoma of the cervix, its detection has been rarely reported in cutaneous SCC. In our case, the association of mucinous metaplasia and oncogenic high-risk HPV 18 in a cutaneous SCC may be of interest to the dermatopathologist. Further observations need to confirm whether the histopathologic finding of mucinous metaplasia in an atypical squamous cell proliferation could be a clue for investigating the presence of oncogenic high-risk HPV infection, with particular regard to HPV 18 subtype. PMID:20847640

Caputo, Valentina; Colombi, Roberto; Ribotta, Marisa; Rongioletti, Franco

2011-05-01

165

Current understanding of precursors to pancreatic cancer.  

PubMed

Precursors to pancreatic cancer have been investigated for a century. Previous studies have revealed three distinct precursors, i.e. mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and pancreatic intraepithelial neoplasia (PanIN), harboring identical or similar genetic alterations as does invasive pancreatic carcinoma. The current understanding of precursors to pancreatic cancer can be illustrated by progressive pathways from noninvasive MCN, IPMN, and PanIN toward invasive carcinoma. MCNs consist of ovarian-type stroma and epithelial lining with varying grades of atypia, and are occasionally associated with invasive adenocarcinoma. The epithelium of noninvasive IPMNs shows a variety of different directions of differentiation, including gastric, intestinal, pancreatobiliary (PB), and oncocytic types. IPMNs can also harbor varying grades of architectural and cytologic atypia. IPMNs confined to branch ducts are mostly the gastric type, and IPMNs involving the main ducts are often intestinal type, while PB and oncocytic types are rare. Small (<1 cm) IPMNs of the gastric type are not always morphologically distinguishable from low-grade PanINs. Mucin expression profiles suggest intestinal-type IPMNs progress to mucinous noncystic (colloid) carcinoma, while PB-type IPMNs progress toward ductal adenocarcinoma. It is a well-described paradigm that PanIN lesions progress toward ductal adenocarcinoma through step-wise genetic alterations. The activation of Hedgehog and Notch signaling pathways in PanIN lesions as well as in pancreatic adenocarcinoma suggest that developmental pathways may be disregulated during carcinogenesis of the pancreas. Further study is needed to elucidate the pathways from precursors toward invasive carcinoma of the pancreas. PMID:17520195

Takaori, Kyoichi

2007-01-01

166

A phase II study of alternating cycles of split course radiation therapy and gemcitabine chemotherapy for inoperable pancreatic or biliary tract carcinoma.  

PubMed

Because of increased toxicity, full doses of gemcitabine and radiation therapy cannot routinely be given concurrently. The purpose of the present study was to determine the toxicity and response to treatment with full-dose gemcitabine given between cycles of split-course radiation therapy (nonconcurrent treatment) for inoperable periampullary adenocarcinoma. Treatment consisted of 3 6 week courses for a total of 18 weeks: 1000 mg/m gemcitabine intravenous bolus once a week x 2 weeks; 1 week break; 2 weeks of radiation therapy (1.8 Gy per fraction); 1 week break x 3. The total dose of radiation consisted of 45 Gy to the tumor + regional nodes followed by a 5.4-Gy boost. Patients were restaged at week 15 and at the completion of all treatment. Patients underwent resection if there was sufficient response. A total of 42 patients (40 pancreatic, 1 gallbladder, 1 biliary tract) were enrolled between March 1999 and July 2002. All but 2 medically inoperable patients had evidence of major vessel involvement. Median age was 63 years (range, 40-80 years). All patients were evaluable for response. There were 10 objective partial responses (24%). Six responders underwent resection with a mean survival of 18 months. Mean survival for all 42 patients was 10.3 months (range, 2.0-32.5 months; median, 9.5 months). Four patients experienced grade 3 or 4 gastrointestinal toxicity. Alternating cycles of split-course radiotherapy and gemcitabine chemotherapy permits the delivery of full doses of both modalities with acceptable tolerance. Despite the prolongation in radiation treatment time because of split-course treatment, patients with sufficient response were able to undergo resection. PMID:15923794

Lin, Lilie L; Picus, Joel; Drebin, J A; Linehan, David C; Solis, Juan; Strasberg, Steven M; Tan, Benjamin; Thorstad, Wade L; Myerson, Robert

2005-06-01

167

The Epidemiology of Pancreatitis and Pancreatic Cancer  

PubMed Central

Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in the US. Chronic pancreatitis, although lower in incidence, significantly reduces patients’ quality of life. Pancreatic cancer has high mortality and is 1 of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect Blacks more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. PMID:23622135

Yadav, Dhiraj; Lowenfels, Albert B.

2013-01-01

168

Research of Recognition Method of Discrete Wavelet Feature Extraction and PNN Classification of Rats FT-IR Pancreatic Cancer Data.  

PubMed

Sprague-Dawley (SD) rats' normal and abnormal pancreatic tissues are determined directly by attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy method. In order to diagnose earlier stage of SD rats pancreatic cancer rate with FT-IR, a novel method of extraction of FT-IR feature using discrete wavelet transformation (DWT) analysis and classification with the probability neural network (PNN) was developed. The differences between normal pancreatic and abnormal samples were identified by PNN based on the indices of 4 feature variants. When error goal was 0.01, the total correct rates of pancreatic early carcinoma and advanced carcinoma were 98% and 100%, respectively. It was practical to apply PNN on the basis of ATR-FT-IR to identify abnormal tissues. The research result shows the feasibility of establishing the models with FT-IR-DWT-PNN method to identify normal pancreatic tissues, early carcinoma tissues, and advanced carcinoma tissues. PMID:25548717

Wan, Chayan; Cao, Wenqing; Cheng, Cungui

2014-01-01

169

Research of Recognition Method of Discrete Wavelet Feature Extraction and PNN Classification of Rats FT-IR Pancreatic Cancer Data  

PubMed Central

Sprague-Dawley (SD) rats' normal and abnormal pancreatic tissues are determined directly by attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy method. In order to diagnose earlier stage of SD rats pancreatic cancer rate with FT-IR, a novel method of extraction of FT-IR feature using discrete wavelet transformation (DWT) analysis and classification with the probability neural network (PNN) was developed. The differences between normal pancreatic and abnormal samples were identified by PNN based on the indices of 4 feature variants. When error goal was 0.01, the total correct rates of pancreatic early carcinoma and advanced carcinoma were 98% and 100%, respectively. It was practical to apply PNN on the basis of ATR-FT-IR to identify abnormal tissues. The research result shows the feasibility of establishing the models with FT-IR-DWT-PNN method to identify normal pancreatic tissues, early carcinoma tissues, and advanced carcinoma tissues. PMID:25548717

Wan, Chayan; Cao, Wenqing; Cheng, Cungui

2014-01-01

170

[Nutrition in acute pancreatitis].  

PubMed

Nutritional concepts in acute pancreatitis have changed. Early enteral nutrition widely replaced parenteral nutrition alone in severe acute pancreatitis. First trials suggest early oral refeeding as nutritional treatment of choice in patients with mild acute pancreatitis. In this review, we summarise the current knowledge on nutrition in acute pancreatitis and discuss future developments. PMID:20922640

Teich, N; Mössner, J

2010-10-01

171

Tumor markers in pancreatic cancer. Sensitivity and specificity of CA 19-9.  

PubMed

The tumor marker CA 19-9 is based on monoclonal antibody to colonic carcinoma cell lines. In this study, the utility of the tumor marker in the diagnosis of pancreatic carcinoma was evaluated. CA 19-9 is strongly expressed in most tissue specimens obtained from pancreatic carcinomas. However, this antigen is also found in normal pancreas and specimens from chronic pancreatitis. The CA 19-9 is released into the circulation, and was found at increased concentrations (greater than 37 U/ml) in 87% of the patients with pancreatic carcinoma n = 145, as compared with only 13% in the group of patients with benign diseases n = 1,081 and 29% of those with extrapancreatic malignancies n = 691 (P less than 0.0001). The preoperatively raised CA 19-9 concentration in patients with stage I pancreatic carcinoma decreases after curative resection of the carcinoma to values within the normal range. However, in no CA 19-9 estimation following palliative surgical intervention of stage III and IV patients or in cases of inoperable carcinomas was a serum concentration of less than 37 U/ml recorded. Accordingly, the median survival of stage I patients was 29 months, and of stage III, IV and patients with inoperable carcinomas 6 months only. PMID:2613165

Safi, F; Roscher, R; Beger, H G

1989-12-01

172

Is alcoholic pancreatitis associated with enteroviral infection?  

PubMed Central

AIM: To investigate whether enteroviral infection might trigger acute pancreatitis in patients made susceptible due to high alcohol consumption. METHODS: Patients with alcohol-induced acute pancreatitis were analyzed for signs of simultaneous or preceding enteroviral infection. We studied the serum samples of 40 patients hospitalized for alcohol-induced acute pancreatitis and 40 controls recruited from an alcohol detoxification center. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect enterovirus RNA and diagnose acute viremia. Immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) enteroviral antibodies were measured using enzyme immunoassay to detect subacute and previous infections. The samples were considered positive when the antibody titers were ? 15 IU. Furthermore, using RT-PCR, we studied pancreatic biopsy samples obtained during surgery from nine patients with chronic pancreatitis, one patient with acute pancreatitis and ten control patients with pancreatic carcinoma for evidence of persisting enteroviral RNA in the pancreatic tissue. RESULTS: No enterovirus RNA indicating acute viremia was detected by RT-PCR in the serum samples of any patient or control. A high incidence of positive antibody titers was observed in both study groups: IgM antibodies had positive titers in 5/40 (13%) vs 4/40 (10%), P = 0.723; IgG in 15/40 (38%) vs 19/40 (48%), P = 0.366; and IgA in 25/40 (63%) vs 33/40 (83%), P = 0.045, patients and controls, respectively. Ten (25%) patients had severe pancreatitis and two (5%) required treatment in intensive care. The median length of hospitalization was 7 d (range: 3-47 d). The severity of acute pancreatitis or the length of hospitalization was not associated with enteroviral IgM, IgG or IgA antibodies. Five pancreatic biopsy samples tested positive with RT-PCR, three (8%) in the control group and two (5%) in the patient group (P = 0.64). CONCLUSION: The rate of enteroviral infection is not increased in patients with alcohol-induced acute pancreatitis when compared to alcoholics with similar high alcohol use. PMID:23840120

Khan, Jahangir; Nordback, Isto; Seppänen, Hanna; Lappalainen-Lehto, Riitta; Järvinen, Satu; Oikarinen, Sami; Tauriainen, Sisko; Räty, Sari; Hyöty, Heikki; Sand, Juhani

2013-01-01

173

Novel serum tumor marker, RCAS1, in pancreatic diseases  

PubMed Central

AIM: As tumor markers for pancreatic carcinoma, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been used, but the sensitivity and specificity are not enough for the diagnosis of pancreatic carcinoma. METHODS: A novel serum tumor marker, RCAS1, was compared with two conventional serum tumor markers, CEA (highly specific for pancreatic cancer) and CA 19-9 (highly sensitive for pancreatic cancer), in 48 patients with pancreatic exocrine tumors. RESULTS: When the diagnosis of benign or malignant conditions was examined by one tumor marker, the sensitivity of RCAS1 alone (55%) was higher than that of CEA alone (27%) and the specificity of RCAS1 alone (92%) was greater than that of CA19-9 alone (78%). When examined by a combination of two markers, the sensitivity of a combination of RCAS1 and CA19-9 (95%) was superior to those of CA19-9 alone (78%), RCAS1 alone (55%, P = 0.002), CEA alone (27%) (P<0.001), RCAS1 and CEA (59%) and CA19-9 and CEA (82%). CONCLUSION: These results suggest that the combination of RCAS1 and CA19-9 is highly sensitive for pancreatic carcinoma. PMID:16127752

Yamaguchi, Koji; Enjoji, Munechika; Nakashima, Manabu; Nakamuta, Makoto; Watanabe, Takashi; Tanaka, Masao

2005-01-01

174

Increased telomerase activities in human pancreatic duct adenocarcinomas.  

PubMed

Telomerase is a key enzyme with regard to immortalization of cancer cells and increased activity has been demonstrated in various human malignant neoplasms. Since little is known of its role in pancreatic cancers, we investigated changes in telomerase activity in human pancreatic duct adenocarcinomas and compared the frequency of increased telomerase activity with the presence of K-ras gene mutations. The samples were obtained from 38 pancreatic duct adenocarcinomas and 7 tumor surrounding tissues at surgical resection. Telomerase activity was examined by telomeric repeat amplification protocol assay and terminal restriction fragment (TRF) length was examined by Southern analysis. K-ras mutation was examined by means of polymerase chain reaction-single strand conformation polymorphism analysis. Among 38 pancreatic carcinomas, 32 (84%) exhibited increased telomerase activities with no apparent relation to the histological type of tumor, tumor size, regional lymphnode involvement and distant metastasis or clinical stage. In tissue surrounding the tumor, telomerase activity was not detected. TRF length tended to be reduced in pancreatic carcinomas. Mutations of K-ras gene were found in 24 out of the 38 (63%) cases. Among the 38 cases, 14 showed increased telomerase activity without K-ras mutation and 4 cases showed K-ras mutation without telomerase activity. These results suggest that increased telomerase activity might be a sensitive genetic diagnostic marker and could be a target for future therapy of pancreatic duct carcinomas. PMID:9414659

Tsutsumi, M; Tsujiuchi, T; Ishikawa, O; Majima, T; Yoshimoto, M; Sasaki, Y; Fukuda, T; Oohigashi, H; Konishi, Y

1997-10-01

175

Epidermal Growth Factor Receptor Inhibition Strategies in Pancreatic Cancer: Past, Present and the Future  

Microsoft Academic Search

Summary Pancreatic carcinoma is an unusually lethal disease and to date treatment with standard chemotherapy has yielded disappointing results. The epidermal growth factor receptor (EGFR) is known to be over-expressed in pancreatic cancer and there is data to suggest that this molecular characteristic may be a poor prognostic factor as it may denote a more aggressive form of the disease.

Michael Cohenuram; Muhammad Wasif Saif

176

Polyarthritis and bone lesions complicating traumatic pancreatitis in two children.  

PubMed Central

The association of bone lesions, polyarthritis and cutaneous nodules with pancreatic disease is being recognized and reported more frequently. In adults all forms of pancreatitis and carcinoma of the pancreas have been involved, but in the few children described these complications have been associated with acute traumatic pancreatitis. This paper describes two cases of acute traumatic pancreatitis in which polyarthritis and limb pains were noted after 2 to 3 weeks. In one child osteolytic lesions and periostitis were seen on roentgenograms 7 weeks after the onset of pancreatitis. In the other child minor roentgenographic changes were not seen until 5 months after the onset; however, bone scans showed clear-cut abnormalities after 1 month. Almost complete resolution could be expected within a year. Serum lipase and amylase concentrations remained elevated during the acute illness. Disseminated fat necrosis is apparently related to the excess amounts of circulating lipase. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:647564

Goluboff, N.; Cram, R.; Ramgotra, B.; Singh, A.; Wilkinson, G. W.

1978-01-01

177

Morphologic and molecular analysis of 39 spontaneous feline pulmonary carcinomas.  

PubMed

The present study was performed to determine the morphologic change and selected molecular features of spontaneous lung tumors in cats examined at the North Carolina State University Veterinary Teaching Hospital. Thirty-nine primary lung carcinomas represented 0.69% of all feline cases admitted to the hospital. Most lung tumors were observed in aged cats (P < .0001), and no sex predilection was found (P < .4241). Persian cats with pulmonary carcinoma were overrepresented in the data set, at least 4 times more frequently than other breeds. The histologic tumor types included adenocarcinoma (64.1%), bronchioloalveolar carcinoma (20.5%), and adenosquamous carcinoma (15.4%). Metastasis was observed in about 80% of 39 cases, with decreasing order of intrapulmonary metastasis, intrathoracic carcinomatosis, regional lymph nodes, and distant organs, including digits. The size of the largest tumor mass was significantly associated with metastatic potential (P < .001). Based on immunohistochemistry, more than 80% (20 of 24) of feline lung tumors were positively labeled with either surfactant protein A or thyroid transcription factor 1. Epidermal growth factor receptor mutant and p53 proteins were detected in approximately 20% (5 of 24) and 25% (6 of 24) of the feline lung tumor cases, respectively. Limited sequencing analysis of K-ras and p53 genes in 3 selected normal and neoplastic lung tissues did not reveal any alteration. Results indicate that primary lung carcinomas are rare but aggressive tumors in cats, thereby warranting further studies on molecular carcinogenesis. PMID:21900542

D'Costa, S; Yoon, B-I; Kim, D-Y; Motsinger-Reif, A A; Williams, M; Kim, Y

2012-11-01

178

Hormonal Factors and Pancreatic Cancer in Women  

Microsoft Academic Search

PURPOSE: The aim of the study was to evaluate hormonal risk factors for carcinoma of the exocrine pancreas among postmenopausal women.METHODS: Mailed questionnaire data from 52 cases and 233 population-based controls in Ontario were used to assess parity, age at first birth, and other hormonal factors on pancreatic cancer risk.RESULTS: Reduced risk was seen with three or more pregnancies [adjusted

Nancy Kreiger; Jeanie Lacroix; Margaret Sloan

2001-01-01

179

Advances in the pathology of penile carcinomas.  

PubMed

The incidence of penile cancer varies from country to country, with the highest figures reported for countries in Africa, South America, and Asia and lowest in the United States and Europe. Causes of this variation are not clear, but they are thought to be related to human papillomavirus infection, smoking, lack of circumcision, chronic inflammation, and poor genital hygiene. Most penile tumors are squamous cell carcinomas, and a variegated spectrum of distinct morphologies is currently recognized. Each one of these subtypes has distinctive pathologic and clinical features. About half of penile carcinomas are usual squamous cell carcinomas, and the rest corresponds to verrucous, warty, basaloid, warty-basaloid, papillary, pseudohyperplastic, pseudoglandular, adenosquamous, sarcomatoid, and cuniculatum carcinomas. Previous studies have found a consistent association of tumor cell morphology and human papillomavirus presence in penile carcinomas. Those tumors composed of small- to intermediate-sized, basaloid ("blue") cells are often human papillomavirus positive, whereas human papillomavirus prevalence is lower in tumors showing large, keratinizing, maturing eosinophilic ("pink") cells. Human papillomavirus-related tumors affect younger patients, whereas human papillomavirus-unrelated tumors are seen in older patients with phimosis, lichen sclerosus, or squamous hyperplasia. This morphologic distinctiveness is also observed in penile intraepithelial neoplasia. The specific aim of this review is to provide a detailed discussion on the macroscopic and microscopic features of all major subtypes of penile cancer. We also discuss the role of pathologic features in the prognosis of penile cancer, the characteristics of penile precursor lesions, and the use of immunohistochemistry for the diagnosis of invasive and precursor lesions. PMID:22595011

Chaux, Alcides; Cubilla, Antonio L

2012-06-01

180

Human Papillomavirus-Related Carcinomas of the Sinonasal Tract  

PubMed Central

High risk human papillomavirus (HPV) is an established cause of head and neck carcinomas arising in the oropharynx. The presence of HPV has also been reported in some carcinomas arising in sinonasal tract, but little is known about their overall incidence or their clinicopathologic profile. The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. P16 immunohistochemistry and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcomes data were extracted from patient medical records. Of 161 sinonasal carcinomas, 34 (21%) were positive for high risk HPV DNA, including type 16 (82%), type 31/33 (12%), and type 18 (6%). HPV-positive carcinomas consisted of 28 squamous cell carcinomas and variants (15 non- or partially-keratinizing, 4 papillary, 5 adenosquamous, 4 basaloid), 1 small cell carcinoma, 1 sinonasal undifferentiated carcinoma, and 4 carcinomas that were difficult to classify but exhibited adenoid cystic carcinoma-like features. Immunohistochemistry for p16 was positive in 59/161 (37%) cases, and p16 expression strongly correlated with the presence of HPV DNA: 33 of 34 (97%) HPV positive tumors exhibited high p16 expression, whereas only 26 of 127 (20%) HPV negative tumors were p16 positive (p < .0001). The HPV-related carcinomas occurred in 19 men and 15 women ranging in age from 33 to 87 years (mean 54). A trend toward improved survival was observed in the HPV-positive group (hazard ratio=0.58, 95% confidence interval [0.26, 1.28]). The presence of high risk HPV in 21% of sinonasal carcinomas confirms HPV as an important oncologic agent of carcinomas arising in the sinonasal tract. While non-keratinizing squamous cell carcinoma is the most common histologic type, there is a wide morphologic spectrum of HPV-related disease that includes a variant that resembles adenoid cystic carcinoma. The distinctiveness of these HPV-related carcinomas of the sinonasal tract with respect to risk factors, clinical behavior, and response to therapy remains to be clarified. PMID:23095507

Bishop, Justin A.; Guo, Theresa W.; Smith, David F.; Wang, Hao; Ogawa, Takenori; Pai, Sara I.; Westra, William H.

2012-01-01

181

Strategies for early detection of resectable pancreatic cancer  

PubMed Central

Pancreatic cancer is difficult to diagnose at an early stage and generally has a poor prognosis. Surgical resection is the only potentially curative treatment for pancreatic carcinoma. To improve the prognosis of this disease, it is essential to detect tumors at early stages, when they are resectable. The optimal approach to screening for early pancreatic neoplasia has not been established. The International Cancer of the Pancreas Screening Consortium has recently finalized several recommendations regarding the management of patients who are at an increased risk of familial pancreatic cancer. In addition, there have been notable advances in research on serum markers, tissue markers, gene signatures, and genomic targets of pancreatic cancer. To date, however, no biomarkers have been established in the clinical setting. Advancements in imaging modalities touch all aspects of the clinical management of pancreatic diseases, including the early detection of pancreatic masses, their characterization, and evaluations of tumor resectability. This article reviews strategies for screening high-risk groups, biomarkers, and current advances in imaging modalities for the early detection of resectable pancreatic cancer. PMID:25170207

Okano, Keiichi; Suzuki, Yasuyuki

2014-01-01

182

Pancreatitis-imaging approach.  

PubMed

Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a signi?cant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrast-enhanced computed tomography (MD-CECT) the most used imaging technique. However, magnetic resonance imaging (MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI. PMID:25133027

Busireddy, Kiran K; AlObaidy, Mamdoh; Ramalho, Miguel; Kalubowila, Janaka; Baodong, Liu; Santagostino, Ilaria; Semelka, Richard C

2014-08-15

183

Cryosurgery for pancreatic cancer.  

PubMed

The procedure of pancreatic cryosurgery is performed with intraoperative or percutaneous approaches. Based on current data and our initial experience, cryoablation appears to be a feasible, potentially safe and promising option in patients with locally advanced and unresectable pancreatic cancer. It is suggested that there are almost no known contraindications to the use of cryosurgery for pancreatic cancer. For most patients with pancreatic cancer, cryosurgery can substitute conventional surgery. PMID:25083453

Xu, Kecheng; Niu, Lizhi; Yang, Daming

2013-02-01

184

Cryosurgery for pancreatic cancer  

PubMed Central

The procedure of pancreatic cryosurgery is performed with intraoperative or percutaneous approaches. Based on current data and our initial experience, cryoablation appears to be a feasible, potentially safe and promising option in patients with locally advanced and unresectable pancreatic cancer. It is suggested that there are almost no known contraindications to the use of cryosurgery for pancreatic cancer. For most patients with pancreatic cancer, cryosurgery can substitute conventional surgery. PMID:25083453

Xu, Kecheng; Yang, Daming

2013-01-01

185

Endometrial carcinoma recurring as carcinosarcoma: report of two cases.  

PubMed

Endometrial carcinosarcoma is a rare, aggressive disease, accounting for approximately 3% of all uterine neoplasms. The emergence of sarcomatous elements is considered the evolution of subclones arising from high grade endometrial carcinomas. Here, we report two cases of primary endometrial carcinomas recurring as carcinosarcoma. Case 1. a 58-year-old postmenopausal woman diagnosed to have a poorly differentiated endometrial endometrioid adenocarcinoma (FIGO stage IB) developed an intra-abdominal recurrence of disease after 17 months from diagnosis. Histopathological analysis documented a biphasic neoplasia consisting of an epithelial (grade 3 endometrial endometrioid adenocarcinoma) and a sarcomatous component. Salvage chemotherapy with cisplatin, ifosfamide, epirubicin, and then with taxotere was attempted. The patient died after 2 months. Case 2. A 56-year-old woman with a diagnosis of grade 3 endometrial adenosquamous carcinoma of the endometrium (FIGO stage IIIA) experienced pelvic recurrence after five months from completion of chemotherapy. Definitive histology was malignant mixed mesodermal tumor with focal areas of chondrosarcomatous elements. The patient was triaged to exclusive concomitant chemoradiotherapy and salvage chemotherapy. The patient died after 3 months. We describe two cases of high grade endometrial carcinomas recurring as carcinosarcoma, thus providing evidence that the metaplastic sarcomatous evolution is a very rare event which can occur in patients with anaplastic endometrial cancer. PMID:17646054

Ferrandina, G; Zannoni, G F; Martinelli, E; Vellone, V; Prisco, M G; Scambia, G

2007-01-01

186

In vitro modeling of human pancreatic duct epithelial cell transformation defines gene expression changes induced by K-ras oncogenic activation in pancreatic carcinogenesis.  

PubMed

Genetic analysis of pancreatic ductal adenocarcinomas and their putative precursor lesions, pancreatic intraepithelial neoplasias (PanIN), has shown a multistep molecular paradigm for duct cell carcinogenesis. Mutational activation or inactivation of the K-ras, p16(INK4A), Smad4, and p53 genes occur at progressive and high frequencies in these lesions. Oncogenic activation of the K-ras gene occurs in >90% of pancreatic ductal carcinoma and is found early in the PanIN-carcinoma sequence, but its functional roles remain poorly understood. We show here that the expression of K-ras(G12V) oncogene in a near diploid HPV16-E6E7 gene immortalized human pancreatic duct epithelial cell line originally derived from normal pancreas induced the formation of carcinoma in 50% of severe combined immunodeficient mice implanted with these cells. A tumor cell line established from one of these tumors formed ductal cancer when implanted orthotopically. These cells also showed increased activation of the mitogen-activated protein kinase, AKT, and nuclear factor-kappaB pathways. Microarray expression profiling studies identified 584 genes whose expression seemed specifically up-regulated by the K-ras oncogene expression. Forty-two of these genes have been reported previously as differentially overexpressed in pancreatic cancer cell lines or primary tumors. Real-time PCR confirmed the overexpression of a large number of these genes. Immunohistochemistry done on tissue microarrays constructed from PanIN and pancreatic cancer samples showed laminin beta3 overexpression starting in high-grade PanINs and occurring in >90% of pancreatic ductal carcinoma. The in vitro modeling of human pancreatic duct epithelial cell transformation may provide mechanistic insights on gene expression changes that occur during multistage pancreatic duct cell carcinogenesis. PMID:15958547

Qian, Jiaying; Niu, Jiangong; Li, Ming; Chiao, Paul J; Tsao, Ming-Sound

2005-06-15

187

Mechanistic analysis of pancreatic ductal carcinogenesis in hamsters.  

PubMed

In this article, we introduce our rapid-production model for pancreatic duct adenocarcinomas and describe the mechanisms of pancreatic duct carcinogenesis so far elucidated in Syrian golden hamsters. It is evident that a series of histogenetic steps are involved, leading from hyperplasia through atypical hyperplasia to intraductal carcinoma and invasive carcinoma. As DNA alters, K-ras mutation appears to be an early event, whereas p53 mutations generally occur in the tumor-progression phase. The induced cancer cells may show autocrine growth, secreting TGF-alpha and vascular endothelial growth factor (VEGF), and are immortalized with a shortened TRF length and increased telomerase activity. The rapid-production model of pancreatic duct adenocarcinomas has not only provided a major stimulus to understanding induction mechanisms but should also serve as a bioassay to facilitate the identification of dietary risk factors and the search for appropriate chemopreventive or chemotherapeutic agents or both to help control this deadly disease. PMID:9548670

Konishi, Y; Tsutsumi, M; Tsujiuchi, T

1998-04-01

188

Pancreatic cancer genomics: insights and opportunities for clinical translation  

PubMed Central

Pancreatic cancer is a highly lethal tumor type for which there are few viable therapeutic options. It is also caused by the accumulation of mutations in a variety of genes. These genetic alterations can be grouped into those that accumulate during pancreatic intraepithelial neoplasia (precursor lesions) and thus are present in all cells of the infiltrating carcinoma, and those that accumulate specifically within the infiltrating carcinoma during subclonal evolution, resulting in genetic heterogeneity. Despite this heterogeneity there are nonetheless commonly altered cellular functions, such as pathways controlling the cell cycle, DNA damage repair, intracellular signaling and development, which could provide for a variety of drug targets. This review aims to summarize current knowledge of the genetics and genomics of pancreatic cancer from its inception to metastatic colonization, and to provide examples of how this information can be translated into the clinical setting for therapeutic benefit and personalized medicine. PMID:23673020

2013-01-01

189

[A case report of total remnant pancreatectomy for ductal carcinoma after distal pancreatectomy for invasive intraductal papillary mucinous carcinoma].  

