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Sample records for pancreatic adenosquamous carcinoma

  1. Adenosquamous carcinoma of the pancreas: preoperative diagnosis and molecular alterations.

    PubMed

    Murakami, Yoshiaki; Yokoyama, Takashi; Yokoyama, Yujiro; Kanehiro, Tetsuya; Uemura, Kenichiro; Sasaki, Masaru; Morifuji, Masahiko; Sueda, Taijiro

    2003-01-01

    Adenosquamous carcinoma of the pancreas is a rare tumor which has a less favorable prognosis than common ductal cell carcinoma of the pancreas, and a definite preoperative diagnosis of this tumor is quite difficult. We herein report two cases of this rare variant. The patients were a 41-year-old man (patient 1) and a 67-year-old woman (patient 2). Patient 1 had a hypoechoic mass measuring 3 cm in the uncus of the pancreas, while patient 2 had a huge mass, measuring 8 cm, in the tail of the pancreas. Patient 2 was successfully diagnosed preoperatively as having an adenosquamous carcinoma, by cytological examination of the pure pancreatic juice obtained by endoscopic retrograde pancreatic juice aspiration. A pylorus-preserving pancreatoduodenectomy was performed for patient 1, and a distal pancreatectomy with resection of the spleen and the left kidney was performed for patient 2. Subsequent pathological findings of these two tumors revealed adenosquamous carcinoma of the pancreas. K- ras point mutation, p53 overexpression, and telomerase activity in both tumor specimens were detected by the mutant allele specific amplification method, immunohistochemical staining, and telomeric repeat amplification protocol assay, respectively. The two patients died of recurrent disease 5 and 4 months, respectively, after surgery. Cytological examination of pure pancreatic juice is a useful modality for the preoperative diagnosis of this tumor, and frequent molecular alterations may be associated with the poor prognosis of adenosquamous carcinoma of the pancreas.

  2. [A Case of Adenosquamous Carcinoma of the Ascending Colon].

    PubMed

    Hijikawa, Takeshi; Yoshida, Ryo; Yamada, Masanori; Nakatani, Kazuyoshi; Tokuhara, Katsuji; Kitade, Hiroaki; Shikata, Nobuaki; Yoshioka, Kazuhiko; Kon, Masanori

    2015-10-01

    We report a case of adenosquamous carcinoma of the colon. A 70-year-old woman underwent a colonoscopic examination because of a positive fecal occult blood test. Colonoscopy demonstrated a type 2 tumor of the ascending colon, and a biopsy specimen showed poorly-moderately differentiated tubular adenocarcinoma. We performed a right hemicolectomy with D2 lymphadenectomy. The histopathology of the tumor demonstrated adenosquamous adenocarcinoma. Primary adenosquamous carcinoma of the colon is relatively rare and has a poor prognosis. Therefore, adenosquamous carcinoma of the colon may require strict follow-up.

  3. Pulmonary adenosquamous carcinoma in a dog.

    PubMed

    Sato, T; Ito, J; Shibuya, H; Asano, K; Watari, T

    2005-12-01

    A mass that developed in the lung of a 10-year-old mixed-breed dog was pathologically examined. Histopathological examination showed papillary and tubular growth of glandular epithelium-like cells in some areas and growth of squamous cells arranged in nests in other areas, showing coexistence of adenocarcinoma and squamous cell carcinoma in a lung tumour. Immunohistochemical staining with anti-keratin-cytokeratin antibody was strongly positive for cytoplasms in both components. Electron microscopically, the neoplastic cells of the adenocarcinoma component had features of glandular cells, with microvilli, numerous free ribosomes, large round secretory granules and intercellular desmosomes. Non-keratinized squamous cells had tonofilaments and intercellular desmosomes. These findings led to the diagnosis of primary adenosquamous carcinoma, which demonstrates phenotypic profiles characteristic of both epidermal keratinocytes and glandular epithelium.

  4. Clinical characteristics of adenosquamous esophageal carcinoma

    PubMed Central

    Yendamuri, Sai; Malhotra, Usha; Hennon, Mark; Miller, Austin; Groman, Adrienne; Halloon, Alaa

    2017-01-01

    Background Current published information of adenosquamous carcinoma (ASC) of the esophagus in the United States is limited to isolated case reports. We sought to study the clinical characteristics of this tumor using the Surveillance, Epidemiology and End Results (SEER) database. Methods Relevant data of all patients with esophageal cancer in the SEER database diagnosed from 1998–2010 was obtained. Demographic, grade, stage, treatment and survival characteristics of patients with ASC were summarized and compared to those patients with adenocarcinoma (ACA) and squamous cell carcinoma (SqCC). Univariate analyses across comparison groups were performed using Wilcoxon rank sum test for continuous covariates and the Pearson Chi-square test for categorical covariates. To evaluate the association of selected covariates to survival by histology, unadjusted and adjusted proportional hazards models were generated for the entire study population. To further control for the difference in covariates among the histology groups, propensity weighted Cox regression modeling was performed using the inverse propensity to treat weighting (IPTW) approach. Results Of 29,890 patients with the histological subgroups, only 284 patients had ASC (1%). Patients with ACA had a higher grade (72.9% with grade III/IV) and presented with advanced stage (48.2% distant disease) than their comparison group. Patients with ASC had worse overall survival compared to ACA but not SqCC in both univariate and multivariate analyses (OR =0.76; P<0.05 and OR =0.86; P<0.05 respectively). These results were further confirmed by the propensity weighted Cox regression analysis. Analysis of the ASC population alone demonstrated that decreasing stage, radiation therapy (OR =0.59; P<0.001) and surgery (OR =0.86; P<0.001) were associated with better overall survival, but grade was not. Conclusions ASC of the esophagus is a rare histological variant comprising 1% of esophageal ACA in the Unites States. This

  5. Adenosquamous carcinoma of vesicovaginal fistula: a rare entity.

    PubMed

    Tabali, Rudresh; Ramkumar, Aravind

    2014-01-01

    A 56-year-old lady presented with a vesicovaginal fistula (VVF) along with past history of abdominal hysterectomy. Biopsy of the fistulous tract showed squamous cell carcinoma (SCC). Patient underwent radical cystourethrectomy, total vaginectomy, and bilateral pelvic lymph node dissection along with ileal conduit. The final histopathology report of the resected specimen showed adenosquamous carcinoma in VVF. As this is a rare entity, we are reporting this case.

  6. [A case of adenosquamous carcinoma of the ascending colon].

    PubMed

    Toyoda, Tetsutaka; Nishimura, Yoji; Yatsuoka, Toshimasa; Yokoyama, Yasuyuki; Shimada, Ryu; Ishikawa, Hideki; Fukuda, Takashi; Amikura, Katsumi; Kawashima, Yoshiyuki; Sakamoto, Hirohiko; Tanaka, Yoichi; Nishimura, Yu

    2014-11-01

    A 6 8-year-old man was admitted to our hospital with lower abdominal pain. Lower gastrointestinal endoscopy showed type 2 advanced cancer in the ascending colon. Histopathological examination after endoscopical biopsy revealed both moderately differentiated adenocarcinoma and well-differentiated squamous carcinoma. Subsequently, right hemicolectomy was performed. The tumor was 55 × 40 mm in size and was diagnosed as an adenosquamous carcinoma A, type 2, pSS, pN0, sH0, sP0, sM0, fStageII. Adenosquamous carcinoma is extremely rare, represents about 0.1% of all colorectal cancer, and usually has a poor prognosis. Thirty-one months after surgery, the patient is still in good health and displays no signs of recurrence.

  7. Primary gastric adenosquamous carcinoma in an Indian male.

    PubMed

    Bansal, Rinkesh Kumar; Sharma, Praveen; Kaur, Ramneet; Arora, Anil

    2013-01-01

    Adenosquamous carcinoma (ASC) of the stomach is a very rare tumor comprising less than 0.5% of all stomach malignancies. Here, we report a case of a 37-year-old male, who presented with upper gastrointestinal bleeding in the form of hematemesis and malena. A subtotal gastrectomy was done in view of massive uncontrolled bleed. Histology showed evidence of ASC of the body and antrum with metastasis to the liver, perigastric lymph nodes and peritoneal and pleural cavity.

  8. Adenosquamous Carcinoma of Extrahepatic Bile Duct: A Case Report

    PubMed Central

    Lim, Sin Hyung; Kim, Anna; Cha, Sang Woo; Jung, Sung Hee; Go, Hoon; Lee, Woong Chul

    2007-01-01

    Most malignant tumors originating from the biliary tract are adenocarcinomas, and adenosqamous carcinoma of Klatskin's tumor is a very rare finding. An 83-yr-old man was admitted to our hospital because of jaundice. The abdominal computed tomography and magnetic resonance cholangiopancreatography revealed wall thickening and luminal stenosis of both the intrahepatic duct confluent portion and the common hepatic duct. These findings were compatible with Klatskin's tumor, Bismuth type III. Considering the patient's old age, palliative combined modality therapy was performed. After percutaneous transhepatic biliary drainage, biopsy was performed via percutaneous transhepatic cholangioscopy. The histopathologic findings showed adenosquamous carcinoma. External radiotherapy and intraluminal brachytherapy through the endobiliary Y-type stent were then done. Nine months after the radiotherapy, the laboratory findings and the abdominal computed tomography revealed biliary obstruction and progressive hepatic metastasis. The combined modality therapy of external radiotherapy, intraluminal brachytherapy and stenting assisted him to live a normal life until he finally experienced biliary obstruction. PMID:17939340

  9. Adenosquamous carcinoma of the oesophagus in a dog.

    PubMed

    Okanishi, H; Shibuya, H; Miyasaka, T; Asano, K; Sato, T; Watari, T

    2015-08-01

    A six-year-old mixed-breed male dog weighing 7.0 kg was presented with chronic vomiting and regurgitation. Endoscopic examination revealed prominent oesophageal dilation in the thoracic region, multiple small greyish-white nodules over the oesophageal lumen and cauliflower-like masses in the caudal oesophagus. Histopathological studies revealed a characteristic pattern of coexisting elements of infiltrating adenocarcinoma and squamous cell carcinoma. Immunohistochemical staining with anti-cytokeratin AE1 + AE3 was positive in both types of neoplastic cells. Neoplastic glandular cells stained positively for cytokeratin 8 while neoplastic squamous cells stained positively for cytokeratin 5/6. On the basis of these findings, the dog was diagnosed with oesophageal adenosquamous carcinoma. The case history and findings suggest that the malignancy might have developed from Barrett's oesophagus following irritation of the oesophageal mucosa due to chronic vomiting and regurgitation.

  10. Adenosquamous carcinoma of paranasal sinuses and Kartagener syndrome: an unusual combination.

    PubMed

    Naqvi, Syeda Uzma; Hussain, Syed Iqbal; Quadri, Shaheen

    2014-03-01

    A 34 years old non-smoker male patient reported with growth of right maxillary region which on histopathology confirmed adenosquamous carcinoma of nose and paranasal sinus. Patient also had total situs inversus including dextrocardia, bronchiectasis and sinusitis. His blood group was AB negative. This association of Kartagener syndrome with adenosquamous carcinoma of paranasal sinuses has never been reported. Carcinoma of paranasal sinuses accounts only 0.3% of all cancers. Adenosquamous carcinoma makes only 2% of the nose and paranasal sinuses tumours. Kartagener syndrome, AB negative blood group and adenosquamous carcinoma of paranasal sinuses all are extremely rare clinical conditions found in populations and the combination of all three in the same patient have never been reported to the best of authors' knowledge.

  11. Primary adenosquamous carcinoma of the liver: a case report

    PubMed Central

    Nam, Kyung Han; Kim, Ji Yeon

    2016-01-01

    Adenosquamous carcinoma of the liver is a rare variant of cholangiocarcinoma. It is known to be a highly aggressive tumor with a poor prognosis, but its pathogenesis remains unclear owing to limited data in the literature. We report a case of 56-year-old woman who presented with a 1-week history of epigastric pain. Magnetic resonance imaging revealed a 6.5-cm ill-defined mass with low signal intensity in the left lobe of the liver, which was suspicious of cholangiocarcinoma. The patient underwent left hemihepatectomy. Microscopically, the tumor consisted of malignant glandular and squamous components and staged as pT2aN1. Despite postoperative chemoradiation, the patient had recurrence 8 months after surgery. PMID:28081592

  12. Characterization of primary pulmonary adenosquamous carcinoma-associated pleural effusion.

    PubMed

    Stewart, Jennifer; Holloway, Andrew; Rasotto, Roberta; Bowlt, Kelly

    2016-03-01

    A 10-year-old, female spayed Shih Tzu was presented due to weight loss, increased respiratory effort and lethargy, determined to be secondary to a congenital para-esophageal diaphragmatic defect with partial herniation of the stomach and spleen. Four days following reduction surgery of the displaced abdominal organs thoracic effusion developed. Thoracic fluid evaluation revealed a cell-rich, protein-poor modified transudate with neutrophils, reactive mesothelial cells, and atypical epitheloid cells which occasionally appeared to be keratinizing, consistent with neoplastic exfoliation. Thoracic effusion recurred 2 days later, with similar characteristics as the initial sample. Computed tomography (CT) indicated consolidation and displacement of the right middle and accessory lung lobes. Exploratory thoracic surgery demonstrated a thickened, hyperemic right middle lung lobe, and thickened pericardial diaphragmatic ligament. Histologic evaluation of these tissues identified a primary pulmonary adenosquamous carcinoma with intravascular and pleural invasion. Based on these cytologic, histologic, and clinical findings, we conclude that primary pulmonary carcinomas may involve superficial thoracic structures and exfoliate into a thoracic effusion.

  13. Fatal submucosal invasive gastric adenosquamous carcinoma detected at surveillance after gastric endoscopic submucosal dissection

    PubMed Central

    Shirahige, Akinori; Suzuki, Haruhisa; Oda, Ichiro; Sekiguchi, Masau; Mori, Genki; Abe, Seiichiro; Nonaka, Satoru; Yoshinaga, Shigetaka; Sekine, Shigeki; Kushima, Ryoji; Saito, Yutaka; Fukagawa, Takeo; Katai, Hitoshi

    2015-01-01

    An 80-year-old man was under annual surveillance esophagogastroduodenoscopy after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Two years after the initial ESD, a 0-IIc type metachronous EGC lesion, 8 mm in size, without an ulcer scar, was found in the gastric antrum. The estimated tumor depth was up to the mucosa, and biopsy revealed well and poorly differentiated adenocarcinoma. ESD was performed for this lesion and en bloc resection with negative margins was achieved. Histopathological examination revealed an adenosquamous carcinoma 8 mm in size invading the deep submucosal layer (1600 μm), with lymphovascular invasion, consistent with the diagnosis of non-curative resection. Additional gastrectomy was recommended for this patient; however, two months after the ESD, preoperative computed tomography revealed multiple liver metastases, and the patient was considered as an unsuitable candidate for surgical resection. Systemic chemotherapy was therefore started; however, the patient died of gastric cancer 27 mo after the second ESD. Early gastric adenosquamous carcinoma localized to the mucosa and submucosa is extremely rare and its clinical behavior is not well known. The present report is very significant in that it underscores the distinct possibility of gastric adenosquamous carcinoma being very aggressive and fatal even when detected at an early cancer. PMID:25892891

  14. Tracking the Clonal Evolution of Adenosquamous Carcinoma, a Rare Variant of Intraductal Papillary Mucinous Neoplasm of the Pancreas.

    PubMed

    Matsuzaka, Suguru; Karasaki, Hidenori; Ono, Yusuke; Ogata, Munehiko; Oikawa, Kensuke; Tamakawa, Susumu; Chiba, Shin-Ichi; Muraki, Miho; Yokochi, Tomoki; Funakoshi, Hiroshi; Kono, Toru; Nagashima, Kazuo; Mizukami, Yusuke

    2016-07-01

    Adenosquamous carcinoma (ASC) is an uncommon variant of pancreatic neoplasm. We sought to trace the mode of tumor progression using specimens of ASC associated with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. A resected specimen of the primary pancreatic ASC, developed in a 72-year-old man, was subjected to mutation profiling using amplicon-targeted sequencing and digital polymerase chain reaction. DNA was isolated from each histological compartment including noninvasive IPMN, squamous cell carcinoma (SCC), and adenocarcinoma (AC). Histologically, an IPMN with a large mural nodule was identified. The invasive tumor predominantly consisted of SCC, and a smaller AC was found around the lesion. Squamous metaplasias were sporadically distributed within benign IPMNs. Mutation alleles KRAS and GNAS were identified in all specimens of IPMN including the areas of squamous metaplasia. In addition, these mutations were found in SCC and AC. Clear transition from flat/low-papillary IPMN to SCC indicated a potent invasion front, and the SCC compartment was genetically unique, because the area has a higher frequency of mutation KRAS. The invasive tumors with distinct histological appearances shared the form of noninvasive IPMN as a common precursor, rather than de novo cancer, suggesting the significance of a genetic profiling scheme of tumors associated with IPMN.

  15. [Comparative clinico-morphological characteristics of the variants of adeno-squamous carcinoma and adenocarcinoma of the endometrium].

    PubMed

    Smirnov, O A; Smirnova, O N

    1985-01-01

    A clinico-morphological analysis of the data available on cases of adeno-squamous carcinoma (72) and endometrial adenocarcinoma (102) pointed to a correlation between the decrease in the degree of cell differentiation in said neoplasms and the decline in the frequency of hyperestrimism and metabolic-endocrine disorders. As a result over 70% of well-differentiated cell tumors were referred to one pathogenetic pattern of endometrial carcinoma (after Bokhman) and more than 50% of poorly-differentiated cell tumors--to another one. These findings further support the rationale for distinguishing the well- and poorly-differentiated cell patterns of adeno-squamous carcinoma. They may be used in establishing individual prognosis as well as choosing optimal scheme of treatment.

  16. Transplantable pancreatic acinar carcinoma

    SciTech Connect

    Warren, J.R.; Reddy, J.K.

    1981-03-15

    Fragments of the nafenopin-induced pancreatic acinar cell carcinoma of rat have been examined in vitro for patterns of intracellular protein transport and carbamylcholine-induced protein discharge. Continuous incubation of the fragments with (3H)-leucine for 60 minutes resulted in labeling of rough endoplasmic reticulum, Golgi cisternae, and mature zymogen granules, revealed by electron microscope autoradiography. This result indicates transport of newly synthesized protein from the rough endoplasmic reticulum to mature zymogen granules in approximately 60 minutes. The secretagogue carbamylcholine induced the discharge of radioactive protein by carcinoma fragments pulse-chase labeled with (3H)-leucine. A maximal effective carbamylcholine concentration of 10(-5) M was determined. The acinar carcinoma resembles normal exocrine pancreas in the observed rate of intracellular protein transport and effective secretagogue concentration. However, the acinar carcinoma fragments demonstrated an apparent low rate of carbamylcholine-induced radioactive protein discharge as compared with normal pancreatic lobules or acinar cells. It is suggested that the apparent low rate of radioactive protein discharge reflects functional immaturity of the acinar carcinoma. Possible relationships of functional differentiation to the heterogeneous cytodifferentiation of the pancreatic acinar carcinoma are discussed.

  17. Primary adenosquamous carcinoma of the esophagus: an analysis of 39 cases

    PubMed Central

    Ni, Peng-Zhi; Yang, Yu-Shang; Hu, Wei-Peng; Wang, Wen-Ping; Yuan, Yong

    2016-01-01

    Background Adenosquamous carcinoma (ASC) of the esophagus is an uncommon type of malignant esophageal neoplasm containing both squamous cell carcinoma (SCC) and adenocacinoma (AC) components. The aim of this study was to explore the clinical characteristics and prognosis of esophageal ASC. Methods A retrospective review of esophageal ASC patients who underwent transthoracic esophagectomy with lymphadenectomy in our hospital from July 2007 to April 2014. Results A total of 39 (1.0%) esophageal ASC patients among 3855 patients with esophageal cancers were collected to analyze. There were 34 men and 5 women with a median age of 61.0 years (range from 39–85). Median follow-up time was 30.0 months and median survival time was 44.4 months. The 1-, 3- and 5-year overall survival rates were 82.1%, 51.6% and 37.5%, respectively. Compared to esophageal SCC and AC, there were no significant difference in survive time (P=0.616). Thirty five (92.1%) of the 38 patients who underwent preoperative endoscopic biopsy were misdiagnosed, mostly as SCC. Fifteen patients (38.5%) were found to have lymph node metastasis. Thirty two patients (82.1%) had a poorly differentiated or undifferentiated tumor. According to the 2009 American Joint Committee on Cancer (AJCC) staging system for esophageal squamous cell carcinoma, 3 patients were at Stage I, 21 patients at Stage II and 15 patients at Stage III. In univariate analysis, pT stage, lymph node metastasis and pTNM Stage significantly influenced survive time. In multivariate analysis, however, only lymph node metastasis (P=0.003; 95% CI: 1.626–10.972) was found to be the independent prognostic factor. Conclusions Primary ASC of the esophagus is a rare disease with difficultly to be histologically confirmed by endoscopic biopsy. The prognosis of esophageal ASC was no worse than esophageal SCC and AC. Lymph node metastasis is the most influent prognostic factor. The TNM staging system of esophageal SCC is applicable for esophageal ASC

  18. Atypical breast adenosquamous carcinoma following acute myeloid leukemia in a middle-aged woman: A case report

    PubMed Central

    Hashemi, Seyed Mehdi; Mahmoudi Shan, Shokoufeh; Jahantigh, Mahdi; Allahyari, Abolghasem

    2017-01-01

    Adenosquamous carcinoma of the breast is a rare cancer that develops as glands and tubules admixed with solid nests of squamous cells in a spindle cell background. Furthermore, its occurrence following AML is also rare. To the best of our knowledge, based on a review of the relevant literature, thus far there have not been any welldocumented cases. In the present case report, we report on a middle-aged woman with a 2year history of acute myeloid leukemia (AML) who was admitted to hospital due to a mass in the right breast, with concurrent cutaneous lesions on the breast. The clinical and pathological investigations resulted in the diagnosis of adenosquamous carcinoma of the breast. The patient underwent a modified radical mastectomy (MRM). Subsequently, the patient received chemotherapy, involved-field radiation therapy and target therapy. At 9 months after the final cycle of chemotherapy, and while she was on targeted therapy with trastuzumab (6 mg administered every 3 weeks), the patient presented with extensive dermatomal skin lesions. A biopsy report revealed metastatic lesions of invasive ductal carcinoma in the abdomen, so chemotherapy resumed with a course lasting for 6 cycles, with the identical treatments, but lacking trastuzumab.

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

    SciTech Connect

    Huang, Yi-Ting; Wang, Chun-Chieh; Tsai, Chien-Sheng; Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh; Lee, Steve P.; Hong, Ji-Hong

    2012-10-01

    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.

  20. IMAGING DIAGNOSIS: COMPUTED TOMOGRAPHIC FINDINGS IN A CASE OF ADENOSQUAMOUS CARCINOMA OF THE HEAD AND NECK IN A CAT.

    PubMed

    Chow, Kathleen Ella; Krockenberger, Mark; Collins, David

    2016-01-01

    A 15-year-old female spayed domestic long-haired cat was referred for trismus, hypersalivation, and bilateral ocular discharge. On examination, the cat showed pain on palpation of the left zygomatic arch, palpable crepitus of the frontal region, and limited retropulsion of both globes. A contrast-enhanced sinonasal computed tomographic study was performed, showing facial distortion and extensive osteolysis of the skull, extending beyond the confines of the sinonasal and paranasal cavities. Additionally, soft tissue and fluid accumulation were observed in the nasal cavities and paranasal sinuses. Postmortem biopsy samples acquired from the calvarium yielded a histologic diagnosis of sinonasal adenosquamous carcinoma, a rare and particularly aggressive neoplasm previously only reported in the esophagus of one cat.

  1. Immunotherapy of pancreatic carcinoma.

    PubMed

    Märten, Angela

    2008-05-01

    Patients with carcinoma of the exocrine pancreas have especially poor prognosis with a five-year survival rate of <1% and a median survival of 4-6 months. Pancreatic carcinoma is a systemic disease, insensitive to radiotherapy and mostly to chemotherapy. Accordingly, new treatment modalities are worth being investigated. One of the promising approaches is immunotherapy. Several phase I/II trials that have been published show interesting results, whereupon antibody-based strategies seem to fail and unspecific stimulation or vaccination with peptides look encouraging. Furthermore, phase II trials dealing with combination therapies are highly promising. One of them, a combination of chemoradiotherapy plus interferon-alpha is currently tested in a randomized phase III trial. As most of the trials had enrolled only limited numbers of patients and most of the trials were not conducted and/or reported according to the new standards it is difficult to draw final conclusions from the discussed trials. Immuno-monitoring was performed only in 40% of the discussed publications. In all cases immune responses were observed and correlation with the clinical outcome is discussed. Immunotherapy of pancreatic adenocarcinoma and especially combination therapies including immunotherapy is an up-and-coming approach and needs to be investigated in well conducted phase III randomized controlled trials accompanied by appropriate immuno-monitoring.

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

    SciTech Connect

    Huang, Yi-Ting; Wang, Chun-Chieh; Tsai, Chien-Sheng; Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh; Hsueh, Swei; Chen, Chien-Kuang; Lee, Steve P.; Hong, Ji-Hong

    2011-06-01

    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.

  3. MCM2 and TIP30 are prognostic markers in squamous cell/adenosquamous carcinoma and adenocarcinoma of the gallbladder

    PubMed Central

    Liu, Ziru; Yang, Zhulin; Jiang, Song; Zou, Qiong; Yuan, Yuan; Li, Jinghe; Li, Daiqiang; Liang, Lufeng; Chen, Meigui; Chen, Senlin

    2016-01-01

    The clinicopathological and biological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder remain to be fully elucidated, due to the fact that it is a rare gallbladder cancer subtype. In the current study, the expression of minichromosome maintenance complex component 2 (MCM2) and HIV-1 tat interactive protein 2 (TIP30) was measured in 46 cases of SC/ASC and 80 adenocarcinomas (AC) using immunohistochemistry. Positive MCM2 and negative TIP30 expression were significantly associated with large tumor size, high TNM stage, invasion, lymph node metastasis and lack of surgical curability in SC/ASC and AC. Positive MCM2 and negative TIP30 expression were significantly associated with poor differentiation in AC, whereas only MCM2 was correlated with differentiation in SC/ASC. Univariate Kaplan-Meier analysis demonstrated that positive MCM2 and negative TIP30 expression, the degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis and surgical curability were significantly associated with post-operative survival in patients with SC/ASC and AC. Multivariate Cox regression analysis demonstrated that positive MCM2 and negative TIP30 expression, the degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis and lack of surgical curability were also independent predictors of poor prognosis in patients with SC/ASC and AC. These data suggest that positive MCM2 and negative TIP30 expression are closely correlated with the clinical, pathological and biological parameters, in addition to poor prognosis in patients with gallbladder cancer. PMID:27748889

  4. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma

    PubMed Central

    Kuroda, Hiromasa; Kimura, Tadashi

    2017-01-01

    Objective To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. Methods The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. Results The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). Conclusion Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC. PMID:28028992

  5. Inflammatory pancreatic masses: problems in differentiating focal pancreatitis from carcinoma

    SciTech Connect

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

    1984-01-01

    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.

  6. Pancreatic carcinoma: results with fast neutron therapy

    SciTech Connect

    Kaul, R.; Cohen, L.; Hendrickson, F.; Awschalom, M.; Hrejsa, A.F.; Rosenberg, I.

    1981-02-01

    Results of therapy in 31 of 50 patients who were treated for advanced pancreatic carcinoma at Fermi National Accelerator Laboratory are presented here. To date, six patients are alive and four are free of disease. Since the main reason for failure was lack of control of primary tumor, the tumor dose has been increased by 15%. Based on our results, a nationwide study has been launched to assess the effectiveness of neutrons vs photons in the treatment of locally advanced pancreatic carcinoma.

  7. Computed tomographic appearance of resectable pancreatic carcinoma

    SciTech Connect

    Itai, Y.; Araki, T.; Tasaka, A.; Maruyama, M.

    1982-06-01

    Thirteen patients with resectable pancreatic carcinoma were examined by computed tomography (CT). Nine had a mass, 2 had dilatation of the main pancreatic duct, 1 appeared to have ductal dilatation, and 1 had no sign of abnormality. Resectable carcinoma was diagnosed retrospectively in 8 cases, based on the following criteria: a mass with a distinct contour, frequently containing a tiny or irregular low-density area and accompanied by dilatation of the caudal portion of the main pancreatic duct without involvement of the large vessels, liver, or lymph nodes. Including unresectable cancer, chronic pancreatitis, and obstructive jaundice from causes other than cancer, the false-positive rate was less than 6%. However, a small cancer without change in pancreatic contour is difficult to detect with CT.

  8. PD-L1 expression in lung adenosquamous carcinomas compared with the more common variants of non-small cell lung cancer

    PubMed Central

    Shi, Xiaohua; Wu, Shafei; Sun, Jian; Liu, Yuanyuan; Zeng, Xuan; Liang, Zhiyong

    2017-01-01

    Lung adenosquamous cell carcinomas (ASCs) is a rare variant of NSCLC with a poorer prognosis and fewer treatment option than the more common variants. PD-L1 expression is reported to be the predictor of clinical response in trials of NSCLC. In our study, PD-L1 expression was evaluated via immunohistochemistry using a specific monoclonal antibody (SP263), and PD-L1 mRNA expression was evaluated via in situ hybridization. This study included 51 ASCs, 133 lung adenocarcinomas, and 83 lung squamous cell carcinomas (SCC). Similar results were obtained for PD-L1 expression measured at the mRNA and protein level (k coefficient, 0.851, P = 1.000). PD-L1 expression was significantly higher in the squamous versus glandular component of the 36 ASCs in which the components were analyzed separately. The PD-L1 expression rate was similar in the squamous cell component of ASCs and lung SCC (38.89% vs. 28.92%, P = 0.293), so does the adenocarcinoma component of ASCs and lung adenocarcinomas (11.11% vs 13.53%, P = 1.000). PD-L1 expression correlated significantly with lymphovascular invasion (P = 0.016), but not with EGFR, KRAS, and ALK mutations in lung ASCs. Anit-PD-L1 is a promising treatment option in lung ASC cases in which PD-L1 upregulated and EGFR mutations are present. PMID:28387300

  9. Contrast-enhanced ultrasonograpic studies on pancreatic carcinoma with special reference to staining and muscular arterial vessels.

    PubMed

    Suga, Hideya; Okabe, Yoshinobu; Tsuruta, Osamu; Naito, Yoshiki; Kinoshita, Hisafumi; Toyonaga, Atsushi; Ono, Naofumi; Oho, Kazuhiko; Kojiro, Masamichi; Sata, Michio

    2014-01-01

    Comparative study of contrast-enhanced ultrasonography (CE-US) and histopathology of surgically resected specimens in 13 patients with pancreatic carcinoma. A time intensity curve was used to determine the percentage brightness increase in cancerous and normal regions and the patients were divided into two groups, hyperperfusion, with a percentage brightness increase over 80% (n=6) and hypoperfusion, with an increase of less than 80% (n=7) on CE-US. The hyperperfusion group included well-differentiated tubular adenocarcinoma, adenosquamous cell carcinoma and acinar cell carcinoma, while all 7 patients in the hypoperfusion group had moderately differentiated tubular adenocarcinoma. Immunological staining (α-SMA and anti-CD34) of the resected specimens showed significantly higher microartery count (MAC) in the hyperperfusion group (p<0.005) than in the hypoperfusion group or normal pancreas. In the normal pancreas, the mean vessel diameter was significantly higher (over 100 μm) than in the hyperperfusion group (30 μm; p<0.005). It was concluded that a muscular arterial vessel density of less than 30 μm is an important factor in determining staining degree and carcinoma progression by CE-US in pancreatic carcinoma.

  10. CT guided interstitial therapy of pancreatic carcinoma

    SciTech Connect

    Haaga, J.R.; Owens, D.B.; Kellermeyer, R.W.; Shina, D.; Pilai, K.; Began, N.

    1987-11-01

    We describe the use of percutaneous CT guidance for localization and placement of /sup 192/Ir sources into a patient with pancreatic carcinoma. We have shown the feasibility of this procedure and the lack of complications which are probably due to minimal damage to tissue involved. Computed tomography is ideally suited for percutaneous implantation because it provides the most accurate method for needle placement within the abdomen.

  11. Carbohydrate antigen 19-9 for differential diagnosis of pancreatic carcinoma and chronic pancreatitis

    PubMed Central

    Su, Si-Biao; Qin, Shan-Yu; Chen, Wen; Luo, Wei; Jiang, Hai-Xing

    2015-01-01

    AIM: To evaluate the utility of carbohydrate antigen 19-9 (CA19-9) for differential diagnosis of pancreatic carcinoma and chronic pancreatitis. METHODS: We searched the literature for studies reporting the sensitivity, specificity, and other accuracy measures of serum CA19-9 levels for differentiating pancreatic carcinoma and chronic pancreatitis. Pooled analysis was performed using random-effects models, and receiver operating characteristic (ROC) curves were generated. Study quality was assessed using Standards for Reporting Diagnostic Accuracy and Quality Assessment for Studies of Diagnostic Accuracy tools. RESULTS: A total of 34 studies involving 3125 patients with pancreatic carcinoma and 2061 patients with chronic pancreatitis were included. Pooled analysis of the ability of CA19-9 level to differentiate pancreatic carcinoma and chronic pancreatitis showed the following effect estimates: sensitivity, 0.81 (95%CI: 0.80-0.83); specificity, 0.81 (95%CI: 0.79-0.82); positive likelihood ratio, 4.08 (95%CI: 3.39-4.91); negative likelihood ratio, 0.24 (95%CI: 0.21-0.28); and diagnostic odds ratio, 19.31 (95%CI: 14.40-25.90). The area under the ROC curve was 0.88. No significant publication bias was detected. CONCLUSION: Elevated CA19-9 by itself is insufficient for differentiating pancreatic carcinoma and chronic pancreatitis, however, it increases suspicion of pancreatic carcinoma and may complement other clinical findings to improve diagnostic accuracy. PMID:25892884

  12. Beer and its Non-Alcoholic Compounds: Role in Pancreatic Exocrine Secretion, Alcoholic Pancreatitis and Pancreatic Carcinoma

    PubMed Central

    Gerloff, Andreas; Singer, Manfred V; Feick, Peter

    2010-01-01

    In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated. PMID:20617020

  13. CT pancreatogram in carcinoma of the pancreas and chronic pancreatitis

    SciTech Connect

    Karasawa, E.; Goldberg, H.I.; Moss, A.A.; Federle, M.P.; London, S.S.

    1983-08-01

    CT has made it possible to determine the contour of the pancreatic duct, to measure its caliber, and to detect dilatation of the duct. CT scans of 75 patients with pancreatic carcinoma and of 45 patients with chronic pancreatitis were obtained. Dilatation of the pancreatic duct was seen in 56% of patients with carcinoma, and in 70% of those with tumors confined to the pancreatic head and body. Smooth dilatation (43%) or beaded dilatation (40%) were most commonly associated with carcinoma. Ductal dilatation was present in 58% of the patients with chronic pancreatitis, and irregular dilatation was seen in 73% of the patients in this group. About half of the patients who had irregular dilatation had calculi within the ducts. Eight cases of dilatation of the duct with no detectible pancreatic mass were seen in a subgroup of 13 patients who had small carcinomas of the pancreas (tumor size of 3 cm or less). Our findings indicate that a dilated pancreatic duct with a smooth contour and a ratio of duct to total gland width of 0.50 or greater suggests carcinoma as the underlying pathology.

  14. Epidermal growth factor and its receptors in human pancreatic carcinoma

    SciTech Connect

    Chen, Y.F.; Pan, G.Z.; Hou, X.; Liu, T.H.; Chen, J.; Yanaihara, C.; Yanaihara, N. )

    1990-05-01

    The role of epidermal growth factor (EGF) in oncogenesis and progression of malignant tumors is a subject of vast interest. In this study, radioimmunoassay and radioreceptor assay of EGF were established. EGF contents in malignant and benign pancreatic tumors, in normal pancreas tissue, and in culture media of a human pancreatic carcinoma cell line were determined. EGF receptor binding studies were performed. It was shown that EGF contents in pancreatic carcinomas were significantly higher than those in normal pancreas or benign pancreatic tumors. EGF was also detected in the culture medium of a pancreatic carcinoma cell line. The binding of 125I-EGF to the pancreatic carcinoma cells was time and temperature dependent, reversible, competitive, and specific. Scatchard analysis showed that the dissociation constant of EGF receptor was 2.1 X 10(-9) M, number of binding sites was 1.3 X 10(5) cell. These results indicate that there is an over-expression of EGF/EGF receptors in pancreatic carcinomas, and that an autocrine regulatory mechanism may exist in the growth-promoting effect of EGF on tumor cells.

  15. Non-focal enlargement in pancreatic carcinoma

    SciTech Connect

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

    1982-07-01

    Pancreatic adenocarcinoma can appear radiographically as enlargement of the major part of the pancreas. In this series, part or all of three or more pancreatic segments (head, neck, body, and tail) were involved in 27% of patients with adenocarcinoma who had computed tomography. Differentiation from pure pancreatitis may require additional radiographic studies. The varied tissue composition of a pancreas enlarged by adenocarcinoma will often require biopsy of multiple sites for confirmation.

  16. Pancreatic carcinoma masked as fever of unknown origin

    PubMed Central

    Shi, Ning; Xing, Cheng; Chang, Xiaoyan; Dai, Menghua; Zhao, Yupei

    2016-01-01

    Abstract Background: Pancreatic carcinoma is a highly lethal malignancy. Common presenting features of pancreatic cancer include anorexia, asthenia, weight loss, pain, and obstructive jaundice. Nevertheless, fever as a symptom, or even primary manifestation of pancreatic cancer is rather rare. Methods: Here, we report a 63-year-old male patient presenting with daily fevers, night sweats, and fatigue of 2-month duration. Laboratory findings showed elevated white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and serum C-reactive protein (CRP). A computed tomography scan demonstrated a tumor between the duodenum and pancreatic head. Chest radiograph was normal. Results: The patient underwent an uneventful tumor resection. Histological examination of a surgical specimen demonstrated an undifferentiated adenocarcinoma originated from pancreatic head. The tumor was compatible with TNM stage IIA (T3N0M0). Complete resolution of the fever was achieved on post-operative day 4 and no recurrence of the tumor or neoplastic fever happen during the 39-month follow-up. Conclusion: Pancreatic adenocarcinoma could manifest as neoplastic fever at the time of diagnosis. If the tumor is resectable, surgical resection is a safe and curative form of therapy not only for the fever but also for the original carcinoma. PMID:27583884

  17. The role of radiotherapy in multimodal treatment of pancreatic carcinoma

    PubMed Central

    2010-01-01

    Pancreatic ductal carcinoma is one of the most lethal malignancies, but in recent years a number of positive developments have occurred in the management of pancreatic carcinoma. This article aims to give an overview of the current knowledge regarding the role of radiotherapy in the treatment of pancreatic ductal adenocarcinoma (PDAC). The results of meta-analyses, phase III-studies, and phase II-studies using chemoradiotherapy and chemotherapy for resectable and non-resectable PDAC were reviewed. The use of radiotherapy is discussed in the neoadjuvant and adjuvant settings as well as in the locally advanced situation. Whenever possible, radiotherapy should be performed as simultaneous chemoradiotherapy. Patients with PDAC should be offered entry into clinical trials to identify optimal treatment results. PMID:20615227

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

    PubMed Central

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

    2016-01-01

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

  19. Isolated pancreatic metastasis of hepatocellular carcinoma after curative resection.

    PubMed

    Woo, Sang Myung; Park, Joong-Won; Han, Sung-Sik; Choi, Joon-Il; Lee, Woo Jin; Park, Sang Jae; Hong, Eun Kyung; Kim, Chang-Min

    2010-04-15

    Hepatocellular carcinoma (HCC) is a highly malignant tumor and extrahepatic metastasis is not rare. The most common organ of HCC metastasis is lung, followed by bone and adrenal gland. To the best of our knowledge, isolated pancreatic metastasis of HCC that developed after curative resection has not been described previously. We report a case of solitary pancreatic metastasis of HCC, which was found 28 mo after left hemihepatectomy for HCC. The lesion was successfully resected with the pancreas, and no other metastatic lesions have been found in follow-up.

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

    PubMed

    Naeyaert, Charlotte; de Clerck, Frederik; De Wilde, Vincent

    2016-12-01

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

  1. Photodynamic therapy for pancreatic and biliary tract carcinoma

    NASA Astrophysics Data System (ADS)

    Pereira, Stephen P.

    2009-02-01

    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.

  2. [Surgical treatment and prognosis of pancreatic neuroendocrine carcinoma].

    PubMed

    Zhang, J W; Che, X; Lan, Z M; Chen, Y T; Huang, X H; Jiang, Q L; Wang, C F

    2016-12-23

    Objective: Pancreatic neuroendocrine carcinoma (pNEC) is a highly malignant tumor.This study aimed to evaluate the role of surgery and the prognosis for patients with pancreatic neuroendocrine carcinoma (pNEC). Methods: We collected and reviewed all clinical data of patients who underwent radical surgery for pNEC from Jan 2000 through Jan 2016 in our hospital. Cox-regression analysis wasused to evaluate the factors potentially influencing survival. Results: Twenty patients including 11 males and 9 females (median age, 62.5 years) were included in this study. All patients underwent radical surgery and 17 cases received postoperative platinum-based chemotherapy.The median follow-up time was 41 months (range, 1 to 127 months). The 1-, 3-, and 5-year survival rates of the patients were 66.7%, 51.5% and 28.1%, with a median survival time of 75.3 months.The multivariate analysis indicated that tumor size and Ki-67 index were of prognostic significance. Conclusions: Pancreatic neuroendocrine carcinomas are rare but increasing in incidence. Patients with localized nonmetastatic primary tumors seem to benefit from surgery. Early diagnosis and multimodality therapy are key points of an improved survival.

  3. High risk factors of pancreatic carcinoma.

    PubMed

    Camara, Soriba Naby; Yin, Tao; Yang, Ming; Li, Xiang; Gong, Qiong; Zhou, Jing; Zhao, Gang; Yang, Zhi-Yong; Aroun, Tajoo; Kuete, Martin; Ramdany, Sonam; Camara, Alpha Kabinet; Diallo, Aissatou Taran; Feng, Zhen; Ning, Xin; Xiong, Jiong-Xin; Tao, Jing; Qin, Qi; Zhou, Wei; Cui, Jing; Huang, Min; Guo, Yao; Gou, Shan-Miao; Wang, Bo; Liu, Tao; Olivier, Ohoya Etsaka Terence; Conde, Tenin; Cisse, Mohamed; Magassouba, Aboubacar Sidiki; Ballah, Sneha; Keita, Naby Laye Moussa; Souare, Ibrahima Sory; Toure, Aboubacar; Traore, Sadamoudou; Balde, Abdoulaye Korse; Keita, Namory; Camara, Naby Daouda; Emmanuel, Dusabe; Wu, He-Shui; Wang, Chun-You

    2016-06-01

    Over the past decades, cancer has become one of the toughest challenges for health professionals. The epidemiologists are increasingly directing their research efforts on various malignant tumor worldwide. Of note, incidence of cancers is on the rise more quickly in developed countries. Indeed, great endeavors have to be made in the control of the life-threatening disease. As we know it, pancreatic cancer (PC) is a malignant disease with the worst prognosis. While little is known about the etiology of the PC and measures to prevent the condition, so far, a number of risk factors have been identified. Genetic factors, pre-malignant lesions, predisposing diseases and exogenous factors have been found to be linked to PC. Genetic susceptibility was observed in 10% of PC cases, including inherited PC syndromes and familial PC. However, in the remaining 90%, their PC might be caused by genetic factors in combination with environmental factors. Nonetheless, the exact mechanism of the two kinds of factors, endogenous and exogenous, working together to cause PC remains poorly understood. The fact that most pancreatic neoplasms are diagnosed at an incurable stage of the disease highlights the need to identify risk factors and to understand their contribution to carcinogenesis. This article reviews the high risk factors contributing to the development of PC, to provide information for clinicians and epidemiologists.

  4. CT and MR imaging patterns for pancreatic carcinoma invading the extrapancreatic neural plexus (Part II): Imaging of pancreatic carcinoma nerve invasion

    PubMed Central

    Zuo, Hou-Dong; Tang, Wei; Zhang, Xiao-Ming; Zhao, Qiong-Hui; Xiao, Bo

    2012-01-01

    Computed tomography (CT) and magnetic resonance imaging (MRI) are excellent modalities which have the ability to detect, depict and stage the nerve invasion associated with pancreatic carcinoma. The aim of this article is to review the CT and MR patterns of pancreatic carcinoma invading the extrapancreatic neural plexus and thus provide useful information which could help the choice of treatment methods. Pancreatic carcinoma is a common malignant neoplasm with a high mortality rate. There are many factors influencing the prognosis and treatment options for those patients suffering from pancreatic carcinoma, such as lymphatic metastasis, adjacent organs or tissue invasion, etc. Among these factors, extrapancreatic neural plexus invasion is recognized as an important factor when considering the management of the patients. PMID:22328967

  5. Evaluating IPMN and pancreatic carcinoma utilizing quantitative histopathology.

    PubMed

    Glazer, Evan S; Zhang, Hao Helen; Hill, Kimberly A; Patel, Charmi; Kha, Stephanie T; Yozwiak, Michael L; Bartels, Hubert; Nafissi, Nellie N; Watkins, Joseph C; Alberts, David S; Krouse, Robert S

    2016-10-01

    Intraductal papillary mucinous neoplasms (IPMN) are pancreatic lesions with uncertain biologic behavior. This study sought objective, accurate prediction tools, through the use of quantitative histopathological signatures of nuclear images, for classifying lesions as chronic pancreatitis (CP), IPMN, or pancreatic carcinoma (PC). Forty-four pancreatic resection patients were retrospectively identified for this study (12 CP; 16 IPMN; 16 PC). Regularized multinomial regression quantitatively classified each specimen as CP, IPMN, or PC in an automated, blinded fashion. Classification certainty was determined by subtracting the smallest classification probability from the largest probability (of the three groups). The certainty function varied from 1.0 (perfectly classified) to 0.0 (random). From each lesion, 180 ± 22 nuclei were imaged. Overall classification accuracy was 89.6% with six unique nuclear features. No CP cases were misclassified, 1/16 IPMN cases were misclassified, and 4/16 PC cases were misclassified. Certainty function was 0.75 ± 0.16 for correctly classified lesions and 0.47 ± 0.10 for incorrectly classified lesions (P = 0.0005). Uncertainty was identified in four of the five misclassified lesions. Quantitative histopathology provides a robust, novel method to distinguish among CP, IPMN, and PC with a quantitative measure of uncertainty. This may be useful when there is uncertainty in diagnosis.

  6. Expression of claudin-5 in canine pancreatic acinar cell carcinoma - An immunohistochemical study.

    PubMed

    Jakab, Csaba; Rusvai, Miklós; Gálfi, Péter; Halász, Judit; Kulka, Janina

    2011-03-01

    Claudin-5 is an endothelium-specific tight junction protein. The aim of the present study was to detect the expression pattern of this molecule in intact pancreatic tissues and in well-differentiated and poorly differentiated pancreatic acinar cell carcinomas from dogs by the use of cross-reactive humanised anticlaudin-5 antibody. The necropsy samples taken from dogs included 10 nonneoplastic pancreatic tissues, 10 well-differentiated pancreatic acinar cell carcinomas, 10 poorly differentiated pancreatic acinar cell carcinomas, 5 intrahepatic metastases of well-differentiated and 5 intrahepatic metastases of poorly differentiated acinar cell carcinomas. A strong lateral membrane claudin-5 positivity was detected in exocrine cells in all intact pancreas samples. The endocrine cells of the islets of Langerhans and the epithelial cells of the ducts were negative for claudin-5. The endothelial cells of vessels and lymphatic channels in the stroma of the intact pancreas showed strong membrane positivity for this claudin. All well-differentiated exocrine pancreas carcinomas and all poorly-differentiated pancreatic acinar cell carcinoma samples showed a diffuse loss of claudin-5 expression. The claudin-5-positive peritumoural vessels and lymphatic channels facilitated the detection of vascular invasion of the claudin-5-negative cancer cells. In liver metastasis samples, the pancreatic carcinomas were negative for claudin-5. It seems that the loss of expression of claudin-5 may lead to carcinogenesis in canine exocrine pancreatic cells.

  7. [Efficacy of neoadjuvant chemotherapy for resectable pancreatic carcinoma].

    PubMed

    Motoi, Fuyuhiko; Kawaguchi, Kei; Aoki, Takeshi; Kudo, Katsumasa; Yabuuchi, Shinichi; Fukase, Koji; Mizuma, Masamichi; Sakata, Naoaki; Otsutomo, Shigeru; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Okada, Takaho; Yoshida, Hiroshi; Naitoh, Takeshi; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki

    2013-11-01

    Surgery followed by adjuvant chemotherapy is standard care for resectable pancreatic carcinoma. The maximum estimated 2-year survival rate associated with this strategy is nearly 50%. The use of neoadjuvant therapy for pancreatic cancer remains controversial, and its efficacy has not been elucidated. To evaluate the efficacy of neoadjuvant chemotherapy for planned pancreatic cancer resection, the oncological outcomes of neoadjuvant gemcitabine plus S-1 combination therapy( GS therapy) and a surgery-first approach were retrospectively compared. Patients with planned pancreatic cancer resection and without major artery abutments were enrolled in this study. There were 39 cases of neoadjuvant GS therapy (N group) and 93 cases of the surgery-first approach( S group). Survival and surrogate markers, including the R0 rate, the "true R0 rate"( R0 with tumor marker normalization after resection), and N0 rate, were compared. The groups did not differ significantly in terms of age, gender, or tumor location. The resection rates of the N and S groups were similar (92% and 86%, respectively). The median survival of the N group (39.4 months) was significantly longer than that of the S group (20.8 months) in intention-to-treat analysis (p=0.0009). The R0, true R0, and N0 rates of the N group (85%, 69%, and 44%, respectively) were higher than those of the S group( 72%, 48%, and 24%, respectively). In conclusion, this retrospective analysis showed that neoadjuvant GS therapy might be more effective than the standard surgery-first strategy in terms of oncological outcomes for resectable pancreatic cancer. A prospective randomized study, Prep-02/JSAP-05, which compares neoadjuvant therapy to the surgery-first approach, is ongoing (UMIN-No. 000009634).

  8. Metastatic pancreatic islet cell carcinoma to the orbit: a case report.

    PubMed

    Nasr, Amin M.; Teichmann, Klaus; Dabbagh, Najwa; Huaman, Antonio M.