PubMed

Recently, the number of case reports detailing cancer recurrence in the pancreatic remnants, following surgical resection of intraductal papillary-mucinous carcinoma (IPMC) of the pancreas has increased. We report the case of a 74-year-old woman who underwent pancreatic resection twice in a 3-year period for primary IPMC and remnant pancreatic ductal carcinoma. We first performed distal pancreatectomy for branched IPMC in the pancreatic tail. Histopathological examination revealed invasive IPMC and the negative margin of the pancreatic duct. The expression of tumor markers gradually increased in the 2 years and 4 months after the initial surgery, and a tumor was detected in the remnant pancreas. We performed total remnant pancreatectomy. The recurrent tumor consisted of moderately differentiated adenocarcinoma. Currently, the patient is alive without recurrence for a year since the second resection. This experience suggests that careful surveillance is necessary for IPMC. PMID:23268003

Okubo, Keita; Hama, Naoki; Kobayashi, Shogo; Eguchi, Hidetoshi; Akita, Hirofumi; Wada, Hiroshi; Kawamoto, Koichi; Marubashi, Shigeru; Tanemura, Masahiro; Umeshita, Koji; Mori, Masaki; Doki, Yuichiro; Nagano, Hiroaki

2012-11-01

190

ADJUVANT THERAPY IN PANCREATIC CANCER: PHASE I TRIAL OF RADIATION DOSE ESCALATION WITH CONCURRENT FULL-DOSE GEMCITABINE  

Microsoft Academic Search

Purpose: To determine the maximal tolerated dose of radiation delivered to the primary tumor bed, in combination with full-dose gemcitabine (1000 mg\\/m 2 weekly 3), after resection of pancreatic cancer. Methods and Materials: Patients with resected pancreatic carcinoma and poor prognostic features, a positive resection margin, or involved lymph nodes were eligible. Radiotherapy (RT) was directed at the preoperative tumor

AARON M. ALLEN; MARK M. ZALUPSKI; JOHN M. ROBERTSON; FREDERIC E. ECKHAUSER; DIANE SIMONE; DIANE BROWN; GWEN HEJNA; DANIEL NORMOLLE; THEODORE S. LAWRENCE; CORNELIUS J. MCGINN

2004-01-01

191

Organoid models of human and mouse ductal pancreatic cancer.  

PubMed

Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

Boj, Sylvia F; Hwang, Chang-Il; Baker, Lindsey A; Chio, Iok In Christine; Engle, Dannielle D; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D; Wilson, John P; Feigin, Michael E; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H M; Molenaar, I Quintus; Borel Rinkes, Inne H; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J; Iacobuzio-Donahue, Christine; Leach, Steven D; Pappin, Darryl J; Hammell, Molly; Klimstra, David S; Basturk, Olca; Hruban, Ralph H; Offerhaus, George Johan; Vries, Robert G J; Clevers, Hans; Tuveson, David A

2015-01-15

192

Non-umbilical cutaneous metastasis of a pancreatic adenocarcinoma  

PubMed Central

Pancreatic adenocarcinoma is one of the deadliest human malignancies with the majority of cases diagnosed late in the course of the disease. Cutaneous metastases originating from pancreatic cancer are rare. The most common site reported is the umbilicus. Non-umbilical cutaneous metastases are far less common with only a few cases reported in the literature. Our case involved a 43-year-old man with pancreatic carcinoma who was offered resection and a Whipple procedure was planned. Intraoperatively, the patient was found to have a widely metastatic disease not seen on preoperative imaging. Postoperatively, cutaneous metastasis in the scalp was discovered. Although rare, the recognition of non-umbilical cutaneous metastases of pancreatic adenocarcinoma can be of value because they can not only detect an underlying tumour but also guide management. PMID:23307465

Kaoutzanis, Christodoulos; Chang, Myungwon C; Abdul Khalek, Feras J; Kreske, Edward

2013-01-01

193

Diabetes and Pancreatic Cancer  

PubMed Central

Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer after cigarette smoking and obesity. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5- to 2.0-fold increase in the risk of pancreatic cancer. A causal relationship between diabetes and pancreatic cancer is also supported by findings from prediagnostic evaluations of glucose and insulin levels in prospective studies. Insulin resistance and associated hyperglycemia, hyperinsulinemia, and inflammation have been suggested to be the underlying mechanisms contributing to development of diabetes-associated pancreatic cancer. Signaling pathways that regulate the metabolic process also play important roles in cell proliferation and tumor growth. Use of the antidiabetic drug metformin has been associated with reduced risk of pancreatic cancer in diabetics and recognized as an antitumor agent with the potential to prevent and treat this cancer. On the other hand, new-onset diabetes may indicate subclinical pancreatic cancer, and patients with new-onset diabetes may constitute a population in whom pancreatic cancer can be detected early. Biomarkers that help define high-risk individuals for clinical screening for pancreatic cancer are urgently needed. Why pancreatic cancer causes diabetes and how diabetes affects the clinical outcome of pancreatic cancer have yet to be fully determined. Improved understanding of the pathological mechanisms shared by diabetes and pancreatic cancer would be the key to the development of novel preventive and therapeutic strategies for this cancer. PMID:22162232

Li, Donghui

2011-01-01

194

Inherited Pancreatic Cancer Syndromes  

PubMed Central

Pancreatic cancer remains one of the most challenging of all cancers. Genetic risk factors are believed to play a major role, but other than genes coding for blood group, genetic risks for sporadic cases remain elusive. However, several germline mutations have been identified that lead to hereditary pancreatic cancer, familial pancreatic cancer and increased risk for pancreatic cancer as part of a familial cancer syndrome. The most important genes with variants increasing risk for pancreatic cancer include BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1 and STK11. Recognition of members of high-risk families is important for understanding pancreatic cancer biology, for recommending risk reduction strategies and, in some cases, initiating cancer surveillance programs. Because the best methods for surveillance have not been established the recommendation to refer at-risk patients to centers with ongoing research programs in pancreatic cancer surveillance is supported. PMID:23187834

Solomon, Sheila; Das, Siddhartha; Brand, Randall; Whitcomb, David C

2012-01-01

195

Diabetes and pancreatic cancer.  

PubMed

The relationship between diabetes and pancreatic cancer is complex. Diabetes or impaired glucose tolerance is present in more than 2/3rd of pancreatic cancer patients. Epidemiological studies have consistently shown a modest increase in the risk of pancreatic cancer in type 2 diabetes, with an inverse relationship to duration of disease. Additionally, recent studies suggest that anti-diabetic medications may modulate the risk of pancreatic cancer in type 2 diabetes. Subjects >50 years of age with new onset diabetes are at higher risk of having pancreatic cancer. However, to screen new-onset diabetes for pancreatic cancer, additional markers are needed that can distinguish pancreatic cancer-associated diabetes from type 2 diabetes. PMID:23207610

Muniraj, T; Chari, S T

2012-12-01

196

Diabetes and pancreatic cancer  

PubMed Central

The relationship between diabetes and pancreatic cancer is complex. Diabetes or impaired glucose tolerance is present in more than 2/3rd of pancreatic cancer patients. Epidemiological studies have consistently shown a modest increase in the risk of pancreatic cancer in type 2 diabetes, with an inverse relationship to duration of disease. Additionally, recent studies suggest that anti-diabetic medications may modulate the risk of pancreatic cancer in type 2 diabetes. Subjects >50 years of age with new onset diabetes are at higher risk of having pancreatic cancer. However, to screen new-onset diabetes for pancreatic cancer, additional markers are needed that can distinguish pancreatic cancer-associated diabetes from type 2 diabetes. PMID:23207610

MUNIRAJ, T.; CHARI, S. T.

2014-01-01

197

Difficulty with diagnosis of malignant pancreatic neoplasms coexisting with chronic pancreatitis  

PubMed Central

Chronic pancreatitis is a relatively common disease. We encountered two different cases of belatedly demonstrated pancreatic carcinoma featuring underlying chronic pancreatitis. The first case was one that was highly suspected as that of a malignancy based upon imaging study, but unfortunately, it could not be confirmed by intra-operative cytology at that time. Following this, the surgeon elected to perform only conservative bypass surgery for obstructive biliary complication. Peritoneal carcinomatosis was later noted and the patient finally died. The second case, a malignant mucinous neoplasm, was falsely diagnosed as a pseudocyst, based upon the lesion’s sonographic appearance and associated elevated serum amylase levels. After suffering repeated hemoptysis, the patient was found to exhibit lung metastasis and peritoneal seeding. We reviewed some of the literature, including those studies discussing chronic pancreatitis predisposing to a malignant change. These two case analyses illustrate clearly that the diagnosis for such conditions, which is simply based upon imagery or pathological considerations may end up being one of a mistaken malignancy. Some of our suggestions for the treatment of such malignancies as revealed herein include, total pancreatomy for univocal mass lesion, and needle aspiration of lesion-contained tissue for amylase, CA199 and CEA levels for a suspicious cystic pancreatic mass. PMID:16124071

Leung, Ting-Kai; Lee, Chi-Ming; Wang, Fong-Chieh; Chen, Hsin-Chi; Wang, Hung-Jung

2005-01-01

198

Pancreatic ductal adenocarcinoma with autoimmune pancreatitis-like histologic and immunohistochemical features.  

PubMed

Autoimmune pancreatitis (AIP) often manifests as a mass lesion causing obstructive jaundice, clinically mimicking pancreatic carcinoma. A diagnosis of AIP may obviate the need for surgical resection, as most patients respond to steroid treatment. However, it is not clear whether these 2 conditions can coexist. In this study, 105 specimens resected for pancreatic ductal adenocarcinoma (PDAC) that also have changes of chronic pancreatitis were examined for features considered to be characteristic of AIP. Of 105 cases of PDAC with changes of chronic pancreatitis, 10 (9.5%) exhibited histologic features of AIP, including exuberant fibrosis, lymphoplasmacytic infiltration, obliterative phlebitis, or granulocytic epithelial lesions. Of these 10 cases, 7 had more than 20 immunoglobulin G4+ plasma cells per high-power field. Of these 7 cases, 5 were analyzed for Kirsten rat sarcoma viral oncogene mutation and SMAD4 expression. Three cases showed K-ras mutation and/or loss of SMAD4 expression in benign AIP-like areas. These findings suggest 2 possibilities: first, AIP-like lesions may occur in a small but significant portion of PDAC cases; second, some PDACs may arise in a background of AIP. Therefore, caution is necessary when making a diagnosis of AIP by needle biopsy of a mass lesion, and patients with a tentative AIP diagnosis should be closely followed up clinically. PMID:24457081

Zhang, Xuefeng; Liu, Xiuli; Joseph, Loren; Zhao, Lei; Hart, John; Xiao, Shu-Yuan

2014-03-01

199

Mucoepidermoid Carcinoma of the Intrapancreatic Common Bile Duct: Immunohistochemical Profile, Prognosis, and Review of the Literature  

PubMed Central

Mucoepidermoid carcinoma of the bile duct is a rare entity. Only one mucoepidermoid carcinoma from the common bile duct has been reported in the Korean literature. Herein, we present the first in the English literature. The tumor arose in the intrapancreatic (distal) common bile duct in an 83-year-old woman who presented with obstructive jaundice and elevated liver enzymes. The tumor invaded the underlying pancreas and peripancreatic adipose tissue and showed pagetoid spread into the extrapancreatic common bile duct and cystic duct. The tumor exhibited nests of malignant cells with diffuse CK7 and MUC1 positivity. The basal cells were p63 and CK5/6 positive. The luminal cells were stained with carcinoembryonic antigen, MUC5, and mucicarmine and were focally positive for CK20. There was focal MUC4 staining on the apical luminal border. The neoplastic cells were negative for MUC2 and HER2-neu. We discuss the clinical presentation, diagnostic features, immunohistochemical profile, and prognosis of mucoepidermoid carcinoma of the common bile duct. The features of this neoplasm are further compared with mucoepidermoid carcinoma of the hepatobiliary system, adenosquamous carcinoma, and mucoepidermoid carcinoma of other organs. PMID:24367734

Moul, Adrienne E.; Bejarano, Pablo A.; Casillas, Javier; Levi, Joe U.; Garcia-Buitrago, Monica T.

2013-01-01

200

Human pancreatic cancer-associated antigens detected by murine monoclonal antibodies.  

PubMed

Two monoclonal antibodies, YPan1 and YPan2, were produced from spleen cells of mice immunized against a human pancreatic cancer cell line, Capan-2, which also reacted with eight other human pancreatic carcinoma cell lines and with sections of cancerous human pancreas tissue. Reactivity was also found with colonic and stomach carcinoma tissues. Whereas YPan1 reacted strongly with normal pancreatic tissue, it bound weakly, if at all, to a variety of other normal tissues. YPan1 reacted with both the membranes and cytoplasm of pancreatic adenocarcinoma cells and with constituents of normal pancreatic ductal cells and duct luminal contents. YPan2, on the other hand, reacts to a greater degree with intracytoplasmic constituents in pancreatic adenocarcinoma cells. Unlike YPan1, YPan2 reacted weakly with only one of 16 cases of normal pancreas. Pretreatment of the tissue with neuraminidase abolished YPan1's reactivity, which indicated that sialic acid may be involved in the antigenic activity of the molecule(s) recognized by YPan1. Neuraminidase pretreatment had no effect on YPan2 reactivity. Neither YPan1 nor YPan2 competed with 19-9 monoclonal antibody in binding to soluble CA 19-9 antigen. These results suggest that these monoclonal antibodies are of potential use in the diagnosis of pancreatic carcinoma. PMID:4063969

Yuan, S Z; Ho, J J; Yuan, M; Kim, Y S

1985-12-01

201

Pancreatic Cancer Stage 2B  

MedlinePLUS

... My Pictures Browse Search Quick Search Image Details Pancreatic Cancer Stage 2B View/Download: Small: 720x576 View Download Add to My Pictures Title: Pancreatic Cancer Stage 2B Description: Stage IIB pancreatic cancer; illustration ...

202

Chronic Pancreatitis (Beyond the Basics)  

MedlinePLUS

... Irritable bowel syndrome (Beyond the Basics) Patient information: Pancreatic cancer (Beyond the Basics) Clinical manifestations and diagnosis of ... of the upper intestine ? An increased risk of pancreatic cancer PANCREATITIS DIAGNOSIS It can be difficult to diagnose ...

203

Pancreatic Cancer Stage 2A  

MedlinePLUS

... My Pictures Browse Search Quick Search Image Details Pancreatic Cancer Stage 2A View/Download: Small: 720x576 View Download Add to My Pictures Title: Pancreatic Cancer Stage 2A Description: Stage IIA pancreatic cancer; drawing ...

204

Recombinant toxin DAB389EGF is cytotoxic to human pancreatic cancer cells.  

PubMed

Few malignancies have frustrated the persistent efforts of the oncologist like pancreatic cancer. Pancreatic cancer is usually unresectable at the time of diagnosis because of metastasis or local extension. Despite the aggressive nature of this deadly disease, systemic treatment options are limited. Even the recent introduction of the deoxycytidine analogue gemcitabine does not extend median survival of responders beyond a year. Clearly, alternative, more effective regimens are needed for treating pancreatic carcinoma. In pancreatic cancer, there is overexpression of growth factors and growth factor receptors, including epidermal growth factor receptor (EGFR). Targeted toxins consist of a targeting polypeptide covalently linked to a peptide toxin. DAB(389)EGF is a fusion protein composed of the catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor (EGF). The authors have previously shown that DAB(389)EGF is selectively toxic to EGFR-overexpressing cells, including human brain tumour and lung carcinoma cell lines. Pancreatic adenocarcinoma should be responsive to this fusion protein based on its EGFR overexpression. However, the cytotoxic effect of DAB(389)EGF on human pancreatic carcinoma cell lines has yet to be explored. The authors describe preliminary data showing the potent cytotoxicity of DAB(389)EGF to human pancreatic carcinoma cell lines. Because of the nonspecific toxicity to liver and kidney (which possess EGFR) of systemic administration, they also propose a potential novel drug delivery system for direct toxin implantation into pancreatic tumours using endoscopic ultrasound guided fine-needle injection (EUS-FNI). Hopefully, the use of these targeted therapeutic approaches in combination with other modalities may further extend survival and quality of life in patients with pancreatic adenocarcinoma. PMID:14519080

Mishra, Girish; Liu, Tie Fu; Frankel, Arthur E

2003-10-01

205

Minireview on laparoscopic hepatobiliary and pancreatic surgery  

PubMed Central

The first laparoscopic cholecystectomy was performed in the mid-1980s. Since then, laparoscopic surgery has continued to gain prominence in numerous fields, and has, in some fields, replaced open surgery as the preferred operative technique. The role of laparoscopy in staging cancer is controversial, with regards to gallbladder carcinoma, pancreatic carcinoma, hepatocellular carcinoma and liver metastasis from colorectal carcinoma, laparoscopy in conjunction with intraoperative ultrasound has prevented nontherapeutic operations, and facilitated therapeutic operations. Laparoscopic cholecystectomy is the preferred option in the management of gallbladder disease. Meta-analyses comparing laparoscopic to open distal pancreatectomy show that laparoscopic pancreatectomy is safe and efficacious in the management of benign and malignant disease, and have better patient outcomes. A pancreaticoduodenectomy is a more complex operation and the laparoscopic technique is not feasible for this operation at this time. Robotic assisted pancreaticoduodenectomy has been tried with limited success at this time, but with continuing advancement in this field, this operation would eventually be feasible. Liver resection remains to be the best management for hepatocellular carcinoma, cholangiocarcinoma and colorectal liver metastases. Systematic reviews and meta-analyses have shown that laparoscopic liver resections result in patients with equal or less blood loss and shorter hospital stays, as compared to open surgery. With improving equipment and technique, and the incorporation of robotic surgery, minimally invasive liver resection operative times will improve and be more efficacious. With the incorporation of robotic surgery into hepatobiliary surgery, donor hepatectomies have also been completed with success. The management of benign and malignant disease with minimally invasive hepatobiliary and pancreatic surgery is safe and efficacious. PMID:24634709

Tan-Tam, Clara; Chung, Stephen W

2014-01-01

206

Chronic Pancreatitis: Evolving Paradigms  

Microsoft Academic Search

Chronic pancreatitis (CP) is characterized by progressive fibrosis, pain and\\/or loss of exocrine and endocrine functions. With the identification and characterization of pancreatic stellate cells (PSCs), the pathogenesis of CP and pancreatic fibrosis is now better understood. Molecular mediators shown to regulate the pathogenesis include transforming growth factor-?, platelet-derived growth factor, and proinflammatory cytokines such as interleukin (IL)-1, IL-6 and

Rupjyoti Talukdar; Nripen Saikia; Dinesh Kumar Singal; Rakesh Tandon

2006-01-01

207

Precursors to pancreatic cancer.  

PubMed

Infiltrating ductal adenocarcinoma of the pancreas is believed to arise from morphologically distinct noninvasive precursor lesions. These precursors include the intraductal papillary mucinous neoplasm, the mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia. Intraductal papillary mucinous neoplasms are grossly visible mucin-producing epithelial neoplasms that arise in the main pancreatic duct or one of its branches. The cysts of mucinous cystic neoplasms do not communicate with the major pancreatic ducts, and these neoplasms are characterized by a distinct ovarian-type stroma. Pancreatic intraepithelial neoplasia is a microscopic lesion. This article focuses on the clinical significance of these three important precursor lesions, with emphasis on their clinical manifestations, detection, and treatment. PMID:17996793

Hruban, Ralph H; Maitra, Anirban; Kern, Scott E; Goggins, Michael

2007-12-01

208

Pancreatitis is a risk factor for pancreatic cancer  

Microsoft Academic Search

Background & Aims: The Department of Veterans Affairs (VA) maintains a computerized file of all hospital discharges since 1970. In taking advantage of this large database, the present study aimed to determine whether pancreatitis is a risk factor for pancreatic cancer. Methods: A case control study compared the occurrence of pancreatitis in 2639 patients with pancreatic cancer and a matched

Pradeep Bansal; Amnon Sonnenberg

1995-01-01

209

Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer  

ClinicalTrials.gov

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

2015-02-04

210

Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer  

ClinicalTrials.gov

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

2014-12-23

211

REGULATION OF PANCREATIC CANCER GROWTH BY SUPEROXIDE  

PubMed Central

K-ras mutations have been identified in up to 95% of pancreatic cancers, implying their critical role in the molecular pathogenesis. Expression of K-ras oncogene in an immortalized human pancreatic ductal epithelial cell line, originally derived from normal pancreas (H6c7), induced the formation of carcinoma in mice. We hypothesized that K-ras oncogene correlates with increased non-mitochondrial-generated superoxide (O2·?), which could be involved in regulating cell growth contributing to tumor progression. In the H6c7 cell line and its derivatives, H6c7er-Kras+ (H6c7 cells expressing K-ras oncogene), and H6c7eR-KrasT (tumorigenic H6c7 cells expressing K-ras oncogene), there was an increase in hydroethidine fluorescence in cell lines that express K-ras. Western blots and activity assays for the antioxidant enzymes that detoxify O2·? were similar in these cell lines suggesting that the increase in hydroethidine fluorescence was not due to decreased antioxidant capacity. To determine a possible non-mitochondrial source of the increased levels of O2·?, Western analysis demonstrated the absence of NADPH oxidase-2 (NOX2) in H6c7 cells but present in the H6c7 cell lines expressing K-ras and other pancreatic cancer cell lines. Inhibition of NOX2 decreased hydroethidine fluorescence and clonogenic survival. Furthermore, in the cell lines with the K-ras oncogene, overexpression of superoxide dismutases, that detoxify non-mitochondrial sources of O2·?, and treatment with the small molecule O2·? scavenger Tempol, also decreased hydroethidine fluorescence, inhibited clonogenic survival and inhibited growth of tumor xenografts. Thus, O2·? produced by NOX2 in pancreatic cancer cells with K-ras, may regulate pancreatic cancer cell growth. PMID:22392697

Du, Juan; Nelson, Elke S.; Simons, Andrean L.; Olney, Kristen E.; Moser, Justin C.; Schrock, Hannah E.; Wagner, Brett A.; Buettner, Garry R.; Smith, Brian J.; Teoh, Melissa L.T.; Tsao, Ming-Sound; Cullen, Joseph J.

2012-01-01

212

Diagnostic problems in precancerous lesions and invasive carcinomas of the penis.  

PubMed

Penile precancerous and invasive lesions exhibit a variegated morphology. Although the diagnosis and classification of penile tumors is straightforward in most cases, a few entities are problematic, especially to pathologists from countries in which penile cancer is rarely encountered. The differential diagnosis of squamous hyperplasias from differentiated penile intraepithelial neoplasia or from extremely low-grade invasive neoplasms (eg, pseudohyperplastic and verrucous carcinomas) may be particularly difficult. Similarly, given the morphologic features shared by all verruciform tumors (ie, verrucous, warty, papillary, and cuniculatum carcinomas, along with giant condylomas), it is challenging at times to distinguish one from another. At the other end of the spectrum, because of their lack of differentiation, it is sometimes difficult to classify high-grade carcinomas, such as basaloid and sarcomatoid, which may have etiologic/prognostic implications. Penile mixed tumors, harboring more than 1 histologic subtype and grade, constitute a frequent finding in routine pathology. The recognition of distinctive morphologic patterns and histologic grades in these tumors is important because these features could be related to etiologic factors, such as human papillomavirus infection, or they could influence outcome. Penile tumors with glandular features (eg, adenosquamous and mucoepidermoid carcinomas), although rare, may be confused with the more common pseudoglandular (adenoid, acantholytic) variant of squamous cell carcinomas, their main mimicker. In this review we provide clues that may help in the differential diagnosis of these lesions. PMID:22641956

Chaux, Alcides; Cubilla, Antonio L

2012-05-01

213

Endoscopic pancreatic duct stent placement for inflammatory pancreatic diseases  

PubMed Central

The role of endoscopic therapy in the management of pancreatic diseases is continuously evolving; at present most pathological conditions of the pancreas are successfully treated by endoscopic retrograde cholangio-pancreatography (ERCP) or endoscopic ultrasound (EUS), or both. Endoscopic placement of stents has played and still plays a major role in the treatment of chronic pancreatitis, pseudocysts, pancreas divisum, main pancreatic duct injuries, pancreatic fistulae, complications of acute pancreatitis, recurrent idiopathic pancreatitis, and in the prevention of post-ERCP pancreatitis. These stents are currently routinely placed to reduce intraductal hypertension, bypass obstructing stones, restore lumen patency in cases with dominant, symptomatic strictures, seal main pancreatic duct disruption, drain pseudocysts or fluid collections, treat symptomatic major or minor papilla sphincter stenosis, and prevent procedure-induced acute pancreatitis. The present review aims at updating and discussing techniques, indications, and results of endoscopic pancreatic duct stent placement in acute and chronic inflammatory diseases of the pancreas. PMID:18023085

Testoni, Pier Alberto

2007-01-01

214

Deciphering the Role of Stroma in Pancreatic Cancer  

PubMed Central

Purpose of review This review intends to describe recent studies on pancreatic tumor associated stroma and potential opportunities and limitations to its targeting. Recent findings One of the defining features of pancreatic cancer is extensive desmoplasia, or an inflammatory, fibrotic reaction. Carcinoma cells live in this complex microenvironment which is comprised of extracellular matrix (ECM), diffusible growth factors, cytokines and a variety of non-epithelial cell types including endothelial cells, immune cells, fibroblasts, myofibroblasts and stellate cells. In addition to the heterogeneity noted in the non-neoplastic cells within the tumor microenvironment, it has also been recognized that neoplastic cancer cells themselves are heterogeneous, and include a subpopulation of stem-cell like cells within tumors termed cancer stem cells. Due to the failure of current therapeutics to improve outcomes in patients with pancreatic cancer, new therapeutic avenues targeting different components of the tumor microenvironment are being investigated. In this review article, we will focus on recent studies regarding the function of the tumor stroma in pancreatic cancer and therapeutic treatments that are being advanced to target the stroma as a critical part of tumor management. Summary Recent studies have shed new light on the contribution of the pancreatic cancer fibroinflammatory stroma to pancreatic cancer biology. Additional studies are needed to better define its full contribution to tumor behavior and how to best understand the optimal ways to develop therapies that counteract its pro-neoplastic properties. PMID:23892539

Waghray, Meghna; Yalamanchili, Malica; di Magliano, Marina Pasca; Simeone, Diane M.

2014-01-01

215

Inhibition of pancreatic tumoral cells by snake venom disintegrins.  

PubMed

Pancreatic cancer often has a poor prognosis, even when diagnosed early. Pancreatic cancer typically spreads rapidly and is rarely detected in its early stages, which is a major reason it is a leading cause of cancer death. Signs and symptoms may not appear until pancreatic cancer is quite advanced, and complete surgical removal is not possible. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. The importance of integrins in several cell types that affect tumor progression has made them an appealing target for cancer therapy. Some of the proteins found in the snake venom present a great potential as anti-tumor agents. In this study, we summarize the activity of two integrins antagonist, recombinant disintegrins mojastin 1 and viridistatin 2, on human pancreatic carcinoma cell line (BXPC-3). Both recombinant disintegrins inhibited some essential aspects of the metastasis process such as proliferation, adhesion, migration, and survival through apoptosis, making these proteins prominent candidates for the development of drugs for the treatment of pancreatic cancer. PMID:25450798

Lucena, Sara; Castro, Roberto; Lundin, Courtney; Hofstetter, Amanda; Alaniz, Amber; Suntravat, Montamas; Sánchez, Elda Eliza

2015-01-01

216

Pathogenesis of pancreatic infection.  

PubMed Central

John Hunter studied comparative anatomy of the pancreas but was unaware of pancreatic infection which is now the leading cause of mortality in pancreatitis. This was investigated using a feline model of pancreatitis. Pathogens spread to the healthy and inflamed gland from many sources including colon, gallbladder, or a septic focus and by various routes including the circulation, reflux into the pancreatic duct or by transmural migration from the colon. Colonisation risk was proportional to necrosis and inflammation, confirming clinical observations. These studies showed that pathogens frequently colonised the pancreas, but infection developed only in animals with pancreatitis. In cats with pancreatitis, phagocytic function was reduced by 28%. This was probably owing to phagocytic capacity being overwhelmed by protease-antiprotease complexes because, in humans, granulocyte and lymphocyte function was normal. These experiments suggested that it would be difficult to prevent pancreatic colonisation, but indicated some types of therapy may have potential. These were investigated using this animal model of pancreatic infection. Treatment with either cefotaxime or levamisole (an immunostimulant) were effective. However, the anti-inflammatory drug dopamine, which reduced inflammation, did not eradicate all pathogens. PMID:8712649

Widdison, A. L.

1996-01-01

217

MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells  

PubMed Central

The transition of chronic pancreatic fibroinflammatory disease to neoplasia is a primary example of the paradigm linking inflammation to carcinogenesis. However, the cellular and molecular mediators bridging these entities are not well understood. Because TLR4 ligation can exacerbate pancreatic inflammation, we postulated that TLR4 activation drives pancreatic carcinogenesis. In this study, we show that lipopolysaccharide accelerates pancreatic tumorigenesis, whereas TLR4 inhibition is protective. Furthermore, blockade of the MyD88-independent TRIF pathway is protective against pancreatic cancer, whereas blockade of the MyD88-dependent pathway surprisingly exacerbates pancreatic inflammation and malignant progression. The protumorigenic and fibroinflammatory effects of MyD88 inhibition are mediated by dendritic cells (DCs), which induce pancreatic antigen–restricted Th2-deviated CD4+ T cells and promote the transition from pancreatitis to carcinoma. Our data implicate a primary role for DCs in pancreatic carcinogenesis and illustrate divergent pathways in which blockade of TLR4 signaling via TRIF is protective against pancreatic cancer and, conversely, MyD88 inhibition exacerbates pancreatic inflammation and neoplastic transformation by augmenting the DC–Th2 axis. PMID:22908323

Ochi, Atsuo; Nguyen, Andrew H.; Bedrosian, Andrea S.; Mushlin, Harry M.; Zarbakhsh, Saman; Barilla, Rocky; Zambirinis, Constantinos P.; Fallon, Nina C.; Rehman, Adeel; Pylayeva-Gupta, Yuliya; Badar, Sana; Hajdu, Cristina H.; Frey, Alan B.; Bar-Sagi, Dafna

2012-01-01

218

MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells.  