    1998-03-01

    We report a rare case of pancreatic islet cell carcinoma metastatic to the orbit in a 29-year-old woman. The initial symptomatology, progression of the disease, and radiologic and histopathologic findings are presented and discussed.

  9. Characterization and utilization of a monoclonal antibody against pancreatic carcinoma

    SciTech Connect

    Kurtzman, S.H.; Sindelar, W.F.; Atcher, R.W.; Mitchell, J.B.; DeGraff, W.G.; Gamson, J.; Russo, A.; Friedman, A.M.; Hines, J.J.

    1994-10-01

    A monoclonal antibody was produced against a human pancreatic adenocarcinoma line and was found to react with several different human carcinomas by immunoperoxidase staining of fixed tissues. The original cells used to generate the monoclonal antibody were treated with detergent to lyse the cell membrane. A membrane associated protein of molecular weight 35kD was isolated from this detergent lysed preparation and found to be recognized by the monoclonal antibody. The binding constant of the antigen antibody reaction on the cells is 5 x 10{sup {minus}5}. It was further determined that there are 700,000 binding sites per cell. Kinetics of the antigen-antibody reaction under several conditions were also explored.

  10. Therapy of human pancreatic carcinoma based on suppression of HMGA1 protein synthesis in preclinical models.

    PubMed

    Trapasso, Francesco; Sarti, Manuela; Cesari, Rossano; Yendamuri, Sai; Dumon, Kristoffel R; Aqeilan, Rami I; Pentimalli, Francesca; Infante, Luisa; Alder, Hansjuerg; Abe, Nobutsugu; Watanabe, Takashi; Viglietto, Giuseppe; Croce, Carlo M; Fusco, Alfredo

    2004-09-01

    Pancreatic carcinoma is one of the most aggressive tumors, and, being refractory to conventional therapies, is an excellent target for new therapeutic approaches. Based on our previous finding of high HMGA1 expression in pancreatic cancer cells compared to normal pancreatic tissue, we evaluated whether suppression of HMGA1 protein expression could be a treatment option for patients affected by pancreatic cancer. Here we report that HMGA1 proteins are overexpressed in pancreatic carcinoma cell lines, and their downregulation through an adenovirus carrying the HMGA1 gene in an antisense orientation (Ad Yas-GFP) results in the death of three human pancreatic carcinoma cell lines (PANC1, Hs766T and PSN1). Pretreatment of PANC1 and PSN1 cells with Ad Yas-GFP suppressed and reduced, respectively, their ability to form xenograft tumors in nude mice. To further verify the role of HMGA1 in pancreatic tumorigenesis, we used a HMGA1 antisense phosphorothioate oligodeoxynucleotide (ODN); its addition induced a decrease in HMGA1 protein levels and a significant reduction of the proliferation rate of PANC1-, Hs766T- and PSN1-treated cells. Therefore, suppression of HMGA1 protein synthesis by an HMGA1 antisense approach seems to be a feasible treatment strategy in pancreatic carcinomas.

  11. Superficial necrolytic dermatitis in a dog with an insulin-producing pancreatic islet cell carcinoma.

    PubMed

    Isidoro-Ayza, M; Lloret, A; Bardagí, M; Ferrer, L; Martínez, J

    2014-07-01

    A 10-year-old dog presented with convulsive crisis and symmetrical hyperkeratotic cutaneous lesions affecting the abdomen, inguinal area, eyelids, muzzles, both pinnae, and all the paw pads. Hypoglycemia and hyperinsulinemia were the main biochemical findings. A mass 2 cm in diameter was detected within the left pancreatic lobe by ultrasonography. It was surgically removed and histologically and immunohistochemically diagnosed as an insulin-producing pancreatic islet cell carcinoma. The animal was eventually euthanized due to lack of clinical improvement. At necropsy, metastatic nodules were observed in the pancreatic lymph nodes and liver. Histopathological findings of cutaneous lesions were highly suggestive of superficial necrolytic dermatitis and were interpreted as a paraneoplastic syndrome derived from the islet cell carcinoma. To the authors' knowledge, this is the first report of superficial necrolytic dermatitis associated with an insulin-producing pancreatic neuroendocrine carcinoma in dogs.

  12. Intraoperative electron beam irradiation for patients with unresectable pancreatic carcinoma

    SciTech Connect

    Shipley, W.U.; Wood, W.C.; Tepper, J.E.; Warshaw, A.L.; Orlow, E.L.; Kaufman, S.D.; Battit, G.E.; Nardi, G.L.

    1984-09-01

    Since 1978 we have used electron beam intraoperative radiation therapy (IORT) to deliver higher radiation doses to pancreatic tumors than are possible with external beam techniques while minimizing the dose to the surrounding normal tissues. Twenty-nine patients with localized, unresectable, pancreatic carcinoma were treated by electron beam IORT in combination with conventional external radiation therapy (XRT). The primary tumor was located in the head of the pancreas in 20 patients, in the head and body in six patients, and in the body and tail in three. Adjuvant chemotherapy was given in 23 of the 29 patients. The last 13 patients have received misonidazole (3.5 mg/M2) just prior to IORT (20 Gy). At present 14 patients are alive and 11 are without evidence of disease from 3 to 41 months after IORT. The median survival is 16.5 months. Eight patients have failed locally in the IORT field and two others failed regionally. Twelve patients have developed distant metastases, including five who failed locally or regionally. We have seen no local recurrences in the 12 patients who have been treated with misonidazole and have completed IORT and XRT while 10 of 15 patients treated without misonidazole have recurred locally. Because of the shorter follow-up in the misonidazole group, this apparent improvement is not statistically significant. Fifteen patients (52%) have not had pain following treatment and 22 (76%) have had no upper gastrointestinal or biliary obstruction subsequent to their initial surgical bypasses and radiation treatments. Based on the good palliation generally obtained, the 16.5-month median survival, and the possible added benefit from misonidazole, we are encouraged to continue this approach.

  13. Differential gene expression of the key signalling pathway in para-carcinoma, carcinoma and relapse human pancreatic cancer.

    PubMed

    Chang, Zheng-Yan; Sun, Ran; Ma, Yu-Shui; Fu, Da; Lai, Xiao-Long; Li, Yu-Sheng; Wang, Xing-Hong; Zhang, Xiao-Ping; Lv, Zhong-Wei; Cong, Xian-Ling; Li, Wen-Ping

    2014-04-01

    Pancreatic cancer (PC) has a high rate of mortality and a poorly understood mechanism of progression. Investigation of the molecular mechanism of PC and exploration of the specific markers for early diagnosis and specific targets of therapy are key points to prevent and treat PC effectively and to improve their prognosis. In our study, expression profiles experiment of para-carcinoma, carcinoma and relapse human PC was performed using Agilent human whole genomic oligonucleotide microarrays with 45 000 probes. Differentially expressed genes related with PC were screened and analysed further by Gene Ontology term analysis and Kyoto encyclopaedia of genes and genomes pathway analysis. Our results showed that there were 3853 differentially expressed genes associated with pancreatic carcinogenesis and relapse. In addition, our study found that PC was related to the Jak-STAT signalling pathway, PPAR signalling pathway and Calcium signalling pathway, indicating their potential roles in pancreatic carcinogenesis and progress.

  14. Relative decreased splenic uptake of Tc-99m-sulfur colloid in patients with pancreatic carcinoma

    SciTech Connect

    Tatum, J.L.; Burke, T.S.; Fratkin, M.J.; Sharpe, A.R. Jr.; Goodrich, J.K.

    1982-01-01

    Relative spleen/liver activity ratio was determined from posterior projection images using a photodensitometric method. Ratios from scans of 22 patients with proven pancreatic carcinoma (12 from rectilinear scans and 10 from scintillation camera images) were determined and compared to studies from patients documented as normal and to randomly selected liver/spleen imaging studies which had been previously interpreted as normal. The mean ratio from the pancreatic carcinoma group was significantly lower than the means of the respective normal groups (p(t) less than .0001 for rectilinear scans and p(t) less than .001 for scintigrams). There was no significant difference between the means of the proven normal and randomly selected normal groups or between the two pancreatic carcinoma groups. Splenic vascular alteration is discussed as a possible reason for decreased splenic distribution of Tc-99m-sulfur colloid in this patient group.

  15. [Contribution of endoscopic ultrasound to the diagnosis of pancreatic metastases from renal carcinoma. Apropos of two cases].

    PubMed

    Repiso, Alejandro; Gómez-Rodríguez, Rafael; Aso, Sonsoles; Domper, Francisco; Buendía, Encarnación; González de Frutos, Concepción; Pérez-Grueso, María José; Rodríguez-Merlo, Rufo; Carrobles, José María

    2007-03-01

    Pancreatic metastases represent 2% of pancreatic tumors. The neoplasms most frequently metastasizing to the pancreas are breast, lung, melanoma and kidney tumors. We present the cases of two patients with pancreatic metastases from renal carcinoma diagnosed 4 and 8 years after the diagnosis and surgical treatment of the primary renal tumor. In both patients, endoscopic ultrasound was useful in the detection and characterization of these pancreatic lesions and allowed fine-needle aspiration for cytological study to be performed.

  16. Intrapancreatic distal common bile duct carcinoma: Analysis, staging considerations, and comparison with pancreatic ductal and ampullary adenocarcinomas.

    PubMed

    Gonzalez, Raul S; Bagci, Pelin; Basturk, Olca; Reid, Michelle D; Balci, Serdar; Knight, Jessica H; Kong, So Yeon; Memis, Bahar; Jang, Kee-Taek; Ohike, Nobuyuki; Tajiri, Takuma; Bandyopadhyay, Sudeshna; Krasinskas, Alyssa M; Kim, Grace E; Cheng, Jeanette D; Adsay, N Volkan

    2016-11-01

    Distal common bile duct carcinoma is a poorly characterized entity for reasons such as variable terminology and difficulty in determining site of origin of intrapancreatic lesions. We compared clinicopathologic features of pancreatobiliary-type adenocarcinomas within the pancreas, but arising from the distal common bile duct, with those of pancreatic and ampullary origin. Upon careful review of 1017 pancreatoduodenectomy specimens with primary adenocarcinoma, 52 (5%) qualified as intrapancreatic distal common bile duct carcinoma. Five associated with an intraductal papillary neoplasm were excluded; the remaining 47 were compared to 109 pancreatic ductal adenocarcinomas and 133 ampullary carcinomas. Distal common bile duct carcinoma patients had a younger median age (58 years) than pancreatic ductal adenocarcinoma patients (65 years) and ampullary carcinoma patients (68 years). Distal common bile duct carcinoma was intermediate between pancreatic ductal adenocarcinoma and ampullary carcinoma with regard to tumor size and rates of node metastases and margin positivity. Median survival was better than for pancreatic ductal adenocarcinoma (P=0.0010) but worse than for ampullary carcinoma (P=0.0006). Distal common bile duct carcinoma often formed an even band around the common bile duct and commonly showed intraglandular neutrophil-rich debris and a small tubular pattern. Poor prognostic indicators included node metastasis (P=0.0010), lymphovascular invasion (P=0.0299), and margin positivity (P=0.0069). Categorizing the tumors based on size also had prognostic relevance (P=0.0096), unlike categorization based on anatomic structures invaded. Primary distal common bile duct carcinoma is seen in younger patients than pancreatic ductal adenocarcinoma or ampullary carcinoma. Its prognosis is significantly better than pancreatic ductal adenocarcinoma and worse than ampullary carcinoma, at least partly because of differences in clinical presentation. Use of size-based criteria

  17. Neurogenin 3-directed cre deletion of Tsc1 gene causes pancreatic acinar carcinoma.

    PubMed

    Ding, Li; Han, Lingling; Li, Yin; Zhao, Jing; He, Ping; Zhang, Weizhen

    2014-11-01

    The role of tuberous sclerosis complex (TSC) in the pathogenesis of pancreatic cancers remains largely unknown. The present study shows that neurogenin 3 directed Cre deletion of Tsc1 gene induces the development of pancreatic acinar carcinoma. By cross-breeding the Neurog3-cre mice with Tsc1 (loxp/loxp) mice, we generated the Neurog3-Tsc1-/- transgenic mice in which Tsc1 gene is deleted and mTOR signaling activated in the pancreatic progenitor cells. All Neurog3-Tsc1-/- mice developed notable adenocarcinoma-like lesions in pancreas starting from the age of 100 days old. The tumor lesions are composed of cells with morphological and molecular resemblance to acinar cells. Metastasis of neoplasm to liver and lung was detected in 5% of animals. Inhibition of mTOR signaling by rapamycin significantly attenuated the growth of the neoplasm. Relapse of the neoplasm occurred within 14 days upon cessation of rapamycin treatment. Our studies indicate that activation of mTOR signaling in the pancreatic progenitor cells may trigger the development of acinar carcinoma. Thus, mTOR may serve as a potential target for treatment of pancreatic acinar carcinoma.

  18. Defect in assimilation following combined radiation and chemotherapy in patients with locally unresectable pancreatic carcinoma

    SciTech Connect

    Barkin, J.S.; Kalser, M.H.; Thomsen, S.; Redlhammer, D.

    1982-11-15

    The relative contributions of high-dose irradiation and/or chemotherapy to the nutritional problems of patients with inoperable pancreatic carcinoma were evaluated by study of pancreatic exocrine function and jejunal function and morphologic findings in ten patients before and after treatment. Nutrient assimilation studies included determination of serum carotene levels, D-xylose absorption and fat absorption. Crosby capsule biopsy specimen of jejunal mucosa were evaluated with light microscopy. Fat assimilation was the only parameter of nutritional function to significantly worsen after therapy. Low serum carotene levels present in the patients before therapy remained low but did not significantly change after treatment. D-xylose absorption and the morphologic structure of the jejunal mucosa were normal before and after treatment. These findings support the previous observations that the nutritional problems of the patient with inoperable pancreatic carcinoma are due to pancreatic insufficiency and that high dose irradiation and chemotherapy can exacerbate the pancreatic insufficiency but do not produce jejunal dysfunction. Therefore, it is suggested that pancreatic exocrine replacement therapy may improve the nutritional status of these patients.

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

    SciTech Connect

    Burmer, G.C.; Rabinovitch, P.S.; Loeb, L.A. )

    1991-06-01

    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.

  20. [Concomitant gastric and pancreatic metastases from renal cell carcinoma: case study].

    PubMed

    Portanova, Michel; Yabar, Alejandro; Lombardi, Emilio; Vargas, Fernando; Mena, Víctor; Carbajal, Ramiro; Palacios, Néstor; Orrego, Jorge

    2006-01-01

    This report describes the case of a patient who underwent total gastrectomy, splenectomy and pancreatomy corporo-postero as a consequence of gastric and pancreatic metastasis from carcinoma to clear cells, five years after having undergone radical nephrectomy. Upper digestive bleeding was the first symptom, and pancreatic lesion was detected in previous CT scans. There are many documented cases of pancreatic metastasis, but only eight gastric metastasis in the last 15 years, although we did not find reports about surgical treatment for concomitant gastric and pancreatic injury. Surgical treatment which in some reports include highly complex surgeries such as gastrectomies with combined resections of invaded organs and pancreatoduodenectomy, are good options for select cases, because good survival rates have been reported.

  1. Prognostic parameters determining survival in pancreatic carcinoma and, in particular, after palliative treatment.

    PubMed

    Ridwelski, K; Meyer, F; Ebert, M; Malfertheiner, P; Lippert, H

    2001-01-01

    Prognosis and outcome of patients with pancreatic carcinoma is poor. The aim of the study was to investigate (1) which factors of medical history and clinical status as well as which laboratory parameters determine survival in pancreatic carcinoma and (2) whether specific data can be used as prognostic parameters or for early diagnosis of pancreatic carcinoma. In total, 287 patients with pancreatic carcinoma were enrolled in the study. In 193 subjects, only palliative treatment was possible. Survival was assessed using univariate survival probability curves by Kaplan-Meier. Comparison of patient groups with regard to survival was achieved using the log-rank test. Multivariate analysis was carried out using the Cox regression model. Overall, 22 factors, showing a significant impact on survival in pancreatic carcinoma were found, e.g., tumor-associated factors such as (1) tumor stage according to the UICC classification including TNM-based staging, grading, tumor site, and vascular infiltration; (2) preoperative habits and signs and symptoms (physical condition, pain, loss of appetite, ethanol consumption); (3) change of laboratory parameters (CA 19-9, bilirubin, prothrombin time, urea, C-reactive protein), and (4) type of intervention (surgical approach, R0/1/2 resection). Using multivariate analysis, seven factors (UICC tumor stage and site, surgical intervention including number of resected lymph nodes, chemotherapy, occurence of a carcinoma in relatives, preoperative physical condition, night sweat) were determined. In the 193 patients with palliative treatment, only ten factors (among them UICC tumor stage including the presence of metastases; data from the medical history such as physical condition, loss of appetite, and carcinoma in relatives, and laboratory parameters including prothrombin time, protein content, and aspartate aminotransferase levels) were found to be important. Chemotherapy had the strongest impact on survival which was confirmed by

  2. Surgical management of hepato-pancreatic metastasis from renal cell carcinoma

    PubMed Central

    Chatzizacharias, Nikolaos A; Rosich-Medina, Anais; Dajani, Khaled; Harper, Simon; Huguet, Emmanuel; Liau, Siong S; Praseedom, Raaj K; Jah, Asif

    2017-01-01

    AIM To investigate the outcomes of liver and pancreatic resections for renal cell carcinoma (RCC) metastatic disease. METHODS This is a retrospective, single centre review of liver and/or pancreatic resections for RCC metastases between January 2003 and December 2015. Descriptive statistical analysis and survival analysis using the Kaplan-Meier estimation were performed. RESULTS Thirteen patients had 7 pancreatic and 7 liver resections, with median follow-up 33 mo (range: 3-98). Postoperative complications were recorded in 5 cases, with no postoperative mortality. Three patients after hepatic and 5 after pancreatic resection developed recurrent disease. Median overall survival was 94 mo (range: 23-94) after liver and 98 mo (range: 3-98) after pancreatic resection. Disease-free survival was 10 mo (range 3-55) after liver and 28 mo (range 3-53) after pancreatic resection. CONCLUSION Our study shows that despite the high incidence of recurrence, long term survival can be achieved with resection of hepatic and pancreatic RCC metastases in selected cases and should be considered as a management option in patients with oligometastatic disease. PMID:28255428

  3. Efficacy of Contrast-enhanced Harmonic Endoscopic Ultrasonography in the Diagnosis of Pancreatic Ductal Carcinoma

    PubMed Central

    Uekitani, Toshiyuki; Kaino, Seiji; Harima, Hirofumi; Suenaga, Shigeyuki; Sen-yo, Manabu; Sakaida, Isao

    2016-01-01

    Background/Aims: Distinguishing pancreatic ductal carcinoma (DC) from other pancreatic masses remains challenging. This study aims at evaluating the efficacy of contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) in the diagnosis of DC. Patients and Methods: Forty-nine patients with solid pancreatic mass lesions underwent CEH-EUS. EUS (B-mode) was used to evaluate the inner echoes, distributions, and borders of the masses. The vascular patterns of the masses were evaluated with CEH-EUS at 30–50 s (early phase) and 70–90 s (late phase) after the administration of Sonazoid®. Results: The final diagnoses included DCs (37), mass-forming pancreatitis (6), endocrine neoplasms (3), a solid pseudopapillary neoplasm (1), a metastatic carcinoma (1), and an acinar cell carcinoma (1). The sensitivity, specificity, and accuracy of the diagnoses of DC in hypoechoic masses using EUS (B-mode) were 89.2%, 16.7%, and 71.4%, respectively. The sensitivity, specificity, and accuracy for the diagnosis of DC in hypovascular masses using CEH-EUS were 73.0%, 91.7%, and 77.6% in the early phase and 83.8%, 91.7%, and 85.7% in the late phase, respectively. Conclusions: CEH-EUS for the diagnosis of DC is superior to EUS. CEH-EUS in the late phase was particularly efficacious in the diagnosis of DC. PMID:27184637

  4. Hematoporphyrin derivative uptake and photodynamic therapy in pancreatic carcinoma

    SciTech Connect

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

    1988-05-01

    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.

  5. A comparative proteomic study of plasma in feline pancreatitis and pancreatic carcinoma using 2-dimensional gel electrophoresis to identify diagnostic biomarkers: A pilot study

    PubMed Central

    Meachem, Melissa D.; Snead, Elisabeth R.; Kidney, Beverly A.; Jackson, Marion L.; Dickinson, Ryan; Larson, Victoria; Simko, Elemir

    2015-01-01

    While pancreatitis is now recognized as a common ailment in cats, the diagnosis remains challenging due to discordant results and suboptimal sensitivity of ultrasound and specific feline pancreatic lipase (Spec fPL) assay. Pancreatitis also shares similar clinical features with pancreatic carcinoma, a rare but aggressive disease with a grave prognosis. The objective of this pilot study was to compare the plasma proteomes of normal healthy cats (n = 6), cats with pancreatitis (n = 6), and cats with pancreatic carcinoma (n = 6) in order to identify potential new biomarkers of feline pancreatic disease. After plasma protein separation by 2-dimensional gel electrophoresis, protein spots were detected by Coomassie Brilliant Blue G-250 staining and identified by mass spectrometry. Alpha-1-acid glycoprotein (AGP), apolipoprotein-A1 (Apo-A1), and apolipoprotein-A1 precursor (Pre Apo-A1) appeared to be differentially expressed, which suggests the presence of a systemic acute-phase response and alteration of lipid metabolism in cats with pancreatic disease. Future studies involving greater case numbers are needed in order to assess the utility of these proteins as potential biomarkers. More sensitive proteomic techniques may also be helpful in detecting significant but low-abundance proteins. PMID:26130850

  6. Pancreatic ducts as an important route of tumor extension for acinar cell carcinoma of the pancreas.

    PubMed

    Ban, Daisuke; Shimada, Kazuaki; Sekine, Shigeki; Sakamoto, Yoshihiro; Kosuge, Tomoo; Kanai, Yae; Hiraoka, Nobuyoshi

    2010-07-01

    Acinar cell carcinoma (ACC) of the pancreas is very rare, which usually grows expansively. Recently, a variant of ACC with predominant growth in the pancreatic ducts has been proposed, and is speculated to have potentially less aggressive behavior. The aim of this study was to investigate how the pancreatic duct system is related to the growth and extension of ACC. We reviewed the detailed gross and histologic features of 13 cases of ACC, of which 7 (54%) showed intraductal polypoid growth (IPG) of the tumor in the large pancreatic ducts with a mean IPG length of 24.8 mm. Tumors with IPG were found to spread characteristically along the pancreatic ducts as extending polypoid projections, filling the ducts and destroying the duct walls, although tumors did not tend to extend beyond the pancreatic parenchyma. Comparison of the clinicopathologic characteristics showed that ACC with IPG had less infiltrative features including lymphatic, venous, and neural invasion, formation of tumor thrombus in the portal vein, nodal metastasis, and invasion beyond the pancreas to the surrounding organs; death in only 1 case (14%) of ACC with IPG was the result of ACC itself. In contrast, ACC without IPG frequently showed more infiltrative growth, and was the cause of death in 50% of patients with this type of tumor. Intraductal dissemination of ACC in pancreatic ducts was proven in 1 case of ACC with IPG. These findings suggest that a significant proportion of ACC shows IPG, which is potentially linked to less aggressive clinicopathologic characteristics.

  7. Percutaneous Irreversible Electroporation of Locally Advanced Pancreatic Carcinoma Using the Dorsal Approach: A Case Report

    SciTech Connect

    Scheffer, Hester J. Melenhorst, Marleen C. A. M.; Vogel, Jantien A.; Tilborg, Aukje A. J. M. van; Nielsen, Karin Kazemier, Geert; Meijerink, Martijn R.

    2015-06-15

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively.

  8. Postmortem examination of 22 pancreatic carcinoma patients treated with helium ion irradiation

    SciTech Connect

    Woodruff, K.H.; Castro, J.R.; Quivey, J.M.; Saunders, W.M.; Chen, G.T.; Lyman, J.T.; Pitluck, S.; Tobias, C.A.; Walton, R.E.; Peters, T.C.

    1984-02-01

    Postmortem findings are available in this report in 22 patients with pancreatic carcinoma treated with helium ions at Lawrence Berkeley Laboratory; California. This represents the largest group evaluated histologically in the literature and is the first report evaluating effects of particle radiation in pancreatic tissue. Patient survival after therapy averaged 9 months. Most died of infection and/or pulmonary emboli. Local control was achieved in 27%. The pancreatic tumors had histologically more severe radiation changes than nontumor bearing pancreas. Irradiated bone marrow was severely hypocellular, and irradiated skin was atrophic. Five patients had radiation injury in the gastrointestinal tract. The spinal cord, liver, and kidneys showed no damage. This study demonstrates the safety of helium particle irradiation with present therapeutic planning. Injury to tumor was seen without excessive damage to adjacent tissues.

  9. Comparison of CT and angiography in assessing resectability of pancreatic carcinoma

    SciTech Connect

    Jafri, S.Z.H.; Aisen, A.M.; Glazer, G.M.; Weiss, C.A.

    1984-03-01

    A retrospective study of 27 patients with pancreatic carcinoma compared computed tomography (CT) and angiography in their ability to predict resectability of the neoplasm, using encasement of the splanchnic vessels as the criterion for nonresectability. Five patients had resectable tumor at surgery; the other 22 had unresectable disease. Tumor involvement of the splanchnic vessels was determined in 18 patients by CT examination and in 19 patients by angiography. Several other patients were found to have liver metastases, resulting in a radiologic diagnosis of nonresectability in 20 patients overall. All patients considered to have unresectable disease on the basis of either radiologic method proved to have unresectable tumor at surgery. CT is about as accurate as angiography in assessing resectability of pancreatic carcinoma.

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

    SciTech Connect

    Davis, S.; Yamamoto, T.

    1986-09-01

    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.

  11. Pain Analysis in Patients with Pancreatic Carcinoma: Irreversible Electroporation versus Cryoablation

    PubMed Central

    Li, Jiannan; Sheng, Shihou; Zhang, Kai

    2016-01-01

    The aim of this article is to evaluate and compare the postprocedure pain in patients with pancreatic carcinoma treated with irreversible electroporation (IRE) and cryoablation (CRYO). We compared 22 patients with 22 lesions in pancreas treated with IRE and 26 patients with 27 lesions treated with cryosurgery. All the patients in the two groups were under celiac plexus block (CPB) treatment to alleviate the postprocedure pain. A numerical rating scale (VAS) consisting of 11-point scales and the 24 h total hydromorphone use were recorded for the analysis of the pain level in the patients who underwent these two technologies separately. Other parameters, such as the complications and the ECOG performance status, were also noted. Statistical analysis was performed by Fisher's exact test, the Chi-square test, and Student's t-test. All the pancreatic carcinoma patients in our study were reported to have postprocedure pain in the two groups. But there was no significant difference in the mean pain score (4.95 (IRE) versus 4.85 (CRYO); P = 0.52) and 24 h total hydromorphone use (3.89 mg (IRE) versus 3.97 mg (CRYO); P = 0.30). IRE is comparable to cryotherapy in the amount of pain that patients with pancreatic carcinoma experience. PMID:28074177

  12. Differentiation of pancreatic acinar carcinoma cells cultured on rat testicular seminiferous tubular basement membranes

    SciTech Connect

    Watanabe, T.K.; Hansen, L.J.; Reddy, N.K.; Kanwar, Y.S.; Reddy, J.K.

    1984-11-01

    The use of rat testicular seminiferous tubular basement membrane (STBM) segments as a model substratum for the in vitro maintenance of tumor cells dissociated from a transplantable pancreatic acinar rat carcinoma is described. Ultrastructurally pure, hollow tubular segments of STBM were prepared by mechanical disaggregation, DNase digestion, and deoxycholate treatment. Dissociated pancreatic acinar carcinoma cells adhered readily to STBM segments within 1 to 6 hr, and these STBM-tumor cell aggregates were maintained for up to 7 days in serum-free chemically defined medium supplemented with hydrocortisone, insulin, vitamin C, and soybean trypsin inhibitor. The tumor cells formed acinar-like clusters and displayed intercellular junctions and polarization of secretory granules toward the center of these clusters. By 4 days, virtually all cells of this acinar carcinoma maintained on STBM in supplemented chemically defined medium contained numerous secretory granules. Cell replication, as determined by (/sup 3/H)thymidine autoradiography, ceased within 18 hr of attachment of neoplastic cells to STBM; however, all cells incorporated (/sup 3/H)leucine as evidenced by light and electron microscopic autoradiography. In addition, two-dimensional analysis and fluorography of newly synthesized secretory proteins discharged by these cells in response to carbamylcholine revealed the presence of Mr 24,000 protein and 19 other secretory proteins characteristic of this tumor. The culture system utilizing STBM and supplemented chemically defined medium should allow investigation of the effects of a variety of factors on morphogenesis, cytodifferentiation, and gene expression in pancreatic acinar tumors.

  13. Characterization of 47D10, a glycoprotein associated with pancreatic carcinoma

    SciTech Connect

    Ho, M.K.; Kato, K.P.; Murray, J.H.; Wolfe, H.; Rabin, H.; Carney, W.P.

    1986-03-05

    A mouse monoclonal antibody (MAb), 47D10, was raised against a human lung adenocarcinoma cell line, A549. 47D10 bound to lines derived from breast, colon, lung, and pancreatic tumors, but not to normal fibroblasts. Granulocytes also expressed 47D10 but red blood cells and lymphocytes were negative. Immunoperoxidase staining of paraffin-embedded tissues indicated that 47D10 was reactive with 36 out of 38 cases of pancreatic adenocarcinoma, but not with chronic pancreatitis, regenerative pancreas or normal pancreas. The 47D10 antigen was a group of surface glycoproteins ranging from 63-97Kd (average Mr 85Kd). The antigen could be labeled by /sup 35/S-methionine, /sup 125/I, tritiated glucosamine, fucose, and mannose. Pulse-chase labeling showed that the 63-97Kd mature antigens were derived from precursors of 63Kd and 65Kd. The mature antigen was sensitive to endoglycosidase F (endo F) whereas the precursors were susceptible to both endoglycosidase H and endo F. Endo F digestion resulted in a polypeptide of 38Kd. Therefore, the 47D10 antigen is composed of at least 55% N-linked carbohydrates. The 47D10 MAb seems to be distinct from previously identified MAb against pancreatic tumors and may be useful in the diagnosis of pancreatic carcinoma.

  14. Intravenous phentolamine infusion alleviates the pain of abdominal visceral cancer, including pancreatic carcinoma.

    PubMed

    Yasukawa, Masako; Yasukawa, Ken'ichi; Kamiizumi, You; Yokoyama, Ryouji

    2007-01-01

    This case report series describes eight patients (four patients with pancreatic carcinoma, one patient with hepatocellular carcinoma, one patient with gastric and rectal carcinoma, one with sigmoid colon cancer, and one with rectal cancer), whose abdominal cancer pain was treated with intravenous phentolamine infusion at 80 mg x day(-1) for 2 days. All but one of the patients had already been treated with opioids. All eight patients complained of severe abdominal pain; in five patients the pain radiated to the back, and there was associated anal pain in two patients. Analgesia was achieved in three patients; pain alleviation was obtained in four patients, but was not sustained in two of these four patients; and the treatment in one patient could not be judged for efficacy because epidural morphine was used together with the phentolamine. Adverse effects of phentolamine were tachycardia and/or hypotension.

  15. Quantification of pancreatic secretory trypsin inhibitor in colonic carcinoma and normal adjacent colonic mucosa.

    PubMed Central

    Bohe, H; Bohe, M; Jönsson, P; Lindström, C; Ohlsson, K

    1992-01-01

    AIMS: To measure the content of immunoreactive human pancreatic secretory trypsin inhibitor (irPSTI) in colonic carcinoma and adjacent normal colonic mucosa. METHODS: From a stable hybridoma cell line producing monoclonal antibodies specific for human PSTI, a specific enzyme linked immunosorbent assay (ELISA) for human PSTI was developed. In a precipitation assay system these antibodies bound human PSTI in a dose-dependent manner. The specimens were obtained from resectional surgery. RESULTS: The content of irPSTI was 19.9 micrograms/g protein (0.55 micrograms/g tissue wet weight) in colonic carcinoma. In adjacent normal colonic mucosa 43.6 micrograms/g protein (1.12 micrograms/g tissue wet weight) was shown. CONCLUSIONS: The enzymatic degradation of surrounding tissue necessary for tumour cell invasion could be facilitated by this relative deficit of the inhibitor in infiltrative carcinoma. PMID:1479031

  16. MicroRNA-7 functions as a tumor-suppressor gene by regulating ILF2 in pancreatic carcinoma.

    PubMed

    Bi, Yiliang; Shen, Wei; Min, Min; Liu, Yan

    2017-04-01

    Interleukin enhancer binding factor 2 (ILF2) has been found to be markedly upregulated in pancreatic carcinoma and is involved in the pathogenesis of pancreatic carcinoma. Thus, ILF2 may be a potential target for therapy. Yet, the regulatory mechanisms of ILF2 in pancreatic carcinoma remain largely elusive. In the present study, we demonstrated that ILF2 functioned as an oncogene and regulated epithelial-mesenchymal transition (EMT)-associated genes in pancreatic carcinoma PANC-1 cells. MicroRNA-7 (miR-7) suppressed ILF2 mRNA expression and the protein level in PANC-1 cells. Contrary to ILF2, miRNA-7 functioned as a tumor-suppressor gene and negatively regulated EMT-associated genes in the PANC-1 cells. Curcumin, a polyphenol natural product isolated from the rhizome of the plant Curcuma longa, has emerged as a promising anticancer therapeutic agent. We found that treatment with curcumin increased miR-7 expression and suppressed ILF2 protein in the PANC-1 cells. Thus, we identified ILF2 as a new downstream target gene of curcumin. The results revealed that ILF2 is regulated by miR-7 and suggest that downregulation of miR-7 may be an important factor for the ILF2 overexpression in pancreatic carcinoma.

  17. MicroRNA-7 functions as a tumor-suppressor gene by regulating ILF2 in pancreatic carcinoma

    PubMed Central

    Bi, Yiliang; Shen, Wei; Min, Min; Liu, Yan

    2017-01-01

    Interleukin enhancer binding factor 2 (ILF2) has been found to be markedly upregulated in pancreatic carcinoma and is involved in the pathogenesis of pancreatic carcinoma. Thus, ILF2 may be a potential target for therapy. Yet, the regulatory mechanisms of ILF2 in pancreatic carcinoma remain largely elusive. In the present study, we demonstrated that ILF2 functioned as an oncogene and regulated epithelial-mesenchymal transition (EMT)-associated genes in pancreatic carcinoma PANC-1 cells. MicroRNA-7 (miR-7) suppressed ILF2 mRNA expression and the protein level in PANC-1 cells. Contrary to ILF2, miRNA-7 functioned as a tumor-suppressor gene and negatively regulated EMT-associated genes in the PANC-1 cells. Curcumin, a polyphenol natural product isolated from the rhizome of the plant Curcuma longa, has emerged as a promising anticancer therapeutic agent. We found that treatment with curcumin increased miR-7 expression and suppressed ILF2 protein in the PANC-1 cells. Thus, we identified ILF2 as a new downstream target gene of curcumin. The results revealed that ILF2 is regulated by miR-7 and suggest that downregulation of miR-7 may be an important factor for the ILF2 overexpression in pancreatic carcinoma. PMID:28259961

  18. Metastasized pancreatic carcinoma with neoadjuvant FOLFIRINOX therapy and R0 resection

    PubMed Central

    Schneitler, Sophie; Kröpil, Patric; Riemer, Jasmin; Antoch, Gerald; Knoefel, Wolfram Trudo; Häussinger, Dieter; Graf, Dirk

    2015-01-01

    Patients with metastasized carcinoma of the pancreas have a very poor prognosis, and long-term survival cannot be expected. This case report describes two patients with an initial diagnosis of metastatic pancreatic cancer, both with hepatic metastases and one with an additional peritoneal carcinomatosis. Initially, both patients were treated intravenously with the FOLFIRINOX chemotherapy regimen, consisting of 5-FU, folinic acid, irinotecan and oxaliplatin. Surprisingly, the FOLFIRINOX treatment resulted in complete resolution of the hepatic metastases in both patients, with no lesions detectable by computed tomography scan. Furthermore, treatment response included decreased diameter of the primary tumor in the tail of the pancreas and disappearance of the additional peritoneal carcinomatosis. Both patients were discussed by our multidisciplinary tumor board, which recommended surgical resections of the carcinoma. The R0 resection of the primary tumor was successful in both cases and, interestingly, the resected tissues showed no evidence of the hepatic metastases intraoperatively. In the first case, the patient received a postoperative 6-mo course of adjuvant chemotherapy with gemcitabine. In the second case, the patient continued to receive the FOLFIRINOX regimen for an additional 6 mo postoperatively. At 12 mo after the operation, a nonresectable retroperitoneal lymph node metastasis was detected in the first patient, whereas the second patient remained in complete remission at the time of this report (5 mo after the adjuvant therapy was discontinued). This case report is the first of its kind to describe two cases of hepatic metastatic pancreatic carcinoma that were resectable following treatment with FOLFIRINOX. Further studies are required to examine the role of FOLFIRINOX as a neoadjuvant treatment option in subgroups of patients with initially metastasized pancreatic carcinoma. PMID:26034375

  19. Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma

    PubMed Central

    Kimbara, Shiro; Kondo, Shunsuke

    2016-01-01

    Pancreatic adenocarcinoma (PAC) is one of the most deadly malignant neoplasms, and the efficacy of conventional cytotoxic chemotherapy is far from satisfactory. Recent research studies have revealed that immunosuppression and inflammation are associated with oncogenesis, as well as tumor development, invasion, and metastasis in PAC. Thus, immunosuppression-related signaling, especially that involving immune checkpoint and inflammation, has emerged as novel treatment targets for PAC. However, PAC is an immune-resistant tumor, and it is still unclear whether immune checkpoint or anti-inflammation therapies would be an ideal strategy. In this article, we will review immune checkpoint and inflammation as potential targets, as well as clinical trials and the prospects for immunotherapy in PAC. PMID:27672267

  20. Pancreatic panniculitis associated with acinar cell carcinoma of the pancreas: a case report.

    PubMed

    Zheng, Zhen Jiang; Gong, Jun; Xiang, Guang Ming; Mai, Gang; Liu, Xu Bao

    2011-05-01

    Pancreatic panniculitis is a rare type of disorder associated with pancreatic diseases. We describe here a case of 54-year-old man who was admitted to the Department of Dermatology with the diagnosis of erythema nodosum. The patient presented with a 9-month history of painful erythematous nodules on the extremities, joint pain and swelling, and weight loss. A highly elevated level of pancreatic lipase was found on the laboratory examinations. The biopsy specimens from the skin lesions showed subcutaneous fat necrosis. Abdominal computed tomography (CT) revealed a large mass with central necrosis in the body and tail of the pancreas. Distal pancreatectomy, splenectomy and partial transverse colectomy were successfully performed on day 17 of the hospitalization. The histopathologic findings supported the diagnosis of acinar cell carcinoma of the pancreas (ACCP). Postoperatively, the level of serum lipase returned to normal, and the skin lesions and joint manifestations gradually regressed. However, the swelling did not significantly resolve in the left knee. In view of the non-specific clinical presentation of this disease, clinicians should be alert and have a high index of suspicion for pancreatic panniculitis.

  1. Iodine-125 implant and external beam irradiation in patients with localized pancreatic carcinoma. [Efficacy and complications

    SciTech Connect

    Shipley, W.U.; Nardi, G.L.; Cohen, A.M.; Ling, C.C.

    1980-02-15

    Twelve patients with biopsy-proven clinically localized ductal pancreatic cancers (less than 7 cm in greatest diameter) judged unsuitable for resection were treated by bypass surgery, an Iodine-125 implant (20 to 39 mCi), and postoperative irradiation (4000 to 4500 rads). The potential problems of significant bleeding, pancreatic fistula, or pancreatitis were not experienced. A local recurrence developed in one patient and two recurred in regional lymph nodes. The projected median survival of the group is 11 months with four of the 12 patients still surviving. For purposes of comparison all patients with pancreatic ductal carcinoma treated by radical resection during a similar time were evaluated. All ten have died with a median survival of six months. Twelve of 22 (55%) of the combined implanted and resected groups have developed distant metastasis. Further pursuit of intraoperative techniques of irradiation in combination with adjuvant multidrug chemotherapy seems indicated in an attempt to prolong patient survival which is now limited by hematogenous metastases.

  2. Endosonography and cytology in diagnosing and staging pancreatic body and tail carcinoma: Preliminary results of endosonographic guided puncture

    SciTech Connect

    Tio, T.L.; Sie, L.H.; Tytgat, G.N.J. Academic Medical Center, Amsterdam )

    1993-01-01

    Endosonography was performed in diagnosing and staging pancreatic body and tail carcinoma in two patients. In the first case endoscopy, abdominal ultrasound, and computed tomography were nondiagnostic in diagnosing the origin of submucosal gastric abnormalities. Endosonography diagnosed a pancreatic tail carcinoma with submucosal gastric involvement, and this was confirmed by endosonographic-guided cytology. Fundus varices due to segmented splenic vein involvement were found. Surgery was not recommended due to the advanced disease. In the second case pancreatic body carcinoma was diagnosed by ERCP and computed tomography. Transcutaneous ultrasonographic-guided cytological puncture confirmed the diagnosis. Endosonography revealed additional information of segmental portal hypertension with fundic varices due to splenic vein involvement. Autopsy confirmed the endosonographic diagnosis. 18 refs., 5 figs.

  3. Diagnosis of primary squamous cell carcinoma of the pancreas using endoscopic ultrasound-guided core needle biopsy.

    PubMed

    Kashani, Amir; Kahn, Melissa; Jamil, Laith H

    2015-05-16

    Primary squamous cell carcinoma (SCC) of the pancreas is a particularly rare entity. Diagnosis of this tumor is tentatively made after ruling out metastatic SCC from another primary site and adenosquamous carcinoma (ASC) of the pancreas. Here we discuss the case of a 76-year-old woman who was found to have a solitary pancreatic lesion and multiple hepatic lesions. Results of computed tomography-guided biopsy of the liver lesions were consistent with a metastatic carcinoma displaying squamous differentiation; therefore, an endoscopic ultrasound (EUS)-guided core-needle biopsy (CNB) of the pancreatic mass was performed. Meticulous histopathological examination of the pancreatic specimen at multiple levels revealed moderately well-differentiated SCC with no glandular component. An extensive metastatic work-up did not reveal an extra-pancreatic origin for this SCC; hence, a diagnosis of primary SCC of the pancreas was established. To our knowledge, this is the first report of the diagnosis of a primary SCC of the pancreas using EUS-guided CNB. We believe that CNB has a diagnostic yield equivalent to that of fine-needle aspiration for recognizing pancreatic adenocarcinoma; however, when cytological examinations reveal atypical squamous epithelial cells suggestive of malignancy, CNB may provide a better tissue specimen, from which to determine the presence of a glandular component. Such an assessment will differentiate pancreatic SCC from ASC.

  4. Scintigraphic detection of gastric and pancreatic carcinomas with In-111 ZCE 025 monoclonal antibody

    SciTech Connect

    Abdel-Nabi, H.H.; Schwartz, A.N.; Wechter, D.G.; Higano, C.S.; Ortman-Nabi, J.A.; Unger, M.W. )

    1991-01-01

    We have evaluated the role of In-111 anti-CEA (carcinoembryonic antigen) monoclonal antibody ZCE 025 in 8 patients. Three patients had a confirmed diagnosis of gastric carcinoma. Three had a confirmed diagnosis of pancreatic carcinoma. Two patients had elevated serum levels of CEA with no known primary. Each patient received 5.5 mCi In-111 ZCE 025 infused at doses of 10-80 mg. Planar and single photon emission computed tomography (SPECT) imaging at 3 and 7 days after infusion detected 9 of 12 known tumor sites and all 5 of the previously identified sites of metastasis. In-111 ZCE 025 MoAb imaging also found 6 previously unsuspected tumor sites and changed the preoperative evaluation in 50% of the patients studied. It changed the clinical management in 2 patients and established the site of primary involvement in 2 others. There were no clinical or biochemical reactions. In-111 ZCE 025 monoclonal antibody scintigraphy is a useful adjunct in the evaluation of patients with either gastric or pancreatic carcinoma. It may have a beneficial impact on the surgical decision making in these patients.

  5. A case report of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct.

    PubMed

    Okazaki, Mitsuyoshi; Makino, Isamu; Kitagawa, Hirohisa; Nakanuma, Shinichi; Hayashi, Hironori; Nakagawara, Hisatoshi; Miyashita, Tomoharu; Tajima, Hidehiro; Takamura, Hiroyuki; Ohta, Tetsuo

    2014-01-21

    We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct. A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor. Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas, accompanied with severe dilatation of the main pancreatic duct, which was diagnosed as an intraductal papillary-mucinous neoplasm. We performed distal pancreatectomy and splenectomy. The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma (giant cell type) and adenocarcinoma in the pancreas. There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct. The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery. In this case, we could observe a remarkable intraductal tumor growth into the main pancreatic duct. We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth.

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

    PubMed Central

    Andoh, Yoshiaki; Makino, Naohiko; Yamakawa, Mitsunori

    2013-01-01

    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

  7. Immunotherapy for patients with advanced pancreatic carcinoma: a promising treatment

    PubMed Central

    Liu, Jing; Lian, Zhouyang; Liang, Long; Chen, Wenbo; Luo, Xiaoning; Pei, Shufang; Mo, Xiaokai; Zhang, Lu; Huang, Wenhui; Ouyang, Fusheng; Guo, Baoliang; Liang, Changhong; Zhang, Shuixing

    2017-01-01

    There are limited data on the safety and efficacy of immunotherapy for patients with advanced pancreatic cancer (APC). A meta-analysis of single-arm trials is proposed to assess the efficacy and safety of immunotherapy for APC. Eighteen relevant studies involving 527 patients were identified. The pooled disease control rate (DCR), overall survival (OS), progression free survival (PFS), and 1-year survival rate were estimated as 59.32%, 7.90 months, 4.25 months, and 30.12%, respectively. Subgroup analysis showed that the pooled OS, PFS, and 1-year survival rate were significantly higher for autologous activated lymphocyte therapy compared with peptide-based vaccine therapy (OS: 8.28 months vs. 7.40 months; PFS: 6.04 months vs. 3.86 months; 1-year survival rate: 37.17% vs. 19.74%). Another subgroup analysis demonstrated that the pooled endpoints were estimated as obviously higher for immunotherapy plus chemotherapy compared with immunotherapy alone (DCR: 62.51% vs. 47.63%; OS: 8.67 months vs. 4.91 months; PFS: 4.91 months vs. 3.34 months; 1-year survival rate: 32.32% vs. 21.43%). Of the included trials, seven trials reported no treatment related adverse events , five trials reported (16.6 3.9) % grade 3 adverse events and no grade 4 adverse events. In conclusion, immunotherapy is safe and effective in the treatment of APC. PMID:27992378

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

    PubMed

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

    1980-10-01

    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.

  9. Combination Chemotherapy With or Without Oregovomab Followed by Stereotactic Body Radiation Therapy and Nelfinavir Mesylate in Treating Patients With Locally Advanced Pancreatic Cancer

    ClinicalTrials.gov

    2017-02-28

    Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma; Stage I Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

  10. Sudden disappearance of the blood flow in a case of pancreatic acinar cell carcinoma.

    PubMed

    Kanno, Atsushi; Masamune, Atsushi; Hamada, Shin; Kikuta, Kazuhiro; Kume, Kiyoshi; Hirota, Morihisa; Shima, Kentaro; Okada, Takaho; Motoi, Fuyuhiko; Fujishima, Fumiyoshi; Ishida, Kazuyuki; Unno, Michiaki; Shimosegawa, Tooru

    2014-01-01

    A 55-year-old man was referred to our hospital for a further examination of a pancreatic cystic tumor with a solid component exhibiting vascularity. A few days later, the patient was admitted with a complaint of sudden severe epigastric pain. Enhanced CT showed the loss of vascularity in the tumor. In particular, contrast-enhanced endoscopic ultrasonography (EUS) clearly demonstrated the disappearance of the blood flow, and a histological examination revealed acinar cell carcinoma with central necrosis. To our knowledge, this is the first case in the literature of acinar cell carcinoma associated with the sudden disappearance of vascularity. In this case, contrast-enhanced harmonic EUS was especially useful for assessing the degree of vascularity.

  11. Altered coupling of muscarinic acetylcholine receptors in pancreatic acinar carcinoma of rat

    SciTech Connect

    Chien, J.L.; Warren, J.R.

    1986-03-05

    The structure and function of muscarinic acetylcholine receptors (mAChR) in acinar carcinoma cells have been compared to mAChR in normal pancreatic acinar cells. Similar 80 kD proteins identified by SDS-PAGE of tumor and normal mAChR affinity-labeled with the muscarinic antagonist /sup 3/H-propylbenzilyl-choline mustards, and identical binding of the antagonist N-methylscopolamine to tumor and normal cells (K/sub D/approx.4x10/sup -10/ M), indicate conservation of mAChR proteins in carcinoma cells. Carcinoma mAChR display homogeneous binding of the agonists carbamylcholine (CCh), K/sub D/approx.3x10/sup -5/ M, and oxotremorine (Oxo), K/sub D/approx.x10/sup -6/ M, whereas normal cells display heterogeneous binding, with a minor component of high affinity interactions for CCh, K/sub D/approx.3x10/sup -6/ M, and Oxo, K/sub D/approx.2x/sup -17/ M, and a major component of low affinity interactions for CCh, K/sub D/approx.1x10/sup -4/ M, and Oxo, K/sub D/approx.2x10/sup -5/ M. Both carcinoma and normal cells exhibit concentration-dependent CCh-stimulated increase in cytosolic free Ca/sup 2 +/, as measured by intracellular Quin 2 fluorescence and /sup 45/Ca/sup 2 +/ efflux. However, carcinoma cells demonstrate 50% maximal stimulation of intracellular Ca/sup 2 +/ release at a CCh concentration (EC/sub 50/approx.6x10/sup -7/ M) one log below that observed for normal cells. The authors propose an altered coupling of mAChR to intracellular Ca/sup 2 +/ homeostasis in carcinoma cells, which is manifest as a single activated receptor state for agonist binding, and increased sensitivity to muscarinic receptor stimulation of Ca/sup 2 +/ release.

  12. CA19-9: A promising tumor marker for pancreatic carcinoma

    SciTech Connect

    Sakahara, H.; Endo, K.; Nakajima, K.; Hidaka, A.; Nakashima, T.; Ohta, H.; Torizuka, K.; Naito, A.; Suzuki, T.