PubMed

The transition of chronic pancreatic fibroinflammatory disease to neoplasia is a primary example of the paradigm linking inflammation to carcinogenesis. However, the cellular and molecular mediators bridging these entities are not well understood. Because TLR4 ligation can exacerbate pancreatic inflammation, we postulated that TLR4 activation drives pancreatic carcinogenesis. In this study, we show that lipopolysaccharide accelerates pancreatic tumorigenesis, whereas TLR4 inhibition is protective. Furthermore, blockade of the MyD88-independent TRIF pathway is protective against pancreatic cancer, whereas blockade of the MyD88-dependent pathway surprisingly exacerbates pancreatic inflammation and malignant progression. The protumorigenic and fibroinflammatory effects of MyD88 inhibition are mediated by dendritic cells (DCs), which induce pancreatic antigen-restricted Th2-deviated CD4(+) T cells and promote the transition from pancreatitis to carcinoma. Our data implicate a primary role for DCs in pancreatic carcinogenesis and illustrate divergent pathways in which blockade of TLR4 signaling via TRIF is protective against pancreatic cancer and, conversely, MyD88 inhibition exacerbates pancreatic inflammation and neoplastic transformation by augmenting the DC-Th2 axis. PMID:22908323

Ochi, Atsuo; Nguyen, Andrew H; Bedrosian, Andrea S; Mushlin, Harry M; Zarbakhsh, Saman; Barilla, Rocky; Zambirinis, Constantinos P; Fallon, Nina C; Rehman, Adeel; Pylayeva-Gupta, Yuliya; Badar, Sana; Hajdu, Cristina H; Frey, Alan B; Bar-Sagi, Dafna; Miller, George

2012-08-27

219

Pancreatic cancer...107 Chapter 10  

E-print Network

NICR/NCRI Pancreatic cancer...107 Chapter 10: Pancreatic cancer (C25) KEY FINDINGS - INCIDENCE. #12;Cancer in Ireland 1994-2004: A comprehensive report 108...Pancreatic cancer 10.1: Incidence Pancreatic cancer made up 2.4% of all male and 2.6% of all female cancers (excluding NMSC) in Ireland during

Paxton, Anthony T.

220

Pancreatic Stellate Cells: Partners in Crime with Pancreatic Cancer Cells  

Microsoft Academic Search

Pancreatic stellate cells (PSC) produce the stromal reaction in pancreatic cancer, but their role in cancer progression is not fully elucidated. We examined the influence of PSCs on pancreatic cancer growth using (a) an orthotopic model of pancreatic cancer and (b) cultured human PSCs (hPSC) and human pancreatic cancer cell lines MiaPaCa-2 and Panc-1. Athymic mice received an intrapancreatic injection

Alain Vonlaufen; Swapna Joshi; Changfa Qu; Phoebe A. Phillips; Zhihong Xu; Nicole R. Parker; Cheryl S. Toi; Romano C. Pirola; Jeremy S Wilson; David Goldstein; Minoti V Apte

2008-01-01

221

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

ClinicalTrials.gov

Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Duct Cell Adenocarcinoma of the Pancreas; Localized Unresectable Adult Primary Liver Cancer; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Gallbladder Cancer; Recurrent Pancreatic Cancer; Stage II Gallbladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IV Pancreatic Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer

2013-05-07

222

Expression and Diagnostic Value of HE4 in Pancreatic Adenocarcinoma.  

PubMed

Human epididymis protein 4 (HE4) is a recognized biomarker in ovarian and endometrial cancer and over-expressed in pancreatic adenocarcinoma. The diagnostic value of HE4 in pancreatic adenocarcinoma remains unknown. Here we elucidate mRNA, protein and serum level of HE4 in pancreatic adenocarcinoma. HE4 mRNA level in tumor adjacent tissues and pancreatic adenocarcinoma tissues were tested by real time-PCR. Tissue microarray containing normal, adenocarcinoma, and adjacent pancreatic tissue was tested by immunohistochemistry (IHC). Serum level of HE4, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3) and carbohydrate antigen 125 (CA125) were detected by ELISA assay in control and tumor patients. Further we compared the sensitivity and specificity of determining HE4, CA19-9, CA15-3, and CA125 for diagnosis of pancreatic adenocarcinoma and assessed the complementary diagnostic value of HE4, CA19-9, CA15-3 and CA125. Real time PCR showed significantly increased HE4 mRNA level in pancreatic adenocarcinoma compared with control. Result of IHC showed that HE4 significantly higher expressed in the human pancreatic carcinoma tissues than in both normal and adjacent non-tumorous pancreatic tissues, and the staining intensity is inversely correlated with the clinical stage. HE4 was highly expressed in early stage of pancreatic adenocarcinoma. Serum HE4 level is higher in cases with pancreatic adenocarcinoma than in the controls. Serum HE4 levels could research to a sensitivity of 45.83% and specificity of 93.75% when the Cutoff was set at 4.59 ng/mL. The Combined HE4 and CA19-9 increased the sensitivity to 83.33%; and interestingly, the combination of HE4 with CA15-3 led to the most powerful sensitivity of 87.5%. Combined with CA19-9 and CA15-3, HE4 could be a potential biomarker to improve the diagnostic power for pancreatic adenocarcinoma. PMID:25642754

Huang, Tianhe; Jiang, Shi-Wen; Qin, Liangyi; Senkowski, Christopher; Lyle, Christian; Terry, Karen; Brower, Steven; Chen, Haibin; Glasgow, Wayne; Wei, Yongchang; Li, Jinping

2015-01-01

223

CAM 17.1--a new diagnostic marker in pancreatic cancer.  

PubMed

CAM 17.1-Ab is a recently described monoclonal antibody that detects a mucus glycoprotein with high specificity for intestinal mucus, particularly in the colon, small intestine, biliary tract and pancreas. We investigated the expression and release of CAM 17.1 in pancreatic carcinoma cell lines and tissue specimens of normal pancreas, chronic pancreatitis and pancreatic cancer. CAM 17.1 was weakly expressed on normal ductal cells and chronic pancreatitis, whereas it was overexpressed in pancreatic cancer. Serum analysis using a new enzyme-linked antibody sandwich assay (CAM 17.1/WGA) of patients with chronic pancreatitis, pancreatic cancer or other gastrointestinal cancer and of healthy blood donors revealed a high sensitivity (67%) and excellent specificity (90%) of CAM 17.1/WGA assay in pancreatic cancer. In comparison with the tumour marker CA19-9, the sensitivity of the CAM 17.1/WGA assay was similar to the sensitivity of CA 19-9 (67% and 76%, P = 0.22), whereas the specificity of CAM 17.1/WGA assay was higher than in CA 19-9 (90% compared with 78% in chronic pancreatitis, P > 0.05). PMID:8980403

Gansauge, F; Gansauge, S; Parker, N; Beger, M I; Poch, B; Link, K H; Safi, F; Beger, H G

1996-12-01

224

Dietary modulation of azaserine-induced pancreatic carcinogenesis in the rat.  

PubMed

Because diet has been shown to modulate the incidence of a wide variety of chemically induced cancers in experimental animals, various dietary constituents were evaluated for their ability to modulate the incidence of pancreatic exocrine cancer in male Wistar/Lewis rats given injections of the pancreatic carcinogen, azaserine. Ten different diet regimens were fed. The incidence of pancreatic cancers in rats fed a control diet was compared to that in groups fed diets formulated to evaluate the effect of caloric restriction, high protein, low protein, low fat, cyclopropenoid fatty acids, lipotrope deficiency, high unsaturated fat, and high saturated fat. The incidence of pancreatic adenomas and carcinomas was evaluated by light microscopy. The number of pancreatic neoplasms was reduced in carcinogen-treated groups which were underfed the control diet or fed the diet high in protein. Pancreatic carcinogenesis appeared to be enhanced in two groups which were fed diets containing 20% corn oil, i.e., high in unsaturated fat; whereas, the group fed a diet high in saturated fat had the same incidence of neoplasms as did the group fed the control diet. The pancreatic neoplasms from groups in which the incidence was enhanced by diet showed less evidence of acinar cell differentiation and displayed diverse histological types. In the lipotrope-deficient group, there was a significantly increased incidence of hepatocellular carcinoma; however, a low incidence of liver tumors was encountered in all other dietary groups. PMID:7459874

Roebuck, B D; Yager, J D; Longnecker, D S

1981-03-01

225

Diagnosis of autoimmune pancreatitis.  

PubMed

Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to IgG4 (lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum IgG4 and positive serum autoantibodies, abundant infiltration of IgG4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology (IAP). PMID:25469024

Matsubayashi, Hiroyuki; Kakushima, Naomi; Takizawa, Kohei; Tanaka, Masaki; Imai, Kenichiro; Hotta, Kinichi; Ono, Hiroyuki

2014-11-28

226

Pleuropulmonary complications of pancreatitis  

PubMed Central

Pancreatitis, in common with many other upper abdominal diseases, often leads to pleuropulmonary complications. Radiological evidence of pleuropulmonary abnormality was found in 55% of 58 cases examined retrospectively. The majority of such abnormalities are not specific for pancreatitis; but a particular category of pleural effusions, rich in pancreatic enzymes, is a notable exception. A patient with this type of effusion, complicated by a spontaneous bronchopleural fistula and then by an empyema, is reported. The literature relating to pancreatic enzyme-rich pleural effusions (pathognomonic of pancreatitis) is reviewed. Of several possible mechanisms involved in pathogenesis, transdiaphragmatic lymphatic transfer of pancreatic enzymes, intrapleural rupture of mediastinal extensions of pseudocysts, and diaphragmatic perforation are the most important. The measurement of pleural fluid amylase, at present little employed in this country, has considerable diagnostic value. Enzyme-rich effusions are more commonly left-sided, are often blood-stained, are frequently associated with pancreatic pseudocysts, and—if long standing—may be complicated by a bronchopleural fistula. Images PMID:4872925

Kaye, Michael D.

1968-01-01

227

Can Pancreatic Cancer Be Found Early?  

MedlinePLUS

... Topic Signs and symptoms of pancreatic cancer Can pancreatic cancer be found early? Pancreatic cancer is hard to ... Testing: What You Need to Know . Testing for pancreatic cancer in people at high risk For people in ...

228

Molecular Profiling of Pancreatic Adenocarcinoma and Chronic Pancreatitis Identifies Multiple Genes Differentially Regulated in Pancreatic Cancer 1  

Microsoft Academic Search

The molecular basis of pancreatic cancer is not understood. Previous attempts to determine the specific genes expressed in pancreatic cancer have been hampered by similarities between adenocarcinoma and chronic pancreatitis. In the current study, microarrays (Affymetrix) were used to profile gene expression in pancreatic adenocarcinoma (10), pancreatic cancer cell lines (7), chronic pancreatitis (5), and normal pancreas (5). Molecular profiling

Craig D. Logsdon; Diane M. Simeone; Charles Binkley; Thiruvengadam Arumugam; Joel K. Greenson; Thomas J. Giordano; David E. Misek; Samir Hanash

2003-01-01

229

Molecular marker from pancreatic 'juices' helps identify pancreatic cancer  

Cancer.gov

Researchers at Mayo Clinic have developed a promising method to distinguish between pancreatic cancer and chronic pancreatitis — two disorders that are difficult to tell apart. A molecular marker obtained from pancreatic "juices" can identify almost all cases of pancreatic cancer, their study shows. The findings were being presented at Digestive Disease Week 2013 in Orlando, Fla. Pancreatic cancer and chronic pancreatitis both produce the same signs of disease in the pancreas, such as inflammation, but cancer in the organ is a life-threatening disorder that must be treated immediately and aggressively.

230

Hypermethylation of Multiple Genes in Pancreatic Adenocarcinoma1  

Microsoft Academic Search

Hypermethylation of CpG islands is a common mechanism by which tumor suppressor genes are inactivated. We studied 45 pancreatic carcino- mas and 14 normal pancreata for aberrant DNA methylation of CpG islands of multiple genes and clones using methylation-specific PCR (MSP) and bisulfite-modified sequencing. Using MSP, we detected aberrant methylation of at least one locus in 60% of carcinomas. The

Takashi Ueki; Minoru Toyota; Taylor Sohn; Charles J. Yeo; Jean-Pierre J. Issa; Ralph H. Hruban; Michael Goggins

2000-01-01

231

[Pancreatic extract therapy in exocrine pancreatic insufficiency].  

PubMed

The authors consider the different strategies in long term enzyme replacement therapy in relation to the complex mechanics at the basis of pancreas exocrine insufficiency. This condition occurs in chronic pancreatitis and is present in Cystic Fibrosis, the most common potentially lethal inherited disorder of Caucasians. Pancreatic exocrine insufficiency occurs in the vast majority of cystic fibrosis affected children and is now becoming a frequent pathology in adults for the better life expectancy and the recent acknowledgements in this disease. The principal aims of research in enzyme replacement therapy have been directed at the formulation of products with high enzyme concentration, to the prevention of gastric acid inactivation of enzymes and to the better mixing of the preparations with meals. The authors consider all the different enzyme preparations from pancreatin powder to the 1st. generation of enteric coated tablets and examine the advantages of administering H-2 receptor antagonists or antacids and the possibility of stimulating bicarbonate secretion as an adjunct to pancreatic enzyme replacement therapy. Significant benefits in pancreatic insufficiency therapy have derived from the introduction of enteric coated microspheres which ensure a consistent level of enzymes to reach the duodenum mixed with the meal and which are resistant to gastric acid inactivation as well. PMID:8286485

Santini, B; Ivaldi, A P

1993-09-01

232

Pathology and genetics of pancreatic neoplasms with acinar differentiation  

PubMed Central

Pancreatic neoplasms with acinar differentiation, including acinar cell carcinoma, pancreatoblastoma, and carcinomas with mixed differentiation, are distinctive pancreatic neoplasms with a poor prognosis. These neoplasms are clinically, pathologically, and genetically unique when compared to other more common pancreatic neoplasms. Most occur in adults, although pancreatoblastomas usually affect children under 10 years old. All of these neoplasms exhibit characteristic histologic features including a solid or acinar growth pattern, dense neoplastic cellularity, uniform nuclei with prominent nucleoli, and granular eosinophilic cytoplasm. Exocrine enzymes are detectable by immunohistochemistry and, for carcinomas with mixed differentiation, neuroendocrine or ductal lineage markers are also expressed. The genetic alterations of this family of neoplasms largely differ from conventional ductal adenocarcinomas, with only rare mutations in TP53, KRAS, and p16, but no single gene or neoplastic pathway is consistently altered in acinar neoplasms. Instead, there is striking genomic instability, and a subset of cases has mutations in the APC/?-catenin pathway, mutations in SMAD4, RAF gene family fusions, or microsatellite instability. Therapeutically targetable mutations are often present. This review summarizes the clinical and pathologic features of acinar neoplasms and reviews the current molecular data on these uncommon tumors. PMID:25441307

Wood, Laura D.; Klimstra, David S.

2015-01-01

233

Pancreatic Exocrine Function Testing  

PubMed Central

It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each. PMID:6176075

Goff, John S.

1981-01-01

234

Familial Pancreatic Cancer  

PubMed Central

Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer. PMID:24281205

Lynch, Henry T.; Lynch, Jane F.; Lanspa, Stephen J.

2010-01-01

235

Pancreatic Cancer Action Network  

MedlinePLUS

Skip to content Top Menu Facing Pancreatic Cancer One-on-One Support Overview Call us with your questions Email us with your questions Request an information packet Recently Diagnosed Overview Get ...

236

[Nutrition in acute pancreatitis].  

PubMed

Nutritional concepts in acute pancreatitis are undergoing a rapid change. An early start of nutrition via nasojejunal tubes is about to replace parenteral nutrition. Yesterday it was believed that the pancreas had to be put at rest. Thus, stimulation of pancreatic secretion by enteral nutrition was believed to be detrimental. However, on comparing the results of enteral with those of parenteral nutrition, the pancreatic infection rates, rate of surgical interventions, days of hospital stay, and costs are found to be significantly reduced. Whether or not enteral nutrition decreases mortality has not been clearly proven. Pancreatitis is associated with the risk of paralytic ileus. Thus, data suggesting that one does not have to feed via a nasojejunal tube but rather via an easier to place nasogastric tube, are provocative. Numerous questions still have to be answered such as composition of tube diet, nutrition in mild to moderate pancreatitis, ways to reduce pain and composition of diet when oral refeeding is started. The nutrition of tomorrow may implicate immunonutrition. There are only a few small studies suggesting beneficial effects by supplementation of tube feeding with MCT/LCT triglycerides, glutamine, arginin, omega-3-fatty acids, nucleotides. So far, these supplements have failed to show efficacy for clinically relevant endpoints. In an recently published study, prebiotics were associated with a high complication rate. In this review, we summarise the current knowledge on nutrition in acute pancreatitis and discuss future developments. PMID:18759203

Mössner, J; Teich, N

2008-08-01

237

Tropical chronic pancreatitis.  

PubMed

Tropical chronic pancreatitis (TCP) is a juvenile form of chronic calcific non-alcoholic pancreatitis, seen almost exclusively in the developing countries of the tropical world. The classical triad of TCP consists of abdominal pain, steatorrhoea, and diabetes. When diabetes is present, the condition is called fibrocalculous pancreatic diabetes (FCPD) which is thus a later stage of TCP. Some of the distinctive features of TCP are younger age at onset, presence of large intraductal calculi, more aggressive course of the disease, and a high susceptibility to pancreatic cancer. Pancreatic calculi are the hallmark for the diagnosis of TCP and in non-calcific cases ductal dilation on endoscopic retrograde cholangiopancreatography, computed tomography, or ultrasound helps to identify the disease. Diabetes is usually quite severe and of the insulin requiring type, but ketosis is rare. Microvascular complications of diabetes occur as frequently as in type 2 diabetes but macrovascular complications are uncommon. Pancreatic enzyme supplements are used for relief of abdominal pain and reducing the symptoms related to steatorrhoea. Early diagnosis and better control of the endocrine and exocrine dysfunction could help to ensure better survival and improve the prognosis and quality of life of TCP patients. PMID:14654569

Barman, K K; Premalatha, G; Mohan, V

2003-11-01

238

Genetics of pancreatitis  

PubMed Central

Purpose of review Chronic pancreatitis is a syndrome characterized by chronic inflammation of the pancreas, with variable pain, calcifications, necrosis, fatty replacement, fibrosis and scarring and other complications. Disease susceptibility, severity, progression and pain patterns vary widely and do not necessarily parallel one another. Much of the variability in susceptibility to recurrent acute and chronic pancreatitis is now clearly shown to be related to genetic differences between patients. This review highlights recent advances and future directions in genetic research. Recent findings The strongest risk factors are associated with genetic variations in PRSS1, SPINK1, CFTR, and to a lesser extent, CTRC and CASR. The latest research suggest that a single factor rarely causes pancreatitis, and the majority of patients with recurrent acute and chronic pancreatitis have multiple variants in a gene, or epistatic interactions between multiple genes, coupled with environmental stressors. Summary Pancreatic diseases have a strong genetic component. Rather than a classic Mendelian disorder, recurrent acute and chronic pancreatitis represents truly complex diseases with the interaction and synergism of multiple genetic and environmental factors. The future will require new predictive models to guide prevention and therapy. PMID:21844754

LaRusch, Jessica; Whitcomb, David C.

2013-01-01

239

Contrast-enhanced ultrasonographic findings in three dogs with pancreatic insulinoma.  

PubMed

Abdominal ultrasonography is one of the most common diagnostic imaging modalities used for dogs with suspected insulinoma; however, pancreatic masses are clearly identified in fewer than half of affected dogs and benign pancreatic nodules can be difficult to differentiate from malignant ones. The purpose of this prospective study was to describe contrast-enhanced ultrasonography (CEUS) characteristics of confirmed pancreatic insulinoma in a group of dogs. Inclusion criteria were as follows: (1) repeated hypoglycemia (blood glucose levels <60 mg/dl, twice or more); (2) elevated blood insulin levels with hypoglycemia; (3) pancreatic nodules detected with conventional ultrasonography; and (4) histological confirmation of pancreatic islet cell carcinoma. Immediately following conventional ultrasonography of the entire abdomen, CEUS of the pancreatic nodule and adjacent parenchyma was performed using contrast-specific technology pulse inversion imaging and perflubutane microbubble contrast agent. Three dogs met inclusion criteria. Pancreatic nodules in all the three dogs became more clearly demarcated after injection of the contrast agent. Each nodule showed different enhancement patterns: markedly hyperechoic for 5 s, slightly hyperechoic for 1 s, and clearly hypoechoic for over 30 s. These results were not in complete agreement with previously reported CEUS findings in human patients with insulinoma. All nodules were surgically resected and histopathologically confirmed as malignant insulinomas. Findings from the current study indicated that contrast-enhanced ultrasound may help to increase conspicuity of pancreatic insulinomas in dogs and that enhancement characteristics may be more variable in dogs than in humans. PMID:24846763

Nakamura, Kensuke; Lim, Sue-Yee; Ochiai, Kenji; Yamasaki, Masahiro; Ohta, Hiroshi; Morishita, Keitaro; Takagi, Satoshi; Takiguchi, Mitsuyoshi

2015-01-01

240

Histogenesis of pancreatic carcinogenesis in the hamster: ultrastructural evidence  

SciTech Connect

Pancreatic carcinogenesis in the Syrian hamster, induced by ..beta..-oxidized derivatives of N-nitroso-di-n-propylamine, constitutes a valuable model of human cancer of the exocrine pancreas. In both species the majority of tumors are adenocarcinomas: superficially, on the basis of their histological appearance, these appear to be ductal in origin. However, sequential analysis, by electron microscopy, of the development of pancreatic neoplasia in the hamster model indicates that acinar cells may participate in the histogenesis of ductal adenomas and carcinomas. Acinar cells appear to undergo changes in differentiation, including pseudoductular transformation, giving rise to a new population of cells that resemble ductular or centroacinar types. This new population may then proliferate to form, first, cystic foci and subsequently cytadenomas and adenocarcinomas. Mucous metaplasia appears to develop at late stages of tumor development. Although the participation of ductular and centroacinar cells in pancreatic carcinogenesis cannot be excluded, very few tumors arise from the ductal epithelium. It is possible that some human pancreatic adenocarcinomas may also have their origin from dysplastic acinar cells, by analogy with the hamster model: focal acinar dyplasia being common in human pancreatic cancer patients. 90 references, 18 figures.

Flaks, B.

1984-06-01

241

[Differential genetic pathway of duct and acinar carcinomas of the pancreas].  

PubMed

Genetic pathways of various types of pancreatic carcinoma are described. There are many differences in the genetic pathway between duct carcinogenesis and acinar carcinogensis. K-ras mutation is a key event in the early stage of pancreatic duct carcinogenesis and various gene alterations accumulate from precancerous ductal lesions until the development of carcinomas. Therefore, inhibition of K-ras gene mutation might be important for the prevention, and the combination of therapeutic agents against some target genes might be needed for therapy of ductal carcinomas. PMID:15918556

Tsutsumi, Masahiro

2005-05-01

242

Environmental Risk Factors for Chronic Pancreatitis and Pancreatic Cancer  

Microsoft Academic Search

Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ?10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits

Claudia Nitsche; Peter Simon; F. Ulrich Weiss; Gabriele Fluhr; Eckhard Weber; Simone Gärtner; Claas O. Behn; Matthias Kraft; Jörg Ringel; Ali Aghdassi; Julia Mayerle; Markus M. Lerch

2011-01-01

243

Pancreatic trauma: a concise review.  

PubMed

Traumatic injury to the pancreas is rare and difficult to diagnose. In contrast, traumatic injuries to the liver, spleen and kidney are common and are usually identified with ease by imaging modalities. Pancreatic injuries are usually subtle to identify by different diagnostic imaging modalities, and these injuries are often overlooked in cases with extensive multiorgan trauma. The most evident findings of pancreatic injury are post-traumatic pancreatitis with blood, edema, and soft tissue infiltration of the anterior pararenal space. The alterations of post-traumatic pancreatitis may not be visualized within several hours following trauma as they are time dependent. Delayed diagnoses of traumatic pancreatic injuries are associated with high morbidity and mortality. Imaging plays an important role in diagnosis of pancreatic injuries because early recognition of the disruption of the main pancreatic duct is important. We reviewed our experience with the use of various imaging modalities for diagnosis of blunt pancreatic trauma. PMID:24379625

Debi, Uma; Kaur, Ravinder; Prasad, Kaushal Kishor; Sinha, Saroj Kant; Sinha, Anindita; Singh, Kartar

2013-12-21

244

Pancreatic trauma: A concise review  

PubMed Central

Traumatic injury to the pancreas is rare and difficult to diagnose. In contrast, traumatic injuries to the liver, spleen and kidney are common and are usually identified with ease by imaging modalities. Pancreatic injuries are usually subtle to identify by different diagnostic imaging modalities, and these injuries are often overlooked in cases with extensive multiorgan trauma. The most evident findings of pancreatic injury are post-traumatic pancreatitis with blood, edema, and soft tissue infiltration of the anterior pararenal space. The alterations of post-traumatic pancreatitis may not be visualized within several hours following trauma as they are time dependent. Delayed diagnoses of traumatic pancreatic injuries are associated with high morbidity and mortality. Imaging plays an important role in diagnosis of pancreatic injuries because early recognition of the disruption of the main pancreatic duct is important. We reviewed our experience with the use of various imaging modalities for diagnosis of blunt pancreatic trauma. PMID:24379625

Debi, Uma; Kaur, Ravinder; Prasad, Kaushal Kishor; Sinha, Saroj Kant; Sinha, Anindita; Singh, Kartar

2013-01-01

245

Genetics Home Reference: Hereditary pancreatitis  

MedlinePLUS

... to the pancreas increase the risk of developing pancreatic cancer. The risk is particularly high in people with ... history of cancer. In affected individuals who develop pancreatic cancer, it is typically diagnosed in mid-adulthood. Complications ...

246

Metabolic pancreatitis: Etiopathogenesis and management  

PubMed Central

Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis. PMID:24083160

Kota, Sunil Kumar; Krishna, S.V.S.; Lakhtakia, Sandeep; Modi, Kirtikumar D.

2013-01-01

247

Protection Against Chronic Pancreatitis and Pancreatic Fibrosis in Mice Over-Expressing Pancreatic Secretory Trypsin Inhibitor  

PubMed Central

Objectives Mutations in the gene encoding for pancreatic secretory trypsin inhibitor (PSTI) can contribute to chronic pancreatitis. In the current study, we tested whether over-expression of pancreatic secretory trypsin inhibitor-I in mice protects against chronic pancreatitis and pancreatic fibrosis. Methods Rat PSTI-I expression was targeted to pancreatic acinar cells in transgenic mice. Chronic pancreatitis was achieved by intraperitoneal injection of caerulein for 10 weeks. Pancreatitis severity was assessed by histological grading of inflammatory infiltrate, atrophy, and fibrosis; quantitation of myeloperoxidase (MPO) activity; quantitative morphometric analysis of collagen content; and measurements of type I collagen, fibronectin, and TGF? mRNA expression. Results Caerulein administration to nontransgenic mice produced histological evidence of inflammatory infiltrate, glandular atrophy, and parenchymal fibrosis, and increased collagen production, MPO activity, and collagen I and fibronectin mRNA levels. In caerulein-treated PSTI transgenic mice, there were significant reductions in inflammatory infiltrate, MPO activity, fibrosis, and collagen I and fibronectin mRNA levels. Transgenic mice treated with caerulein had significantly less collagen than nontransgenic mice. Conclusions The severity of chronic pancreatitis and pancreatic fibrosis is significantly reduced in mice expressing rat pancreatic secretory trypsin inhibitor-I. We propose that pancreatic trypsin inhibitors play a protective role in the pancreatic response to repeated injurious events. PMID:19904222

Nathan, Jaimie D.; Romac, Joelle; Peng, Ruth Y.; Peyton, Michael; Rockey, Don C.; Liddle, Rodger A.

2009-01-01

248

Nutrition, Inflammation, and Acute Pancreatitis  

PubMed Central

Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis. PMID:24490104

Petrov, Max

2013-01-01

249

Genetic issues in pediatric pancreatitis  

Microsoft Academic Search

The number of hospitalizations in children with acute and chronic pancreatitis is increasing and accounts for significant\\u000a morbidity. Acute pancreatitis is a reversible event involving diffuse inflammation of the pancreas with variable involvement\\u000a of other regional tissues, remote organs, or both, whereas chronic pancreatitis is a process that produces irreversible changes\\u000a in the pancreatic structure and function. Mutations in the

Leena Kandula; David C. Whitcomb; Mark E. Lowe

2006-01-01

250

Tonsil neuroendocrine carcinoma concurrent with hepatocellular carcinoma: A case report  

PubMed Central

The majority of neuroendocrine tumors appear to be sporadic. Neuroendocrine carcinoma (NEC) typically arises in pancreatic, parathyroid and adrenal glands, but rarely arises in salivary glands. NEC of the tonsil is a rare type of tumor and the concurrent presentation of hepatocellular carcinoma (HCC) is considered to be more uncommon. There are few case reports of NEC of the tonsil in the literature and to date no studies have been conducted to establish its optimal management. The current study presents a case of a 72-year-old male who presented with left neck and tonsil tumors. A biopsy from the tonsil revealed a NEC, and computed tomography showed liver cirrhosis, multiple liver cancers and portal vein thrombosis, as well as metastasis to the hilar, abdomen and retroperitoneum. Histological examination of the hepatic revealed primary HCC. To the best of our knowledge, this is a condition that has not previously been reported. PMID:25120653

YUAN, YAN; ZOU, QING-FENG; HU, XIAO-YE; LIU, MEI-YUAN

2014-01-01

251

Alphai-Antitrypsin in Pancreatitis  

Microsoft Academic Search

A possible relationship between ?1-antitrypsin deficiency and pancreatitis was studied. Pi phenotype distribution in a group of 90 patients with proven pancreatitis was compared to a control group of 549 randomly selected blood donors. No significant differences were found between the patient group and the controls, nor between acute and chronic forms of pancreatitis. It is concluded that ?1-antitrypsin phenotype

C. Braxel; J. Versieck; G. Lemey; L. Vanballenberghe; F. Barbier

1982-01-01

252

Acute pancreatitis associated with bulimia.  