    1984-01-01

    In order to evaluate CA19-9 as a tumor marker for pancreatic carcinoma (PC), serum levels of CA19-9 were compared with those of CEA and elastase-1 in 56 patients, consisted of 43 cases with histologically proven adenocarcinomas and 13 cases with chronic pancreatitis. Serum levels were determined by using RIA kit obtained from CIS, France (CA19-9 and CEA) and Abbot (elastase-1). CA19-9 gave the highest accuracy among tumor markers the authors have studied and serum levels were markedly elevated over 100U/ml in 30 (70%) cases with PC, whereas none in chronic pancreatitis. CA19-9 values were closely related to the tumor size and the presence or absence of metastsis on CT findings. Small tumors of less than 3cm in diameter, although the site of tumor was limited to the head of the pancreas, showed positive results in 2 out of 5 cases. Furthermore, CA19-9 was at a level of less than 22U/ml in 98 normal controls and was found to be elevated in only 4 (3%) out of 124 patients with benign diseases, including liver diseases, gastric ulcer, cholelithiasis, and so on. These results indicate that CA19-9 is much better in diagnosis and management of PC than is CEA.

  13. Fat necrosis with features of erythema nodosum in a patient with metastatic pancreatic carcinoma.

    PubMed

    Durden, F M; Variyam, E; Chren, M M

    1996-01-01

    A 59-year-old man presented with painful subcutaneous nodules on the anterior surfaces of the legs. He had received oral antibiotics and supportive care for presumed cellulitis and thrombophlebitis, but had minimal improvement. Five months earlier, he had undergone pancreaticoduodenectomy for acinar pancreatic carcinoma; at that time, the serum level of amylase had been normal, but the level of lipase was elevated. The patient denied fever, rigors, arthritis/arthralgia, or pleuritic pain. His medications included aspirin, furosemide, ranitidine, and nortriptyline. He denied any allergies. Physical examination revealed numerous firm, tender, erythematous and violaceous, subcutaneous nodules on the lower extremities, with marked bilateral pitting edema (Fig. 1). Skin biopsy of a representative lesion revealed septal panniculitis, consistent with erythema nodosum (Fig. 2). None of the characteristic changes of pancreatic fat necrosis was present. The patient was treated with aspirin, 650 mg orally, q 6 h, and indomethacin, 50 mg orally, q 12 h, but he continued to develop new nodules; prednisone, 60 mg orally was begun. Although he reported improvement in symptoms, the nodules failed to respond clinically and older nodules ulcerated along the medical aspect of the right leg (Fig. 3). The complete blood count was normal, except for hemoglobin, 10.9 mg per dL. Routine serum biochemical studies were also normal, except for albumin, 3.1 mg per dL, LDH, 312 U per L, and SGOT, 51 U per L. Serum amylase was 14 U per L (normal per 30 to 115 U per L) and serum lipase was 54,160 U per L (normal 0 to 200 U per L). Chest roentgenogram and tuberculin skin test were negative. A CT scan of the abdomen revealed extensive liver metastases. A second biopsy of the skin and subcutis of a necrotic nodule revealed lobular panniculitis with the characteristic picture seen in pancreatic fat necrosis (Fig. 4). The patient was presumed to have metastatic pancreatic carcinoma and pancreatic fat

  14. Thickening of the celiac axis and/or superior mesenteric artery: a sign of pancreatic carcinoma on computed tomography

    SciTech Connect

    Megibow, A.J.; Bosniak, M.A.; Ambos, M.A.; Beranbaum, E.R.

    1981-11-01

    Of 53 patients with carcinoma of the pancreas studied by computed tomography, 20 (37.7%) had apparent thickening of either the celiac axis or superior mesenteric artery. In 6 of them, the pancreatic mass was poorly defined. The frequency of this sign, correlation with angiographic findings, and pathogenesis are discussed.

  15. A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma

    PubMed Central

    Yan, Li; Chen, Yong-Liang; Su, Ming; Liu, Tian; Xu, Kai; Liang, Feng; Gu, Wan-Qing; Lu, Shi-Chun

    2016-01-01

    Background: Locally advanced pancreatic carcinoma (LAPC) is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation (IRE) has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC. Methods: Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE. Results: All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed (16%): two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge. Conclusions: IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy. PMID:27958223

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

    PubMed

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

    1996-02-01

    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

  17. Pancreatitis

    MedlinePlus

    ... removal is sometimes performed along with a sphincterotomy. Stent placement. Using the endoscope, the doctor places a ... a narrowed pancreatic or bile duct. A temporary stent may be placed for a few months to ...

  18. Nitric oxide signaling pathway activation inhibits the immune escape of pancreatic carcinoma cells

    PubMed Central

    LU, YEBIN; HU, JUANJUAN; SUN, WEIJIA; DUAN, XIAOHUI; CHEN, XIONG

    2014-01-01

    The aim of the present study was to investigate the effect of the nitric oxide signaling pathway on immune escape; thus, a tumorigenesis model was established using nude mice. The mice were inoculated with pancreatic carcinoma cells and divided into two groups, a glyceryl trinitrate (GTN) and a placebo group. When tumor volumes reached 150 mm3, the mice in the GTN group were treated with GTN transdermal patches (dose, 7.3 μg/h) while the mice in the placebo group were administered untreated patches. Following treatment, the tumor volume was recorded every 3–4 days and after 28 days, the tumors were analyzed. The results indicated that GTN treatment may reduce the levels of soluble major histocompatibility complex class I chain-related molecules, and natural killer group 2 member D, as well as inhibiting tumor growth. PMID:25364398

  19. An Unusual Presentation of Isolated Leptomeningeal Disease in Carcinoma of Unknown Primary With Pancreatic Features.

    PubMed

    Anne, Madhurima; Ahmad, Nazish; Lee, Paul; Aziz, Mohamed; Lebowicz, Yehuda

    2013-01-01

    Leptomeningeal disease (LMD) can occur in a small percentage of patients with active metastatic cancer. However, we report a case of LMD occurring during disease remission in a patient with carcinoma of unknown primary with panreaticobiliary features. A 45-year-old woman was found with mediastinal and abdominal lymphadenopathy with lymph node biopsy consistent with adenocarcinoma, expressing immunomarkers CK7, CK20, and Ca19-9 along with markedly elevated serum Ca19-9 level. The patient was started on a pancreatic cancer directed chemotherapy regimen of Folfirinox (5-fluorouracil, leucovorin, oxaliplatin, irinotecan) and achieved complete response. She was then noted to have slowly rising Ca19-9 level that did not correlate with her lack of evidence of systemic disease progression. Eventually, she presented with neurologic symptoms and was found on imaging to have isolated LMD.

  20. Recycling of epidermal growth factor in a human pancreatic carcinoma cell line

    SciTech Connect

    Korc, M.; Magun, B.E.

    1985-09-01

    PANC-1 human pancreatic carcinoma cells readily bound and internalized /sup 125/I-labeled epidermal growth factor (EGF). Bound /sup 125/I-labeled EGF was then partially processed to a number of high molecular weight acidic species. Percoll gradient centrifugation of cell homogenates indicated that the majority of /sup 125/I activity localized to several intracellular vesicular compartments. Both intact EGF and its processed species were subsequently released into the incubation medium. A major portion of the released radioactivity was capable of rebinding to the cell. Only a small amount of bound /sup 125/I-labeled EGF was degraded to low molecular weight products, and this degradation was completely blocked by methylamine. These findings suggest that in PANC-1 cells, bound EGF undergoes only limited processing. Both intact EGF and its major processed species bypass the cellular degradative pathways, are slowly released from the cell, and then rebind to the cell.

  1. Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

    ClinicalTrials.gov

    2017-02-24

    BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Metastatic Pancreatic Adenocarcinoma; PALB2 Gene Mutation; Pancreatic Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  2. Isoalantolactone Induces Reactive Oxygen Species Mediated Apoptosis in Pancreatic Carcinoma PANC-1 Cells

    PubMed Central

    Khan, Muhammad; Ding, Chuan; Rasul, Azhar; Yi, Fei; Li, Ting; Gao, Hongwen; Gao, Rong; Zhong, Lili; Zhang, Kun; Fang, Xuedong; Ma, Tonghui

    2012-01-01

    Isoalantolactone, a sesquiterpene lactone compound possesses antifungal, antibacteria, antihelminthic and antiproliferative activities. In the present study, we found that isoalantolactone inhibits growth and induces apoptosis in pancreatic cancer cells. Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of reactive oxygen species, cardiolipin oxidation, reduced mitochondrial membrane potential, release of cytochrome c and cell cycle arrest at S phase. N-Acetyl Cysteine (NAC), a specific ROS inhibitor restored cell viability and completely blocked isoalantolactone-mediated apoptosis in PANC-1 cells indicating that ROS are involved in isoalantolactone-mediated apoptosis. Western blot study showed that isoalantolactone increased the expression of phosphorylated p38 MAPK, Bax, and cleaved caspase-3 and decreased the expression of Bcl-2 in a dose-dependent manner. No change in expression of phosphorylated p38 MAPK and Bax was found when cells were treated with isoalantolactone in the presence of NAC, indicating that activation of these proteins is directly dependent on ROS generation. The present study provides evidence for the first time that isoalantolactone induces ROS-dependent apoptosis through intrinsic pathway. Furthermore, our in vivo toxicity study demonstrated that isoalantolactone did not induce any acute or chronic toxicity in liver and kidneys of CD1 mice at dose of 100 mg/kg body weight. Therefore, isoalantolactone may be a safe chemotherapeutic candidate for the treatment of human pancreatic carcinoma. PMID:22532787

  3. Hepatoid carcinoma of the pancreas with lymphoid stroma: first description of the clinical, morphological, immunohistochemical, and molecular characteristics of an unusual pancreatic carcinoma.

    PubMed

    Vanoli, Alessandro; Argenti, Francesca; Vinci, Alessio; La Rosa, Stefano; Viglio, Alessandra; Riboni, Roberta; Necchi, Vittorio; Pugliese, Luigi; Sessa, Fausto; Pietrabissa, Andrea; Paulli, Marco

    2015-08-01

    We report a case of tumour in the head of the pancreas observed in a 57-year-old man with a history of worsening jaundice and elevated alpha-fetoprotein (AFP) serum level, who underwent Whipple pancreatoduodenectomy. Histologically, the tumour was predominantly composed of solid sheets of large eosinophilic cells with a prominent lymphoid infiltration without association neither with DNA microsatellite instability nor Epstein-Barr virus infection. The tumour was diffusely and strongly positive for hepatocyte paraffin-1 (Hep Par-1) and glypican-3 leading to the diagnosis of hepatoid carcinoma. Strong cytoplasmic staining for AFP was focally observed. Moreover, tumour cells showed countless cytoplasmic eosinophilic globules immunoreactive for the stress protein p62. A primary hepatocellular carcinoma of the liver was ruled out by careful clinical analysis. Hepatoid carcinoma is an extremely rare pancreatic neoplasm, and here, we describe the first case of such variant associated with lymphoid stroma. The characteristic histologic features and the immunophenotypic profile help in distinguishing this carcinoma from other pancreatic tumours, notably from medullary carcinoma.

  4. Radiation promotes epithelial-to-mesenchymal transition and invasion of pancreatic cancer cell by activating carcinoma-associated fibroblasts

    PubMed Central

    Li, Doudou; Qu, Chao; Ning, Zhouyu; Wang, Haiyong; Zang, Kun; Zhuang, Liping; Chen, Lianyu; Wang, Peng; Meng, Zhiqiang

    2016-01-01

    The tumor microenvironment is of crucial importance affecting treatment and prognosis. High degree of carcinoma-associated fibroblast (CAF) infiltration occurs in pancreatic cancer, though its effect on radiotherapy remains unclear. In this study, we demonstrated that radiation enhanced the migration- and invasion-promoting capacity of CAFs both in vitro and in vivo in a lung metastasis model. Radiation exposure increased the expression of CXCL12 by CAFs. CAF-derived CXCL12 promoted tumor cell EMT and invasion directly, acting through CXCR4 on pancreatic cancer cells. In addition, we showed that CXCL12-CXCR4 signaling promoted pancreatic cancer cell EMT and invasion by activating the P38 pathway. Therefore, our study concluded that radiation promoted pancreatic cancer cell invasion and EMT by activating CAFs, while inhibiting the CXCL12/CXCR4 interaction between pancreatic cancer cells and CAFs could potentially attenuate tumor cell invasion induced by radiation, which provides an opportunity for the development of novel therapeutic targets to improve the prognosis for human pancreatic cancer treated with radiation therapy. PMID:27822411

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

    ClinicalTrials.gov

    2016-09-21

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

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

    SciTech Connect

    Ikeda, O. Kusunoki, S.; Kudoh, K.; Takamori, H.; Tsuji, T.; Kanemitsu, K.; Yamashita, Y.

    2006-06-15

    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.

  7. Radiation therapy combined with Adriamycin or 5-fluorouracil for the treatment of locally unresectable pancreatic carcinoma. Gastrointestinal Tumor Study Group

    SciTech Connect

    Not Available

    1985-12-01

    One hundred fifty-seven patients with locally unresectable pancreatic carcinoma were randomly allocated to therapy with radiation and 5-fluorouracil or radiation and Adriamycin (doxorubicin). A total of 138 of 143 analyzable patients have died, and no differences in the relative survival impact of the treatments have been observed. Toxicity on the Adriamycin arm was more substantial and primarily attributable to Adriamycin chemotherapy after the completion of radiotherapy.

  8. A spindle cell anaplastic pancreatic carcinoma with rhabdoid features following curative resection

    PubMed Central

    Abe, Tomoyuki; Amano, Hironobu; Hanada, Keiji; Okazaki, Akihisa; Yonehara, Shuji; Kuranishi, Fumito; Nakahara, Masahiro; Kuroda, Yoshinori; Noriyuki, Toshio

    2016-01-01

    Anaplastic pancreatic carcinoma (ANPC) accounts for ~5% of all pancreatic ductal adenocarcinoma cases. Due to its rarity, its clinical features and surgical outcomes remain to be clearly understood. A 74-year-old woman was admitted to Onomichi General Hospital (Onomichi, Japan) in April 2015 without any significant past medical history. Contrast-enhanced computed tomography (CT) revealed a 9.5×8.0 cm tumor in the body and tail of the pancreas. The patient developed acute abdominal pain 3 weeks later and the CT revealed massive abdominal bleeding caused by tumor rupture. The tumor increased in size and reached 12.0×10.0 cm in maximal diameter. The tumor doubling time was estimated to be 13 days. 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT confirmed the absence of distant metastasis since FDG accumulation was detected only in the tumor lesion. Emergency distal pancreatectomy and splenectomy were performed. Histologically, the tumor was classified as a spindle cell ANPC with rhabdoid features. The patient succumbed to mortality 8 months following the surgery while undergoing systemic adjuvant chemotherapy for multiple liver metastases. ANPC is difficult to detect in the early stages due to its progressive nature and atypical radiological findings. Long-term survival can be achieved only by curative resection; therefore, surgical resection must be performed whenever possible, even if the chance of long-term survival following surgery is considered dismal. As the present case suggested, spindle cell ANPC with rhabdoid features is highly aggressive and curative-intent resection must not be delayed. PMID:27446572

  9. Pancreatic carcinomas deposit laminin-5, preferably adhere to laminin-5, and migrate on the newly deposited basement membrane.

    PubMed Central

    Tani, T.; Lumme, A.; Linnala, A.; Kivilaakso, E.; Kiviluoto, T.; Burgeson, R. E.; Kangas, L.; Leivo, I.; Virtanen, I.

    1997-01-01

    We studied the adhesion mechanism of pancreatic carcinoma using in vitro adhesion and migration assays of stable cell lines and tumors grown from these cell lines in nude mice. We also compared the results with the expression profiles of laminins and their receptors in pancreatic carcinomas to evaluate the relevance of these mechanisms in vivo. All of the cell lines preferably adhered to laminin-5, irrespective of their capability to synthesize laminin-5. Cell migration was studied in the presence of hepatocyte growth factor, as it increased the speed of migration manyfold. Herbimycin A treatment and antibodies against the beta 1 and alpha 3 integrin subunits and laminin alpha 3 chain almost entirely blocked cell migration of the BxPC-3 cell line, whereas migration was nearly unaffected by RGD peptide and only moderately inhibited by antibody against the alpha 6 integrin subunit. Indirect immunofluorescence microscopy of wounded BxPC-3 cells suggested a rapid endocytosis of alpha 3 integrin subunit in the cells at the margin of the wound and a rapid, polarized rearrangement of the alpha 6 beta 4 integrin. Especially HGF-treated cultures showed a prominent cytoplasmic reaction for laminin-5 at the margin of the wound. Xenografted cells formed tumors that produced and deposited the same laminin chains as the in vitro cultures. Frozen sections of human pancreatic carcinomas showed reactivity for laminin chains suggestive for expression of laminin-1 and laminin-5. Both xenografted tumors and human pancreatic carcinomas also showed stromal reactivity for laminin-5. Electron microscopy of the human tumors suggested that this was due to an abundant reduplication the basement-membrane-like material around the nests of malignant cells. Our results suggest that pancreatic carcinomas synthesize and deposit laminin-5 in the basement membrane in an abnormal manner. Invading cells adhere to this newly produced basement membrane and migrate on it by using the alpha 3 beta 1

  10. Targeted Therapies Provide Treatment Options for Poorly Differentiated Pancreatic Neuroendocrine Carcinomas.

    PubMed

    Gilabert, Marine; Rho, Young Soo; Kavan, Petr

    2017-01-01

    Poorly differentiated pancreatic neuroendocrine carcinoma (PD pNECs) is a rare disease that has a poor prognosis and is treated with systemic chemotherapy as the standard of care. We present 6 cases of chemo-naïve patients diagnosed with PD pNECs who refused systemic chemotherapy and received targeted therapies with sunitinib (37.5 mg/day, 5 patients) or the mammalian target of rapamycin (mTOR) inhibitor everolimus (10 mg/day, 1 patient) as the first-line treatment. We evaluated the drugs' toxicities and survival. The median age of the patients was 55 years (4 males, 2 females, functioning tumor in 1 of 6 patients). The median of the Ki67 index was 45% (range 20-80). Targeted therapies were combined with somatostatin analogues in 4 of 6 patients (30 mg Sandostatine LAR monthly). Toxicities (acute and late) were manageable and no toxicities necessitated cessation of treatment. All patients had progression-free survival during the 15-month treatment and an overall survival of more than 2 years after diagnosis. Even though this is a small cohort of selected patients, we conclude that sunitinib or everolimus are both feasible and safe and have encouraging results of efficacy as first-line therapies for PD pNEC.

  11. Overexpression and clinical significance of MYC-associated zinc finger protein in pancreatic carcinoma

    PubMed Central

    Zhu, Xiaonian; Luo, Wei; Liang, Wenjin; Tang, Fen; Bei, Chunhua; Ren, Yuan; Qin, Linyuan; Tan, Chao; Zhang, Ying; Tan, Shengkui

    2016-01-01

    This study aimed to investigate the expression and clinical significance of MYC-associated zinc finger protein (MAZ) in pancreatic carcinoma (PC), and the biological functions of MAZ in PC cells. MAZ expression was detected in 57 PC tissues and 41 paired adjacent nontumor tissues by immunohistochemistry. Compared to the expression in adjacent nontumor tissues, MAZ was significantly higher expressed in PC tissues (P<0.0001). In addition, MAZ expression had a significant correlation with certain clinical characteristics of PC patients, such as age, tumor diameter, tumor number, and the serum level of CA199 (P<0.05). The survival analysis showed that the survival time of PC patients with high expression of MAZ was significantly lower than patients with low expression of MAZ (P=0.0365). After MAZ was knocked down in PANC-1 cells by RNA interference, the cells’ ability to proliferate, invade, and migrate was decreased significantly (P<0.01). Moreover, MAZ expression was found to be associated with Ki-67, a cell proliferation marker, in PC tissues, further supporting the idea that MAZ promotes PC cell proliferation. Our study clarifies an oncogenic role of MAZ in pathogenesis of PC and provides MAZ as a biomarker in the treatment and prognosis of PC. PMID:28008270

  12. Perspectives of TGF-β inhibition in pancreatic and hepatocellular carcinomas

    PubMed Central

    Tijeras-Raballand, Annemilaï; de Mestier, Louis; Cros, Jérome; Faivre, Sandrine; Raymond, Eric

    2014-01-01

    Advanced pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC) are non-curable diseases with a particularly poor prognosis. Over the last decade, research has increasingly focused on the microenvironment surrounding cancer cells, and its role in tumour development and progression. PDAC and HCC differ markedly regarding their pathological features: PDAC are typically stromal-predominant, desmoplastic, poorly vascularized tumours, whereas HCC are cellular and highly vascularized. Despite these very different settings, PDAC and HCC share transforming growth factor-β (TGF-β) as a common key-signalling mediator, involved in epithelial-to-mesenchymal transition, invasion, and stroma-tumour dialogue. Recently, novel drugs blocking the TGF-β pathway have entered clinical evaluation demonstrating activity in patients with advanced PDAC and HCC. TGF-β signalling is complex and mediates both pro- and anti-tumoural activities in cancer cells depending on their context, in space and time, and their microenvironment. In this review we provide a comprehensive overview of the role of the TGF-β pathway and its deregulation in PDAC and HCC development and progression at the cellular and microenvironment levels. We also summarize key preclinical and clinical data on the role of TGF-β as a target for therapeutic intervention in PDAC and HCC, and explore perspectives to optimize TGF-β inhibition therapy PMID:24393789

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

    PubMed

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

    1993-12-10

    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.

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

    PubMed Central

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

    2012-01-01

    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

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

    PubMed

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

    2012-04-01

    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.

  16. Smad4 inhibits cell migration via suppression of JNK activity in human pancreatic carcinoma PANC-1 cells

    PubMed Central

    ZHANG, XUEYING; CAO, JUNXIA; PEI, YUJUN; ZHANG, JIYAN; WANG, QINGYANG

    2016-01-01

    Smad4 is a common Smad and is a key downstream regulator of the transforming growth factor-β signaling pathway, in which Smad4 often acts as a potent tumor suppressor and functions in a highly context-dependent manner, particularly in pancreatic cancer. However, little is known regarding whether Smad4 regulates other signaling pathways involved in pancreatic cancer. The present study demonstrated that Smad4 downregulates c-Jun N-terminal kinase (JNK) activity using a Smad4 loss-of-function or gain-of-function analysis. Additionally, stable overexpression of Smad4 clearly affected the migration of human pancreatic epithelioid carcinoma PANC-1 cells, but did not affect cell growth. In addition, the present study revealed that upregulation of mitogen-activated protein kinase phosphatase-1 is required for the reduction of JNK activity by Smad4, leading to a decrease in vascular endothelial growth factor expression and inhibiting cell migration. Overall, the present findings indicate that Smad4 may suppress JNK activation and inhibit the tumor characteristics of pancreatic cancer cells. PMID:27123137

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

    SciTech Connect

    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

    2014-11-07

    Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: 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/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31{sup +} 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.

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

    PubMed

    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

    2013-10-01

    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.

  19. Anticancer effects of an oncolytic parvovirus combined with non-conventional therapeutics on pancreatic carcinoma cell lines.

    PubMed

    Raykov, Z; Georgieva, P B; Angelova, A; Galabov, A S; Rommelaere, J

    2009-01-01

    Standard therapies such as surgery and chemotherapy offer only minimal improvement in pancreatic cancer. However, the viruses killing cancer cells and substances like some antibiotics and phytoalexins with anticancer potential may represent a candidate non-conventional mean of cancer treatment in the future. In this study, the effect of infection with oncolytic H-1 parvovirus (H-1PV) combined with antibiotic norfloxacin (NFX) or phytoalexin resveratrol on the survival of cell lines Panc-1 and BxPC3 derived from human pancreatic carcinoma was tested. Whereas H-1PV with NFX exerted a synergistic effect, H-1PV with resveratrol resulted in an additive effect only. All the effects were partial, but they were more pronounced in Panc-1 compared to BxPC3 cells.

  20. Oncocytic-type intraductal papillary mucinous neoplasm (IPMN)-derived invasive oncocytic pancreatic carcinoma with brain metastasis - a case report.

    PubMed

    Chiang, Kun-Chun; Yu, Chi-Chang; Chen, Jim-Ray; Huang, Yu-Ting; Huang, Cheng-Cheng; Yeh, Chun-Nan; Tsai, Chien-Sheng; Chen, Li-Wei; Chen, Hsien-Cin; Hsu, Jun-Te; Wang, Cheng-Hsu; Chen, Huang-Yang

    2012-07-09

    Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC) and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.

  1. Co-expression of CD133, CD44v6 and human tissue factor is associated with metastasis and poor prognosis in pancreatic carcinoma.

    PubMed

    Chen, Kai; Li, Zhonghu; Jiang, Peng; Zhang, Xi; Zhang, Yujun; Jiang, Yan; He, Yu; Li, Xiaowu

    2014-08-01

    The metastasis-related molecules CD133, CD44v6 and human tissue factor (TF) have been shown to be associated with tumor invasion and metastasis. This study aimed to determine whether co-expression of these three molecules was associated with metastasis and overall prognosis in pancreatic carcinoma. We analyzed the expression profiles of these three molecules by immunohistochemistry and evaluated the relationship of their expression profiles with metastasis and prognosis in 109 pancreatic carcinomas. The results showed that the expression levels of CD133, CD44v6 and TF were increased in pancreatic carcinoma. Co-expression of CD133, CD44v6 and TF (tri-expression) was also detected in pancreatic carcinoma. Clinical analysis showed that individual expression of CD133, CD44v6 or TF was associated with vessel invasion, lymph node metastasis and liver metastasis, while tri-expression was associated with lymph node metastasis. Survival analysis showed that patients with co-expression of CD133 and TF or tri-expression had lower and the lowest overall survival rates, respectively. Univariate analysis showed that T-factor, lymph node metastasis, TNM stage, and individual levels or tri-expression of CD133, CD44v6 and TF were survival risk factors. Multivariate analysis showed that tri-expression of CD133, CD44v6 and TF was an independent predictor of survival. These results suggest that overexpression of CD133, CD44v6 and TF is associated with pancreatic carcinoma metastasis. Tri-expression of these three molecules may be a useful predictor for pancreatic carcinoma prognosis.

  2. Dendritic cell immunotherapy combined with gemcitabine chemotherapy enhances survival in a murine model of pancreatic carcinoma.

    PubMed

    Ghansah, Tomar; Vohra, Nasreen; Kinney, Kathleen; Weber, Amy; Kodumudi, Krithika; Springett, Gregory; Sarnaik, Amod A; Pilon-Thomas, Shari

    2013-06-01

    Pancreatic cancer is an extremely aggressive malignancy with a dismal prognosis. Cancer patients and tumor-bearing mice have multiple immunoregulatory subsets including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) that may limit the effectiveness of anti-tumor immunotherapies for pancreatic cancer. It is possible that modulating these subsets will enhance anti-tumor immunity. The goal of this study was to explore depletion of immunoregulatory cells to enhance dendritic cell (DC)-based cancer immunotherapy in a murine model of pancreatic cancer. Flow cytometry results showed an increase in both Tregs and MDSC in untreated pancreatic cancer-bearing mice compared with control. Elimination of Tregs alone or in combination with DC-based vaccination had no effect on pancreatic tumor growth or survival. Gemcitabine (Gem) is a chemotherapeutic drug routinely used for the treatment for pancreatic cancer patients. Treatment with Gem led to a significant decrease in MDSC percentages in the spleens of tumor-bearing mice, but did not enhance overall survival. However, combination therapy with DC vaccination followed by Gem treatment led to a significant delay in tumor growth and improved survival in pancreatic cancer-bearing mice. Increased MDSC were measured in the peripheral blood of patients with pancreatic cancer. Treatment with Gem also led to a decrease of this population in pancreatic cancer patients, suggesting that combination therapy with DC-based cancer vaccination and Gem may lead to improved treatments for patients with pancreatic cancer.

  3. Role of the WWOX gene, encompassing fragile region FRA16D, in suppression of pancreatic carcinoma cells.

    PubMed

    Nakayama, Shunji; Semba, Shuho; Maeda, Naoko; Aqeilan, Rami I; Huebner, Kay; Yokozaki, Hiroshi

    2008-07-01

    The WW-domain-containing oxidoreductase (WWOX) gene spans the common chromosomal fragile site FRA16D (16q23.2) and is believed to be a tumor suppressor in various human malignancies. We have previously shown frequent down-modulation of Wwox expression in pancreatic carcinoma (PC); however, biological function of Wwox in pancreatic duct carcinogenesis remains unknown. In PANC-1 (Wwox-negative) PC-derived cells, restoration of recombinant WWOX gene expression with adenoviral gene delivery (Ad-WWOX) effectively increased the number of cells with subG(1) DNA contents in a multiplicity of infection-dependent manners: Ad-WWOX infection up-regulated caspase-3 activity and reduced procaspase-3 and procaspase-8 levels. We also confirmed that restoration of WWOX gene suppressed cell growth in vitro and tumorigenicity in vivo. In addition, transduction of wild-type WWOX-expressing vector inhibited PANC-1 colony formation; however, substitution of Y33 of Wwox with arginine did not lead to inhibition of colony formation, suggesting the biological significance of the WW1 domain of Wwox for its tumor-suppressing activity. In PC tissue samples, abundant cytoplasmic Wwox expression was detected in the normal pancreatic duct epithelium, whereas Wwox expression was frequently reduced not only in a large fraction of PC but also in precancerous lesions in accord with the pancreatic intraepithelial neoplasia (PanIN) grade, which was closely correlated with patients' poorer outcome. Interestingly, the existence of Wwox expression was associated with elevated mothers against decapentaplegic homolog 4 (Smad4) protein levels in vitro and in vivo. These findings suggest that down-modulation of Wwox expression is an early event and may be associated with the down-regulation of Smad4 protein levels during pancreatic duct carcinogenesis.

  4. Differentiation of pancreatic carcinoma and mass-forming focal pancreatitis: qualitative and quantitative assessment by dynamic contrast-enhanced MRI combined with diffusion-weighted imaging

    PubMed Central

    Zhang, Ting-Ting; Wang, Li; Liu, Huan-huan; Zhang, Cai-yuan; Li, Xiao-ming; Lu, Jian-ping; Wang, Deng-bin

    2017-01-01

    Differentiation between pancreatic carcinoma (PC) and mass-forming focal pancreatitis (FP) is invariably difficult. For the differential diagnosis, we qualitatively and quantitatively assessed the value of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in PC and FP in the present study. This study included 32 PC and 18 FP patients with histological confirmation who underwent DCE-MRI and DWI. The time-signal intensity curve (TIC) of PC and FP were classified into 5 types according to the time of reaching the peak, namely, type I, II, III, IV, and V, respectively, and two subtypes, namely, subtype-a (washout type) and subtype-b (plateau type) according to the part of the TIC profile after the peak. Moreover, the mean and relative apparent diffusion coefficient (ADC) value between PC and FP on DWI were compared. The type V TIC was only recognized in PC group (P < 0.01). Type IV b were more frequently observed in PC (P = 0.036), while type- IIa (P < 0.01), type- Ia (P = 0.037) in FP. We also found a significant difference in the mean and relative ADC value between PC and FP. The combined image set of DCE-MRI and DWI yielded an excellent sensitivity, specificity, and diagnostic accuracy (96.9%, 94.4%, and 96.0%). The TIC of DCE-MRI and ADC value of DWI for pancreatic mass were found to provide reliable information in differentiating PC from FP, and the combination of DCE-MRI and DWI can achieve a higher sensitivity, specificity, and diagnostic accuracy. PMID:27661003

  5. No Effect of Dietary Aspartame or Stevia on Pancreatic Acinar Carcinoma Development, Growth, or Induced Mortality in a Murine Model

    PubMed Central

    Dooley, James; Lagou, Vasiliki; Dresselaers, Tom; van Dongen, Katinka A.; Himmelreich, Uwe; Liston, Adrian

    2017-01-01

    Pancreatic cancer has an extremely poor prognosis, largely due to a poor record for early detection. Known risk factors for pancreatic cancer include obesity, diet, and diabetes, implicating glucose consumption and regulation as a key player. The role of artificial sweeteners may therefore be pertinent to disease kinetics. The oncogenic impact of artificial sweeteners is a highly controversial area. Aspartame, one of the most studied food additives, is widely recognized as being generally safe, although there are still specific areas where research is incomplete due to study limitations. Stevia, by contrast, has been the subject of relatively few studies, and the potential health benefits are based on extrapolation rather than direct testing. Here, we used longitudinal tracking of pancreatic acinar carcinoma development, growth, and lethality in a sensitized mouse model. Despite exposure to aspartame and stevia from the in utero stage onward, we found no disease modification activity, in either direction. These results contribute to the data on aspartame and stevia safety, while also reducing confidence in several of the purported health benefits. PMID:28232906

  6. 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

    2017-04-13

    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

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

    PubMed

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

    2011-11-01

    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.

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

    PubMed Central

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

    2011-01-01

    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

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

    SciTech Connect

    Swartz, Michael J.; Hsu, Charles C.; Pawlik, Timothy M.; Winter, Jordan; Hruban, Ralph H.; Guler, Mehmet; Schulick, Richard D.; Cameron, John L.; Laheru, Daniel A.; Wolfgang, Christopher L.; Herman, Joseph M.

    2010-03-01

    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.

  10. 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

    Ikeda, Osama Tamura, Yoshitaka; Nakasone, Yutaka; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Yamashita, Yasuyuki; Takamori, Hiroshi; Kanemitsu, Keiichiro; Baba, Hideo

    2007-09-15

    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

  11. Individual in-vitro sensitivities of human pancreatic carcinoma cell lines to photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Moesta, K. T.; Dmytrijuk, Andrew; Schlag, Peter M.; Mang, Thomas S.

    1992-06-01

    Photodynamic therapy (PDT) is a promising alternative in the treatment of pancreatic cancer in man, due to the low sensitivity of the normal pancreas to PDT as shown in preclinical studies. Investigations on four human pancreatic cancer lines (MIA PaCa-2, PaCa 1, PaCa 3, and CAPAN 2) in vitro demonstrated a considerable variety in PDT-sensitivity proportional to the degree of differentiation, which was related to photosensitizer-uptake (PhotofrinTM). The well differentiated pancreatic tumor line Capan 2 showed a close relationship between high cell density and increased PDT-resistance. The Photofrin uptake of Capan 2 at high cell densities could be increased by short trypsinization prior to photosensitizer exposure. The data supports the hypothesis that a complex intercellular organization reduces the cell surface available for photosensitizer uptake and may cause the relative PDT resistance of normal pancreatic tissues and highly differentiated tumors.

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

    PubMed Central

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

    2014-01-01

    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

  13. Partial Resection of the Pancreatic Head and Duodenum for Management of Carcinoma of the Ampulla of Vater: A Case Report.

    PubMed

    Liu, Xiao-Fang; Tang, Kun; Sun, Fu-Bo; Sui, Lu-Lu; Xu, Gang

    2016-03-01

    A 57-year-old woman presented with spontaneous pain in the upper right quadrant of the abdominal region of one year's duration. Contrast-enhanced computed tomography (CT), magnetic resonance imaging, and magnetic resonance cholangiopancreaticography revealed the presence of a tumour in the periampullary region, gallstones, cholecystitis, and biliary obstruction, as well as atrophy of the pancreas and dense adhesions involving the pancreas, portal vein, and superior mesenteric vein. Duodenoscopy revealed a papillary neoplasm, measuring 2.5×3 cm, in the descending duodenum. Pathological analysis of the duodenoscopic biopsy suggested carcinoma of the ampulla of Vater. Partial resection of the pancreatic head and duodenum, together with lymph node dissection and digestive tract reconstruction, was performed. Postoperatively, the patient recovered well. CT at 14 months postoperatively showed no recurrence or metastasis. This surgical procedure avoids the potential risk of pancreaticoduodenectomy and retains the function of the pancreas as much as possible, while achieving radical tumour resection.

  14. Inhibition of mutant KrasG12D-initiated murine pancreatic carcinoma growth by a dual c-Raf and soluble epoxide hydrolase inhibitor t-CUPM.

    PubMed

    Liao, Jie; Hwang, Sung Hee; Li, Haonan; Yang, Yihe; Yang, Jun; Wecksler, Aaron T; Liu, Jun-Yan; Hammock, Bruce D; Yang, Guang-Yu

    2016-02-28

    Mutant Kras and chronic pancreatitis are the most common pathological events involved in human pancreatic cancer. It has been demonstrated that c-Raf is responsible for transmitting signals from mutant Ras to its downstream signals including MEK-ERK and for initiating carcinogenesis. The soluble epoxide hydrolase (sEH), a pro-inflammatory enzyme, generally inactivates anti-inflammatory and anti-pain epoxyeicosatrienoic acids (EETs). Herein, we have synthesized a novel compound of trans-4-{4-[3-(4-chloro-3-trifluoromethyl-phenyl)-ureido]-cyclohexyloxy}-pyridine-2-carboxylic acid methylamide (t-CUPM) via modifying the central phenyl ring of sorafenib and confirmed its dual inhibition of sEH and c-Raf by recombinant kinase activity assay. Pharmacokinetic analysis revealed that oral dosing of t-CUPM resulted in higher blood levels than that of sorafenib throughout the complete time course (48 h). The effect of t-CUPM on the inhibition of mutant Kras(G12D)-initiated murine pancreatic cancer cell growth was determined using the mouse pancreatic carcinoma cell model obtained from LSL-Kras(G12D)/Pdx1-Cre mice and showed that t-CUPM significantly inhibited this murine pancreatic carcinoma cell growth both in vitro and in mice in vivo. Inhibition of mutant Kras-transmitted phosphorylations of cRAF/MEK/ERK was demonstrated in these pancreatic cancer cells using Western blot assay and immunohistochemical approach. Modulation of oxylipin profile, particularly increased EETs/DHET ratio by sEH inhibition, was observed in mice treated with t-CUPM. These results indicate that t-CUPM is a highly potential agent to treat pancreatic cancer via simultaneously targeting c-Raf and sEH.

  15. 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

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

    2014-08-01

    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 μg/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.

  16. Ellagic acid inhibits the proliferation of human pancreatic carcinoma PANC-1 cells in vitro and in vivo.

    PubMed

    Cheng, Hao; Lu, Chenglin; Tang, Ribo; Pan, Yiming; Bao, Shanhua; Qiu, Yudong; Xie, Min

    2017-01-25

    Ellagic aicd (EA), a dietary polyphenolic compound found in plants and fruits, possesses various pharmacological activities. This study investigated the effect of EA on human pancreatic carcinoma PANC-1 cells both in vitro and in vivo; and defined the associated molecular mechanisms. In vitro, the cell growth and repairing ability were assessed by CCK-8 assay and wound healing assay. The cell migration and invasion activity was evaluated by Tanswell assay. In vivo, PANC-1 cell tumor-bearing mice were treated with different concentrations of EA. We found that EA significantly inhibited cell growth, cell repairing activity, and cell migration and invasion in a dose-dependent manner. Treatment of PANC-1 xenografted mice with EA resulted in significant inhibition in tumor growth and prolong mice survival rate. Furthermore, flow cytometric analysis showed that EA increased the percentage of cells in the G1 phase of cell cycle. Western blot analysis revealed that EA inhibited the expression of COX-2 and NF-κB. In addition, EA reversed epithelial to mesenchymal transition by up-regulating E-cadherin and down-regulating Vimentin. In summary, the present study demonstrated that EA inhibited cell growth, cell repairing activity, cell migration and invasion in a dose-dependent manner. EA also effectively inhibit human pancreatic cancer growth in mice. The anti-tumor effect of EA might be related to cell cycle arrest, down-regulating the expression of COX-2 and NF-κB, reversing epithelial to mesenchymal transition by up-regulating E-cadherin and down-regulating Vimentin. Our findings suggest that the use of EA would be beneficial for the management of pancreatic cancer.

  17. Granulocyte colony-stimulating factor-producing pancreatic anaplastic carcinoma in ascitic fluid at initial diagnosis: A case report.

    PubMed

    Kubota, Nao; Naito, Yoshiki; Kawahara, Akihiko; Taira, Tomoki; Yamaguchi, Tomohiko; Yoshida, Tomoko; Abe, Hideyuki; Takase, Yorihiko; Fukumitsu, Chihiro; Murata, Kazuya; Ishida, Yusuke; Okabe, Yoshinobu; Kimura, Yoshizo; Tanigawa, Masahiko; Mihara, Yutaro; Nakayama, Masamichi; Yamaguchi, Rin; Akiba, Jun; Yano, Hirohisa

    2017-02-10

    Granulocyte colony-stimulating factor (G-CSF)-producing pancreatic tumors are extremely rare. These tumors have an aggressive clinical course and no established treatment. Here, we report an autopsy case of G-CSF-production in pancreatic anaplastic carcinoma (PAC). A 72-year-old woman presented with a large pancreatic head mass and multiple liver metastases. Laboratory data showed leukocytosis (leukocyte count 113.3 × 10(3) /µL) and high serum G-CSF levels (441 pg/mL; normal range: <39.0 pg/mL). The ascitic fluid was submitted to our pathology laboratory at initial diagnosis. Cytopathology showed that smears from the ascitic fluid were highly cellular and contained numerous malignant cells, mainly in loose groupings. Occasional pseudoglandular formations and giant cells were also present. The malignant cells were round, and no spindle-shaped cells were visible. The nuclei were round to ovoid with coarsely granular chromatin and large prominent nucleoli. Upon immunocytochemistry, tumor cells were positive for G-CSF and vimentin; there was no E-cadherin expression. Histopathological examination of the tumor showed a mixed composition of adenocarcinomatous and sarcomatous regions. Upon immunohistochemistry, both components were positive for G-CSF. Few CD34-positive myeloblasts were observed in the bone marrow. Thus, we diagnosed this as a case of G-CSF production in PAC with leukocytosis. To the best of our knowledge, this is the first report on G-CSF expression immunocytochemically confirmed in PAC. Diagn. Cytopathol. © 2017 Wiley Periodicals, Inc.

  18. Immunoscintigraphy of human pancreatic carcinoma in nude mice with I-131-F(ab')/sub 2/-fragments of monoclonal antibodies

    SciTech Connect

    Senekowitsch, R.; Maul, F.D.; Wenisch, H.J.C.; Kriegel, H.; Hor, G.

    1985-05-01

    In the present study radioiodinated F(ab')/sub 2/-fragments of CA19-9 and antibody that reacts specifically with human gastrointestinal cancer were examined for their ability to detect human pancreatic carcinoma hosted in nude mice. Tumor-bearing mice received 80..mu..Ci of I-131-F(ab')/sub 2/ with a specific activity of 1.8..mu..Ci/..mu..g. All mice were imaged after the injection and every 24hr up to 6 days. The retained radioactivity was also registered with a whole-body counter immediately after imaging. As a control F(ab's)/sub 2/ of a nonspecific antibody were administered in parallel to another group of animals bearing the same tumor. Three animals of each group were killed at 1,2,4 and 8 days for determination of the distribution of both labeled antibody-fragments. On scintigraphic images obtained with the CA19-9-F(ab')/sub 2/ the tumors could be visualized 24hr after injection, the best dilineation however was achieved 96hr p.i.. The biodistribution data exhibited a more rapid blood clearance for the specific fragments compared to that for the unspecific ones. Tumors showed an increase in uptake up to 48hr reaching 1.7% of the injected dose per gram, declining to values of 0.08%/g at day 6 p.i.. The highest tumor-to-blood ratios were found after 96h. They were 7 for the CA19-9-fragments compared to 1.5 for the unspecific fragments. The whole body counting revealed a more rapid excretion for the fragments of the specific monoclonal antibodies than for the unspecific ones. In summary the authors were able to show that CA19-9-F(ab')/sub 2/-fragments can be used for immunodetection of human pancreatic carcinoma hosted in nude mice.

  19. The prognostic influence of the proliferative discordance in metastatic pancreatic neuroendocrine carcinoma revealed by peptide receptor radionuclide therapy

    PubMed Central

    Montanier, Nathanaëlle; Joubert-Zakeyh, Juliette; Pétorin, Caroline; Montoriol, Pierre François; Maqdasy, Salwan; Kelly, Antony

    2017-01-01

    Abstract Rationale: Pancreatic neuroendocrine tumors (pNET) are rare slowly growing tumors with a high metastatic potential. Peptide receptor radionuclide therapy (PRRT) with radiolabeled analogues has been developed as a new tool for the management of metastatic well-differentiated (grade 1 and 2) neuroendocrine tumors expressing somatostatin receptor (SSTR2). Chemotherapy is the mainstay in the management of grade 3 (G3) unresectable pancreatic neuroendocrine carcinoma (pNEC). To date, no study has evaluated the efficacy of PRRT in such tumors. Diagnoses and interventions: We describe a case of a progressive G3 pNEC with huge liver metastases successfully treated with PRRT (177Lu DOTATATE). Outcomes: Complete remission was obtained for 3 years. Indeed, the mitotic index was low (as G2 tumors) but with a very high Ki-67 index (45%–70%). Such discordance between the proliferative markers should consider the use of PRRT before chemotherapy in unresectable metastatic G3 tumors expressing SSTR2. Lessons: This case supports the hypotheses highlighting the heterogeneity of G3 pNEC. The latter should be subdivided into 2 distinct categories: proliferation-discordant (well differentiated) and concordant (poorly differentiated) NEC. PRRT could be suggested for the former group before the conventional chemotherapy. PMID:28178157

  20. An Investigation Of Photodynamic Therapy In The Treatment Of Pancreatic Carcinoma: Dihematoporphyrin Ether Uptake And Photobleaching Kinetics

    NASA Astrophysics Data System (ADS)

    Mang, Thomas S.; Wieman, Thomas J.

    1988-02-01

    Results of dihematoporphyrin ether (DHE) uptake and fluorescence kinetics show that the concentration in the pancreas is on the order of 40-60 μg DHE/g of tissue at an injected dose of 40 mg/kg. Previously concentrations on this order have only been found in organs of the reticuloendothelial system. Two intrapancreatic carcinoma models, one of acinar origin (rat) and one of ductal orgin (hamster), were studied. Both showed equal or higher concentrations of DHE as compared to normal pancreas when fluorescence measurements and chemical extraction procedures were performed. Photodynamic therapy (PDT) treatment of the normal pancreas and pancreatic tumors yielded atypical results. When the normal pancreas with DHE present is exposed to 630 nm light from a dye laser (75 mW/cm2, 30 min), the normal photobleaching measurable by fluorescence decay does not occur. Yet, the pancreatic tumor responds with a relatively normal fluorescence decay pattern, with hemorrhaging and a resultant loss of measurable DHE concentration. These results represent the emergence of an entirely new modality, with substantial potential for the treatment of cancer of the pancreas.

  1. Differential HPV16 variant distribution in squamous cell carcinoma, adenocarcinoma and adenosquamous cell carcinoma.

    PubMed

    Nicolás-Párraga, S; Alemany, L; de Sanjosé, S; Bosch, F X; Bravo, I G

    2017-05-01

    Human Papillomavirus 16 (HPV16) causes 70% of invasive cervical cancers (ICC) worldwide. Interaction between HPV16 genetic diversity, host genetics and target tissue largely determine the chances to trigger carcinogenesis. We have analyzed the differential prevalence of viral variants in 233 HPV16-monoinfected squamous (SCC), glandular (ADC) and mixed (ADSC) ICCs from four continents, assessing the contribution of geographical origin and cancer histology. We have further quantified the contribution of viral variants and cancer histology to differences in age at tumor diagnosis. The model fitted to the data explained 97% of the total variance: the largest explanatory factors were differential abundance among HPV16 variants (78%) and their interaction with cancer histology (9.2%) and geography (10.1%). HPV16_A1-3 variants were more prevalent in SCC while HPV16_D variants were increased in glandular ICCs. We confirm further a non-random geographical structure of the viral variants distribution. ADCs were diagnosed at younger ages than SCCs, independently of the viral variant triggering carcinogenesis. HPV16 variants are differentially associated with histological ICCs types, and ADCs are systematically diagnosed in younger women. Our results have implications for the implementation of cervical cancer screening algorithms, to ensure proper early detection of elusive ADCs.

  2. TP53 alterations in pancreatic acinar cell carcinoma: new insights into the molecular pathology of this rare cancer.

    PubMed

    La Rosa, Stefano; Bernasconi, Barbara; Frattini, Milo; Tibiletti, Maria Grazia; Molinari, Francesca; Furlan, Daniela; Sahnane, Nora; Vanoli, Alessandro; Albarello, Luca; Zhang, Lizhi; Notohara, Kenji; Casnedi, Selenia; Chenard, Marie-Pierre; Adsay, Volkan; Asioli, Sofia; Capella, Carlo; Sessa, Fausto

    2016-03-01

    The molecular alterations of pancreatic acinar cell carcinomas (ACCs) are poorly understood and have been reported as being different from those in ductal adenocarcinomas. Loss of TP53 gene function in the pathogenesis of ACCs is controversial since contradictory findings have been published. A comprehensive analysis of the different possible genetic and epigenetic mechanisms leading to TP53 alteration in ACC has never been reported and hence the role of TP53 in the pathogenesis and/or progression of ACC remains unclear. We investigated TP53 alterations in 54 tumor samples from 44 patients, including primary and metastatic ACC, using sequencing analysis, methylation-specific multiplex ligation probe amplification, fluorescence in situ hybridization, and immunohistochemistry. TP53 mutations were found in 13 % of primary ACCs and in 31 % of metastases. Primary ACCs and metastases showed the same mutational profile, with the exception of one case, characterized by a wild-type sequence in the primary carcinoma and a mutation in the corresponding metastasis. FISH analysis revealed deletion of the TP53 region in 53 % of primary ACCs and in 50 % of metastases. Promoter hypermethylation was found in one case. The molecular alterations correlated well with the immunohistochemical findings. A statistically significant association was found between the combination of mutation of one allele and loss of the other allele of TP53 and worse survival.