PubMed

Acute pancreatitis developed in an 18-year-old woman after multiple episodes of bulimia. The pancreatitis was severe and the patient developed a pseudocyst. Eating disorders may be associated with acute pancreatitis, and so we review the literature on this possibility. PMID:6586819

Marano, A R; Sangree, M H

1984-06-01

253

Decreased mortality from necrotizing pancreatitis  

Microsoft Academic Search

Background: Necrotizing pancreatitis has been associated with mortality rates of 25% to 80%. We reviewed our experience to determine whether aggressive debridement and comprehensive critical care improves survival.Methods: The records of 989 patients with the diagnosis of pancreatitis admitted between January 1990 and September 1997 were retrospectively reviewed. Twenty-six patients required surgery for necrotizing pancreatitis and are the subjects of

Dmitry Oleynikov; Craig Cook; Barbara Sellers; Mary C Mone; Richard Barton

1998-01-01

254

Management of Nonfunctioning Islet Cell Carcinomas  

Microsoft Academic Search

.   Tumors arising from the pancreatic islet cells are rare and represent a heterogeneous group of benign or malignant lesions.\\u000a Most tumors present with well characterized syndromes, whereas others appear to be nonfunctioning. The clinical features of\\u000a 11 men and 7 women with nonfunctioning islet cell carcinomas operated on between 1983 and 1998 were reviewed. The median patient\\u000a age was

Detlef K. Bartsch; Thomas Schilling; Annette Ramaswamy; Berthold Gerdes; Ilhan Celik; Hans-Joachim Wagner; Babette Simon; Matthias Rothmund

2000-01-01

255

Pharmacokinetically Guided Everolimus in Patients With Breast Cancer, Pancreatic Neuroendocrine Tumors, or Kidney Cancer  

ClinicalTrials.gov

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

2014-11-04

256

Genetic Instability in Pancreatic Cancer and Poorly Differentiated T^pe of Gastric Cancer1  

Microsoft Academic Search

To examine genetic instability during carcinogenesis, we screened 171 carcinomas of the breast, liver, proximal colon, stomach, pancreas, uterine cervix, and ovary for replication error at four microsatellite marker loci on chromosomes 2, 3, and 17. A significantly high incidence of genetic instability was observed in pancreatic (6 of 9 tumors) and gastric cancers (22 of 57 cases). In other

Hye-Jung Han; Akio Yanagisawa; Yo Kato; Jae-Gahb Park; Yusuke Nakamura

1993-01-01

257

Pancreatic panniculitis: a rare complication of pancreatitis secondary to ERCP.  

PubMed

Panniculitis is an uncommon and rare complication of systemic fat necrosis in patients with pancreatic diseases. The skin manifestations are independent of the severity of the pancreatic pathology and can occur at any time. The lesions can precede, be concomitant with or rarely follow the pancreatic illness. We report a case of acute pancreatitis post Endoscopic Retrograde Cholangio Pancreatography (ERCP) for common bile duct stone, with subcutaneous panniculitis. We noted a complete resolution within two weeks after the treatment of the pancreatic pathology. PMID:24630514

Makhoul, Elias; Yazbeck, Charbel; Urbain, Daniel; Mana, Fazia; Mahanna, Saba; Akiki, Bassem; Elias, Edouard

2014-03-01

258

Clinical pancreatic disorder I: Acute pancreatitis  

PubMed Central

The Annual American Pancreas Club is an important event for communicating around clinical pancreatic disorders, just as the European, Japanese, Indian, and the International Pancreatic association. Even though the meeting is only 1½ day there were 169 different abstracts and a “How do I do it session.” Among all these abstracts on the pancreas there are some real pearls, but they are almost always well hidden, never highlighted – all abstracts are similarly presented – and will too soon be forgotten. The present filing of the abstracts is one way (not the way) to get the pancreatic abstracts a little more read and a little more remembered – and perhaps a little more cited. It should also be understood that most of the abstracts are short summaries of hundreds of working hours (evenings, nights, weekends, holidays, you name them …) in the laboratory or in the clinic, often combined with blood, sweat and tears. The authors should be shown at least some respect, and their abstracts should not only be thought of as “just another little abstract” – and the best respect they can be shown are that they will be remembered to be another brick in our scientific wall. Now the pancreatic abstracts of American Pancreas Club 2011 are gathered and filed with the aim to give them a larger audience than they have had in their original abstract book. However, it is obvious that most of clinical fellows do not have time to read all the abstracts. For them I have made a “clinical highlight section” of 10 percent of all the pancreatic abstracts. If someone else should have done some collection of abstract, there should probably have been other selections, but as this is not the case, the editor's choices are the highlighted ones. The article as series I of clinical highlight section is present, and more series will be present in the following issues. If readers will remember some of the abstracts better after reading this “abstract of abstracts”, it was worth the efforts – and without efforts there will be little progress. PMID:22555122

Andrén-Sandberg, Åke

2011-01-01

259

Clinical pancreatic disorder I: Acute pancreatitis.  

PubMed

The Annual American Pancreas Club is an important event for communicating around clinical pancreatic disorders, just as the European, Japanese, Indian, and the International Pancreatic association. Even though the meeting is only 1½ day there were 169 different abstracts and a "How do I do it session." Among all these abstracts on the pancreas there are some real pearls, but they are almost always well hidden, never highlighted - all abstracts are similarly presented - and will too soon be forgotten. The present filing of the abstracts is one way (not the way) to get the pancreatic abstracts a little more read and a little more remembered - and perhaps a little more cited. It should also be understood that most of the abstracts are short summaries of hundreds of working hours (evenings, nights, weekends, holidays, you name them …) in the laboratory or in the clinic, often combined with blood, sweat and tears. The authors should be shown at least some respect, and their abstracts should not only be thought of as "just another little abstract" - and the best respect they can be shown are that they will be remembered to be another brick in our scientific wall.Now the pancreatic abstracts of American Pancreas Club 2011 are gathered and filed with the aim to give them a larger audience than they have had in their original abstract book. However, it is obvious that most of clinical fellows do not have time to read all the abstracts. For them I have made a "clinical highlight section" of 10 percent of all the pancreatic abstracts. If someone else should have done some collection of abstract, there should probably have been other selections, but as this is not the case, the editor's choices are the highlighted ones.The article as series I of clinical highlight section is present, and more series will be present in the following issues. If readers will remember some of the abstracts better after reading this "abstract of abstracts", it was worth the efforts - and without efforts there will be little progress. PMID:22555122

Andrén-Sandberg, Ake

2011-07-01

260

Fibrocalculous pancreatic diabetes (FCPD).  

PubMed

Fibrocalculous pancreatic diabetes (FCPD) is an uncommon form of diabetes that occurs as a result of chronic calcific pancreatitis, in the absence of alcohol abuse. The disease is restricted to tropical regions of the world, and southern India has the highest known prevalence of FCPD. The typical patient with FCPD is a lean adolescent or young adult of either sex, presenting with history of recurrent bouts of abdominal pain and steatorrhea. Demonstration of large, discrete pancreatic calculi by plain radiographs or ultrasonography of the abdomen is diagnostic. While the exact etiology of FCPD is unknown, genetic, nutritional and inflammatory factors have been hypothesized to play a role. Diabetes in FCPD is often brittle and difficult to control; most patients require multiple doses of insulin for control of glycemia. However, in spite of high blood glucose levels, patients rarely develop ketosis. Malabsorption responds to pancreatic enzyme supplementation. Surgical removal of stones is indicated for symptomatic relief of intractable pain. While patients with FCPD develop microvascular complications as frequently as those with type 2 diabetes, macrovascular disease is uncommon. Development of pancreatic malignancy is the most dreaded complication and should be suspected in any patient who complains of weight loss, back pain or jaundice. PMID:25395047

Unnikrishnan, Ranjit; Mohan, Viswanathan

2014-11-14

261

Squamous Cell Carcinoma  

MedlinePLUS

... and treatments Q - T Squamous cell carcinoma Squamous cell carcinoma Squamous cell carcinoma : This man's skin has ... SCC is highly curable. Learn more about squamous cell carcinoma: Squamous cell carcinoma: Signs and symptoms Squamous ...

262

Basal Cell Carcinoma  

MedlinePLUS

... and treatments A - D Basal cell carcinoma Basal cell carcinoma Basal cell carcinoma: This skin cancer often ... skin tissue and bone. Learn more about basal cell carcinoma: Basal cell carcinoma: Signs and symptoms Basal ...

263

Imaging in pancreatic transplants  

PubMed Central

Pancreatic transplantation, performed alone or in conjunction with kidney transplantation, is an effective treatment for advanced type I diabetes mellitus and select patients with type II diabetes mellitus. Following advancements in surgical technique, postoperative management, and immunosuppression, pancreatic transplantation has significantly improved the length and quality of life for patients suffering from pancreatic dysfunction. While computed tomography (CT) and magnetic resonance imaging (MRI) have more limited utility, ultrasound is the preferred initial imaging modality to evaluate the transplanted pancreas; gray-scale assesses the parenchyma and fluid collections, while Doppler interrogation assesses vascular flow and viability. Ultrasound is also useful to guide percutaneous interventions for the transplanted pancreas. With knowledge of the surgical anatomy and common complications, the abdominal radiologist plays a central role in the perioperative and postoperative evaluation of the transplanted pancreas. PMID:25489127

Heller, Matthew T; Bhargava, Puneet

2014-01-01

264

Imaging of surgical margin in pancreatic metastasis using two-photon excited fluorescence microscopy  

NASA Astrophysics Data System (ADS)

Two-photon excited fluorescence (TPEF) microscopy, has become a powerful tool for imaging unstained tissue samples at subcellular level in biomedical research. The purpose of this study was to determine whether TPEF imaging of histological sections without H-E staining can be used to identify the boundary between normal pancreas and pancreatic metastasis from renal cell carcinoma (RCC). The typical features such as the significant increase of cancerous nests, the absence of pancreatic ductal, the appearance of cancer cells were observed to present the boundary between normal pancreas and pancreatic metastasis from RCC. These results correlated well with the corresponding histological outcomes. With the advent of clinically miniaturized TPEF microscopy and integrative endoscopy, TPEF microscopy has the potential application on surgical location of pancreatic metastasis from RCC in the near future.

Chen, Jing; Hong, Zhipeng; Chen, Hong; Chen, Youting; Xu, Yahao; Zhu, Xiaoqin; Zhuo, Shuangmu; Shi, Zheng; Chen, Jianxin

2014-09-01

265

Precursor Lesions for Sporadic Pancreatic Cancer: PanIN, IPMN, and MCN  

PubMed Central

Pancreatic cancer is still a dismal disease. The high mortality rate is mainly caused by the lack of highly sensitive and specific diagnostic tools, and most of the patients are diagnosed in an advanced and incurable stage. Knowledge about precursor lesions for pancreatic cancer has grown significantly over the last decade, and nowadays we know that mainly three lesions (PanIN, and IPMN, MCN) are responsible for the development of pancreatic cancer. The early detection of these lesions is still challenging but provides the chance to cure patients before they might get an invasive pancreatic carcinoma. This paper focuses on PanIN, IPMN, and MCN lesions and reviews the current level of knowledge and clinical measures. PMID:24783207

Distler, M.; Aust, D.; Weitz, J.; Pilarsky, C.; Grützmann, Robert

2014-01-01

266

Endotherapy in chronic pancreatitis.  

PubMed

Chronic pancreatitis (CP) is a progressive disease with irreversible changes in the pancreas. Patients commonly present with pain and with exocrine or endocrine insufficiency. All therapeutic efforts in CP are directed towards relief of pain as well as the management of associated complications. Endoscopic therapy offers many advantages in patients with CP who present with ductal calculi, strictures, ductal leaks, pseudocyst or associated biliary strictures. Endotherapy offers a high rate of success with low morbidity in properly selected patients. The procedure can be repeated and failed endotherapy is not a hindrance to subsequent surgery. Endoscopic pancreatic sphincterotomy is helpful in patients with CP with minimal ductal changes while minor papilla sphincterotomy provides relief in patients with pancreas divisum and chronic pancreatitis. Extracorporeal shock wave lithotripsy is the standard of care in patients with large pancreatic ductal calculi. Long term follow up has shown pain relief in over 60% of patients. A transpapillary stent placed across the disruption provides relief in over 90% of patients with ductal leaks. Pancreatic ductal strictures are managed by single large bore stents. Multiple stents are placed for refractory strictures. CP associated benign biliary strictures (BBS) are best treated with multiple plastic stents, as the response to a single plastic stent is poor. Covered self expanding metal stents are increasingly being used in the management of BBS though further long term studies are needed. Pseudocysts are best drained endoscopically with a success rate of 80%-95% at most centers. Endosonography (EUS) has added to the therapeutic armamentarium in the management of patients with CP. Drainage of pseudcysts, cannulation of inaccessible pancreatic ducts and celiac ganglion block in patients with intractable pain are all performed using EUS. Endotherapy should be offered as the first line of therapy in properly selected patients with CP who have failed to respond to medical therapy and require intervention. PMID:24115811

Tandan, Manu; Nageshwar Reddy, D

2013-10-01

267

Gallstone pancreatitis: a review.  

PubMed

Gallstone disease is the most common cause of acute pancreatitis in the Western world. In most cases, gallstone pancreatitis is a mild and self-limiting disease, and patients may proceed without complications to cholecystectomy to prevent future recurrence. Severe disease occurs in about 20% of cases and is associated with significant mortality; meticulous management is critical. A thorough understanding of the disease process, diagnosis, severity stratification, and principles of management is essential to the appropriate care of patients presenting with this disease. This article reviews these topics with a focus on surgical management, including appropriate timing and choice of interventions. PMID:24679420

Cucher, Daniel; Kulvatunyou, Narong; Green, Donald J; Jie, Tun; Ong, Evan S

2014-04-01

268

[Effect of combination chemotherapy of low-dose CDDP. Continuous infusion of 5-FU, and intermittent CPT-11 administration for 2 advanced pancreatic cancer cases with liver metastasis].  

PubMed

For advanced pancreatic cancer, there is no typical chemotherapy regimen non single chemotherapeutic agent. For example, 5-FU, Doxorubicin, MMC and Epirubicin obtained only 15-24% efficacy, and general combination chemotherapy was FAM, 5-FU+CDDP and 5-FU+Leucovorin for pancreatic cancer. Generally, in pancreatic cancer cases the performance status was poor, and most could not endure the chemotherapy regimen. 5-FU continuous infusion and low-dose CDDP regimen were effective and showed fewer side effects for pancreatic cancer. Then, for 2 cases of advanced pancreatic cancer with liver metastasis, 5-FU continuous infusion + low-dose CDDP + intermittent CPT-11 administration (5-FU 500 mg/body/24 hr + CDDP 5mg x 5 days-6 courses + CPT-11 100 mg-125 mg-150 mg, bolus i.v. intermittently) was effective. Thus, this regimen could well be effective for advanced pancreatic carcinoma. PMID:9757202

Kobayashi, A; Yamaguchi, M

1998-09-01

269

Neurotrophic Factor Artemin Promotes Invasiveness and Neurotrophic Function of Pancreatic Adenocarcinoma In Vivo and In Vitro  

PubMed Central

Objectives The aim of this study was to investigate the effect of the neurotrophic factor Artemin on neuroplasticity and perineural invasion of pancreatic adenocarcinoma. Methods Artemin expressions were detected in human pancreatic adenocarcinoma tissues by Western blot and immunohistochemistry. Artemin overexpression and RNA interference in the pancreatic cancer cell lines were performed to evaluate the effects of Artemin on cell proliferation, invasion, and neurotrophic activity in vitro and in nude orthotopic transplantation tumor models. Results Artemin expression in pancreatic cancer tissues was related to the incidence of lymphatic metastasis and perineural invasion as well as the mean density and total area of nerve fibers. Overexpression of Artemin in pancreatic cancer cell lines improved colony formation, cell migration, matrigel invasion, and neurotrophic activity in vitro. This overexpression also increased the volume of nude orthotopic transplantation tumors; promoted cancer cell invasion of the peripheral organs, nerves, vessels, and lymph nodes; and stimulated the proliferation of peritumoral nerve fibers. Artemin depletion by RNA interference had an inhibitory effect mentioned previously. Conclusions Artemin could promote invasiveness and neurotrophic function of pancreatic adenocarcinoma in vivo and in vitro. Therefore, Artemin could be used as a new therapeutic target of pancreatic carcinoma. PMID:25243385

Gao, Li; Bo, Haiji; Wang, Yang; Zhang, Jing; Zhu, Minghua

2015-01-01

270

Is endosonography an effective method for detection and local staging of the ampullary carcinoma? A prospective study  

Microsoft Academic Search

BACKGROUND: The relatively rare carcinoma of the ampulla of Vater is a neoplasia with a good prognosis compared to pancreatic cancer. Preoperative staging is important in planning the most suitable surgical intervention. AIM: To prospectively evaluate the diagnostic accuracy of Endoscopic Ultrasonography (EUS) in comparison with conventional US and CT scan, in staging of patients with ampullary carcinoma. PATIENTS AND

Panagiotis Skordilis; Ioannis A Mouzas; Philippos D Dimoulios; Georgios Alexandrakis; Joanna Moschandrea; Elias Kouroumalis

2002-01-01

271

Ras Activity Levels Control the Development of Pancreatic Diseases  

PubMed Central

Background & Aims Differentiated pancreatic acinar cells expressing endogenous levels of mutant K-Ras do not spontaneously develop pancreatic ductal adenocarcinoma (PDAC). However, we hypothesized that acinar cells would develop PDAC in the presence of Ras activity levels mimicking those of human tumor cells. Methods We measured Ras activity in PDAC cells from mice and humans using a Raf pull-down assay. We compared the effects of acinar cell expression of mutant K-Ras at endogenous and elevated levels on Ras activity and on the development of PDAC. Results Ras activity was greatly elevated in PDAC cells compared to non-transformed cells expressing endogenous levels of mutant K-Ras. Expression of endogenous levels of mutant K-Ras in differentiated acinar cells resulted in moderately elevated Ras activity and in sparse murine pancreatic intraepithelial neoplasias (mPanINs) that did not spontaneously advance to PDAC unless the tumor suppressor p53 was simultaneous deleted. In contrast, expression of mutant K-Ras at higher levels generated Ras activity equal to that in PDAC. High Ras activity mimicking levels in PDAC led to acinar cell senescence and generated inflammation and fibrosis resembling the histological features of chronic pancreatitis (CP). With higher Ras activity in acinar cells abundant mPanINs formed and spontaneously progressed to both cystic papillary carcinoma (CPC) and metastatic PDAC. Conclusions There is an important relationship between Ras activity levels and the progression of PDAC. Sufficient Ras activity in pancreatic acinar induces several important pancreatic disease manifestations not previously reported and supports a potential direct linkage between CP, CPC and PDAC. PMID:19501586

Ji, Baoan; Tsou, Lilian; Wang, Huamin; Gaiser, Sebastian; Chang, David Z.; Daniluk, Jaroslaw; Bi, Yan; Grote, Tobias; Longnecker, Daniel S.; Logsdon, Craig D.

2009-01-01

272

Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer  

ClinicalTrials.gov

Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage III Endometrial Carcinoma; Stage IV Endometrial Carcinoma

2014-10-09

273

Adrenocortical Carcinoma  

Cancer.gov

In the U.S., an estimated 300 people are diagnosed with adrenocortical carcinoma each year.1 If detected at an early stage, this type of cancer can often be successfully treated. However, almost 70 percent of people are diagnosed with advanced adrenocortical carcinoma.2 For patients at the latest stage of this cancer, less than 20 percent survive five years after diagnosis.

274

Nutrition in chronic pancreatitis  

PubMed Central

The pancreas is a major player in nutrient digestion. In chronic pancreatitis both exocrine and endocrine insufficiency may develop leading to malnutrition over time. Maldigestion is often a late complication of chronic pancreatic and depends on the severity of the underlying disease. The severity of malnutrition is correlated with two major factors: (1) malabsorption and depletion of nutrients (e.g., alcoholism and pain) causes impaired nutritional status; and (2) increased metabolic activity due to the severity of the disease. Nutritional deficiencies negatively affect outcome if they are not treated. Nutritional assessment and the clinical severity of the disease are important for planning any nutritional intervention. Good nutritional practice includes screening to identify patients at risk, followed by a thoroughly nutritional assessment and nutrition plan for risk patients. Treatment should be multidisciplinary and the mainstay of treatment is abstinence from alcohol, pain treatment, dietary modifications and pancreatic enzyme supplementation. To achieve energy-end protein requirements, oral supplementation might be beneficial. Enteral nutrition may be used when patients do not have sufficient calorie intake as in pylero-duodenal-stenosis, inflammation or prior to surgery and can be necessary if weight loss continues. Parenteral nutrition is very seldom used in patients with chronic pancreatitis and should only be used in case of GI-tract obstruction or as a supplement to enteral nutrition. PMID:24259957

Rasmussen, Henrik Højgaard; Irtun, Øivind; Olesen, Søren Schou; Drewes, Asbjørn Mohr; Holst, Mette

2013-01-01

275

Pancreatitis in childhood  

Microsoft Academic Search

Ninety children treated for acute, relapsing, or chronic pancreatitis at the Red Cross War Memorial Children's Hospital, Cape Town, between 1958 and 1982 are reviewed. The commonest cause was Ascaris worms in the bile duct and the next commonest identifiable cause was trauma. Diagnosis was clinical, confirmed by raised amylase levels and radiological or operative findings. Ultrasound was particularly helpful.

Richard D. Spicer; Sidney Cywes

1988-01-01

276

Pancreatitis induced by nitrofurantoin  

Microsoft Academic Search

The case of a woman is described who suffered from acute pancreatitis related to the ingestion of low dose nitrofurantoin, as shown by involuntary rechallenge. Because this is only the second case reported in published works, this side effect must be rare and is probably dependent on individual susceptibility.

J L Christophe

1994-01-01

277

Periampullary and Pancreatic Incidentaloma  

PubMed Central

Background: While incidental masses in certain organs have received particular attention, periampullary and pancreatic incidentalomas (PIs) remain poorly characterized. Methods: We reviewed 1944 consecutive pancreaticoduodenectomies (PD) over an 8-year period (April 1997 to October 2005). A total of 118 patients (6% of all PDs) presented with an incidental finding of a periampullary or pancreatic mass. The PI patients were analyzed and compared with the rest of the cohort (NI, nonincidentaloma group, n = 1826). Results: Thirty-one percent of the PI patients (n = 37) had malignant disease (versus 76% of the NI patients, P < 0.001), 47% (n = 55) had premalignant disease, and the remaining 22% (n = 26) had little or no risk for malignant progression. The 3 most common diagnoses in the PI group were IPMN without invasive cancer (30%), cystadenoma (17%), and pancreatic ductal adenocarcinoma (10%). The PI group had a higher overall complication rate (55% versus 43%, P = 0.02), due in part to a significantly increased rate of pancreatic fistulas (18.4% PI versus 8.5% NI, P < 0.001). Patients in the PI group with malignant disease had a superior long-term survival (median, 30 months, P = 0.01) compared with patients in the NI group with malignant disease (median, 21 months). Conclusions: Incidentally discovered periampullary and pancreatic masses comprise a substantial proportion of patients undergoing PD. Roughly three fourths of these lesions are malignant or premalignant, and amenable to curative resection. Resected malignant PIs have favorable pathologic features as compared with resected malignant NIs, and resection of these early lesions in asymptomatic individuals is associated with improved survival, compared with patients with symptomatic disease. PMID:16633003

Winter, Jordan M.; Cameron, John L.; Lillemoe, Keith D.; Campbell, Kurtis A.; Chang, David; Riall, Taylor S.; Coleman, JoAnn; Sauter, Patricia K.; Canto, Marcia; Hruban, Ralph H.; Schulick, Richard D.; Choti, Michael A.; Yeo, Charles J.

2006-01-01

278

Pancreatic Stellate Cells and Pancreatic Cancer Cells: An Unholy Alliance  

Microsoft Academic Search

Pancreatic cancer—a tumor displaying a particularly abundant stromal reaction—is notorious for its poor prognosis. Recent studies, via newly developed orthotopic models, provide compelling evidence of an important role for pancreatic stellate cells (PSC) in pancreatic cancer progression. Characterization of the mechanisms mediating PSC-cancer interactions will lead to the development of much needed alternative therapeutic approaches to improve disease outcome.

Alain Vonlaufen; Phoebe A. Phillips; Zhihong Xu; David Goldstein; Romano C. Pirola; Jeremy S. Wilson; Minoti V Apte

2008-01-01

279

Role of pancreatic stellate cells in chemoresistance in pancreatic cancer  

PubMed Central

Pancreatic cancer is highly chemoresistant. A major contributing factor is the characteristic extensive stromal or fibrotic reaction, which comprises up to 90% of the tumor volume. Over the last decade there has been intensive research into the role of the pro-fibrogenic pancreatic stellate cells (PSCs) and their interaction with pancreatic cancer cells. As a result of the significant alterations in the tumor microenvironment following activation of PSCs, tumor progression, and chemoresistance is enhanced. This review will discuss how PSCs contribute to chemoresistance in pancreatic cancer. PMID:24782785

McCarroll, Joshua A.; Naim, Stephanie; Sharbeen, George; Russia, Nelson; Lee, Julia; Kavallaris, Maria; Goldstein, David; Phillips, Phoebe A.

2014-01-01

280

Internal pancreatic stent causing irreversible dilatation of pancreatic duct.  

PubMed

A 28-year-old woman underwent a pylorus preserving Whipple procedure for pancreatic serous cystadenoma located on the head of the pancreas. During the operation, an internal stent (7F silastic catheter, 9 cm in length) was placed within the pancreatic duct in the area of pancreaticojejunal end-to-end Dunking type anastomosis to prevent development of fistula. The stent was positioned so that one third of its length would lie into the pancreatic duct, and it was anchored to the periductal pancreatic tissue with only one rapidly absorbable chromic suture. Leakage from the anastomosis was not observed, and she was discharged without any complaint. Early postoperative abdominal CT examination revealed that the stent was retained within the normal caliber pancreatic duct (Fig. 1a). Six months after the operation, she began to complain to epigastric pain triggered by the meals. The laboratory analysis was normal, particularly liver biochemical tests and serum amylase. The internal pancreatic stent within the dilated pancreatic duct was detected by an additional CT examination (Fig. 1b). The stent was removed endoscopically at the third attempt. The pain was resolved after its removal. Control CT examination which was taken at the 18th month after removal of the stent showed dilatation of the pancreatic duct (Fig. 2a). The patient remained free of any complaint, although regressed pancreatic duct dilatation has persisted over 4 years of follow-up (Fig. 2b). PMID:24799775

Hasbahceci, Mustafa; Erol, Cengiz

2014-02-01

281

Current Knowledge on Pancreatic Cancer  

PubMed Central

Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6?months and a dismal 5-year survival rate of 3–5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways. Therefore, the strategies targeting these molecules as well as their downstream signaling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical, and therapeutic aspects of pancreatic cancer. PMID:22655256

Iovanna, Juan; Mallmann, Maria Cecilia; Gonçalves, Anthony; Turrini, Olivier; Dagorn, Jean-Charles

2012-01-01

282

Identification of a Novel Kindred with Familial Pancreatitis and Pancreatic Cancer  

Microsoft Academic Search

Background\\/Aims: Hereditary pancreatic cancer comprises about 10% of pancreatic cancer cases. Multiple causative mutations have been identified. Here we describe a pancreatitis\\/pancreatic cancer (P\\/PC) family, which demonstrates pancreatitis and pancreatic cancer resulting from an uncharacterized mutation. Methods: Family members completed evaluations to determine signs of mutation status. Select patients were screened for mutations associated with hereditary pancreatic diseases. Results: In

Jennifer LaFemina; Penelope A. Roberts; Yin P. Hung; James F. Gusella; Dushyant Sahani; Carlos Fernández-del Castillo; Andrew L. Warshaw; Sarah P. Thayer

2009-01-01

283

A possible involvement of aberrant expression of the FHIT gene in the carcinogenesis of squamous cell carcinoma of the uterine cervix  

PubMed Central

To investigate involvement of an aberrant expression of the FHIT (fragile histidine triad) gene in the process of carcinogenesis and progression in cervical carcinoma, we examined its expression by the reverse transcriptase polymerase chain reaction (RT-PCR) and cDNA sequence method in 32 cervical invasive carcinomas (25 squamous cell carcinomas and seven adeno- or adenosquamous carcinomas) and 18 of its precursor lesions [four low-grade and 14 high-grade cervical intraepithelial neoplasias (CINs)]. We also examined a link between the occurrence of the aberrant expression and human papillomavirus (HPV). We detected the aberrant FHIT transcripts in 11 of 25 (44%) cervical invasive squamous cell carcinomas and in 5 of 14 (36%) high-grade CINs (CIN 2 or 3), whereas they were not found in seven non-squamous type and four low-grade CINs (CIN 1). The alteration patterns of the FHIT gene expression in high-grade CINs were virtually similar to those found in invasive carcinomas, such that the exons 5–7 were consistently deleted associated or unassociated with loss of the exon 4 and/or 8. The incidence of the aberrant expression was not related to the presence of HPV and its type. These data indicate that the aberrant expression of the FHIT gene is observed in precursor lesions of cervical carcinoma as well as invasive carcinomas, with its incidence not increasing with advance of clinical stage. Given the squamous cell type dominant expression, the aberrant expression may play a critical role in the generation of squamous cell carcinoma of the uterine cervix, but not the consequence of the progression of the cancer. © 1999 Cancer Research Campaign PMID:10027335

Nakagawa, S; Yoshikawa, H; Kimura, M; Kawana, K; Matsumoto, K; Onda, T; Kino, N; Yamada, M; Yasugi, T; Taketani, Y

1999-01-01

284

Molecular epidemiology of pancreatic cancer  

Microsoft Academic Search

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Currently there is no early diagnostic\\u000a test and no effective treatment options for this deadly disease. Prevention of pancreatic cancer is difficult because little\\u000a is known about its etiology. The main modifiable risk factors for pancreatic cancer include cigarette smoking and dietary\\u000a factors. Information from molecular

Donghui Li; Li Jiao

2003-01-01

285

[Latest advances in chronic pancreatitis].  