  3. Predictive and prognostic value of preoperative serum tumor markers in resectable adenosqamous lung carcinoma

    PubMed Central

    Yue, Dongsheng; Li, Kai; Jiang, Richeng

    2016-01-01

    Background Adenosquamous carcinoma is a rare and aggressive form of lung cancer. The prognostic and predictive value of preoperative serum tumor markers and frequency of EGFR mutations in adenosquamous lung carcinoma are unclear. Methods We retrospectively analyzed data and samples collected from 106 radically resected adenosquamous lung carcinoma patients with pathological stage I-IIIA between 2008 and 2013. Correlations between serum tumor marker levels and EGFR mutations as well as survival parameters were analyzed and prognostic factors were identified. Results Of the 106 adenosquamous lung carcinoma patients, 29 (27.4%) harbored EGFR mutations. By univariate analysis, advanced clinical stage (P = 0.009 for disease-free survival [DFS]; P = 0.046 for overall survival [OS]), larger tumor size (P = 0.001 for DFS; P = 0.002 for OS), regional lymph node metastasis (P = 0.024 for DFS; P = 0.030 for OS), higher NSE level (P = 0.002 for DFS; P < 0.001 for OS), and higher TMI (tumor marker index) (P = 0.009 for OS) were significantly correlated with a worse prognosis. By multivariate analysis, NSE (P = 0.014) was confirmed as independent predictor for DFS, while NSE (P = 0.001) and TMI (P = 0.038) were independent prognostic factors for OS. Conclusion Adenosquamous lung carcinoma is an aggressive malignancy with relatively high EGFR mutation frequency. Elevated preoperative NSE level and TMI are adverse predictive and prognostic indicators. PMID:27623437

  4. Overexpression of homeobox B-13 correlates with angiogenesis, aberrant expression of EMT markers, aggressive characteristics and poor prognosis in pancreatic carcinoma.

    PubMed

    Zhai, Lu-Lu; Wu, Yang; Cai, Chong-Yang; Tang, Zhi-Gang

    2015-01-01

    To investigate the expression of homeobox B (Hoxb)-13 and analyze its relationship with tumor angiogenesis, epithelial-mesenchymal transition (EMT)-associated markers (E-cadherin and vimentin), clinicopathologic data and prognosis in pancreatic carcinoma. Immunohistochemistry was applied to determine the level of Hoxb-13 expression in tumor tissues and surrounding non-tumor tissues from 85 subjects with pancreatic carcinoma. Besides, vascular endothelial growth factor (VEGF), CD31, E-cadherin and vimentin were also detected in tumor tissues by immunostaining. We found that the level of Hoxb-13 expression was significantly higher in pancreatic carcinoma tissues than in paracarcinomatous tissues (P < 0.05). Hoxb-13 staining was positively correlated with VEGF (r = 0.429, P < 0.001) and microvessel density (MVD) (r = 0.454, P < 0.001). Likewise, Hoxb-13 staining was positively correlated with vimentin (r = 0.448, P < 0.001); while it was negatively correlated with E-cadherin (r = -0.405, P < 0.001). High Hoxb-13 expression was associated with aggressive clinicopathological characteristics, worse disease-free survival (DFS) (P < 0.001) and worse overall survival (OS) (P < 0.001). Multivariate analysis showed that Hoxb-13 was an independent predictor for poor DFS (P < 0.001) and OS (P = 0.002). In conclusion, our data show that overexpressed Hoxb-13 is correlated with tumor angiogenesis, aberrant expression of EMT-associated markers and aggressive clinicopathological characteristics, and serves as a promising marker for unfavourable prognosis in pancreatic carcinoma.

  5. E2F-1 gene therapy induces apoptosis and increases chemosensitivity in human pancreatic carcinoma cells.

    PubMed

    Elliott, Mary Jane; Farmer, Michael R; Atienza, Cesar; Stilwell, Ariel; Dong, Yan Bin; Yang, Hai Liang; Wong, Sandra L; McMasters, Kelly M

    2002-01-01

    Pancreatic cancer is often resistant to conventional chemotherapy. In this study, we examined the role of adenovirus-mediated overexpression of E2F-1 in inducing apoptosis and increasing the sensitivity of pancreatic cancer cells to chemotherapeutic agents. MIA PaCa-2 pancreatic head exocrine adenocarcinoma cells (mutant p53) were treated by mock infection or adenoviruses expressing beta-galactosidase or E2F-1 (Ad-E2F-1) alone or in combination with sublethal concentrations of each chemotherapeutic drug. Cell growth and viability were assessed at selected time points. Apoptosis was evaluated by flow cytometry, characteristic changes in cell morphology and poly (ADP-ribose) polymerase (PARP) cleavage. Western blot analysis was used to examine the expression of E2F-1 and Bcl-2 family member proteins and PARP cleavage. Western blot analysis revealed marked overexpression of E2F-1 at a multiplicity of infection (MOI) of 20 and 70. By 3 days after infection, Ad-E2F-1 treatment at an MOI of 70 resulted in approximately a 20-fold reduction in cell growth and 60% reduction in cell viability as compared to mock-infected cells. Cell cycle analysis, PARP cleavage and changes in cell morphology supported apoptosis as the mechanism of cell death in response to E2F-1. In order to test the efficacy of treatment with a combination of gene therapy and chemotherapy, we utilized concentrations of Ad-E2F-1 which reduced viability to 50% in combination with each chemotherapeutic agent. Cotreatment of the cells with E2F-1 virus and roscovitine (ROS) or etoposide resulted in an additive effect on cell growth inhibition and induction of apoptosis. Interestingly, 5-fluorouracil did not cooperate with Ad-E2F-1 in the mediation of tumor death or inhibition of cell growth. Immunoblotting for Bcl-2 family members revealed no significant changes in the expression levels of Bcl-2, Bcl X(L), Bax or Bak following gene or 'chemogene' therapy with E2F-1. However, a Bax cleavage product was noted

  6. Correlation between Ultrasound Reflection Intensity and Tumor Ablation Ratio of Late-Stage Pancreatic Carcinoma in HIFU Therapy: Dynamic Observation on Ultrasound Reflection Intensity

    PubMed Central

    Ge, Hui-Yu; Miao, Li-Ying; Wang, Jin-Rui; Xiong, Liu-Lin; Yan, Fang; Zheng, Cui-Shan; Jia, Jian-Wen; Cui, Li-Gang; Chen, Wen

    2013-01-01

    The minimally invasive high-intensity focused ultrasound (HIFU) therapy is thermal ablation treatment for late-stage pancreatic carcinoma with widely recognized safety and effectiveness, but there are currently no instant assessment methods for its ablation effect. It is vital to find a real-time high-sensitive assessment method. This research aims to dynamically observe the variation rules of ultrasound reflection intensity, analyze the correlation between ultrasound reflection intensity and tumor ablation ratio, and find out the value of ultrasound reflection intensity in prognosis of HIFU ablation effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects with late-stage pancreatic carcinoma from March 2007 to December 2009 in the study. The variation rules of the ultrasound reflection intensity during HIFU therapy were summarized and the correlation between ultrasound reflection intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio indicated by CT scanning. The conclusion is that variation of ultrasound reflection intensity can be used for initial assessment of tumor ablation in HIFU therapy and early prognosis of overall HIFU ablation, providing important clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound can work as a real-time imaging instrument for observation of HIFU ablation effect in treating late-stage pancreatic carcinoma. PMID:24453916

  7. Effects of a non thermal plasma treatment alone or in combination with gemcitabine in a MIA PaCa2-luc orthotopic pancreatic carcinoma model.

    PubMed

    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

    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.

  8. Correlation between ultrasound reflection intensity and tumor ablation ratio of late-stage pancreatic carcinoma in HIFU therapy: dynamic observation on ultrasound reflection intensity.

    PubMed

    Ge, Hui-Yu; Miao, Li-Ying; Wang, Jin-Rui; Xiong, Liu-Lin; Yan, Fang; Zheng, Cui-Shan; Jia, Jian-Wen; Cui, Li-Gang; Chen, Wen

    2013-01-01

    The minimally invasive high-intensity focused ultrasound (HIFU) therapy is thermal ablation treatment for late-stage pancreatic carcinoma with widely recognized safety and effectiveness, but there are currently no instant assessment methods for its ablation effect. It is vital to find a real-time high-sensitive assessment method. This research aims to dynamically observe the variation rules of ultrasound reflection intensity, analyze the correlation between ultrasound reflection intensity and tumor ablation ratio, and find out the value of ultrasound reflection intensity in prognosis of HIFU ablation effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects with late-stage pancreatic carcinoma from March 2007 to December 2009 in the study. The variation rules of the ultrasound reflection intensity during HIFU therapy were summarized and the correlation between ultrasound reflection intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio indicated by CT scanning. The conclusion is that variation of ultrasound reflection intensity can be used for initial assessment of tumor ablation in HIFU therapy and early prognosis of overall HIFU ablation, providing important clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound can work as a real-time imaging instrument for observation of HIFU ablation effect in treating late-stage pancreatic carcinoma.

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

    PubMed

    Valente, Kari; Yacoub, George; Cappellari, James O; Parks, Graham

    2017-02-01

    A 30-year-old male presented to his doctor with complaints of abdominal pain and was found to have retroperitoneal as well as multiple hepatic masses. A serum alpha-fetoprotein (AFP) level was significantly elevated (17,373 ng mL(-1) ), raising suspicions for a metastatic germ cell tumor. Fine needle aspiration biopsy of the pancreatic lesion revealed atypical epithelioid cells with round nuclei, large prominent nucleoli, and granular cytoplasm. The morphologic differential diagnosis included pancreatic neoplasm, metastatic germ cell tumor, other metastatic carcinoma, and melanoma. An extensive panel of immunohistochemical stains confirmed the diagnosis of acinar cell carcinoma. The diagnosis of acinar cell carcinoma could be confounded by the markedly increased AFP level, particularly in the setting of a retroperitoneal mass in a younger male. The increased AFP level in the setting of an acinar cell tumor is a potential pitfall to correct diagnosis by cytology. As the treatment for these two entities differs considerably, acute awareness of the phenomenon is important. We present a case of pancreatic ACC with an increased AFP level diagnosed on a cytology specimen. Diagn. Cytopathol. 2017;45:133-136. © 2016 Wiley Periodicals, Inc.

  10. Tailored α-methylene-γ-butyrolactones and their effects on growth suppression in pancreatic carcinoma cells.

    PubMed

    Ramachandran, P Veeraraghavan; Pratihar, Debarshi; Nair, Hari Narayanan G; Walters, Matthew; Smith, Sadie; Yip-Schneider, Michele T; Wu, Huangbing; Schmidt, C Max

    2010-11-15

    A selected series of racemic α-methylene-γ-butyrolactones (AMGBL) were synthesized via allylboration and screened against three human pancreatic cancer cell lines (Panc-1, MIA PaCa-2, and BxPC-3). This systematic study established a discernible relationship between the substitution pattern of AMGBL and their anti-proliferative activity. β,γ-diaryl-AMGBLs, particularly those with a trans-relationship exhibited higher potency than parthenolide and LC-1 against all three cell lines.

  11. Growth inhibition and apoptosis induction by alternol in pancreatic carcinoma cells

    PubMed Central

    Cong, Pei-Fang; Qu, Ying-Chun; Chen, Jie-Peng; Duan, Li-Li; Lin, Cheng-Jiang; Zhu, Xiao-Lin; Li-Ling, Jesse; Zhang, Mei-Xia

    2015-01-01

    AIM: To investigate the effect of alternol on pancreatic cancer cells. METHODS: Pancreatic cancer cells PANC-1 and BxPC3 were treated with various concentrations of alternol for 24, 48 and 72 h. Cell proliferation was measured by cell counting. Cell cycle distribution and mitochondrial membrane potential were determined by flow cytometry. Apoptosis was determined by a TdT-mediated dUTP nick end labeling assay and Hoechst staining. Expression of caspase 3, Bcl-2, p53 and p21 was measured by western blotting. RESULTS: Alternol showed dose- and time-dependent inhibition of the proliferation of PANC-1 and BxPC3 cells in vitro. Alternol induced apoptosis and cell cycle arrest at S phase and decreased mitochondrial membrane potential. Alternol activated caspase 3, upregulated p53 and p21 expression, and downregulated Bcl-2 expression in a dose-dependent manner. CONCLUSION: Our results suggested that alternol is a candidate for treatment of pancreatic cancer. PMID:25914461

  12. The Aurora-A-Twist1 axis promotes highly aggressive phenotypes in pancreatic carcinoma.

    PubMed

    Wang, Jing; Nikhil, Kumar; Viccaro, Keith; Chang, Lei; Jacobsen, Max; Sandusky, George; Shah, Kavita

    2017-03-15

    We uncovered a crucial role for the Aurora kinase A (AURKA)-Twist1 axis in promoting epithelial-to-mesenchymal transition (EMT) and chemoresistance in pancreatic cancer. Twist1 is the first EMT-specific target of AURKA that was identified using an innovative screen. AURKA phosphorylates Twist1 at three sites, which results in its multifaceted regulation - AURKA inhibits its ubiquitylation, increases its transcriptional activity and favors its homodimerization. Twist1 reciprocates and prevents AURKA degradation, thereby triggering a feedback loop. Ablation of either AURKA or Twist1 completely inhibits EMT, highlighting both proteins as central players in EMT progression. Phosphorylation-dead Twist1 serves as a dominant-negative and fully reverses the EMT phenotype induced by Twist1, underscoring the crucial role of AURKA-mediated phosphorylation in mediating Twist1-induced malignancy. Likewise, Twist1-overexpressing BxPC3 cells formed large tumors in vivo, whereas expression of phosphorylation-dead Twist1 fully abrogated this effect. Furthermore, immunohistochemical analysis of pancreatic cancer specimens revealed a 3-fold higher level of Twist1 compared to that seen in healthy normal tissues. This is the first study that links Twist1 in a feedback loop with its activating kinase, which indicates that concurrent inhibition of AURKA and Twist1 will be synergistic in inhibiting pancreatic tumorigenesis and metastasis.

  13. Differential ezrin and phosphorylated ezrin expression profiles between pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and invasive ductal carcinoma of the pancreas.

    PubMed

    Oda, Yasunori; Aishima, Shinichi; Morimatsu, Katsuya; Hayashi, Akifumi; Shindo, Koji; Fujino, Minoru; Mizuuchi, Yusuke; Hattori, Masami; Tanaka, Masao; Oda, Yoshinao

    2013-08-01

    Intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanINs) are important premalignant lesions of pancreatic cancer. Ezrin is a member of the ezrin, radixin, and moesin protein family and acts as a cross-linker between the plasma membrane and the actin cytoskeleton. We investigated the roles of ezrin during carcinogenesis in IPMN and invasive ductal carcinoma and examined whether ezrin was a prognostic factor. We examined ezrin and phosphorylated ezrin (p-ezrin) expression in 131 IPMNs, 47 PanINs, and 59 invasive ductal carcinomas by immunohistochemical staining. Ezrin and p-ezrin (tyr354) expressions were significantly higher in IPMN with an associated invasive carcinoma, compared with those in IPMN with high-grade dysplasia (P = .03 and P = .0007, respectively). In all grades of PanINs, ezrin and p-ezrin (tyr353) were highly expressed. In patients with invasive ductal carcinoma, the presence of PanIN-2 or PanIN-3 was significantly correlated with positive ezrin and p-ezrin (tyr353) expression of the invasive ductal carcinoma component (P = .01 and P = .0004). The negative p-ezrin (tyr353) expression group of invasive ductal carcinoma showed a significantly worse prognosis than did the positive p-ezrin (tyr353) expression group by survival analysis (P = .04) and was a statistically significant adverse prognostic factor by both univariate and multivariate analyses (P = .048 and P = .015). Ezrin phosphorylation sites differ between the developments of IPMN and PanIN. Although p-ezrin (tyr354) expression in IPMNs is associated with tumor invasion, p-ezrin (tyr353) expression in invasive ductal carcinoma plays an important role not in tumor invasion and metastasis but in the early development of PanINs.

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

    SciTech Connect

    Valentini, Vincenzo; Morganti, Alessio G.; Macchia, Gabriella Mantini, Giovanna; Mattiucci, Gian C.; Brizi, M. Gabriella; Alfieri, Sergio; Bossola, Maurizio; Pacelli, Fabio; Sofo, Luigi; Doglietto, Giovanbattista; Cellini, Numa

    2008-03-15

    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)

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

    PubMed

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

    2013-10-01

    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.

  16. Lysophosphatidic acid induces both EGFR-dependent and EGFR-independent effects on DNA synthesis and migration in pancreatic and colorectal carcinoma cells.

    PubMed

    Tveteraas, Ingun Heiene; Aasrum, Monica; Brusevold, Ingvild Johnsen; Ødegård, John; Christoffersen, Thoralf; Sandnes, Dagny

    2016-02-01

    Lysophosphatidic acid (LPA) is a small glycerophospholipid ubiquitously present in tissues and plasma. It acts through receptors belonging to the G-protein-coupled receptor (GPCR) family, is involved in several biological processes, and is strongly implicated in different cancers. In this paper, we have investigated the effects of LPA on DNA synthesis and migration in a panel of pancreatic and colon cancer cells, with particular focus on the involvement of the epidermal growth factor (EGF) receptor (EGFR) in LPA-induced signaling. LPA stimulated DNA synthesis and/or migration in all the cell lines included in this study. In five of the six cell lines, LPA induced phosphorylation of the EGFR, and the effects on EGFR and Akt, and in some of the cells also ERK, were sensitive to the EGFR tyrosine kinase inhibitor gefitinib, strongly suggesting LPA-induced EGFR transactivation in these cells. In contrast, in one of the pancreatic carcinoma cell lines (Panc-1), we found no evidence of transactivation of the EGFR. In the pancreatic carcinoma cell lines where transactivation took place (BxPC3, AsPC1, HPAFII), gefitinib reduced LPA-induced DNA synthesis and/or migration. However, we also found evidence of transactivation in the two colon carcinoma cell lines (HT29, HCT116) although gefitinib did not inhibit LPA-induced DNA synthesis or migration in these cells. Taken together, the data indicate that in many gastrointestinal carcinoma cells, LPA uses EGFR transactivation as a mechanism when exerting such effects as stimulation of cell proliferation and migration, but EGFR-independent pathways may be involved instead of, or in concerted action with, the EGFR transactivation.

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

    ClinicalTrials.gov

    2016-07-14

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

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

    PubMed

    Iguchi, H; Hayashi, I; Kono, A

    1990-06-15

    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.

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

    ClinicalTrials.gov

    2016-10-18

    Acinar Cell Carcinoma; Ampulla of Vater Adenocarcinoma; Cholangiocarcinoma; Duodenal Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary Mucinous Neoplasm, Pancreatobiliary-Type; Periampullary Adenocarcinoma

  20. The miR-24-Bim pathway promotes tumor growth and angiogenesis in pancreatic carcinoma.

    PubMed

    Liu, Rui; Zhang, Haiyang; Wang, Xia; Zhou, Likun; Li, Hongli; Deng, Ting; Qu, Yanjun; Duan, Jingjing; Bai, Ming; Ge, Shaohua; Ning, Tao; Zhang, Le; Huang, Dingzhi; Ba, Yi

    2015-12-22

    miRNAs are a group of small RNAs that have been reported to play a key role at each stage of tumorigenesis and are believed to have future practical value. We now demonstrate that Bim, which stimulates cell apoptosis, is obviously down-regulated in pancreatic cancer (PaC) tissues and cell lines. And Bim-related miR-24 is significantly up-regulated in PaC. The repressed expression of Bim is proved to be a result of miR-24, thus promoting cell growth of both cancer and vascular cells, and accelerating vascular ring formation. By using mouse tumor model, we clearly showed that miR-24 promotes tumor growth and angiogenesis by suppressing Bim expression in vivo. Therefore, a new pathway comprising miR-24 and Bim can be used in the exploration of drug-target therapy of PaC.

  1. Crizotinib inhibits metabolic inactivation of gemcitabine in c-Met-driven pancreatic carcinoma.

    PubMed

    Avan, Amir; Caretti, Viola; Funel, Niccola; Galvani, Elena; Maftouh, Mina; Honeywell, Richard J; Lagerweij, Tonny; Van Tellingen, Olaf; Campani, Daniela; Fuchs, Dieter; Verheul, Henk M; Schuurhuis, Gerrit-Jan; Boggi, Ugo; Peters, Godefridus J; Würdinger, Thomas; Giovannetti, Elisa

    2013-11-15

    Pancreatic ductal adenocarcinoma (PDAC) remains a major unsolved health problem. Most drugs that pass preclinical tests fail in these patients, emphasizing the need of improved preclinical models to test novel anticancer strategies. Here, we developed four orthotopic mouse models using primary human PDAC cells genetically engineered to express firefly- and Gaussia luciferase, simplifying the ability to monitor tumor growth and metastasis longitudinally in individual animals with MRI and high-frequency ultrasound. In these models, we conducted detailed histopathologic and immunohistochemical analyses on paraffin-embedded pancreatic tissues and metastatic lesions in liver, lungs, and lymph nodes. Genetic characteristics were compared with the originator tumor and primary tumor cells using array-based comparative genomic hybridization, using frozen specimens obtained by laser microdissection. Notably, the orthotopic human xenografts in these models recapitulated the phenotype of human PDACs, including hypovascular and hypoxic areas. Pursuing genomic and immunohistochemical evidence revealed an increased copy number and overexpression of c-Met in one of the models; we examined the preclinical efficacy of c-Met inhibitors in vitro and in vivo. In particular, we found that crizotinib decreased tumor dimension, prolonged survival, and increased blood and tissue concentrations of gemcitabine, synergizing with a cytidine deaminase-mediated mechanism of action. Together, these more readily imaged orthotopic PDAC models displayed genetic, histopathologic, and metastatic features similar to their human tumors of origin. Moreover, their use pointed to c-Met as a candidate therapeutic target in PDAC and highlighted crizotinib and gemcitabine as a synergistic combination of drugs warranting clinical evaluation for PDAC treatment.

  2. 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)

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

    2014-11-01

    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.

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

    PubMed

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

    2014-12-11

    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.

  4. Interstitial iodine-125 implant in the management of unresectable pancreatic carcinoma

    SciTech Connect

    Syed, A.M.; Puthawala, A.A.; Neblett, D.L.

    1983-09-01

    Eighteen patients with locally advanced adenocarcinoma of the head, body and tail of the pancreas were treated by a combination of biliary bypass, external and interstitial irradiation at Southern California Cancer Center of California Hospital Medical Center, Los Angeles, and Memorial Hospital Medical Center of Long Beach, Long Beach, CA, from July 31, 1975 to December 31, 1980. A dose of 3000 to 5000 rad was delivered to the pancreas and regional lymph nodes by external irradiation utilizing megavoltage units and 10,000 to 15,000 rad to the pancreas and metastatic lymph nodes by permanent Iodine-125 implants. In this group of 18 patients with unresectable carcinoma of the pancreas, excellent palliation of pain, jaundice and vomiting was achieved, with a median survival of 14 months.

  5. Ultrasonically guided percutaneous implantation of iodine-125 seeds in pancreatic carcinoma

    SciTech Connect

    Joyce, F.; Burcharth, F.; Holm, H.H.; Stroyer, I. )

    1990-10-01

    Cancer of the pancreas is most often not diagnosed before it has reached unresectable stages. The development of effective palliative treatment for these patients and for those with recurrence after resection is clearly needed. The present study reports the results of ultrasonically guided percutaneous implantation of {sup 125}I seeds in 19 patients with cancer of the pancreas. Twelve patients had further adjuvant external radiation. Despite satisfactory seed placement and delivery of the planned radiation dose in most cases, clinical improvement was lacking or only slight and short-lived. No difference in survival or palliation was observed between patients treated with seeds alone compared with patients treated with seeds and external radiation. Survival after seed implantation was short (median 140 days, range 7-401 days). Ultrasonically guided percutaneous implantation of {sup 125}I seeds cannot be recommended in the treatment of unresectable carcinoma of the pancreas.

  6. Immunohistochemical Markers Distinguishing Cholangiocellular Carcinoma (CCC) from Pancreatic Ductal Adenocarcinoma (PDAC) Discovered by Proteomic Analysis of Microdissected Cells*

    PubMed Central

    Padden, Juliet; Ahrens, Maike; Kälsch, Julia; Bertram, Stefanie; Megger, Dominik A.; Bracht, Thilo; Eisenacher, Martin; Kocabayoglu, Peri; Meyer, Helmut E.; Sipos, Bence; Baba, Hideo A.; Sitek, Barbara

    2016-01-01

    Cholangiocellular carcinoma (CCC) and pancreatic ductal adenocarcinoma (PDAC) are two highly aggressive cancer types that arise from epithelial cells of the pancreatobiliary system. Owing to their histological and morphological similarity, differential diagnosis between CCC and metastasis of PDAC located in the liver frequently proves an unsolvable issue for pathologists. The detection of biomarkers with high specificity and sensitivity for the differentiation of these tumor types would therefore be a valuable tool. Here, we address this problem by comparing microdissected CCC and PDAC tumor cells from nine and eleven cancer patients, respectively, in a label-free proteomics approach. The novel biomarker candidates were subsequently verified by immunohistochemical staining of 73 CCC, 78 primary, and 18 metastatic PDAC tissue sections. In the proteome analysis, we found 180 proteins with a significantly differential expression between CCC and PDAC cells (p value < 0.05, absolute fold change > 2). Nine candidate proteins were chosen for an immunohistochemical verification out of which three showed very promising results. These were the annexins ANXA1, ANXA10, and ANXA13. For the correct classification of PDAC, ANXA1 showed a sensitivity of 84% and a specificity of 85% and ANXA10 a sensitivity of 90% at a specificity of 66%. ANXA13 was higher abundant in CCC. It presented a sensitivity of 84% at a specificity of 55%. In metastatic PDAC tissue ANXA1 and ANXA10 showed similar staining behavior as in the primary PDAC tumors (13/18 and 17/18 positive, respectively). ANXA13, however, presented positive staining in eight out of eighteen secondary PDAC tumors and was therefore not suitable for the differentiation of these from CCC. We conclude that ANXA1 and ANXA10 are promising biomarker candidates with high diagnostic values for the differential diagnosis of intrahepatic CCC and metastatic liver tumors deriving from PDAC. PMID:26644413

  7. A dosimetric analysis of dose escalation using two intensity-modulated radiation therapy techniques in locally advanced pancreatic carcinoma

    SciTech Connect

    Brown, Michael W.; Ning, Holly; Arora, Barbara; Albert, Paul S.; Poggi, Matthew; Camphausen, Kevin; Citrin, Deborah . E-mail: citrind@mail.nih.gov

    2006-05-01

    Purpose: To perform an analysis of three-dimensional conformal radiation therapy (3D-CRT), sequential boost intensity-modulated radiation therapy (IMRTs), and integrated boost IMRT (IMRTi) for dose escalation in unresectable pancreatic carcinoma. Methods and Materials: Computed tomography images from 15 patients were used. Treatment plans were generated using 3D-CRT, IMRTs, and IMRTi for dose levels of 54, 59.4, and 64.8 Gy. Plans were analyzed for target coverage, doses to liver, kidneys, small bowel, and spinal cord. Results: Three-dimensional-CRT exceeded tolerance to small bowel in 1 of 15 (6.67%) patients at 54 Gy, and 4 of 15 (26.7%) patients at 59.4 and 64.8 Gy. 3D-CRT exceeded spinal cord tolerance in 1 of 15 patients (6.67%) at 59.4 Gy and liver constraints in 1 of 15 patients (6.67%) at 64.8 Gy; no IMRT plans exceeded tissue tolerance. Both IMRT techniques reduced the percentage of total kidney volume receiving 20 Gy (V20), the percentage of small bowel receiving 45 Gy (V45), and the percentage of liver receiving 35 Gy (V35). IMRTi appeared superior to IMRTs in reducing the total kidney V20 (p < 0.0001), right kidney V20 (p < 0.0001), and small bowel V45 (p = 0.02). Conclusions: Sequential boost IMRT and IMRTi improved the ability to achieve normal tissue dose goals compared with 3D-CRT. IMRTi allowed dose escalation to 64.8 Gy with acceptable normal tissue doses and superior dosimetry compared with 3D-CRT and IMRTs.