PubMed

This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the prediction of the fibrosis degree of the gland, the evaluation of patients with asymptomatic hyperenzimemia, the medical and surgical treatment of abdominal pain and the knowledge of the natural history of the autoimmune pancreatitis. In patients with indetermined EUS findings of chronic pancreatitis, a new endoscopic ultrasound examination in the follow-up is of help to confirm or to exclude the disease. Smoking, number of relapses, results of pancreatic function tests and EUS findings allow predicting the degree of pancreatic fibrosis in patients with chronic pancreatitis. Antioxidant therapy has shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Development of intestinal bacterial overgrowth is frequent in patients with chronic pancreatitis, but its impact on symptoms is unknown and deserves further investigations. Finally, autoimmune pancreatitis relapses in about half of the patients with either type 1 or type 2 disease; relapses frequently occur within the first two years of follow-up. PMID:25294271

Domínguez-Muñoz, J Enrique

2014-09-01

286

Helicobacter pylori and pancreatic diseases  

PubMed Central

A possible role for Helicobacter pylori (H. pylori) infection in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and inducing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smoking habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsistent, several meta-analyses have reported an increased risk for pancreatic cancer among H. pylori seropositive individuals. It has been suggested that H. pylori causes autoimmune pancreatitis due to molecular mimicry between H. pylori ?-carbonic anhydrase (?-CA) and human CA type II, and between H. pylori plasminogen-binding protein and human ubiquitin-protein ligase E3 component n-recognin 2, enzymes that are highly expressed in the pancreatic ductal and acinar cells, respectively. Future studies involving large numbers of cases are needed in order to examine the role of H. pylori in autoimmune pancreatitis more fully. Considering the worldwide pancreatic cancer burden, as well as the association between autoimmune pancreatitis and other autoimmune conditions, a complete elucidation of the role played by H. pylori in the genesis of such conditions could have a substantial impact on healthcare. PMID:25400980

Bulajic, Milutin; Panic, Nikola; Löhr, Johannes Matthias

2014-01-01

287

Zebrafish reporter lines reveal in vivo signaling pathway activities involved in pancreatic cancer  

PubMed Central

Pancreatic adenocarcinoma, one of the worst malignancies of the exocrine pancreas, is a solid tumor with increasing incidence and mortality in industrialized countries. This condition is usually driven by oncogenic KRAS point mutations and evolves into a highly aggressive metastatic carcinoma due to secondary gene mutations and unbalanced expression of genes involved in the specific signaling pathways. To examine in vivo the effects of KRASG12D during pancreatic cancer progression and time correlation with cancer signaling pathway activities, we have generated a zebrafish model of pancreatic adenocarcinoma in which eGFP-KRASG12D expression was specifically driven to the pancreatic tissue by using the GAL4/UAS conditional expression system. Outcrossing the inducible oncogenic KRASG12D line with transgenic zebrafish reporters, harboring specific signaling responsive elements of transcriptional effectors, we were able to follow TGF?, Notch, Bmp and Shh activities during tumor development. Zebrafish transgenic lines expressing eGFP-KRASG12D showed normal exocrine pancreas development until 3 weeks post fertilization (wpf). From 4 to 24 wpf we observed several degrees of acinar lesions, characterized by an increase in mesenchymal cells and mixed acinar/ductal features, followed by progressive bowel and liver infiltrations and, finally, highly aggressive carcinoma. Moreover, live imaging analysis of the exocrine pancreatic tissue revealed an increasing number of KRAS-positive cells and progressive activation of TGF? and Notch pathways. Increase in TGF?, following KRASG12D activation, was confirmed in a concomitant model of medulloblastoma (MDB). Notch and Shh signaling activities during tumor onset were different between MDB and pancreatic adenocarcinoma, indicating a tissue-specific regulation of cell signaling pathways. Moreover, our results show that a living model of pancreatic adenocarcinoma joined with cell signaling reporters is a suitable tool for describing in vivo the signaling cascades and molecular mechanisms involved in tumor development and a potential platform to screen for novel oncostatic drugs. PMID:24878567

Schiavone, Marco; Rampazzo, Elena; Casari, Alessandro; Battilana, Giusy; Persano, Luca; Moro, Enrico; Liu, Shu; Leach, Steve D.; Tiso, Natascia; Argenton, Francesco

2014-01-01

288

BRCA and pancreatic cancer.  

PubMed

Germline mutations in BRCA genes have been associated with pancreatic cancer. Laboratory and clinical data suggest that patients with BRCA mutations may be more responsive to therapy consisting of conventional chemotherapy with a poly(ADP-ribose) polymerase inhibitor (PARPi). The most recent data from the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting will be reviewed (Abstracts #11024 and #TPS4144). PMID:23846919

Brennan, Gregory T; Relias, Valerie; Saif, Muhammad Wasif

2013-07-01

289

Pancreatic Cancer Database: an integrative resource for pancreatic cancer.  

PubMed

Pancreatic cancer is the fourth leading cause of cancer-related death in the world. The etiology of pancreatic cancer is heterogeneous with a wide range of alterations that have already been reported at the level of the genome, transcriptome, and proteome. The past decade has witnessed a large number of experimental studies using high-throughput technology platforms to identify genes whose expression at the transcript or protein levels is altered in pancreatic cancer. Based on expression studies, a number of molecules have also been proposed as potential biomarkers for diagnosis and prognosis of this deadly cancer. Currently, there are no repositories which provide an integrative view of multiple Omics data sets from published research on pancreatic cancer. Here, we describe the development of a web-based resource, Pancreatic Cancer Database (http://www.pancreaticcancerdatabase.org), as a unified platform for pancreatic cancer research. PCD contains manually curated information pertaining to quantitative alterations in miRNA, mRNA, and proteins obtained from small-scale as well as high-throughput studies of pancreatic cancer tissues and cell lines. We believe that PCD will serve as an integrative platform for scientific community involved in pancreatic cancer research. PMID:24839966

Thomas, Joji Kurian; Kim, Min-Sik; Balakrishnan, Lavanya; Nanjappa, Vishalakshi; Raju, Rajesh; Marimuthu, Arivusudar; Radhakrishnan, Aneesha; Muthusamy, Babylakshmi; Khan, Aafaque Ahmad; Sakamuri, Sruthi; Tankala, Shantal Gupta; Singal, Mukul; Nair, Bipin; Sirdeshmukh, Ravi; Chatterjee, Aditi; Prasad, T S Keshava; Maitra, Anirban; Gowda, Harsha; Hruban, Ralph H; Pandey, Akhilesh

2014-08-01

290

Chronic pancreatitis: evolving paradigms.  

PubMed

Chronic pancreatitis (CP) is characterized by progressive fibrosis, pain and/or loss of exocrine and endocrine functions. With the identification and characterization of pancreatic stellate cells (PSCs), the pathogenesis of CP and pancreatic fibrosis is now better understood. Molecular mediators shown to regulate the pathogenesis include transforming growth factor-beta, platelet-derived growth factor, and proinflammatory cytokines such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha. Besides these, the roles of cyclooxygenase (COX)-2 and apoptosis-related proteins have also been implicated in the pathogenesis. Furthermore, molecular pathways involving mitogen-activated protein kinases, phosphatidylinositol 3-kinase, Ras superfamily G proteins, serine threonine protein kinase Raf-1 and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) have been elucidated. Newer pathobiologic concepts concerning pain generation have also been put forward. Understanding the pathogenesis has led to the identification of novel molecular targets and the development of newer potential therapeutic agents. Those found to retard the progression of experimental CP and fibrosis in animal models include antioxidants, a Japanese herbal medicine called Saiko-keisi-to (TJ 10), the PPAR-gamma ligand troglitazone, the protease inhibitor Camostat mesilate, and Lovastatin. PMID:16847381

Talukdar, Rupjyoti; Saikia, Nripen; Singal, Dinesh Kumar; Tandon, Rakesh

2006-01-01

291

Clinical significance of soluble form of HLA class I molecule in Japanese patients with pancreatic cancer.  

PubMed

In recent studies a soluble form of human leukocyte antigen class I (sHLA-I) has been found in blood, urine, ascitic fluid, and various other tissues. Research has been focused on the role of sHLA-I in the induction of immunotolerance in organ transplantation. To examine the role of sHLA-I in the immune system of patients with malignancy, we examined serum sHLA-I levels in patients with pancreatic, biliary, hepatic malignancy, and other diseases. We examined sHLA-I levels in the sera of patients with pancreatic cancer (n = 19), benign biliary disease and chronic pancreatitis (n = 20), hepatocellular carcinoma (n = 51), gallbladder cancer (n = 6), cholangiocellular carcinoma (n = 6), and in normal controls (n = 22), using enzyme-linked immunosorbent assay (ELISA). In patients with pancreatic cancer we also analyzed the relationship between sHLA-I and CA19-9, and the specificity and sensitivity of sHLA-I. When patients with acute or chronic hepatitis were excluded from analysis, the mean sHLA-I level in patients with pancreatic cancer was significantly higher than that of normal controls (p < 0.01) and patients with benign disease (p < 0.01), hepatocellular carcinoma (p < 0.01), gallbladder cancer (p < 0.05), and cholangiocarcinoma (p < 0.05). We determined a serum sHLA-I cutoff level for normal controls of 2000 ng/ml; serum levels of sHLA-I were higher than the cutoff in ten patients with pancreatic cancer, and serum levels of CA19-9 were lower than 37 IU/l in 9 of 14 patients; sensitivity and specificity were 88.2% and 85.5%, respectively. Serum levels of sHLA-I in pancreatic cancer patients were higher than in the other diseases, although we found that pancreatic cancer cell lines did not produce the sHLA-I. The evaluation of serum sHLA-I levels could have clinical significance in pancreatic cancer. PMID:11390036

Shimura, T; Tsutsumi, S; Hosouchi, Y; Kojima, T; Kon, Y; Yonezu, M; Kuwano, H

2001-06-01

292

Erlotinib and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney, Colorectal, Head and Neck, Pancreatic, or Non-Small Cell Lung Cancer  

ClinicalTrials.gov

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Colon Cancer; Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Renal Cell Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Untreated Metastatic Squamous Neck Cancer With Occult Primary

2014-06-10

293

Pancreatic polypepetide inhibits pancreatic enzyme secretion via a cholinergic pathway  

SciTech Connect

In rat pancreatic slices, rat pancreatic polypeptide (PP) or C-terminal hexapeptide of PP (PP-(31-36)) inhibited potassium-stimulated amylase release in a dose-dependent manner. The inhibition was unaffected by addition of hexamethonium but blocked by atropine. In contrast, PP-(31-36) did not have any effect on acetylcholine- or cholecystokinin octapeptide-stimulated amylase release. In addition, when pancreatic slices were incubated with ({sup 3}H)choline, PP-(31-36) inhibited the potassium-evoked release of synthesized ({sup 3}H)acetylcholine in a dose-dependent manner. The inhibitory action of PP was unaffected by adrenergic, dopaminergic, or opioid receptor antagonists. Thus PP inhibits pancreatic enzyme secretion via presynaptic modulation of acetylcholine release. This newly identified pathway provides a novel mechanism for hormonal inhibition of pancreatic enzyme secretion via modulation of the classic neurotransmitter function.

Jung, G.; Louie, D.S.; Owyang, C. (Univ. of Michigan Medical Center, Ann Arbor (USA))

1987-11-01

294

A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer  

Microsoft Academic Search

Background:This multicentre randomised phase III trial was designed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer.Methods:Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy. Patients were randomly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only

H Ueno; T Kosuge; Y Matsuyama; J Yamamoto; A Nakao; S Egawa; R Doi; M Monden; T Hatori; M Tanaka; M Shimada; K Kanemitsu

2009-01-01

295

Peroxisome proliferator-activated receptor ? reduces the growth rate of pancreatic cancer cells through the reduction of cyclin D1  

Microsoft Academic Search

Peroxisome proliferator-activated receptor ? (PPAR?) forms a heterodimeric DNA-binding complex with the retinoid X receptor (RXR) and regulates the transcription of its target genes. Activation of PPAR? has been shown to induce G1 arrest and to inhibit cell growth of human pancreatic carcinoma cell lines. The purpose of the present study was to examine the effect of ligand activation of

Miyuki Toyota; Yoshiji Miyazaki; Shinji Kitamura; Yutaka Nagasawa; Tatsuya Kiyohara; Yasuhisa Shinomura; Yuji Matsuzawa

2002-01-01

296

H19-Promoter-Targeted Therapy Combined with Gemcitabine in the Treatment of Pancreatic Cancer  

PubMed Central

Pancreatic cancer is the eighth cancer leading cause of cancer-related death in the world and has a 5-year survival rate of 1–4% only. Gemcitabine is a first line agent for advanced pancreatic therapy; however, its efficacy is limited by its poor intracellular metabolism and chemoresistance. Studies have been conducted in an effort to improve gemcitabine treatment results by adding other chemotherapeutic agents, but none of them showed any significant advantage over gemcitabine monotherapy. We found that 85% of human pancreatic tumors analyzed by in situ hybridization analyses showed moderated to strong expression of the H19 gene. We designed a preclinical study combining gemcitabine treatment and a DNA-based therapy for pancreatic cancer using a non viral vector BC-819 (also known as DTA-H19), expressing the diphtheria toxin A chain under the control of the H19 gene regulatory sequences. The experiments conducted either in an orthotopic and heterotopic pancreatic carcinoma animal model showed better antitumor activity following the sequential administration of the vector BC-819 and gemcitabine as compared to the effect of each of them alone. The results presented in the current study indicate that treatment with BC-819 in combination with gemcitabine might be a viable new therapeutic option for patients with advanced pancreatic cancer. PMID:22701803

Sorin, Vladimir; Ohana, Patricia; Gallula, Jennifer; Birman, Tatiana; Matouk, Imad; Hubert, Ayala; Gilon, Michal; Hochberg, Avraham; Czerniak, Abraham

2012-01-01

297

H19-promoter-targeted therapy combined with gemcitabine in the treatment of pancreatic cancer.  

PubMed

Pancreatic cancer is the eighth cancer leading cause of cancer-related death in the world and has a 5-year survival rate of 1-4% only. Gemcitabine is a first line agent for advanced pancreatic therapy; however, its efficacy is limited by its poor intracellular metabolism and chemoresistance. Studies have been conducted in an effort to improve gemcitabine treatment results by adding other chemotherapeutic agents, but none of them showed any significant advantage over gemcitabine monotherapy. We found that 85% of human pancreatic tumors analyzed by in situ hybridization analyses showed moderated to strong expression of the H19 gene. We designed a preclinical study combining gemcitabine treatment and a DNA-based therapy for pancreatic cancer using a non viral vector BC-819 (also known as DTA-H19), expressing the diphtheria toxin A chain under the control of the H19 gene regulatory sequences. The experiments conducted either in an orthotopic and heterotopic pancreatic carcinoma animal model showed better antitumor activity following the sequential administration of the vector BC-819 and gemcitabine as compared to the effect of each of them alone. The results presented in the current study indicate that treatment with BC-819 in combination with gemcitabine might be a viable new therapeutic option for patients with advanced pancreatic cancer. PMID:22701803

Sorin, Vladimir; Ohana, Patricia; Gallula, Jennifer; Birman, Tatiana; Matouk, Imad; Hubert, Ayala; Gilon, Michal; Hochberg, Avraham; Czerniak, Abraham

2012-01-01

298

Chemoprevention strategies for pancreatic cancer  

Microsoft Academic Search

Pancreatic cancer has a poor prognosis and is often diagnosed at an advanced stage, which makes it difficult to treat. The low survival rate of patients with pancreatic cancer points towards an increased need for novel therapeutic and chemopreventive strategies and also early detection of this disease. Increased consumption of fruits and vegetables has been associated with a reduced risk

Shivendra V. Singh; Randall E. Brand; Silvia D. Stan

2010-01-01

299

Molecular Mechanisms of Alcoholic Pancreatitis  

Microsoft Academic Search

Alcoholic pancreatitis is a major complication of alcohol abuse. Since only a minority of alcoholics develop pancreatitis, there has been a keen interest in identifying the factors that may confer individual susceptibility to the disease. Numerous possibilities have been evaluated including diet, drinking patterns and a range of inherited factors. However, at the present time, no susceptibility factor has been

Minoti V Apte; Ron Pirola; Jeremy S Wilson

2005-01-01

300

Pancreatic cancer biology and genetics  

Microsoft Academic Search

Pancreatic ductal adenocarcinoma is an aggressive and devastating disease, which is characterized by invasiveness, rapid progression and profound resistance to treatment. Advances in pathological classification and cancer genetics have improved our descriptive understanding of this disease; however, important aspects of pancreatic cancer biology remain poorly understood. What is the pathogenic role of specific gene mutations? What is the cell of

Nabeel Bardeesy; Ronald A. DePinho

2002-01-01

301

Myocardial function in acute pancreatitis.  

PubMed Central

Fifteen patients with acute pancreatitis had 68 physiologic cardiopulmonary assessments performed, and they were compared with 61 performed on normal postoperative patients, and 113 on 41 cirrhotics. It was found that the patients with pancreatitis have an elevated cardiac index (CI), which is not due to the hyperdynamic hemodynamic state found in cirrhotics. In spite of this, the Sarnoff curves demonstrated that pancreatitis was accompanied by a myocardial depression p less than 0.03, not found in hyperdynamic cirrhotics. Cirrhotics are unable to increase their oxygen consumption in response to an increase in CI, as do normal patients or those with acute pancreatitis. In cirrhotics the hemodynamic lesion occurs at the capillary level with the opening of arteriovenous shunts which rob the tissues of their nutritive blood supply, while the patient with acute pancreatitis has a primary myocardial depression and his peripheral vasculature reacts like that of a normal person. PMID:7247538

Ito, K; Ramirez-Schon, G; Shah, P M; Agarwal, N; Delguercio, L R; Reynolds, B M

1981-01-01

302

Familial pancreatic cancer: genetic advances  

PubMed Central

Beset by poor prognosis, pancreatic ductal adenocarcinoma is classified as familial or sporadic. This review elaborates on the known genetic syndromes that underlie familial pancreatic cancer, where there are opportunities for genetic counseling and testing as well as clinical monitoring of at-risk patients. Such subsets of familial pancreatic cancer involve germline cationic trypsinogen or PRSS1 mutations (hereditary pancreatitis), BRCA2 mutations (usually in association with hereditary breast–ovarian cancer syndrome), CDKN2 mutations (familial atypical mole and multiple melanoma), or DNA repair gene mutations (e.g., ATM and PALB2, apart from those in BRCA2). However, the vast majority of familial pancreatic cancer cases have yet to have their genetic underpinnings elucidated, waiting in part for the results of deep sequencing efforts. PMID:24395243

Rustgi, Anil K.

2014-01-01

303

Autoimmune pancreatitis: A surgical dilemma.  

PubMed

Autoimmune pancreatitis (AIP) is defined as a particular form of pancreatitis that often manifests as obstructive jaundice associated with a pancreatic mass or an obstructive bile duct lesion, and that has an excellent response to corticosteroid treatment. The prevalence of AIP worldwide is unknown, and it is considered as a rare entity. The clinical and radiological presentation of AIP can mimic bilio-pancreatic cancer, presenting difficulties for diagnosis and obliging the surgeon to balance decision-making between the potential risk presented by the misdiagnosis of a deadly disease against the desire to avoid unnecessary major surgery for a disease that responds effectively to corticosteroid treatment. In this review we detail the current and critical points for the diagnosis, classification and treatment for AIP, with a special emphasis on surgical series and the methods to differentiate between this pathology and bilio-pancreatic cancer. PMID:25066570

Saavedra-Perez, David; Vaquero, Eva C; Ayuso, Juan R; Fernandez-Cruz, Laureano

2014-12-01

304

Familial pancreatic cancer: genetic advances.  

PubMed

Beset by poor prognosis, pancreatic ductal adenocarcinoma is classified as familial or sporadic. This review elaborates on the known genetic syndromes that underlie familial pancreatic cancer, where there are opportunities for genetic counseling and testing as well as clinical monitoring of at-risk patients. Such subsets of familial pancreatic cancer involve germline cationic trypsinogen or PRSS1 mutations (hereditary pancreatitis), BRCA2 mutations (usually in association with hereditary breast-ovarian cancer syndrome), CDKN2 mutations (familial atypical mole and multiple melanoma), or DNA repair gene mutations (e.g., ATM and PALB2, apart from those in BRCA2). However, the vast majority of familial pancreatic cancer cases have yet to have their genetic underpinnings elucidated, waiting in part for the results of deep sequencing efforts. PMID:24395243

Rustgi, Anil K

2014-01-01

305

Endoscopic management of pancreatic pseudocysts and necrosis.  

PubMed

Over the last several years, there have been refinements in the understanding and nomenclature regarding the natural history of acute pancreatitis. Patients with acute pancreatitis frequently develop acute pancreatic collections that, over time, may evolve into pancreatic pseudocysts or walled-off necrosis. Endoscopic management of these local complications of acute pancreatitis continues to evolve. Treatment strategies range from simple drainage of liquefied contents to repeated direct endoscopic necrosectomy of a complex necrotic collection. In patients with chronic pancreatitis, pancreatic pseudocysts may arise as a consequence of pancreatic ductal obstruction that then leads to pancreatic ductal disruption. In this review, we focus on the indications, techniques and outcomes for endoscopic therapy of pancreatic pseudocysts and walled-off necrosis. PMID:25222140

Law, Ryan; Baron, Todd H

2015-02-01

306

Mouse models of pancreatic cancer  

PubMed Central

Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States, and potent therapeutic options are lacking. Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer, currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed. In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes. In the last few years, several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed. These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer. Genetic alterations such as activating mutations in KRas, or TGFb and/or inactivation of tumoral suppressors such as p53, INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice. These mouse models have a spectrum of pathologic changes, from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system. These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches, chemopreventive and/or anticancer treatments. Here, we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments. PMID:22493542

Herreros-Villanueva, Marta; Hijona, Elizabeth; Cosme, Angel; Bujanda, Luis

2012-01-01

307

Radiation Therapy and Cisplatin With or Without Epoetin Alfa in Treating Patients With Cervical Cancer and Anemia  

ClinicalTrials.gov

Anemia; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Drug Toxicity; Radiation Toxicity; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

2014-12-29

308

Radiation Therapy With or Without Cisplatin in Treating Patients With Recurrent Endometrial Cancer  

ClinicalTrials.gov

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma

2015-01-26

309

Cabozantinib-S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer  

ClinicalTrials.gov

Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

2015-01-08

310

Trebananib in Treating Patients With Persistent or Recurrent Endometrial Cancer  

ClinicalTrials.gov

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Endometrioid Stromal Sarcoma; Recurrent Uterine Corpus Carcinoma

2014-12-23

311

Venous complications of pancreatitis: a review.  

PubMed

Pancreatitis is notorious to cause vascular complications. While arterial complications include pseudoaneurysm formation with a propensity to bleed, venous complications can be quite myriad. Venous involvement in pancreatitis often presents with thrombosis. From time to time case reports and series of unusual venous complications associated with pancreatitis have, however, been described. In this article, we review multitudinous venous complications in the setting of pancreatitis and propose a system to classify pancreatitis associated venous complications. PMID:25640778

Aswani, Yashant; Hira, Priya

2015-01-01

312

Changes in antibiotic distribution due to pancreatitis.  

PubMed

This work sought to define how pancreatitis affected antibiotic distribution in a perfused rat pancreas model. The distribution kinetics of four antibiotics were examined in control animals and animals with pancreatitis. Meropenem and piperacillin distributed into the extracellular space, and their distribution kinetics were unaffected by pancreatitis. In contrast, in pancreatic cells from animals with pancreatitis, ciprofloxacin showed a reduced uptake and clindamycin showed a reduced distribution. PMID:21402839

Fanning, Kent J; Robertson, Thomas A; Prins, Johannes B; Roberts, Michael S

2011-06-01

313

Changes in Antibiotic Distribution Due to Pancreatitis?  

PubMed Central

This work sought to define how pancreatitis affected antibiotic distribution in a perfused rat pancreas model. The distribution kinetics of four antibiotics were examined in control animals and animals with pancreatitis. Meropenem and piperacillin distributed into the extracellular space, and their distribution kinetics were unaffected by pancreatitis. In contrast, in pancreatic cells from animals with pancreatitis, ciprofloxacin showed a reduced uptake and clindamycin showed a reduced distribution. PMID:21402839

Fanning, Kent J.; Robertson, Thomas A.; Prins, Johannes B.; Roberts, Michael S.

2011-01-01

314

Minimally invasive treatment of infected pancreatic necrosis  

PubMed Central

Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in the management of infected pancreatic necrosis.

Cebulski, W?odzimierz; S?odkowski, Maciej; Krasnod?bski, Ireneusz W.

2014-01-01

315

Role of the Hypoxia-inducible factor-1 alpha induced autophagy in the conversion of non-stem pancreatic cancer cells into CD133+ pancreatic cancer stem-like cells  

PubMed Central

The initiation and progression of various solid tumors, including pancreatic carcinoma, are driven by a population of cells with stem cell properties, namely cancer stem cells (CSCs). Like their normal counterparts, CSCs are also believed to rely on their own microenvironment termed niches to sustain the population. Hypoxia-inducible factor-1? (HIF-1?) is a major actor in the cell survival response to hypoxia. Recently, several researchers proposed that non-stem cancer cells can convert to stem-like cells to maintain equilibrium. The present study focuses on whether non-stem pancreatic cancer cells can convert to stem-like cells and the role of HIF-1? and autophagy in modulating this conversation. The non-stem pancreatic cancer cells and pancreatic cancer stem-like cells were separated by magnetic sorting column. Intermittent hypoxia enhanced stem-like properties of non-stem pancreatic cancer cells and stimulated the levels of HIF-1?, LC3-II and Beclin. Enhanced autophagy was associated with the elevated level of HIF-1?. The conversation of non-stem pancreatic cancer cells into pancreatic cancer stem-like cells was induced by HIF-1? and autophagy. This novel finding may indicate the specific role of HIF-1? and autophagy in promoting the dynamic equilibrium between CSCs and non-CSCs. Also, it emphasizes the importance of developing therapeutic strategies targeting cancer stem cells as well as the microenvironmental influence on the tumor. PMID:24305593

2013-01-01

316

Biomarkers in pancreatic adenocarcinoma.  

PubMed

Pancreatic adenocarcinoma is a highly aggressive cancer, with a median patient survival of less than one year. Clinically useful biomarkers capable of accurately assessing prognosis, as well as response to therapy, are urgently needed. At the 2014 ASCO Annual Meeting, Maus et al. (Abstract #e15199) and Neuzillet et al. (Abstract #e15200) present data on use of c-met as a prognostic biomarker, and Shultz et al. (Abstract #4133) use a multiplex antibody panel to identify predictive markers of response to gemcitabine and erlotinib. PMID:25076328

Joza, Nicholas; Saif, Muhammad Wasif

2014-07-01

317

Generation of islet-like cell aggregates from human non-pancreatic cancer cell lines.  

PubMed

To explore a novel source for the derivation of islets, we examined the differentiation potential of human non-pancreatic cancer cell lines, HeLa (cervical carcinoma cell line) and MCF-7 (breast cancer cell line). These cells were subjected to a serum-free, three-step sequential differentiation protocol which gave two distinct cell populations: single cells and cellular aggregates. Subsequent analysis confirmed their identity as pancreatic acinar cells and islet-like cell aggregates (ICAs), as evidenced by amylase secretion and diphenylthiocarbazone staining respectively. Reverse transcriptase-PCR and immunocytochemistry assessment of the ICAs revealed the expression of pancreatic specific markers Ngn-3, Glut-2, Pax-6 and Isl-1. These ICAs secreted insulin in response to glucose challenge, confirming their functionality. We propose that ICAs generated from HeLa and MCF-7 cell lines could form a promising in vitro platform of human islet equivalents (hIEQs) for diabetes research. PMID:25257585

Kanafi, Mohammad Mahboob; Mamidi, Murali Krishna; Sureshbabu, Shalini Kashipathi; Shahani, Pradnya; Bhawna, Chandravanshi; Warrier, Sudha R; Bhonde, Ramesh

2015-01-01

318

The actin-bundling protein TRIOBP-4 and -5 promotes the motility of pancreatic cancer cells.  

PubMed

TRIOBP isoforms 4 and 5 (TRIOBP-4/-5) are an actin-bundling protein associated with hearing loss. Here, we showed that TRIOBP-4/-5 was up-regulated in human pancreatic carcinoma cells. Knockdown of TRIOBP-4/-5 led to a loss of filopodia and a decrease in cell motility. Confocal microscopy showed that re-expression of GFP-TRIOBP-4 or -5 restored the filopodial formation in TRIOBP-4/-5-deficient PANC-1 cells. Finally, TRIOBP-4/-5 was shown to be overexpressed in human pancreatic cancer tissues. These results demonstrate a novel role of TRIOBP-4/-5 that promotes the motility of pancreatic cancer cells via regulating actin cytoskeleton reorganization in the filopodia of the cells. PMID:25130170

Bao, Jianjun; Wang, Shuo; Gunther, Laura K; Kitajiri, Shin-Ichiro; Li, Chunying; Sakamoto, Takeshi

2015-01-28

319

Role of endoscopy in the diagnosis of autoimmune pancreatitis and immunoglobulin G4-related sclerosing cholangitis.  

PubMed

Autoimmune pancreatitis (AIP) must be differentiated from pancreatic carcinoma, and immunoglobulin (Ig)G4-related sclerosing cholangitis (SC) from cholangiocarcinoma and primary sclerosing cholangitis (PSC). Pancreatographic findings such as a long narrowing of the main pancreatic duct, lack of upstream dilatation, skipped narrowed lesions, and side branches arising from the narrowed portion suggest AIP rather than pancreatic carcinoma. Cholangiographic findings for PSC, including band-like stricture, beaded or pruned-tree appearance, or diverticulum-like outpouching are rarely observed in IgG4-SC patients, whereas dilatation after a long stricture of the bile duct is common in IgG4-SC. Transpapillary biopsy for bile duct stricture is useful to rule out cholangiocarcinoma and to support the diagnosis of IgG4-SC with IgG4-immunostaining. IgG4-immunostaining of biopsy specimens from the major papilla advances a diagnosis of AIP. Contrast-enhanced endoscopic ultrasonography (EUS) and EUS elastography have the potential to predict the histological nature of the lesions. Intraductal ultrasonographic finding of wall thickening in the non-stenotic bile duct on cholangiography is useful for distinguishing IgG4-SC from cholangiocarcinoma. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used to exclude pancreatic carcinoma. To obtain adequate tissue samples for the histological diagnosis of AIP, EUS-Tru-cut biopsy or EUS-FNA using a 19-gauge needle is recommended, but EUS-FNA with a 22-gauge needle can also provide sufficient histological samples with careful sample processing after collection and rapid motion of the FNA needles within the pancreas. Validation of endoscopic imaging criteria and new techniques or devices to increase the diagnostic yield of endoscopic tissue sampling should be developed. PMID:24712522

Kamisawa, Terumi; Ohara, Hirotaka; Kim, Myung Hwan; Kanno, Atsushi; Okazaki, Kazuichi; Fujita, Naotaka

2014-09-01

320

Severe acute pancreatitis in pregnancy.  

PubMed

This is a case of a pregnant lady at 8 weeks of gestation, who presented with acute abdomen. She was initially diagnosed with ruptured ectopic pregnancy and ruptured corpus luteal cyst as the differential diagnosis. However she then, was finally diagnosed as acute hemorrhagic pancreatitis with spontaneous complete miscarriage. This is followed by review of literature on this topic. Acute pancreatitis in pregnancy is not uncommon. The emphasis on high index of suspicion of acute pancreatitis in women who presented with acute abdomen in pregnancy is highlighted. Early diagnosis and good supportive care by multidisciplinary team are crucial to ensure good maternal and fetal outcomes. PMID:25628906

Abdullah, Bahiyah; Kathiresan Pillai, Thanikasalam; Cheen, Lim Huay; Ryan, Ray Joshua

2015-01-01

321

Acute Pancreatitis Complicating Severe Dengue  

PubMed Central

Dengue is an arthropod borne viral infection endemic in tropical and subtropical continent. Severe dengue is life threatening. Various atypical presentations of dengue have been documented. But we present a rare and fatal complication of severe dengue in form of acute pancreatitis. A 27-year-old male had presented with severe dengue in decompensated shock and with pain in abdomen due to pancreatitis. The pathogenesis of acute pancreatitis in dengue is not clearly understood, but various mechanisms are postulated. The awareness and timely recognition of this complication is very important for proper management. PMID:24926168

Jain, Vishakha; Gupta, OP; Rao, Tarun; Rao, Siddharth

2014-01-01

322

Recent Progress in Pancreatic Cancer  

PubMed Central

Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in our understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. PMID:23856911

Wolfgang, Christopher L.; Herman, Joseph M.; Laheru, Daniel A.; Klein, Alison P.; Erdek, Michael A.; Fishman, Elliot K.; Hruban, Ralph H.

2013-01-01

323

Severe Acute Pancreatitis in Pregnancy  

PubMed Central

This is a case of a pregnant lady at 8 weeks of gestation, who presented with acute abdomen. She was initially diagnosed with ruptured ectopic pregnancy and ruptured corpus luteal cyst as the differential diagnosis. However she then, was finally diagnosed as acute hemorrhagic pancreatitis with spontaneous complete miscarriage. This is followed by review of literature on this topic. Acute pancreatitis in pregnancy is not uncommon. The emphasis on high index of suspicion of acute pancreatitis in women who presented with acute abdomen in pregnancy is highlighted. Early diagnosis and good supportive care by multidisciplinary team are crucial to ensure good maternal and fetal outcomes. PMID:25628906

Abdullah, Bahiyah; Kathiresan Pillai, Thanikasalam; Cheen, Lim Huay; Ryan, Ray Joshua

2015-01-01

324

KRAS in pancreatic cancer.  

PubMed

Pancreatic cancer is one of the most feared malignancies. The most common form of pancreatic cancer is adenocarcinoma arising from the ductal epithelium. KRAS is the most common oncogene that has been found to be mutated. However, targeting KRAS directly has been difficult. We do not know a lot about the relationship between KRAS and other signaling pathways. At the same time, little is known about the non KRAS mutated or wild type (WT) tumors. Most of the data that we have as far, as mutational status is concerned, has been obtained from the tumor itself and not from metastatic lesions. In this review, we discuss two abstracts (Abstracts #e15214 and #e15207) published in conjunction with the 2014 ASCO Annual Meeting. These discuss the relationship between KRAS and other signaling pathways and the differences between mutated KRAS and WT tumors. The studies found low rate of KRAS mutation in cells obtained from ascitic fluid. While the studies are small, these are novel findings that are worth exploring further. They increase our understanding of the biology of the disease and take us a step closer to treating this deadly malignancy. PMID:25076326

Agarwal, Archana; Saif, Muhammad Wasif

2014-07-01

325

Pathophysiology of chronic pancreatitis  

PubMed Central

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma. Despite the heterogeneity in pathogenesis and involved risk factors, processes such as necrosis/apoptosis, inflammation or duct obstruction are involved. This fibrosing process ultimately leads to progressive loss of the lobular morphology and structure of the pancreas, deformation of the large ducts and severe changes in the arrangement and composition of the islets. These conditions lead to irreversible morphological and structural changes resulting in impairment of both exocrine and endocrine functions. The prevalence of the disease is largely dependent on culture and geography. The etiological risk-factors associated with CP are multiple and involve both genetic and environmental factors. Throughout this review the M-ANNHEIM classification system will be used, comprising a detailed description of risk factors such as: alcohol-consumption, nicotine-consumption, nutritional factors, hereditary factors, efferent duct factors, immunological factors and miscellaneous and rare metabolic factors. Increased knowledge of the different etiological factors may encourage the use of further advanced diagnostic tools, which potentially will help clinicians to diagnose CP at an earlier stage. However, in view of the multi factorial disease and the complex clinical picture, it is not surprising that treatment of patients with CP is challenging and often unsuccessful. PMID:24259953

Brock, Christina; Nielsen, Lecia Møller; Lelic, Dina; Drewes, Asbjørn Mohr

2013-01-01

326

Erlotinib Hydrochloride in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery  

ClinicalTrials.gov

Intraductal Papillary Mucinous Neoplasm of the Pancreas; Recurrent Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

2014-10-07

327

[Pain in chronic pancreatitis and pancreatic cancer - treatment options].  

PubMed

Treatment of pain is one of the main pillars of treatment of pancreatic diseases. Abdominal pain is a common and often debilitating symptom in patients with chronic pancreatitis and pancreatic cancer. Treatment involves abstinence from tobacco, alcohol and analgetics and adjunctive agents. Surgical and endoscopic treatment requires careful patient selection based on a detailed analysis of ductal anatomy. The limited possibilities of this therapy are patients without dilatation of the main pancreatic duct. Results of randomized trials suggest that the effect of surgical treatment is sustained over time and more efficient than the endoscopic treatment. Less frequently used options include EUS - assisted celiac plexus blockade, thoracoscopic splanchniectomia or total pancreatectomy with islet cell autotransplantation. These methods are rarely used when all other options have failed and only in carefully selected patients. PMID:24981695

Bojková, Martina; Klva?a, Pavel; Svoboda, Pavel; Kupka, Tomáš; Martínek, Arnošt; Bojko, Marian; Dít?, Petr

2014-03-01

328

Aberrant methylation of suppressor of cytokine signalling-1 (SOCS-1) gene in pancreatic ductal neoplasms  

Microsoft Academic Search

The suppressor of cytokine signalling-1 (SOCS-1) gene is frequently silenced in human hepatocellular carcinoma by aberrant methylation. The aim of this study was to determine if SOCS-1 is inactivated in pancreatic ductal neoplasms, and to investigate if aberrant methylation of this gene affected the Janus kinase\\/signal transducers and activators of transcription (JAK\\/STAT) pathway. Aberrant methylation in the CpG island of

N Fukushima; N Sato; F Sahin; G H Su; R H Hruban; M Goggins

2003-01-01

329

Influence of interferon-alpha combined with chemo (radio) therapy on immunological parameters in pancreatic adenocarcinoma.  

PubMed

Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of 17 patients with pancreatic cancer from the CapRI-2 study, and tumor-bearing mice treated with combination of chemo (radio) therapies with interferon-2?. Low doses of interferon-2? led to a decrease in total leukocyte and an increase in monocyte counts. Furthermore, we observed a positive effect of interferon-2? therapy on the dendritic cells and NK (natural killer) cell activation immediately after the first injection. In addition, we recorded an increased amount of interferon-? and IL-10 in the serum following the interferon-2? therapy. These data clearly demonstrate that pancreatic carcinoma patients also show an immunomodulatory response to interferon-2? therapy. Analysis of immunosuppressive cells in the Panc02 orthotopic mouse model of pancreatic cancer revealed an accumulation of the myeloid-derived suppressor cells in spleens and tumors of the mice treated with interferon-2? and 5-fluorouracil. The direct effect of the drugs on myeloid-derived suppressor cells was also registered in vitro. These data expose the importance of immunosuppressive mechanisms induced by combined chemo-immunotherapy. PMID:24608924

Karakhanova, Svetlana; Mosl, Beate; Harig, Sabine; von Ahn, Katharina; Fritz, Jasmin; Schmidt, Jan; Jäger, Dirk; Werner, Jens; Bazhin, Alexandr V

2014-01-01

330

Influence of Interferon-Alpha Combined with Chemo (Radio) Therapy on Immunological Parameters in Pancreatic Adenocarcinoma  

PubMed Central

Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of 17 patients with pancreatic cancer from the CapRI-2 study, and tumor-bearing mice treated with combination of chemo (radio) therapies with interferon-2?. Low doses of interferon-2? led to a decrease in total leukocyte and an increase in monocyte counts. Furthermore, we observed a positive effect of interferon-2? therapy on the dendritic cells and NK (natural killer) cell activation immediately after the first injection. In addition, we recorded an increased amount of interferon-? and IL-10 in the serum following the interferon-2? therapy. These data clearly demonstrate that pancreatic carcinoma patients also show an immunomodulatory response to interferon-2? therapy. Analysis of immunosuppressive cells in the Panc02 orthotopic mouse model of pancreatic cancer revealed an accumulation of the myeloid-derived suppressor cells in spleens and tumors of the mice treated with interferon-2? and 5-fluorouracil. The direct effect of the drugs on myeloid-derived suppressor cells was also registered in vitro. These data expose the importance of immunosuppressive mechanisms induced by combined chemo-immunotherapy. PMID:24608924

Karakhanova, Svetlana; Mosl, Beate; Harig, Sabine; von Ahn, Katharina; Fritz, Jasmin; Schmidt, Jan; Jäger, Dirk; Werner, Jens; Bazhin, Alexandr V.

2014-01-01

331

Hereditary pancreatitis: new insights, new directions.  

PubMed

Hereditary pancreatitis is an unusual form of acute and chronic pancreatitis with a familial predisposition. Recently, the gene mutations causing most cases of hereditary pancreatitis have been identified in the cationic trypsinogen gene. The known mutations are trypsinogen R117H and N211. These may predispose to acute pancreatitis by eliminating one of the fail-safe mechanisms used by the pancreas to eliminate prematurely activated trypsin. Accumulation of active trypsin mutants are hypothesized to initiate a digestive enzyme activation cascade in the pancreatic acinar cells leading to autodigestion, an intense inflammatory response, and acute pancreatitis. The observation that these patients also develop typical chronic pancreatitis and may later develop pancreatic cancer provides strong evidence that these conditions are linked. Knowledge of the pathophysiological conditions leading to acute and chronic pancreatitis and the development of a transgenic mouse expressing the mutant human trypsinogen genes will provide directions and tools necessary for the effective treatment or prevention of this human disease. PMID:11030605

Whitcomb, D C; Ulrich, C D

1999-07-01

332

Magnetic resonance imaging of pancreatitis: an update.  

PubMed

Magnetic resonance (MR) imaging plays an important role in the diagnosis and staging of acute and chronic pancreatitis and may represent the best imaging technique in the setting of pancreatitis due to its unmatched soft tissue contrast resolution as well as non-ionizing nature and higher safety profile of intravascular contrast media, making it particularly valuable in radiosensitive populations such as pregnant patients, and patients with recurrent pancreatitis requiring multiple follow-up examinations. Additional advantages include the ability to detect early forms of chronic pancreatitis and to better differentiate adenocarcinoma from focal chronic pancreatitis. This review addresses new trends in clinical pancreatic MR imaging emphasizing its role in imaging all types of acute and chronic pancreatitis, pancreatitis complications and other important differential diagnoses that mimic pancreatitis. PMID:25356038

Manikkavasakar, Sriluxayini; AlObaidy, Mamdoh; Busireddy, Kiran K; Ramalho, Miguel; Nilmini, Viragi; Alagiyawanna, Madhavi; Semelka, Richard C

2014-10-28

333

Pancreatic cancer and thromboembolic disease.  

PubMed

Thromboembolic disease is a common complication of pancreatic cancer and is causally associated with the generation of an intrinsic hypercoagulable state. Pancreatic-cancer cells activate platelets and express several procoagulant factors, including tissue factor and thrombin. The activation of coagulation is not simply an epiphenomenon, but might also be related to enhanced tumour growth and angiogenesis. Clinical manifestations of thromboembolic disease in pancreatic cancer include deep venous thrombosis, pulmonary embolism, disseminated intravascular coagulation, portal vein thrombosis, and arterial thromboembolism. Reported incidences of disease range from 17% to 57%. Treatment options include warfarin and low-molecular-weight heparins. Studies over the past decade suggest that long-term use of these heparins in both primary and secondary prevention of venous thromboembolic disease improves outcomes in comparison with warfarin. Further research is needed to understand better the morbidity and mortality associated with this disease in pancreatic cancer and to optimise strategies of prevention and treatment. PMID:15522652

Khorana, Alok A; Fine, Robert L

2004-11-01

334

Vaccine therapy for pancreatic cancer  

PubMed Central

Pancreatic cancer is a lethal disease and currently available therapies have significant limitations. Pancreatic cancer is thus an ideal setting for the development of novel treatment modalities such as immunotherapy. However, relevant obstacles must be overcome for immunotherapeutic regimens against pancreatic cancer to be successful. Vaccine therapy relies on the administration of biological preparations that include an antigen that (at least ideally) is specifically expressed by malignant cells, boosting the natural ability of the immune system to react against neoplastic cells. There are a number of ways to deliver anticancer vaccines. Potent vaccines stimulate antigen presentation by dendritic cells, hence driving the expansion of antigen-specific effector and memory T cells. Unlike vaccines given as a prophylaxis against infectious diseases, anticancer vaccines require the concurrent administration of agents that interfere with the natural predisposition of tumors to drive immunosuppression. The safety and efficacy of vaccines against pancreatic cancer are nowadays being tested in early phase clinical trials. PMID:24498551

Salman, Bulent; Zhou, Donger; Jaffee, Elizabeth M; Edil, Barish H; Zheng, Lei

2013-01-01

335

Pursuing Pancreatic Cancer's Deadly Secret  

MedlinePLUS

... the Pancreatic Cancer Center at the University of Michigan Comprehensive Cancer Center. "This study sheds important light ... the blood cancer multiple myeloma. SOURCE: University of Michigan Health System, news release, Jan. 15, 2015 HealthDay ...

336

Immunotherapy for Advanced Pancreatic Cancer  

Cancer.gov

In this trial, researchers are using a monoclonal antibody called MDX-010 to treat patients with advanced pancreatic cancer. MDX-010 binds to and blocks the activity of an immune response inhibitor molecule called CTLA-4.

337

Advances in Pancreatic Cancer Care  

MedlinePLUS Videos and Cool Tools

REPLAY IN ADVANCES IN PANCREATIC CANCER CARE PYLORUS-PRESERVING PANCREATICODUODENECTOMY (MINI-WHIPPLE PROCEDURE) THOMAS JEFFERSON UNIVERSITY HOSPITAL PHILADELPHIA, PENNSYLVANIA September 18, 2007 00:00:18 ANNOUNCER: Welcome to Thomas ...

338

Drugs Approved for Pancreatic Cancer  

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

339

Dynamic CT of pancreatic tumors  

SciTech Connect

Dynamic computed tomography was performed on 19 patients with clinically diagnosed pancreatic and peripancreatic tumors. There were 10 patients with pancreatic cancer, three with inflammatory pancreatic masses, two with cystadenoma, one with insuloma, and three with peripancreatic tumors. Computed tomography was performed with a Varian-V-360-3 scanner; scanning was for 30 consecutive sec at 3 sec intervals after the bolus injection of 50 ml of contrast medium into the antecubital vein. Dynamic computed tomography (CT) may be more useful than conventional contrast CT because it facilitates: (1) correct evaluation of tumor vascularity allowing a differential diagnosis; (2) location of the boundary between tumor and a nontumor tissue; (3) detection of small tumors; and (4) visualization of pancreatic invasion by peripancreatic tumors. In addition, contrast enhancement and the degree of vascular proliferation can be quantitatively assessed by analyzing time-density curves.

Hosoki, T.

1983-05-01

340

Recent Advances in Autoimmune Pancreatitis  

PubMed Central

Although the pathogenesis of autoimmune pancreatitis remains unclear, this report presents recent evidence of the clinical aspects of this disease: mild abdominal symptoms, usually without acute attacks of pancreatitis; occasional presence of obstructive jaundice; elevated levels of serum gammaglobulin, immunoglobulin (Ig)G, or IgG4; presence of autoantibodies; diffuse enlargement of the pancreas; irregular narrowing of the pancreatic duct (sclerosing pancreatitis), often with intrapancreatic biliary stenosis or coexisting biliary lesions (sclerosing cholangitis similar to primary sclerosing cholangitis) seen on endoscopic retrograde cholangiopancreatography; fibrotic changes with lymphocyte and IgG4-positive plasmacyte infiltration and obliterative phlebitis; occasional association with other systemic lesions (such as sialadenitis), retroperitoneal fibrosis, and interstitial renal tubular disorders; and response to steroid therapy. Based upon these findings, several sets of diagnostic criteria have been proposed. Further studies and international consensus for diagnostic criteria and pathogenetic mechanisms are needed. PMID:21904518

Uchida, Kazushige; Fukui, Toshiro; Matsushita, Mitsunobu; Takaoka, Makoto

2008-01-01

341

Chronic pancreatitis and cystic fibrosis  

PubMed Central

Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited dominant, recessive, or complex as a result of mutations in the above mentioned or yet unidentified genes. Evaluation of patients with CP should include genetic testing. Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterised by pancreatic insufficiency and chronic bronchopulmonary infection. The progression and severity of pulmonary disease differs considerably between people with identical CFTR mutations and does not seem to correlate with the type or class of the CFTR mutation. The identification of further disease modifying genetic factors will increase the pathophysiological understanding and may help to identify new therapeutic targets. PMID:12651880

Witt, H

2003-01-01

342

Acute biliary pancreatitis: diagnosis and treatment.  

PubMed

Gallstones are the commonest cause of acute pancreatitis (AP), a potentially life-threatening condition, worldwide. The pathogenesis of acute pancreatitis has not been fully understood. Laboratory and radiological investigations are critical for diagnosis as well prognosis prediction. Scoring systems based on radiological findings and serologic inflammatory markers have been proposed as better predictors of disease severity. Early endoscopic retrograde cholangiopancreatography (ERCP) is beneficial in a group of patients with gallstone pancreatitis. Laparoscopic cholecystectomy with preoperative endoscopic common bile duct clearance is recommended as a treatment of choice for acute biliary pancreatitis. The timing of cholecystectomy, following ERCP, for biliary pancreatitis can vary markedly depending on the severity of pancreatitis. PMID:19636174

Hazem, Zakaria M

2009-01-01

343

Adjuvant Therapy in Pancreatic Cancer  

Microsoft Academic Search

Pancreatic cancer is one of the major causes of cancer death in Europe with a 5-year survival rate of less than 5%. Although surgery cannot guarantee a cure, the 5-year survival does improve to around 10% following resection and increases to 20–30% with adjuvant chemotherapy. The European Study Group for Pancreatic Cancer (ESPAC) 1 trial was the first adequately powered,

Amy Thomas; Khaled Dajani; John P. Neoptolemos; Paula Ghaneh

2010-01-01

344

Bone morphogenetic protein 4 induces epithelial-mesenchymal transition through MSX2 induction on pancreatic cancer cell line.  

PubMed

In our study, we found that bone morphogenetic protein 4 (BMP4) has a novel effect as an inducer of epithelial-mesenchymal transition (EMT) on Panc-1 cells, a human pancreatic carcinoma cell line. BMP4-treated Panc-1 cells showed loose cell contacts and a scattered, fibroblast-like appearance along with E-cadherin downregulation, Vimentin upregulation and enhanced cell migration, which are characteristic of EMT. BMP4 treatment also induced homeobox gene MSX2 expression, which we previously showed to be associated with EMT in pancreatic carcinoma cells. BMP4 treatment activated the Smad signaling pathway, and extracellular signal-related kinase (ERK) and p38 mitogen-activated kinase (MAPK) pathways in these cells. MSX2 was markedly induced by BMP4 through the ERK and p38 MAPK pathways in collaboration with the Smad signaling pathway. The repression of E-cadherin, induction of Vimentin and enhanced cell migration disappeared when siRNA-based MSX2 downregulated pancreatic cancer cells were treated with BMP4. These findings indicate that BMP4 may be involved in pancreatic carcinoma development through the promotion of EMT and that MSX2 is indispensable to this process. PMID:17516553

Hamada, Shin; Satoh, Kennichi; Hirota, Morihisa; Kimura, Kenji; Kanno, Atsushi; Masamune, Atsushi; Shimosegawa, Tooru

2007-12-01

345

Expression of 16 kDa proteolipid of vacuolar-type H(+)-ATPase in human pancreatic cancer.  

PubMed Central

Recent studies have shown that bafilomycin A1-sensitive vacuolar-type H(+)-ATPase (V-ATPase) plays important roles in cell growth and differentiation. However, there is no published study that has focused on the expression of V-ATPase in human tumour tissues. This study was designed to examine the mRNA and protein levels for the 16 kilodalton (kDa) proteolipid of V-ATPase in human pancreatic carcinoma tissues. We first investigated the mRNA level for V-ATPase in six cases of invasive pancreatic cancers and two normal pancreases, using reverse transcription-polymerase chain reaction technique. Then, we examined immunohistochemically the level of V-ATPase protein in 49 pancreatic cancers and ten benign cystic neoplasms of the pancreas, using antisera raised against the 16 kDa proteolipid. There was a notable difference in the level of V-ATPase mRNA between normal and pancreatic carcinoma tissues, with no evident difference in the expression of the beta-actin gene. Immunohistochemically, 42 out of 46 invasive ductal cancers (92%) displayed a mild to marked immunoreactivity for V-ATPase in the cytoplasm, whereas neither non-invasive ductal cancers nor benign cystic neoplasms expressed detectable immunoreactive proteins. These findings suggest that the overexpression of V-ATPase protein is characteristic of invasive pancreatic tumours. V-ATPase may play some crucial roles in tumour progression. Images Figure 2 Figure 4 Figure 3 PMID:8664121

Ohta, T.; Numata, M.; Yagishita, H.; Futagami, F.; Tsukioka, Y.; Kitagawa, H.; Kayahara, M.; Nagakawa, T.; Miyazaki, I.; Yamamoto, M.; Iseki, S.; Ohkuma, S.

1996-01-01

346

Ovarian Serous Carcinoma  

MedlinePLUS

What is ovarian serous carcinoma? Serous carcinoma is a type of epithelial ovarian cancer, which is the most common kind of ... 95 percent. Who is most likely to have ovarian serous carcinoma? Women with a personal or family ...

347

Liver Hepatocellular Carcinoma  

Cancer.gov

Home Cancers Selected for Study Liver Hepatocellular Carcinoma Liver Hepatocellular Carcinoma Last Updated: May 14, 2013 What is liver cancer?Hepatocellular carcinoma is the most common form of liver cancer in the United States, making up more than

348

Coupling G2/M arrest to the Wnt/?-catenin pathway restrains pancreatic adenocarcinoma.  

PubMed

?-catenin plays a pivotal role in organogenesis and oncogenesis. Alterations in ?-catenin expression are common in pancreatic cancer, which is an extremely aggressive malignancy with a notably poor prognosis. In this report, we analyzed the apoptotic activity of withanolide-D (witha-D), a steroidal lactone that was purified from an Indian medicinal plant, Withania somnifera, and its underlying mechanism of action. Witha-D induced apoptosis in pancreatic ductal adenocarcinoma cells by prompting cell-cycle arrest at the G2/M phase. This lactone abrogated ?-catenin signaling in these cells regardless of disease grade, mutational status, and gemcitabine sensitivity. Witha-D also upregulated E-cadherin in most cells, thereby supporting the inversion of the epithelial-mesenchymal transition. Furthermore, the Akt/Gsk3? kinase cascade was identified as a critical mediator of G2/M regulation and ?-catenin signaling. Witha-D deactivated Akt, which failed to promote Gsk3? deactivation phosphorylation. Consequently, activated Gsk3? facilitated ?-catenin destruction in pancreatic carcinoma cells. The knockdown of Chk1 and Chk2 further activated Akt and reversed the molecular signal. Taken together, the results of the current study represent the first evidence of ?-catenin signal crosstalk during the G2/M phase by functionally inactivating Akt via witha-D treatment in pancreatic cancer cells. In conclusion, this finding suggests the potential identification of a new lead molecule in the treatment of pancreatic adenocarcinoma. PMID:24402132

Sarkar, Sayantani; Mandal, Chandan; Sangwan, Rajender; Mandal, Chitra

2014-02-01

349

Chloroquine targets pancreatic cancer stem cells via inhibition of CXCR4 and hedgehog signaling.  

PubMed

Pancreatic ductal adenocarcinoma is one of the deadliest carcinomas and is characterized by highly tumorigenic and metastatic cancer stem cells (CSC). CSCs evade available therapies, which preferentially target highly proliferative and more differentiated progenies, leaving behind CSCs as a putative source for disease relapse. Thus, to identify potentially more effective treatment regimens, we screened established and new compounds for their ability to eliminate CSCs in primary pancreatic cancer (stem) cells in vitro and corresponding patient-derived pancreatic cancer tissue xenografts in vivo. Intriguingly, we found that in vitro treatment with the antimalarial agent chloroquine significantly decreased CSCs, translating into diminished in vivo tumorigenicity and invasiveness in a large panel of pancreatic cancers. In vivo treatment in combination with gemcitabine was capable of more effectively eliminating established tumors and improved overall survival. The inhibitory effect of chloroquine was not related to inhibition of autophagy, but was due to inhibition of CXCL12/CXCR4 signaling, resulting in reduced phosphorylation of ERK and STAT3. Furthermore, chloroquine showed potent inhibition of hedgehog signaling by decreasing the production of Smoothened, translating into a significant reduction in sonic hedgehog-induced chemotaxis and downregulation of downstream targets in CSCs and the surrounding stroma. Our study demonstrates that via to date unreported effects, chloroquine is an effective adjuvant therapy to chemotherapy, offering more efficient tumor elimination and improved cure rates. Chloroquine should be further explored in the clinical setting as its success may help to more rapidly improve the poor prognosis of patients with pancreatic cancer. PMID:24785258

Balic, Anamaria; Sørensen, Morten Dræby; Trabulo, Sara Maria; Sainz, Bruno; Cioffi, Michele; Vieira, Catarina R; Miranda-Lorenzo, Irene; Hidalgo, Manuel; Kleeff, Joerg; Erkan, Mert; Heeschen, Christopher

2014-07-01

350

Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer.  

PubMed

Conventional treatment approaches have had little impact on the course of pancreatic cancer, which has the highest fatality rate among cancers. Gemcitabine, the primary therapeutic agent for pancreatic carcinoma, produces minimal survival benefit as a single agent. Therefore, numerous efforts have focused on gemcitabine combination treatments. Using a ratio design, this study established that combining pharmacologically achievable concentrations of ascorbate with gemcitabine resulted in a synergistic cytotoxic response in eight pancreatic tumor cell lines. Sensitization was evident regardless of inherent gemcitabine resistance and epithelial-mesenchymal phenotype. Our analysis suggested that the promiscuous oxidative actions of H(2)O(2) derived from pharmacologic ascorbate can culminate in synergism independent of the cancer cell's underlying phenotype and resistance to gemcitabine monotherapy. Gemcitabine-ascorbate combinations administered to mice bearing pancreatic tumor xenografts consistently enhanced inhibition of growth compared to gemcitabine alone, produced 50% growth inhibition in a tumor type not responsive to gemcitabine, and demonstrated a gemcitabine dose-sparing effect. These data support the testing of pharmacologic ascorbate in adjunctive treatments for cancers prone to high failure rates with conventional therapeutic regimens, such as pancreatic cancer. PMID:21402145

Espey, Michael Graham; Chen, Ping; Chalmers, Brian; Drisko, Jeanne; Sun, Andrew Y; Levine, Mark; Chen, Qi

2011-06-01

351

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation.  

PubMed Central

Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia. PMID:8494719

Watanapa, P.; Williamson, R. C.

1993-01-01

352

Pancreatic duct strictures  

Microsoft Academic Search

Opinion statement  \\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a The treatment of pancreatic duct strictures is based on an accurate assessment of the etiology of the disease, and then the\\u000a degree of symptomatology. Our outline for therapy is as follows:\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Exclude a diagnosis of malignancy by using radiologic, endoscopic, histologic, and molecular biologic modalities.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Once a benign stricture has been demonstrated, we favor a

Jawad Ahmad; John Martin

2000-01-01

353

Vaccines for Pancreatic Cancer  

PubMed Central

Pancreatic ductal adenocarcinoma (PDA) remains a highly lethal disease; new therapeutic modalities are urgently needed. A number of immunotherapies tested in pre-clinical models have shown promise. Early phase clinical trials have demonstrated evidence of immune activation that in some cases correlates with clinical response. Moreover, recent evidence delineates inflammation’s intricate role in PDA, even at its earliest stages. PDA is thus ripe for immunotherapy; however, significant challenges remain before success can be realized. Future studies will need to focus on the discovery of novel PDA antigens, and the identification of the multiple immune suppressive pathways within the PDA tumor microenvironment that inhibit an effective PDA targeted immune response. Technologies are now available to rapidly advance discovery. Rapid translation of new discoveries into scientifically driven clinical trials testing combinations of immune agents will likely continue to shift the procarcinogenic tumor environment towards the most potent anticancer response. PMID:23187853

Soares, Kevin C.; Zheng, Lei; Edil, Barish; Jaffee, Elizabeth M.

2012-01-01

354

Treatment of pancreatic pseudocysts with ductal communication by transpapillary pancreatic duct endoprosthesis  

Microsoft Academic Search

Background: Endoscopic treatment of pancreatic pseudocysts via cystenterostomy has been recognized as a successful treatment option in carefully selected patients. Pancreatic transpapillary stenting as an alternative treatment option in patients with pancreatic pseudocysts directly communicating with the main duct has received little consideration. The aim of the current study was to assess the safety and utility of transpapillary pancreatic endo-prosthesis

Marc F. Catalano; Joseph E. Geenen; Michael J. Schmalz; G. Kenneth Johnson; Robert S. Dean; Walter J. Hogan

1995-01-01

355

Pancreatic Cancer Center: Providing the Research Tools Necessary to Advance Pancreatic Cancer Patient Care  

E-print Network

Pancreatic Cancer Center: Providing the Research Tools Necessary to Advance Pancreatic Cancer number of NCI-designated cancer centers have a specialized pancreatic cancer program. The creation of the IUPUI Signature Center for Pancreatic Cancer Research has been the foundation for putting IUPUI, the IU

Zhou, Yaoqi

356

Mabs against Pancreatic cancer Therapeutic antibodies for the treatment of pancreatic cancer  

E-print Network

Mabs against Pancreatic cancer 1 Therapeutic antibodies for the treatment of pancreatic cancer pancreatic cancer inserm-00497886,version1-6Jul2010 Author manuscript, published in "TheScientificWorldJournal (electronic resource) 2010;10:1107-20" DOI : 10.1100/tsw.2010.103 #12;Mabs against Pancreatic cancer 2

Paris-Sud XI, Université de

357

LMO2 Is a Novel Predictive Marker for a Better Prognosis in Pancreatic Cancer1  

PubMed Central

Purpose LIM domain only 2 (LMO2) has been identified as a novel oncogene associated with carcinogenesis and better prognosis in several malignant tumors. We investigate the involvement of LMO2 in pancreatic cancer. Experimental Design We evaluated LMO2 expression in cultured cells, bulk tissues, and microdissected cells from pancreatic cancers by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Results Of 164 pancreatic cancers, 98 (60%) were positive for LMO2 expression. LMO2 was more frequently detected in high-grade pancreatic intraepithelial neoplasia (PanIN) lesions (PanIN-2 and -3) than in low-grade PanIN lesions (PanIN-1A and -1B; P < .001) and was not detected in normal pancreatic ductal epithelium. The LMO2 messenger RNA levels were significantly higher in invasive ductal carcinoma cells than in normal pancreatic cells as evaluated by quantitative reverse transcription-polymerase chain reaction analyses of microdissected cells (P = .036). We also found higher incidence of LMO2 expression in histologic grade G1/G2 cancers than in grade G3 cancers (P < .001). The median survival time of LMO2-positive patients was significantly longer than that of LMO2-negative patients (P < .001), and multivariate analyses revealed that high LMO2 expression was an independent predictor of longer survival (risk ratio, 0.432, P < .001). Even among patients with a positive operative margin, LMO2-positive patients had a significant survival benefit compared with LMO2-negative patients. We further performed a large cohort study (n = 113) to examine the LMO2 messenger RNA levels in formalin-fixed paraffin-embedded samples and found similar results. Conclusions LMO2 is a promising marker for predicting a better prognosis in pancreatic cancer. PMID:19568416

Nakata, Kohei; Ohuchida, Kenoki; Nagai, Eishi; Hayashi, Akifumi; Miyasaka, Yoshihiro; Kayashima, Tadashi; Yu, Jun; Aishima, Shinichi; Oda, Yoshinao; Mizumoto, Kazuhiro; Tanaka, Masao; Tsuneyoshi, Masazumi

2009-01-01

358

Nasopharyngeal carcinoma  

Microsoft Academic Search

Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. The annual incidence of NPC in the UK is 0.3 per million at age 0–14 years, and 1 to 2 per million at age 15–19 years. Incidence is higher in the Chinese and Tunisian populations. Although rare, NPC accounts for about

Bernadette Brennan

2006-01-01

359

Medullary carcinoma of thyroid  

MedlinePLUS

Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC ... Pa: Elsevier Churchill Livingstone; 2013:chap 71. National Cancer Institute: PDQ Thyroid Cancer Treatment. Bethesda, Md: National Cancer Institute. Date ...

360

Hepatocellular carcinoma.  

PubMed

Hepatocellular carcinoma is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. Patients with cirrhosis are at highest risk of developing this malignant disease, and ultrasonography every 6 months is recommended. Surveillance with ultrasonography allows diagnosis at early stages when the tumour might be curable by resection, liver transplantation, or ablation, and 5-year survival higher than 50% can be achieved. Patients with small solitary tumours and very well preserved liver function are the best candidates for surgical resection. Liver transplantation is most beneficial for individuals who are not good candidates for resection, especially those within Milano criteria (solitary tumour ?5 cm and up to three nodules ?3 cm). Donor shortage greatly limits its applicability. Percutaneous ablation is the most frequently used treatment but its effectiveness is limited by tumour size and localisation. In asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread not amenable to curative treatments, chemoembolisation can provide survival benefit. Findings of randomised trials of sorafenib have shown survival benefits for individuals with advanced hepatocellular carcinoma, suggesting that molecular-targeted therapies could be effective in this chemoresistant cancer. Research is active in the area of pathogenesis and treatment of hepatocellular carcinoma. PMID:22353262

Forner, Alejandro; Llovet, Josep M; Bruix, Jordi

2012-03-31

361

Endoscopic sonography and sonographically guided fine-needle aspiration biopsy in the diagnosis of unusual pancreatic metastases from synovial sarcoma.  

PubMed

Pancreatic metastases are commonly solitary solid lesions frequently derived from primary renal cell carcinoma, lung cancer, or melanoma. Very few case reports have described cystic-appearing metastases in the pancreas and even fewer have reported a combination of cystic and solid metastatic lesions. Synovial sarcoma is a rare and aggressive soft tissue neoplasm, frequently metastasizing to the lungs and bones. We present a case of primary synovial sarcoma with multiple solid and cystic-appearing pancreatic metastases diagnosed by endoscopic ultrasound and sonographically guided fine-needle aspiration. PMID:24037719

Krishna, Somashekar G; Rao, Bhavana B; Lee, Jeffrey H

2014-01-01

362

Pancreatic Cancer: Targeted Treatments Hold Promise  

MedlinePLUS

... Tobacco Products Vaccines, Blood & Biologics Articulos en Espanol Pancreatic Cancer: Targeted Treatments Hold Promise Search the Consumer Updates ... Scientists are working to develop breakthrough therapies for pancreatic cancer, one of the deadliest cancers affecting both men ...

363

Cancer Stem Cells Found in Pancreatic Tumors  

Cancer.gov

Researchers have detected cancer stem cells in tumors from patients with pancreatic cancer. Experiments in mice suggest that these cancer stem cells may help explain the aggressive growth and spread of pancreatic tumors seen in patients.

364

Animal models of exocrine pancreatic cancer  

Microsoft Academic Search

Clinically and biologically relevant animal models are manda-tory to further evaluate both the pathophysiology and novel strategies\\u000a for diagnosis and treatment of exocrine pancreatic cancer. This review briefly summarizes the features of human pancreatic\\u000a cancer in order to define requirements for animal models of the disease. The described model systems in rodents include pancreatic\\u000a cancer induced by chemicals, pancreatic cancer

Hubert G. Hotz; O. Joe Hines; Thomas Foitzik; Howard A. Reber

2000-01-01

365

The action of atropine on pancreatic secretion  

PubMed Central

The action of atropine, in preventing pancreatic secretion in response to a parasympathomimetic drug, is analysed. Atropine does not appear to affect the uptake of glycine by the pancreatic cell, or the incorporation of radioactive amino acids into the total pancreatic tissue proteins, or into the proteins of the zymogen granules. The rate of amylase resynthesis in stimulated glands is not affected by atropine. It is suggested that atropine blocks pancreatic secretion in rats by blocking the extrusion of zymogen granules. PMID:13523138

Junqueira, L. C. U.; Rothschild, Hanna A.; Vugman, I.

1958-01-01

366

Review Article: Clinical Nutrition in Pancreatitis  

Microsoft Academic Search

In patients with acute pancreatitis or an acuteflare of chronic pancreatitis, a discrepancy existsbetween increased protein\\/calorie requirements inducedby a hypermetabolic stress state and reducedingestion\\/assimilation of exogenous nutrients, which promotesprogressive nutritional deterioration. Patients withsevere pancreatitis (defined by =3 Ranson criteria,an APACHE II score of =10, development of major organfailure, and\\/or presence of pancreatic necrosis) aremore likely to require aggressive nutritional supportthan

Stephen A. Mcclave; Harvy Snider; Nancy Owens; Leslie K. Sexton

1997-01-01

367

Association of Pancreatic Fatty Infiltration With Pancreatic Ductal Adenocarcinoma  

PubMed Central

OBJECTIVES: Fatty infiltration (FI) in the pancreas is positively correlated with high body mass index (BMI) or obesity, and the prevalence of diabetes mellitus (DM), which are well-known risk factors of pancreatic cancer. However, the association of FI in the pancreas with pancreatic cancer is unclear. Recently, we have shown that Syrian golden hamsters feature FI of the pancreas, the severity of which increases along with the progression of carcinogenesis induced by a chemical carcinogen. To translate the results to a clinical setting, we investigated whether FI in the pancreas is associated with pancreatic cancer in a series of patients who had undergone pancreatoduodenectomy. METHODS: In the series, we identified 102 cases with pancreatic ductal adenocarcinoma (PDAC) and 85 controls with cancers except for PDAC. The degree of FI was evaluated histopathologically from the area occupied by adipocytes in pancreas sections, and was compared between the cases and controls. RESULTS: The degree of FI in the pancreas was significantly higher in cases than in controls (median 26 vs. 15%, P<0.001) and positively associated with PDAC, even after adjustment for BMI, prevalence of DM and other confounding factors (odds ratio (OR), 6.1; P<0.001). BMI was identified as the most significantly associated factor with FI in the pancreas. CONCLUSIONS: There is a positive correlation between FI in the pancreas and pancreatic cancer. PMID:24622469

Hori, Mika; Takahashi, Mami; Hiraoka, Nobuyoshi; Yamaji, Taiki; Mutoh, Michihiro; Ishigamori, Rikako; Furuta, Koh; Okusaka, Takuji; Shimada, Kazuaki; Kosuge, Tomoo; Kanai, Yae; Nakagama, Hitoshi

2014-01-01

368

Immunoregulation in pancreatic cancer patients.  

PubMed

Metastatic pancreatic cancer is one of the most aggressive cancer known in man yet specific antitumor immunity has been demonstrated in lymph nodes draining the sites of pancreatic tumors. Despite this immunity, pancreatic cancer patients suffer a quick demise. To further define tumor immunity in patients with metastatic pancreatic cancer, we sought to characterize helper T cell subsets, serum cytokines, cellular cytotoxicity that is both T-cell and non-T cell mediated, as well as known tumor-derived immunosuppressive products that may be present in their peripheral blood. Significantly heightened levels of interleukin 2 (IL-2), a Th1 cytokine, were found in patients before treatment with chemotherapy while serum IL-10, a Th2 cytokine, were at significantly lower levels than observed in normal donors tested between their fifth and seventh decades of life. IL-10 levels increased progressively with age as a serum-bound protein in normal, healthy donors tested between the ages of 24 through 61. An age associated progression of increased IL-10 levels was not observed in pancreatic cancer patients. Few patients had detectable serum levels of soluble fas ligand but approximately half had elevated levels of a tumor marker, detected with the CA-15.3 assay, known as soluble MUCIN 1 (MUC1). Cell mediated cytotoxicity including T-cell mediated killing of pancreatic tumor cell lines was detected in many patients. These data suggest that pancreatic cancer patients have activated type 1 helper T cells that can support development of cell-mediated immunity, and that their sera contain lowered levels of the "anti-inflammatory" type 2 cytokine, IL-10. PMID:10478644

Plate, J M; Shott, S; Harris, J E

1999-08-01

369

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

PubMed Central

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 lineage and contribute to cell polarity disorders. Surficial retention on tumor cells renders CSPG4 an attractive therapeutic target. Systemic ‘drop and restoration’ alterations accompanying IPMN and PDAC progression indicate that the interference of pancreatic diseases with local and remote shedding/release of sCSPG4 into circulation deserves broad diagnostic exploration. PMID:24932730

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

370

Identification of a Novel Kindred with Familial Pancreatitis and Pancreatic Cancer  

PubMed Central

Background/Aims Hereditary pancreatic cancer comprises about 10% of pancreatic cancer cases. Multiple causative mutations have been identified. Here we describe a pancreatitis/pancreatic cancer (P/PC) family, which demonstrates pancreatitis and pancreatic cancer resulting from an uncharacterized mutation. Methods Family members completed evaluations to determine signs of mutation status. Select patients were screened for mutations associated with hereditary pancreatic diseases. Results In generation II, 12 siblings exhibit 6 cases of pancreatitis, 3 pancreatic cancer, and 2 obligate carrier status. The average age at pancreatitis diagnosis of enrolled members is 32.5 years; average age at pancreatic cancer diagnosis is 59 years. There is no association with known cancer syndromes. Those affected generally present with mild epigastric pain, and CT scans demonstrate characteristic fatty infiltration of the pancreatic body and tail with sparing of the head and neck. Full sequence analysis of genes associated with hereditary pancreatic disease failed to demonstrate known mutations or polymorphisms. Conclusion Based upon pedigree evaluation and preliminary DNA analysis, we believe that the family members with P/PC carry a novel genetic mutation resulting in hereditary pancreatitis. This mutation is autosomal dominant, expressed with high penetrance, and is part of a unique hereditary syndrome that significantly increases pancreatic cancer risk. PMID:19407482

LaFemina, Jennifer; Roberts, Penelope A.; Hung, Yin P.; Gusella, James F.; Sahani, Dushyant; Fernández-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.

2009-01-01

371

The genetic predisposition to fibrocalculous pancreatic diabetes  

Microsoft Academic Search

Summary  Fibrocalculous pancreatic diabetes (previously known as tropical pancreatic diabetes) is a rare cause of diabetes confined to countries within the tropical belt. The aetiology of fibrocalculous pancreatic diabetes is thought to be environmental although the agent(s) is unknown. We have investigated a possible genetic basis of this disease by looking for restriction fragment length polymorphisms of genes implicated in the

P. K. Kambo; G. A. Hitman; V. Mohan; A. Ramachandran; C. Snehalatha; S. Suresh; K. Metcalfe; B. K. Ryait; M. Viswanathan

1989-01-01

372

Proinflammatory cytokines: an insight into pancreatic oncogenesis.  

PubMed

Pancreatic cancer is a highly lethal disease, being one of the five leading death causes among oncologic patients. It is usually diagnosed late due to the paucity of clinical signs, and the current therapy means have limited success. One of the documented risk factors for developing pancreatic adenocarcinoma is chronic pancreatitis. It is postulated that a chronic inflammatory disease has a potential of evolving toward neoplasia, a fact that could account for a percentage of the pancreatic cancers. Starting from this assumption, we intended to analyze the serum reflection of some molecules with proinflammatory roles, and compare them in healthy individuals, in patients with chronic pancreatitis and with pancreatic adenocarcinoma. Additionally, we performed a biochemical and hematological assessment of the study groups, and compared the results with the immunological parameters analyzed in the same subjects. We found significantly higher levels of Tumor Necrosis Factor-alpha and Interleukin 6 in chronic pancreatitis and pancreatic adenocarcinoma sera (with higher levels in the pancreatitis group than in the cancer group), compared to healthy controls. Additionally, we found significantly higher levels of interleukin 8 and Macrophage Inflammatory Protein-3 alpha in pancreatic cancer, compared to chronic pancreatitis and controls. We also identified numerous correlations between the abovementioned cytokines/chemokines and biochemical parameters, not very much studied before. Our results plead for a pathogenic role of chronic inflammation in pancreatic carcinogenesis, thus offering a potential tool for earliy diagnose or targets for therapy. PMID:21462832

Miron, Nicolae; Miron, Mirela-Mihaela; Milea, Viorica Ghizela Iolana; Cristea, Victor

2010-01-01

373

Identification of the Gastrointestinal and Pancreatic Cancer-associated Antigen Detected by Monoclonal Antibody 19-9 in the Sera of Patients as a Mucin1  

Microsoft Academic Search

Monoclonal antibody 19-9, produced by a hybridoma prepared from spleen cells of a mouse immunized with a human colon carcinoma cell line, detects an antigen in the serum from most patients with gastrointestinal and pancreatic cancer (M. Herlyn, H. F. Sears, Z. Steplewski, and H. Koprowski, J. Clin. Immunol., 2: 135-1 40, 1982). The epitope of this antibody is a

John L. Magnani; Zenon Steplewski; Hilary Koprowski; Victor Ginsburg

1983-01-01

374

PCMdb: Pancreatic Cancer Methylation Database  

NASA Astrophysics Data System (ADS)

Pancreatic cancer is the fifth most aggressive malignancy and urgently requires new biomarkers to facilitate early detection. For providing impetus to the biomarker discovery, we have developed Pancreatic Cancer Methylation Database (PCMDB, http://crdd.osdd.net/raghava/pcmdb/), a comprehensive resource dedicated to methylation of genes in pancreatic cancer. Data was collected and compiled manually from published literature. PCMdb has 65907 entries for methylation status of 4342 unique genes. In PCMdb, data was compiled for both cancer cell lines (53565 entries for 88 cell lines) and cancer tissues (12342 entries for 3078 tissue samples). Among these entries, 47.22% entries reported a high level of methylation for the corresponding genes while 10.87% entries reported low level of methylation. PCMdb covers five major subtypes of pancreatic cancer; however, most of the entries were compiled for adenocarcinomas (88.38%) and mucinous neoplasms (5.76%). A user-friendly interface has been developed for data browsing, searching and analysis. We anticipate that PCMdb will be helpful for pancreatic cancer biomarker discovery.

Nagpal, Gandharva; Sharma, Minakshi; Kumar, Shailesh; Chaudhary, Kumardeep; Gupta, Sudheer; Gautam, Ankur; Raghava, Gajendra P. S.

2014-02-01

375

Noninvasive Radiofrequency Field Destruction of Pancreatic Adenocarcinoma Xenografts Treated with Targeted Gold Nanoparticles  

PubMed Central

Purpose Pancreatic carcinoma is one of the deadliest cancers with few effective treatments. Gold nanoparticles (AuNPs) are potentially therapeutic because of the safety demonstrated thus far and their physio-chemical characteristics. We utilized the astounding heating rates of AuNPs in nonionizing radiofrequency (RF) radiation to investigate human pancreatic xenograft destruction in a murine model. Experimental Design Weekly, Panc-1 and Capan-1 human pancreatic carcinoma xenografts in immunocompromised mice were exposed to an RF field 36 hours after treatment (intraperitoneal) with cetuximab or PAM4 antibody conjugated AuNPs, respectively. Tumor sizes were measured weekly while necrosis and cleaved caspase-3 were investigated with H&E staining and immunofluorescence, respectively. In addition, AuNP internalization and cytotoxicity were investigated in vitro with confocal microscopy and flow cytometry, respectively. Results Panc-1 cells demonstrated increased apoptosis with decreased viability after treatment with cetuximab conjugated AuNPs and RF field exposure (p = 0.00005). Differences in xenograft volumes were observed within 2 weeks of initiating therapy. Cetuximab-conjugated and PAM4-conjugated AuNPs demonstrated RF field-induced destruction of Panc-1 and Capan-1 pancreatic carcinoma xenografts after six weeks of weekly treatment (p = 0.004 and p = 0.035, respectively). There was no evidence of injury to murine organs. Cleaved caspase-3 and necrosis were both increased in treated tumors. Conclusions This study demonstrates a potentially novel cancer therapy by non-invasively inducing intracellular hyperthermia with targeted AuNPs in an RF field. While the therapy is dependent on the specificity of the targeting antibody, normal tissues were without toxicity despite systemic therapy and whole body RF field exposure. PMID:21138869

Glazer, Evan S.; Zhu, Cihui; Massey, Katheryn L.; Thompson, C. Shea; Kaluarachchi, Warna D.; Hamir, Amir N.; Curley, Steven A.

2010-01-01

376

A diagnostic pitfall: pancreatic tuberculosis, not pancreatic cancer.  

PubMed

Abdominal tuberculosis (TB) is one of the most common forms of extra-pulmonary tuberculosis and is responsible for considerable morbidity and mortality globally. Tuberculosis can involve any part of the gastrointestinal tract from mouth to anus, the peritoneum, liver, spleen and the pancreatobiliary system. The occurrence of abdominal TB is independent of pulmonary disease in most patients, with a reported incidence of co-existing pulmonary disease varying from 6 to 38% worldwide. We report a case of pancreatic tuberculosis also involving the vertebrae, which was initially treated as a case of pancreatic cancer. PMID:23458046

Samuel, David Olorunfemi; Majid Mukhtar, Adeiza Abdul; Philip, Ibinaiye Oluleke

2013-03-01

377

Tumor-to-Tumor Metastasis: Report of Two Cases of Renal Cell Carcinoma Metastasizing to Microcystic Serous Cystadenoma of the Pancreas.  

PubMed

Metastatic cancer to the pancreas accounts for less than 2% of all pancreatic malignancies. In contrast to other metastatic tumors, renal cell carcinoma (RCC) has a propensity to metastasize as a solitary pancreatic lesion. While symptomatic patients may present with obstructive jaundice, abdominal pain, or gastrointestinal bleeding, the diagnosis of metastatic pancreatic involvement is often made in asymptomatic patients, during follow-up evaluation in the aftermath of an initial diagnosis of renal cell carcinoma. Microcystic serous cystadenoma of the pancreas is an uncommon pancreatic exocrine neoplasm that morphologically resembles conventional (clear cell) RCC, in so far as both tumors are characterized by neoplastic cells with clear cytoplasm, relatively uniform nuclei and scant associated tumor stroma. Herein, we report 2 immunohistochemically confirmed cases of unsuspected metastatic RCC to the pancreas, with the metastatic tumor in each case confined to a preexisting microcystic serous cystadenoma of the pancreas. PMID:24873824

Shah, Lopa; Tiesi, Gregory; Bamboat, Zubin; McCain, Donald; Siegel, Andrew; Mannion, Ciaran

2015-02-01

378

[Pancreatic polypeptide (author's transl)].  

PubMed

Pancreatic Polypeptide (PP) was first described in birds by Kimmel et al. (1968). It was later isolated from the pancreas of several mammalian species by Chance and Jones (1974). It has been demonstrated in the islets of many animal species by immunocytochemical methods. PP levels are assayable in plasma and rise sharply after food intake. The pharmacological properties and physiological role of PP are still ill defined. It appears to have a spectrum of actions peculiar to each species. Recent research on this subject is reviewed in this article. High levels of circulating PP have been demonstrated in juvenile and maturity-onset diabetics, as well as in some patients with islet cell tumors. However no definite clinical syndrome due to hypersecretion of PP as been identified as yet. It remains a matter of speculation that a deficiency of PP might be responsible for some types of obesity. PP-cells are rare in the pancreas of healthy young individuals. Hyperplasia of PP-cells has been observed in a wide variety of pathological conditions, but is most prominent in the pancreas of chronic insulin dependent diabetics. Histologic evidence strongly suggests that PP-cell hyperplasia represents an atypical form of islet regeneration. It is always focal in distribution and is most remarkable in those lobules that have lost the capacity to reproduce islets of normal cytologic composition. PMID:215473

Gepts, W; de Mey, J

1978-12-01

379

Pancreatic surgery: evolution and current tailored approach  

PubMed Central

Surgical resection of pancreatic cancer offers the only chance for prolonged survival. Pancretic resections are technically challenging, and are accompanied by a substantial risk for postoperative complications, the most significant complication being a pancreatic fistula. Risk factors for development of pancreatic leakage are now well known, and several prophylactic pharmacological measures, as well as technical interventions have been suggested in prevention of pancreatic fistula. With better postoperative care and improved radiological interventions, most frequently complications can be managed conservatively. This review also attempts to address some of the controversies related to optimal management of the pancreatic remnant after pancreaticoduodenectomy. PMID:25392836

Mužina Miši?, Dubravka; Glav?i?, Goran

2014-01-01

380

Metabolism addiction in pancreatic cancer  

PubMed Central

Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains largely elusive. Renewed research interest in longstanding doctrines of tumor metabolism has led to the emergence of aberrant signaling pathways as critical factors modulating central metabolic networks that fuel pancreatic tumors. Such pathways, including those of Ras signaling, glutamine-regulatory enzymes, lipid metabolism and autophagy, are directly affected by genetic mutations and extreme tumor microenvironments that typify pancreatic tumor cells. Elucidation of these metabolic networks can be expected to yield more potent therapies against this deadly disease. PMID:24556680

Blum, R; Kloog, Y

2014-01-01

381

Fluid resuscitation in acute pancreatitis  

PubMed Central

Acute pancreatitis remains a clinical challenge, despite an exponential increase in our knowledge of its complex pathophysiological changes. Early fluid therapy is the cornerstone of treatment and is universally recommended; however, there is a lack of consensus regarding the type, rate, amount and end points of fluid replacement. Further confusion is added with the newer studies reporting better results with controlled fluid therapy. This review focuses on the pathophysiology of fluid depletion in acute pancreatitis, as well as the rationale for fluid replacement, the type, optimal amount, rate of infusion and monitoring of such patients. The basic goal of fluid epletion should be to prevent or minimize the systemic response to inflammatory markers. For this review, various studies and reviews were critically evaluated, along with authors’ recommendations, for predicted severe or severe pancreatitis based on the available evidence. PMID:25561779

Aggarwal, Aakash; Manrai, Manish; Kochhar, Rakesh

2014-01-01

382

Novel therapeutic targets for pancreatic cancer.  

PubMed

Pancreatic cancer has become the fourth leading cause of cancer death in the last two decades. Only 3%-15% of patients diagnosed with pancreatic cancer had 5 year survival rate. Drug resistance, high metastasis, poor prognosis and tumour relapse contributed to the malignancies and difficulties in treating pancreatic cancer. The current standard chemotherapy for pancreatic cancer is gemcitabine, however its efficacy is far from satisfactory, one of the reasons is due to the complex tumour microenvironment which decreases effective drug delivery to target cancer cell. Studies of the molecular pathology of pancreatic cancer have revealed that activation of KRAS, overexpression of cyclooxygenase-2, inactivation of p16(INK4A) and loss of p53 activities occurred in pancreatic cancer. Co-administration of gemcitabine and targeting the molecular pathological events happened in pancreatic cancer has brought an enhanced therapeutic effectiveness of gemcitabine. Therefore, studies looking for novel targets in hindering pancreatic tumour growth are emerging rapidly. In order to give a better understanding of the current findings and to seek the direction in future pancreatic cancer research; in this review we will focus on targets suppressing tumour metastatsis and progression, KRAS activated downstream effectors, the relationship of Notch signaling and Nodal/Activin signaling with pancreatic cancer cells, the current findings of non-coding RNAs in inhibiting pancreatic cancer cell proliferation, brief discussion in transcription remodeling by epigenetic modifiers (e.g., HDAC, BMI1, EZH2) and the plausible therapeutic applications of cancer stem cell and hyaluronan in tumour environment. PMID:25152585

Tang, Shing-Chun; Chen, Yang-Chao

2014-08-21

383

Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions.  

PubMed

The clinical management of pancreatic disease is often hampered by a lack of tissue diagnosis. Endoscopic pancreatography offers the opportunity to investigate exfoliated cells. However, the significance of mere cytological investigation is compromised by an insufficient sensitivity. The evaluation of the molecular background of carcinogenesis hopefully is capable of providing more sensitive diagnostic markers. The p16INK4a-/retinoblastoma tumour-suppressive pathway has been shown to be involved in the development of near to all pancreatic neoplasms. p14ARF is another tumour suppressor located in the immediate neighbourhood of p16INK4a. Promoter methylation has been demonstrated to be a major inactivating mechanism of both genes. We sought to further evaluate the role of the gene locus INK4a methylation status in the endoscopic differentiation of chronic inflammatory and neoplastic pancreatic disease. Pancreatic fluid specimens of 61 patients with either pancreatic carcinoma (PCA: 39), chronic pancreatitis (CP: 16) or a normal pancreatogram (NAD: 6) were retrieved. In order to detect methylation of either the p14ARF or the p16INK4a promoter a methylation-specific PCR protocol was applied. While 19 out of 39 patients with PCA showed p16 promoter methylation (49%), none of the 16 patients with CP revealed p16 promoter methylation. p14ARF methylation was found in a lower percentage of PCA specimens and in none of the samples of patients with CP. These results suggest a specific significance of INK4a for the development of malignant pancreatic disease. Our data further indicate a potential role for INK4a methylation as a diagnostic marker in the endoscopic differentiation of benign and malignant pancreatic disease. PMID:12610506

Klump, B; Hsieh, C J; Nehls, O; Dette, S; Holzmann, K; Kiesslich, R; Jung, M; Sinn, U; Ortner, M; Porschen, R; Gregor, M

2003-01-27

384

Ultrasonography in diagnosing chronic pancreatitis: New aspects  

PubMed Central

The course and outcome is poor for most patients with pancreatic diseases. Advances in pancreatic imaging are important in the detection of pancreatic diseases at early stages. Ultrasonography as a diagnostic tool has made, virtually speaking a technical revolution in medical imaging in the new millennium. It has not only become the preferred method for first line imaging, but also, increasingly to clarify the interpretation of other imaging modalities to obtain efficient clinical decision. We review ultrasonography modalities, focusing on advanced pancreatic imaging and its potential to substantially improve diagnosis of pancreatic diseases at earlier stages. In the first section, we describe scanning techniques and examination protocols. Their consequences for image quality and the ability to obtain complete and detailed visualization of the pancreas are discussed. In the second section we outline ultrasonographic characteristics of pancreatic diseases with emphasis on chronic pancreatitis. Finally, new developments in ultrasonography of the pancreas such as contrast enhanced ultrasound and elastography are enlightened. PMID:24259955

Dimcevski, Georg; Erchinger, Friedemann G; Havre, Roald; Gilja, Odd Helge

2013-01-01

385

Nuclear position and shape deformation of chromosome 8 territories in pancreatic ductal adenocarcinoma.  

PubMed

Cell type specific radial positioning of chromosome territories (CTs) and their sub-domains in the interphase seem to have functional relevance in non-neoplastic human nuclei, while much less is known about nuclear architecture in carcinoma cells and its development during tumor progression. We analyzed the 3D-architecture of the chromosome 8 territory (CT8) in carcinoma and corresponding non-neoplastic ductal pancreatic epithelium. Fluorescence-in-situ-hybridization (FISH) with whole chromosome painting (WCP) probes on sections from formalin-fixed, paraffin wax-embedded tissues from six patients with ductal adenocarcinoma of the pancreas was used. Radial positions and shape parameters of CT8 were analyzed by 3D-microscopy. None of the parameters showed significant inter-individual changes. CT8 was localized in the nuclear periphery in carcinoma cells and normal ductal epithelial cells. Normalized volume and surface of CT8 did not differ significantly. In contrast, the normalized roundness was significantly lower in carcinoma cells, implying an elongation of neoplastic cell nuclei. Unexpectedly, radial positioning of CT8, a dominant parameter of nuclear architecture, did not change significantly when comparing neoplastic with non-neoplastic cells. A significant deformation of CT8, however, accompanies nuclear atypia of carcinoma cells. This decreased roundness of CTs may reflect the genomic and transcriptional alterations in carcinoma. PMID:21483101

Timme, Sylvia; Schmitt, Eberhard; Stein, Stefan; Schwarz-Finsterle, Jutta; Wagner, Jenny; Walch, Axel; Werner, Martin; Hausmann, Michael; Wiech, Thorsten

2011-01-01

386

Adjuvant therapy in pancreatic cancer  

PubMed Central

Pancreatic cancer remains one of the leading causes of cancer related death worldwide with an overall five-year survival of less than 5%. Potentially curative surgery, which alone can improve 5-year survival to 10%, is an option for only 10%-20% of patients at presentation owing to local invasion of the tumour or metastatic disease. Adjuvant chemotherapy has been shown to improve 5-year survival to 20%-25% but conflicting evidence remains with regards to chemoradiation. In this article we review the current evidence available from published randomised trials and discuss ongoing phase III trials in relation to adjuvant therapy in pancreatic cancer. PMID:25356036

Jones, Owain Peris; Melling, James Daniel; Ghaneh, Paula

2014-01-01

387

Operative management of acute pancreatitis.  

PubMed

Acute pancreatitis comprises a range of diseases. Clinical manifestations range from mild symptoms to a life-threatening or life-ending process. Operative management is focused on managing the acute complications, the long-term sequelae, or the prevention of recurrent pancreatitis. Using the least amount of intervention is the goal. However, the evolution of videoscopic and endoscopic techniques have greatly expanded the tools available. This article provides a review of the three major categories of operations: ameliorating the emergent problems associated with the inflammatory state, ameliorating chronic sequelae, and prevention of a subsequent episode. PMID:23632146

Martin, Ronald F; Hein, Amanda R

2013-06-01

388

Autoimmune pancreatitis associated with a pancreatic pseudocyst treated by distal pancreatectomy with splenectomy: case report.  

PubMed

Autoimmune pancreatitis is a unique type of chronic pancreatitis, which is rarely associated with pseudocyst. A 48-year-old lady was admitted to our department with a rapidly growing cystic mass in the pancreatic tail with an elevated concentration of serum carbohydrate antigen 19-9 (CA19-9). She had a history of autoimmune pancreatitis and received steroid treatment. Imaging studies demonstrated a cystic mass in the pancreatic tail. The mass kept growing despite restoration of steroid treatment. Eventually, the patient underwent distal pancreatectomy with splenectomy. Histopathological examination revealed the existence of pseudocyst, significant lymphocytic infiltration, and fibrotic change in the pancreatic tail. PMID:25429726

Xu, Xiao-Bo; Wu, Ying-Shen; Wang, Wei-Lin; Zheng, Shu-Sen

2014-01-01

389

Basaloid carcinoma of the pancreas-clinicopathological presentation and oncogenetic snapshot of a rare entity.  

PubMed

We report a case of basaloid pancreatic carcinoma with clinical, pathological, and genomic data. The 73-year-old male patient had jaundice, acholic stool, diarrhea, weight loss, and a large, painless gall bladder. His GGT was highly elevated. The pancreatic head contained a tumor, which was resected by partial pancreatoduodenectomy with pancreato-gastric anastomosis, cholecystectomy, and lymphadenectomy. On gross examination, a 3.8-cm white firm nodule was found, which microscopically was composed of basaloid cell nests with a less than usual desmoplastic stromal background and focally PANIN. Immunohistochemical profile displayed strong CK5/6, CK19, p63, EGFR, vimentin, and evident CK14 expression and absence of expression of CK7, chromogranin, synaptophysin, and BRCA1. A high Ki-67 index and p53 expression were noted. Sequencing of the most frequent 46 oncogenes with ionTorrent (AmpliSeq PCR) method identified PIK3CA, KRAS, and TP53 genes as drivers and variants of the FGFR3, PDGFRA, KIT, KDR, EGFR, RET, and ATM genes. The tumor we report displays histopathological appearances similar to the previously described case and a genomic landscape fitting to the general population of pancreatic carcinomas. We hypothesize that this tumor may belong to the group of DNA damage repair-deficient pancreatic carcinoma subgroup. PMID:25432630

Szasz, A Marcell; Szirtes, Ildiko; Tihanyi, Balazs; Barkaszi, Bernadett; Baranyai, Zsolt; Tihanyi, Tibor; Harsanyi, Laszlo; Timar, Jozsef; Kulka, Janina

2014-11-29

390

Proteomic analysis of pancreatic endocrine tumor cell lines treated with the histone deacetylase inhibitor trichostatin A.  

PubMed

Effects of the histone-deacetylases inhibitor trichostatin A (TSA) on the growth of three different human pancreatic endocrine carcinoma cell lines (CM, BON, and QGP-1) have been assessed via dosage-dependent growth inhibition curves. TSA determined strong inhibition of cell growth with similar IC(50) values for the different cell lines: 80.5 nM (CM), 61.6 nM (BON), and 86 nM (QGP-1), by arresting the cell cycle in G2/M phase and inducing apoptosis. 2DE and nano-RP-HPLC-ESI-MS/MS analysis revealed 34, 33, and 38 unique proteins differentially expressed after TSA treatment in the CM, BON, and QGP-1 cell lines, respectively. The most important groups of modulated proteins belong to cell proliferation, cell cycle, and apoptosis classes (such as peroxiredoxins 1 and 2, the diablo protein, and HSP27). Other proteins pertain to processes such as regulation of gene expression (nucleophosmin, oncoprotein dek), signal transduction (calcium-calmodulin), chromatin, and cytoskeleton organization (calgizzarin, dynein, and lamin), RNA splicing (nucleolin, HNRPC), and protein folding (HSP70). The present data are in agreement with previous proteomic analyses performed on pancreatic ductal carcinoma cell lines (Cecconi, D. et al.., Electrophoresis 2003; Cecconi, D. et al., J. Proteome Res. 2005) and place histone-deacetylases inhibitors among the potentially most powerful drugs for the treatment of pancreatic tumors. PMID:17443844

Cecconi, Daniela; Donadelli, Massimo; Rinalducci, Sara; Zolla, Lello; Scupoli, Maria Teresa; Scarpa, Aldo; Palmieri, Marta; Righetti, Pier Giorgio

2007-05-01

391

Serum Protein Signatures Differentiating Autoimmune Pancreatitis versus Pancreatic Cancer  

PubMed Central

Autoimmune pancreatitis (AIP) is defined by characteristic lymphoplasmacytic infiltrate, ductal strictures and a pancreatic enlargement or mass that can mimic pancreatic cancer (PaCa). The distinction between this benign disease and pancreatic cancer can be challenging. However, an accurate diagnosis may pre-empt the misdiagnosis of cancer, allowing the appropriate medical treatment of AIP and, consequently, decreasing the number of unnecessary pancreatic resections. Mass spectrometry (MS) and two-dimensional differential gel electrophoresis (2D-DIGE) have been applied to analyse serum protein alterations associated with AIP and PaCa, and to identify protein signatures indicative of the diseases. Patients' sera were immunodepleted from the 20 most prominent serum proteins prior to further 2D-DIGE and image analysis. The identity of the most-discriminatory proteins detected, was performed by MS and ELISAs were applied to confirm their expression. Serum profiling data analysis with 2D-DIGE revealed 39 protein peaks able to discriminate between AIP and PaCa. Proteins were purified and further analysed by MALDI-TOF-MS. Peptide mass fingerprinting led to identification of eleven proteins. Among them apolipoprotein A-I, apolipoprotein A-II, transthyretin, and tetranectin were identified and found as 3.0-, 3.5-, 2-, and 1.6-fold decreased in PaCa sera, respectively, whereas haptoglobin and apolipoprotein E were found to be 3.8- and 1.6-fold elevated in PaCa sera. With the exception of haptoglobin the ELISA results of the identified proteins confirmed the 2D-DIGE image analysis characteristics. Integration of the identified serum proteins as AIP markers may have considerable potential to provide additional information for the diagnosis of AIP to choose the appropriate treatment. PMID:24349355

Fritz, Stefan; Hinz, Ulf; Schnölzer, Martina; Kempf, Tore; Warnken, Uwe; Michel, Angelika; Pawlita, Michael; Werner, Jens

2013-01-01

392

Uterine Serous Carcinoma: Increased Familial Risk for Lynch-Associated Malignancies  

PubMed Central

Purpose Serous uterine cancer is not a feature of any known hereditary cancer syndrome. This study evaluated familial risk of cancers for serous uterine carcinoma patients, focusing on Lynch syndrome malignancies. Experimental design Fifty serous or mixed serous endometrial carcinoma cases were prospectively enrolled. Pedigrees were developed for 29 probands and tumors were assessed for DNA mismatch repair abnormalities. Standardized incidence ratios for cancers in relatives were estimated. A second stage analysis was undertaken using data from GOG-210. Incidence data for cancers reported in relatives of 348 serous and mixed epithelial and 624 endometrioid carcinoma patients were compared. Results Nineteen of 29 (65.5%) patients in the single institution series reported a Lynch-related cancer in relatives. Endometrial and ovarian cancers were significantly over-represented and a high number of probands (6/29, 20.7%) reported pancreatic cancers. None of the probands’ tumors had DNA mismatch repair abnormalities. There was no difference in endometrial or ovarian cancer incidence in relatives of serous and endometrioid cancer probands in the case-control study. Pancreatic cancers were, however, significantly more common in relatives of serous cancer patients (OR 2.39, 95% CI 1.06–5.38). Conclusions We identified an excess of endometrial, ovarian, and pancreatic cancers in relatives of serous cancer patients in a single institution study. Follow-up studies suggest only pancreatic cancers are over-represented in relatives. DNA mismatch repair defects in familial clustering of pancreatic and other Lynch-associated malignancies are unlikely. The excess of pancreatic cancers in relatives may reflect an as yet unidentified hereditary syndrome that includes uterine serous cancers. PMID:22246618

Dewdney, Summer B; Kizer, Nora T; Andaya, Abegail A; Babb, Sheri A; Luo, Jingqin; Mutch, David G; Schmidt, Amy P.; Brinton, Louise A; Broaddus, Russell R; Ramirez, Nilsa C; Huettner, Phyllis C; McMeekin, D Scott; Darcy, Kathleen; Ali, Shamshad; Judson, Patricia L.; Mannel, Robert S.; Lele, Shashikant B.; O’Malley, David M; Goodfellow, Paul J

2012-01-01

393

Acute Suppuration of the Pancreatic Duct in a Patient with Tropical Pancreatitis  

PubMed Central

Background/Aim Pancreatic sepsis secondary to infected necrosis, pseudocyst, or pancreatic abscess is a well-known clinical entity. Acute suppuration of the pancreatic duct (ASPD) in the setting of chronic calcific pancreatitis and pancreatic ductal obstruction with septicemia is a rare complication that is seldom reported. It is our aim to report a case of ASPD with Klebsiella ornithinolytica, in the absence of pancreatic abscess or infected necrosis. Case Report A 46-year-old Asian-Indian man with chronic tropical pancreatitis who was admitted with recurrent epigastric pain that rapidly evolved into septic shock. A CT scan of abdomen revealed a dilated pancreatic duct with a large calculus. Broad-spectrum antibiotics, vasopressors and activated recombinant protein C were initiated. Emergency ERCP showed the papilla of Vater spontaneously expelling pus. Probing and stenting was instantly performed until pus drainage ceased. Repeat CT scan confirmed the absence of pancreatic necrosis or fluid collection, and decreasing ductal dilatation. Dramatic clinical improvement was observed within 36 hours after intervention. Blood cultures grew Klebsiella ornithinolytica. The patient completed his antibiotic course and was discharged. Conclusion ASPD without pancreatic abscess or infected necrosis is an exceptional clinical entity that should be included in the differential diagnosis of pancreatic sepsis. A chronically diseased pancreas and diabetes may have predisposed to the uncommon pathogen. The presence of intraductal pancreatic stones obstructing outflow played a major role in promoting bacterial growth, suppuration and septicemia. Immediate drainage of the pancreatic duct with endoscopic intervention is critical and mandatory. PMID:21490834

Deeb, Liliane S.; Bajaj, Jasmeet; Bhargava, Sandeep; Alcid, David; Pitchumoni, C.S.

2008-01-01

394

Antidiabetic Drug Metformin Prevents Progression of Pancreatic Cancer by Targeting in Part Cancer Stem Cells and mTOR Signaling.  

PubMed

Epidemiologic studies have shown that diabetes mellitus is associated positively with increased risk of pancreatic ductal adenocarcinoma (PDAC), and recent meta-analysis studies showed that metformin, reduces the risk of pancreatic cancer (PC). We tested the effects of metformin on pancreatic intraepithelial neoplasia (PanIN) and their progression to PDAC in p48Cre/+.LSL-KrasG12D/+ transgenic mice. Mice fed control diet showed 80% and 62% incidence of PDAC in males and females, respectively. Male mice showed 20% and 26%, and female mice showed 7% and 0% PDAC incidence with 1000- and 2000-ppm metformin treatments, respectively. Both doses of metformin decreased pancreatic tumor weights by 34% to 49% (P < 0.03-0.001). The drug treatment caused suppression of PanIN 3 (carcinoma in situ) lesions by 28% to 39% (P < .002) and significant inhibition of carcinoma spread in the pancreas. The pancreatic tissue and/or serum of mice fed metformin showed a significant inhibition of mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), phosphorylated extracellular signal-regulated kinases (pErk), and insulin-like growth factor 1 (IGF-1) with an increase in phosphorylated 5' adenosine monophosphate kinase (pAMPK), tuberous sclerosis complex 1 (TSC1, TSC2), C-protein and an autophagy related protein 2 (ATG2). The cancer stem cell (CSC) markers were significantly decreased (P < 0.04-0.0002) in the pancreatic tissue. These results suggest that biologic effects of metformin are mediated through decreased CSC markers cluster of differentiation 44 (CD44 and CD133), aldehyde dehydrogenase isoform 1 (ALDH1), and epithelial cell adhesion molecule (EPCAM) and modulation of the mTOR signaling pathway. Our preclinical data indicate that metformin has significant potential for use in clinical trials for PC chemoprevention. PMID:24466367

Mohammed, Altaf; Janakiram, Naveena B; Brewer, Misty; Ritchie, Rebekah L; Marya, Anuj; Lightfoot, Stan; Steele, Vernon E; Rao, Chinthalapally V

2013-12-01

395

Hepatocellular carcinoma.  

PubMed

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with many factors implicated in its development, with chronic infection and cirrhosis by hepatitis B virus (HBV) being the most prevalent. Cirrhosis due to metabolic syndrome, alcohol consumption, viral infection with hepatitis C virus (HCV) is also involved in its development. Treatment of HCC remains unsatisfactory. Therapeutic management for HCC includes liver transplantation, liver resection, ablation, chemoembolization, which depend on the tumor stage, liver function, and patient performance status. The involvement of different signaling pathways in the initiation and modulation of HCC development based on clinical and research data provided a strong rationale for the development of anti-cancer agents targeting key components of the pathways. The complexity of the tumor prevents the major goal of this therapeutic approach, since sorafenib, a multi-kinase inhibitor, is the only successful drug so far that belongs to the target directed therapy in advanced stage HCC. PMID:25182146

Daoudaki, Maria; Fouzas, Ioannis

2014-11-01

396

Study of Positron Emission Tomography and Computed Tomography in Guiding Radiation Therapy in Patients With Stage III Non-small Cell Lung Cancer  

ClinicalTrials.gov

Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

2015-02-12

397

Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery  

ClinicalTrials.gov

Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

2014-12-24

398

Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery  

ClinicalTrials.gov

Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

2015-01-30

399

Ontogeny of pancreatic exocrine function.  

PubMed Central

Exocrine pancreatic proteolytic activity, determined by serial measurement of faecal chymotrypsin concentration, was investigated in 21 preterm infants (23-32 weeks' gestation) during the first 28 days of life. The overall chymotrypsin concentration range was similar to that already described in term infants showing that pancreatic chymotrypsin secretion is equally well developed at birth in the preterm infant. A chymotrypsin concentration peak, seen in term infants at 4 days, did not occur in this study until day 8, suggesting a slower initiation of pancreatic exocrine function in the preterm infant. Median faecal chymotrypsin concentrations, calculated for each baby using data from stools passed between day 2 and day 12 of life, were significantly lower in infants who were small for gestational age when compared with those who were an appropriate size for gestational age. The lower chymotrypsin concentration in infants who were small for gestational age suggests a deleterious effect of intrauterine growth retardation on pancreatic exocrine function which may be a factor in limiting postnatal catch up growth. PMID:2317062

Kolacek, S; Puntis, J W; Lloyd, D R; Brown, G A; Booth, I W

1990-01-01

400

Mouse models of pancreatic cancer  

Microsoft Academic Search

Pancreatic cancer remains one of the most lethal of all human malignancies. Until recently, preclinical studies have been hampered by the absence of mouse models faithfully recapitulating critical elements of the human disease. However, recent months have witnessed a flurry of activity with respect to prospective mouse models. This progress now allows the evaluation of novel strategies for early detection,

Steven D. Leach

2004-01-01

401

Endoscopic Treatment of Pancreatic Calculi  

PubMed Central

Chronic pancreatitis is a progressive inflammatory disease that destroys pancreatic parenchyma and alters ductal stricture, leading to ductal destruction and abdominal pain. Pancreatic duct stones (PDSs) are a common complication of chronic pancreatitis that requires treatment to relieve abdominal pain and improve pancreas function. Endoscopic therapy, extracorporeal shock wave lithotripsy (ESWL), and surgery are treatment modalities of PDSs, although lingering controversies have hindered a consensus recommendation. Many comparative studies have reported that surgery is the superior treatment because of reduced duration and frequency of hospitalization, cost, pain relief, and reintervention, while endoscopic therapy is effective and less invasive but cannot be used in all patients. Surgery is the treatment of choice when endoscopic therapy has failed, malignancy is suspected, or duodenal stricture is present. However, in patients with the appropriate indications or at high-risk for surgery, endoscopic therapy in combination with ESWL can be considered a first-line treatment. We expect that the development of advanced endoscopic techniques and equipment will expand the role of endoscopic treatment in PDS removal. PMID:24944986

Kim, Yong Hoon; Jang, Sung Ill; Rhee, Kwangwon

2014-01-01

402

Endoscopic treatment of pancreatic calculi.  

PubMed

Chronic pancreatitis is a progressive inflammatory disease that destroys pancreatic parenchyma and alters ductal stricture, leading to ductal destruction and abdominal pain. Pancreatic duct stones (PDSs) are a common complication of chronic pancreatitis that requires treatment to relieve abdominal pain and improve pancreas function. Endoscopic therapy, extracorporeal shock wave lithotripsy (ESWL), and surgery are treatment modalities of PDSs, although lingering controversies have hindered a consensus recommendation. Many comparative studies have reported that surgery is the superior treatment because of reduced duration and frequency of hospitalization, cost, pain relief, and reintervention, while endoscopic therapy is effective and less invasive but cannot be used in all patients. Surgery is the treatment of choice when endoscopic therapy has failed, malignancy is suspected, or duodenal stricture is present. However, in patients with the appropriate indications or at high-risk for surgery, endoscopic therapy in combination with ESWL can be considered a first-line treatment. We expect that the development of advanced endoscopic techniques and equipment will expand the role of endoscopic treatment in PDS removal. PMID:24944986

Kim, Yong Hoon; Jang, Sung Ill; Rhee, Kwangwon; Lee, Dong Ki

2014-05-01

403

[Sepsis in acute severe pancreatitis].  

PubMed

Retrospective analysis of 99 consecutive cases of acute severe pancreatitis established presence of systemic inflammation in all patients. Magnitude of acute phase response was characterised by C-reactive protein and Interleukin-6 values. Progression to multiple organ failure raised considerably lethality. Failure developed more frequently in respiratory system, liver and kidneys. General mortality was 38,4%. PMID:16927913

Hotineanu, V F; Balica, I M; Bogdan, V I

2006-01-01

404

Molecular basis of hereditary pancreatitis.  

PubMed

Hereditary pancreatitis (HP) is an autosomal dominant disease. Two heterozygous missense mutations, R122H (R117H) and N29I (N21I), in the cationic trypsinogen gene have been clearly associated with HP. The 'self-destruct' model proposed for the R122H mutation is discussed in connection with the existing theory of pancreatitis, and the basic biochemistry and physiology of trypsinogen, with particular reference to R122 as the primary autolysis site of the cationic trypsinogen. Two different genetic mechanisms are identified which cause the R122H mutation, and gene conversion is the likely cause of the N29I mutation. A unifying model, which highlights an indirect impairment on the R122 autolysis site is hypothesised for the N29I mutation. Possible predisposition to pancreatitis by additional DNA variants in the gene, such as the A16V signal peptide cleavage site mutation and the K23R activation peptide cleavage site mutation is suspected, but not proven. Evidence of genetic heterogeneity of HP is reviewed and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations detected in HP families are re-evaluated. Finally, large scale association studies are expected to clarify the additional variants' role in pancreatitis and to identify new HP genes. PMID:10909845

Chen, J M; Ferec, C

2000-07-01

405

Redox Homeostasis in Pancreatic ? Cells  

PubMed Central

We reviewed mechanisms that determine reactive oxygen species (redox) homeostasis, redox information signaling and metabolic/regulatory function of autocrine insulin signaling in pancreatic ? cells, and consequences of oxidative stress and dysregulation of redox/information signaling for their dysfunction. We emphasize the role of mitochondrion in ? cell molecular physiology and pathology, including the antioxidant role of mitochondrial uncoupling protein UCP2. Since in pancreatic ? cells pyruvate cannot be easily diverted towards lactate dehydrogenase for lactate formation, the respiration and oxidative phosphorylation intensity are governed by the availability of glucose, leading to a certain ATP/ADP ratio, whereas in other cell types, cell demand dictates respiration/metabolism rates. Moreover, we examine the possibility that type 2 diabetes mellitus might be considered as an inevitable result of progressive self-accelerating oxidative stress and concomitantly dysregulated information signaling in peripheral tissues as well as in pancreatic ? cells. It is because the redox signaling is inherent to the insulin receptor signaling mechanism and its impairment leads to the oxidative and nitrosative stress. Also emerging concepts, admiting participation of redox signaling even in glucose sensing and insulin release in pancreatic ? cells, fit in this view. For example, NADPH has been firmly established to be a modulator of glucose-stimulated insulin release. PMID:23304259

Ježek, Petr; Dlasková, Andrea; Plecitá-Hlavatá, Lydie

2012-01-01

406

Genetic progression of pancreatic cancer.  

PubMed

The progression from normal cells to invasive pancreatic ductal adenocarcinoma (PDAC) requires the accumulation of multiple inherited or acquired mutations. Activating point mutations in the KRAS oncogene are prevalent in pancreatic cancer and result in the stimulation of several pathways including the RAF-mitogen-activated protein kinase pathway and the phosphoinositide 3-kinase pathway. Other genetic alterations, including telomere shortening and the inactivation of tumor suppressor genes such as CDKN2A, TP53, and SMAD4, which encode p16, p53, and SMAD4, respectively, also contribute to the progression of pancreatic cancer. These, and other genetic events, can present at different stages in the development of PDAC at histologically defined precursor lesions known as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms, or mucinous cystic neoplasms. Each precursor lesion represents alternate routes to PDAC formation and has a unique presentation and somewhat distinct genetic events controlling its development. Despite the advances in the understanding of the genetics of PDAC, the prognosis for this cancer remains poor, and several important aspects of its pathogenesis must be clarified to improve therapeutics, including the timing and method of metastases, as well as the relationship of the tumor cells with the desmoplastic stroma, which is a characteristic feature of the cancer. This review discusses the principal genetic alterations in PDAC and its precursor lesions, including their effects on promoting carcinogenesis. PMID:24445769

Cowan, Robert W; Maitra, Anirban

2014-01-01

407

Molecular Targeting in Pancreatic Cancer  

Microsoft Academic Search

The mortality and morbidity of tumors of the upper GI tract are formidable with incidence and mortality nearly the same. Therefore, better therapies are necessary, and these are generally molecularly targeted therapies. This chapter focuses on the treatment of pancreatic cancer with targeted therapy. Important cellular pathways are reviewed, including signal transduction, proteasome inhibition, cell cycle, anti-angiogenesis pathways, immunologic therapies,

Scott Wadler

2007-01-01

408

Occupational factors and pancreatic cancer  

Microsoft Academic Search

The relation between occupational factors and pancreatic cancer has been studied by two different approaches: a population based case-control study with two series of controls and a retrospective cohort study based on register data. With both approaches, some support was found for an association with occupational exposure to petroleum products. Associations were also indicated with exposure to paint thinner (case-control

S Norell; A Ahlbom; R Olin; R Erwald; G Jacobson; I Lindberg-Navier; K L Wiechel

1986-01-01

409

Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery  

ClinicalTrials.gov

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

2013-11-06

410

Acute pancreatitis in children and adolescents  

PubMed Central

In this Topic Highlight, the causes, diagnosis, and treatment of acute pancreatitis in children are discussed. Acute pancreatitis should be considered during the differential diagnosis of abdominal pain in children and requires prompt treatment because it may become life-threatening. The etiology, clinical manifestations, and course of acute pancreatitis in children are often different than in adults. Therefore, the specific features of acute pancreatitis in children must be considered. The etiology of acute pancreatitis in children is often drugs, infections, trauma, or anatomic abnormalities. Diagnosis is based on clinical symptoms (such as abdominal pain and vomiting), serum pancreatic enzyme levels, and imaging studies. Several scoring systems have been proposed for the assessment of severity, which is useful for selecting treatments and predicting prognosis. The basic pathogenesis of acute pancreatitis does not greatly differ between adults and children, and the treatments for adults and children are similar. In large part, our understanding of the pathology, optimal treatment, assessment of severity, and outcome of acute pancreatitis in children is taken from the adult literature. However, we often find that the common management of adult pancreatitis is difficult to apply to children. With advances in diagnostic techniques and treatment methods, severe acute pancreatitis in children is becoming better understood and more controllable. PMID:25400985

Suzuki, Mitsuyoshi; Sai, Jin Kan; Shimizu, Toshiaki

2014-01-01

411

Update on surgical treatment of pancreatic neuroendocrine neoplasms  

PubMed Central

Pancreatic neuroendocrine neoplasms (PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential (neurendocrine tumors PNETs) or overt (neuroendocrine carcinomas PNECs) malignant, but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimally-invasive approaches which should be tailored to the individual patient. Generally, surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs, indications for tumor resection are much wider than for pancreatic adenocarcinoma, in many cases due to the relatively benign tumor biology. Thus, patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands, even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However, poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly single-center series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable, ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review, we summarize recent advances in the surgical treatment of PNENs. PMID:25320524

D’Haese, Jan G; Tosolini, Chiara; Ceyhan, Güralp O; Kong, Bo; Esposito, Irene; Michalski, Christoph W; Kleeff, Jörg

2014-01-01

412

What's New in Pancreatic Cancer Research and Treatment?  

MedlinePLUS

... Additional resources for pancreatic cancer What’s new in pancreatic cancer research and treatment? Research into the causes, diagnosis, and treatment of pancreatic cancer is under way in many medical centers throughout ...

413

What Are the Key Statistics about Pancreatic Cancer?  

MedlinePLUS

... factors for pancreatic cancer? What are the key statistics about pancreatic cancer? The American Cancer Society’s most ... risk factors (listed in the next section ). For statistics related to survival, see the section “ Pancreatic cancer ...

414

KL-6 mucin expression in carcinoma of the ampulla of Vater: Association with cancer progression  

PubMed Central

AIM: To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater. METHODS: Ampullary carcinoma tissues were collected from 38 patients who underwent pancreatoduodenectomy or local resection. Tissues were subjected to immunohi-stochemical analysis using KL-6 antibody.