  8. Radiotherapy of unresectable pancreatic carcinoma: a six year experience with 104 patients. [/sup 125/I; Betatron

    SciTech Connect

    Whittington, R.; Dobelbower, R.R.; Mohiuddin, M.; Rosato, F.E.; Weiss, S.M.

    1981-12-01

    From 1974 to 1980, 104 patients with unresectable carcinoma of the pancreas were seen in the Department of Radiation Therapy at Thomas Jefferson University Hospital. Sixty-six patients were accepted for definitive therapy. Of these, 48 patients received precision high dose radiotherapy to a dose of 6800 rad on the 45 MeV Betatron, using either photons alone or mixed photon and high energy electron beams. Eighty-nine percent of the patients completed treatment as per the protocol. Relief of symptoms was obtained in 65% of patients. Median survival was 10 months. In spite of the high doses employed, 67% of the patients had evidence of recurrent tumor in the treatment volume at the time of death. In view of the high incidence of local failure with precision high dose therapy alone, a protocol using Iodine-125 implantation to supplement the external beam therapy was developed in 1978. Since then, 18 patients with disease confined to the region of the pancreas were treated with the combination of Iodine-125 implantation and precision high dose therapy. Eighty-five percent of the patients completed treatment. Follow-up ranges from eight to 22 months. None of the patients completing the treatment protocol have developed local recurrence of tumor. These results are presented together with details of the treatment technique, normal tissue reactions and implications for future approaches to the treatment of localized unresectable cancer of the pancreas.

  9. Radiotherapy of unresectable pancreatic carcinoma: a six year experience with 104 patients

    SciTech Connect

    Whittington, R.; Dobelbower, R.R.; Mohiuddin, M.; Rosato, F.E.; Weiss, S.M.

    1981-12-01

    From 1974 to 1980, 104 patients with unresectable carcinoma of the pancreas were seen in the Department of Radiation Therapy at Thomas Jefferson University Hospital. Sixty-six patients were accepted for definitive therapy. Of these, 48 patients received precision high dose radiotherapy to a dose of 6800 rad on the 45 MeV Betatron, using either photons alone or mixed photon and high energy electron beams. Eighty-nine percent of the patients completed treatment as per the protocol. Relief of symptoms was obtained in 65% of patients. Median survival was 10 months. In spite of the high doses employed, 67% of the patients had evidence of recurrent tumor in the treatment volume at the time of death. In view of the high incidence of local failure with precision high dose therapy alone, a protocol using Iodine-125 implantation to supplement the external beam therapy was developed in 1978. Since then, 18 patients with disease confined to the region of the pancreas were treated with the combination of Iodine-125 implantation and precision high dose therapy. Eighty-five percent of the patients completed treatment. Follow-up ranges from eight to 22 months. None of the patients completing the treatment protocol have developed local recurrence of tumor. These results are presented together with details of the treatment technique, normal tissue reactions and implications for future approaches to the treatment of localized unresectable cancer of the pancreas.

  10. Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells.

    PubMed

    Cengel, Keith A; Voong, K Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B; Stanbridge, Eric; Kao, Gary D; McKenna, W Gillies; Bernhard, Eric J

    2007-04-01

    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor alpha was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers.

  11. Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells1

    PubMed Central

    Cengel, Keith A.; Voong, K. Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B.; Stanbridge, Eric; Kao, Gary D.; McKenna, W. Gillies; Bernhard, Eric J.

    2007-01-01

    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor α was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers. PMID:17460778

  12. Caspase-3 activation downstream from reactive oxygen species in heat-induced apoptosis of pancreatic carcinoma cells carrying a mutant p53 gene.

    PubMed

    Kobayashi, D; Sasaki, M; Watanabe, N

    2001-04-01

    In the present study we investigated the intracellular signaling pathway leading to p53-independent activation of caspase-3 during heat-induced apoptosis of pancreatic carcinoma cells. Induction of mutant p53 protein, but not p21/WAF-1, was observed after heat treatment of both heat-resistant (PANC-1) and heat-sensitive (MIAPaCa-2) cells. A specific inhibitor of caspase-3 (Ac-DMQD-CHO) caused 84% and 92% inhibition of apoptosis in MIAPaCa-2 and PANC-1 cells, respectively. Caspase-3 mRNA expression was increased in both cell lines after heat treatment. Further, heat-induced caspase-3 activity detected by fluorogenic assay in MIAPaCa-2 cells was almost completely inhibited by addition of the antioxidant N-acetyl-L-cysteine. In contrast, Ac-DMQD-CHO had no inhibitory effect on amounts of reactive oxygen species in heat-treated MIAPaCa-2 cells. These results suggest a possible pathway by which reactive oxygen species lead to caspase-3 activation to cause heat-induced death of pancreatic carcinoma cells carrying mutant p53.

  13. Knockdown or inhibition of aldo-keto reductase 1B10 inhibits pancreatic carcinoma growth via modulating Kras-E-cadherin pathway.

    PubMed

    Zhang, Wanying; Li, Haonan; Yang, Yihe; Liao, Jie; Yang, Guang-Yu

    2014-12-28

    Aldo-keto reductase 1B10 (AKR1B10) has relatively specific lipid substrates including carbonyls, retinal and farnesal/geranylgeranial. Metabolizing these lipid substrates appears crucial to carcinogenesis, particularly for farnesal/geranylgeranial that involves protein prenylation. Mutant Kras is a most common active oncogene in pancreatic cancer, and its activation requires protein prenylation. To directly determine the role of AKR1B10 in pancreatic carcinogenesis, we knocked down AKR1B10 in CD18 human pancreatic carcinoma cells using shRNA approach. Silencing AKR1B10 resulted in a significant inhibition of anchor-dependent growth (knockdown cells vs. vector-control cells: 67 ± 9.5 colonies/HPF vs. 170 ± 3.7 colonies/HPF, p < 0.01), invasion index (0.27 vs. 1.00, p < 0.05), and cell migration (at 16 hours 9.2 ± 1.2% vs. 14.0 ± 1.8%, at 24 hours 21.0 ± 1.1% vs. 30.5 ± 3.5%, and at 48 hours 51.9 ± 5.7% vs. 88.9 ± 3.0%, p < 0.01). Inhibition of AKR1B10 by oleanolic acid (OA) showed a dose-dependent inhibition of cell growth with IC50 at 30 µM. Kras pull-down and Western blot analysis revealed a significant down-regulation of active form Kras and phosphorylated C-Raf, and Erk, as well as an up-regulation of E-cadherin. A significant reduction of in vivo tumor growth was observed in nude mice implanted with the CD18 pancreatic carcinoma cells with AKR1B10 knockdown (tumor weight: 0.25 ± 0.06 g vs. 0.52 ± 0.07 g, p = 0.01), and with OA treatment (tumor weight: 0.35 ± 0.05 g vs. 0.52 ± 0.07 g, p = 0.05). Our findings indicate AKR1B10 is a unique enzyme involved in pancreatic carcinogenesis via modulation of the Kras-E-cadherin pathway.

  14. Functional imaging of interstitial brachytherapy in pancreatic carcinoma xenografts using spectral CT: how does iodine concentration correlate with standardized uptake value of 18FDG-PET-CT?

    PubMed Central

    Hu, Shudong; Shi, Xiaofeng; Chen, Yerong; Huang, Wei; Song, Qi; Lin, Xiaozhu; Liu, Yu; Chen, Kemin

    2016-01-01

    Objective: This study aimed to investigate the correlation between iodine concentration (IC) for the quantitative analysis of spectral CT and maximum standardized uptake value (SUVmax) of 18 fludeoxyglucose positron emission tomography–CT (18FDG PET–CT) as an indicator of therapeutic response to interstitial brachytherapy in transplanted human pancreatic carcinomas in BALB/c-nu mice. Methods: Xenograft models were created by subcutaneous injection of SW1990 human pancreatic cancer cell suspensions into immunodeficient BALB/c-nu mice. 30 mice bearing SW1990 human pancreatic cancer cell xenografts were randomly separated into two groups: experimental (n = 15; 1.0 mCi) and control (n = 15, 0 mCi). After 2 weeks of treatment, spectral CT and 18FDG micro-PET–CT scan were performed. IC values and SUVmax in the lesions were measured. IC normalized to the muscle tissue is indicated as nIC. The relationships between the nIC and SUVmax of the transplantation tumours were analysed. Results: 2 weeks after treatment, the nIC in three-phase scans and SUVmax of the experimental group were significantly lower than those of the control group. The nIC values of the three-phase scans have certain positive correlation with the SUVmax values (r = 0.69, p < 0.05; r = 0.73 and p < 0.05; r = 0.80, p < 0.05 in the 10-, 25- and 60-s phase, respectively). Conclusion: Spectral CT could serve as a valuable imaging modality, as our results suggest that nIC correlates with SUVmax of 18FDG PET–CT for evaluating the therapeutic effect of 125I interstitial brachytherapy in a pancreatic carcinoma xenograft. Advances in knowledge: Spectral CT offers opportunities to assess the therapeutic response of pancreatic cancer. This study supports the conclusion that nIC values in spectral CT could also serve as a valuable functional imaging parameter for early monitoring and evaluation of the therapeutic response of 125I interstitial brachytherapy mouse models

  15. Laryngeal Dysplasia, Squamous Cell Carcinoma, and Variants.

    PubMed

    Thompson, Lester D R

    2017-03-01

    Squamous cell carcinoma (SCC) is a malignant epithelial tumor showing evidence of squamous differentiation. It is the most common malignancy of the larynx, with several variants (verrucous, exophytic or papillary, spindle-cell, basaloid, acantholytic, adenosquamous) recognized, with well-established precursor lesions. Dysplasia is now separated into only low-grade and high-grade categories. Each SCC variant has unique cytomorphologic features and histologic differential diagnoses that are important to consider, as management and outcomes are different.

  16. Oncolytic Adenoviral Mutants with E1B19K Gene Deletions Enhance Gemcitabine-induced Apoptosis in Pancreatic Carcinoma Cells and Anti-Tumor Efficacy In vivo

    PubMed Central

    Leitner, Stephan; Sweeney, Katrina; Öberg, Daniel; Davies, Derek; Miranda, Enrique; Lemoine, Nick R.; Halldén, Gunnel

    2010-01-01

    Purpose Pancreatic adenocarcinoma is a rapidly progressive malignancy that is highly resistant to current chemotherapeutic modalities and almost uniformly fatal.We show that a novel targeting strategy combining oncolytic adenoviral mutants with the standard cytotoxic treatment, gemcitabine, can markedly improve the anticancer potency. Experimental Design Adenoviral mutants with the E1B19K gene deleted with and without E3B gene expression (AdΔE1B19K and dl337 mutants, respectively) were assessed for synergistic interactions in combination with gemcitabine. Cell viability, mechanism of cell death, and antitumor efficacy in vivo were determined in the pancreatic carcinoma cells PT45 and Suit2, normal human bronchial epithelial cells, and in PT45 xenografts. Results The ΔE1B19K-deleted mutants synergized with gemcitabine to selectively kill cultured pancreatic cancer cells and xenografts in vivo with no effect in normal cells. The corresponding wild-type virus (Ad5) stimulated drug-induced cell killing to a lesser degree. Gemcitabine blocked replication of all viruses despite the enhanced cell killing activity due to gemcitabine-induced delay in G1/S-cell cycle progression, with repression of cyclin E and cdc25A, which was not abrogated by viral E1A-expression. Synergistic cell death occurred through enhancement of gemcitabine-induced apoptosis in the presence of both AdΔE1B19K and dl337 mutants, shown by increased cell membrane fragmentation, caspase-3 activation, and mitochondrial dysfunction. Conclusions Our data suggest that oncolytic mutants lacking the antiapoptotic E1B19K gene can improve efficacy of DNA-damaging drugs such as gemcitabine through convergence on cellular apoptosis pathways.These findings imply that less toxic doses than currently practicedin the clinic could efficiently target pancreatic adenocarcinomas when combined with adenoviral mutants. PMID:19223497

  17. Hereditary Pancreatitis

    MedlinePlus

    ... meals throughout the day that are high in carbohydrates and low in protein and fat. Pancreatic enzymes ... the Pancreas NPF Centers Pancreatitis Centers Pancreatitis Center Application Pancreatic Cancer Centers Diagnosis of Pancreatic Cancer Pancreas ...

  18. [Chronic pancreatitis, acute pancreatitis].

    PubMed

    Mabuchi, T; Katada, N; Nishimura, D; Hoshino, H; Shimizu, F; Suzuki, R; Sano, H; Kato, K

    1998-11-01

    MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.

  19. Anterior approach to the superior mesenteric artery by using nerve plexus hanging maneuver for borderline resectable pancreatic head carcinoma.

    PubMed

    Mizuno, Shugo; Isaji, Shuji; Tanemura, Akihiro; Kishiwada, Masashi; Murata, Yasuhiro; Azumi, Yoshinori; Kuriyama, Naohisa; Usui, Masanobu; Sakurai, Hiroyuki; Tabata, Masami

    2014-06-01

    To achieve R0 resection for pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head, complete resection of the retropancreatic nerve plexus around the superior mesenteric artery (SMA) is thought to be required. Twenty-five patients with borderline resectable right-sided PDAC were divided into two groups after neoadjuvant chemoradiotherapy: those with portal vein (PV) invasion alone (n = 12), and those with invasion of both PV and SMA (n = 13). A tape for guidance was passed in a space ventral to the SMA and behind the pancreatic parenchyma, followed by resection of the pancreatic parenchyma with the splenic vein. Another tape was passed behind the nerve plexus lateral to the hepatic artery and the SMA ventral to the inferior vena cava and the nerve plexus was dissected, resulting in complete resection of the nerve plexus around the SMA. Pathological findings revealed that the rates of R0, R01 (a margin less than 1 mm) and R1 were 58.3 %, 41.7 % and 0 % in PV group, and 53.8 %, 30.8 % and 15.4 % in PV/A group, respectively. The median survival time was 23.3 and 22.8 months in PV and PV/A groups, respectively. The plexus hanging maneuver for PDAC of the pancreatic head achieved complete resection of the retropancreatic nerve plexus around the SMA, helping to secure a negative surgical margin.

  20. Interferon γ inhibits growth of human pancreatic carcinoma cells via caspase-1 dependent induction of apoptosis

    PubMed Central

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

    2001-01-01

    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 γ (IFN-γ) on growth and survival in human pancreatic cancer cells.
METHODS—IFN-γ 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-γ receptors and downstream effectors, including the putative tumour suppressor interferon regulatory factor 1 (IRF-1). IFN-γ 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-γ 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 γ; apoptosis; caspase-1;interferon regulatory factor; pancreatic cancer PMID:11454803

  1. Cisplatin and Etoposide or Temozolomide and Capecitabine in Treating Patients With Neuroendocrine Carcinoma of the Gastrointestinal Tract or Pancreas That Is Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-01-05

    Colorectal Large Cell Neuroendocrine Carcinoma; Esophageal Large Cell Neuroendocrine Carcinoma; Gallbladder Large Cell Neuroendocrine Carcinoma; Gastric Large Cell Neuroendocrine Carcinoma; Pancreatic Large Cell Neuroendocrine Carcinoma; Small Intestinal Large Cell Neuroendocrine Carcinoma

  2. Induction of Apoptosis in Tumor-Associated Endothelial Cells and Therapy of Orthotopic Human Pancreatic Carcinoma in Nude Mice1

    PubMed Central

    Yokoi, Kenji; Kim, Sun-Jin; Thaker, Premal; Yazici, Sertac; Nam, Do-Hyun; He, Junqin; Sasaki, Takamitsu; Chiao, Paul J; Sclabas, Guido M; Abbruzzese, James L; Hamilton, Stanley R; Fidler, Isaiah J

    2005-01-01

    Abstract Although gemcitabine has been accepted as the first-line chemotherapeutic reagent for advanced pancreatic cancer, improvement of response rate and survival is not sufficient and patients often develop resistance. We hypothesized that the inhibition of phosphorylation of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) on tumor cells and tumor-associated endothelial cells, combined with gemcitabine, would overcome the resistance to gemcitabine in orthotopic pancreatic tumor animal model. L3.6pl, human pancreatic cancer cells growing in the pancreas, and tumor-associated endothelial cells in microorgan environment highly expressed phosphorylated EGFR, VEGFR, and Akt, which regulates antiapoptotic mechanism. Oral administration of AEE788 (dual tyrosine kinase inhibitor against EGFR and VEGFR) inhibited the phosphorylation of EGFR, VEGFR, and Akt on tumor-associated endothelial cells as well as tumor cells. Although intraperitoneal (i.p.) injection of gemcitabine showed limited inhibitory effect on tumor growth, combination with AEE788 and gemcitabine produced nearly 95% inhibition of tumor growth in parallel with a high level of apoptosis on tumor cells and tumor-associated endothelial cells, and decreased microvascular density and proliferation rate. Collectively, these data indicate that dual inhibition of phosphorylation of EGFR and VEGFR, in combination with gemcitabine, produces apoptosis of tumor-associated endothelial cells and significantly suppresses human pancreatic cancer in nude mice. PMID:16026649

  3. Pancreatic cancer: from bench to bedside

    PubMed Central

    Ma, Yaokai; Wu, Qing; Li, Xin; Gu, Xiaoqiang; Xu, Jiahua

    2016-01-01

    Pancreatic cancer is recognized as the king of carcinoma, and the gap between basic research and clinical practice is difficult to improve the treatment effect. Translational medicine builds an important bridge between pancreatic cancer basic research and clinical practice from the pathogenesis, early diagnosis of pancreatic carcinoma, drug screening, treatment strategies and metastasis prediction. This article will carry on the concrete elaboration to the above several aspects. PMID:28090514

  4. Pancreatitis - discharge

    MedlinePlus

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... fluids through an intravenous (IV) tube in your vein and nutrition through a feeding tube or IV. ...

  5. Chronic pancreatitis

    MedlinePlus

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... hospital for: Pain medicines Fluids given through a vein (IV) Stopping food or fluid by mouth to ...

  6. 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

    Su, Chin-Cheng

    2015-04-01

    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.

  7. [A case of chronic pancreatitis occurring in gastric aberrant pancreas poorly distinguishable from gastric aberrant pancreas ductal carcinoma].

    PubMed

    Ogawa, Sayaka; Miyaoka, Youichi; Fujiwara, Aya; Tsukano, Kousuke; Kotani, Satoshi; Yamanouchi, Satoshi; Kusunoki, Ryusaku; Ito, Satoko; Fujishiro, Hirofumi; Kohge, Nariaki; Onuma, Hideyuki

    2015-11-01

    A man in his 40s was referred to our hospital with abdominal pain. A gastric submucosal tumor (SMT) was diagnosed nine years previously, but the patient was lost to follow-up. Upon our evaluation, the SMT had enlarged, as demonstrated by esophagogastroduodenoscopy and abdominal computed tomography. Endoscopic ultrasonography revealed a hypoechoic and isoechoic mosaic mass, which primarily occupied the third and fourth layers of the gastric wall. Aspiration cytodiagnosis was performed, the results of which led to a suspicion of adenocarcinoma arising from gastric ectopic pancreas. Next, we conducted segmental gastrectomy. Pathological examination showed adiponecrosis, a pancreatic stone, chronic inflammatory cell infiltration, and fibrosis. Thus, the patient was diagnosed with chronic pancreatitis occurring in a gastric aberrant pancreas.

  8. Estimating Optimal Dose of Twice-Weekly Gemcitabine for Concurrent Chemoradiotherapy in Unresectable Pancreatic Carcinoma: Mature Results of GEMRT-01 Phase I Trial

    SciTech Connect

    Girard, Nicolas; Mornex, Francoise; Bossard, Nadine; Ychou, Marc; Chauffert, Bruno; Wautot, Virginie

    2010-08-01

    Purpose: To accurately determine the maximal tolerated dose, feasibility, and antitumor activity of concurrent chemoradiotherapy including twice-weekly gemcitabine in patients with unresectable pancreatic adenocarcinoma. Methods and Materials: Eligible patients with histologically proven adenocarcinoma of the pancreas were included in this Phase I trial. Radiotherapy was delivered to a total dose of 50 Gy. Concurrent chemotherapy with twice-weekly gemcitabine was administered during the 5 weeks of radiotherapy, from an initial dose of 30 mg/m{sup 2}. The gemcitabine doses were escalated in 10-mg/m{sup 2} increments in a three-plus-three design, until dose-limiting toxicities were observed. Results: A total of 35 patients were included in the trial. The feasibility of chemoradiotherapy was high, because all the patients received the planned total radiation dose, and 26 patients (74%) received {>=}70% of the planned chemotherapy dose. The mean total delivered dose of gemcitabine was 417 mg/m{sup 2} (i.e., 77% of the prescribed dose). The maximal tolerated dose of twice-weekly gemcitabine was 70 mg/m{sup 2}. Of the 35 patients, 13 had a partial response (37%) and 21 had stable disease (60%). Overall, the median survival and the 6-, 12-, and 18-month survival rates were 10.6 months and 82%, 31%, and 11%, respectively. Survival was significantly longer in patients with an initial performance status of 0 or 1 (p = .004). Conclusion: Our mature data have indicated that gemcitabine doses can be increased {<=}70 mg/m{sup 2}, when delivered twice-weekly with concurrent radiotherapy. This combination shows promises to achieve better recurrence-free and overall survival. These results will serve as a basis for further implementation of the multimodal treatment of locally advanced pancreatic carcinoma.

  9. Calcitriol enhances gemcitabine antitumor activity in vitro and in vivo by promoting apoptosis in a human pancreatic carcinoma model system

    PubMed Central

    Yu, Wei-Dong; Ma, Yingyu; Flynn, Geraldine; Muindi, Josephia R; Kong, Rui-Xian; Trump, Donald L

    2010-01-01

    Gemcitabine is the standard care chemotherapeutic agent to treat pancreatic cancer. Previously we demonstrated that calcitriol (1, 25-dihydroxycholecalciferol) has significant anti-proliferative effects in vitro and in vivo in multiple tumor models and enhances the activity of a variety of chemotherapeutic agents. We therefore investigated whether calcitriol could potentiate the cytotoxic activity of gemcitabine in the human pancreatic cancer Capan-1 model system. Isobologram analysis revealed that calcitriol and gemcitabine had synergistic antiproliferative effect over a wide range of drug concentrations. Calcitriol did not reduce the cytidine deaminase activity in Capan-1 tumors nor in the livers of Capan-1 tumor bearing mice. Calcitriol and gemcitabine combination promoted apoptosis in Capan-1 cells compared with either agent alone. The combination treatment also increased the activation of caspases-8, -9, -6 and -3 in Capan-1 cells. This result was confirmed by substrate-based caspase activity assay. Akt phosphorylation was reduced by calcitriol and gemcitabine combination treatment compared to single agent treatment. However, ERK1/2 phosphorylation was not modulated by either agent alone or by the combination. Tumor regrowth delay studies showed that calcitriol in combination with gemcitabine resulted in a significant reduction of Capan-1 tumor volume compared to single agent treatment. Our study suggests that calcitriol and gemcitabine in combination promotes caspase-dependent apoptosis, which may contribute to increased anti-tumor activity compared to either agent alone. PMID:20699664

  10. MDSC-decreasing chemotherapy increases the efficacy of cytokine-induced killer cell immunotherapy in metastatic renal cell carcinoma and pancreatic cancer.

    PubMed

    Wang, Zibing; Liu, Yuqing; Zhang, Yong; Shang, Yiman; Gao, Quanli

    2016-01-26

    Adoptive immunotherapy using cytokine-induced killer (CIK) cells is a promising cancer treatment, but its efficacy is restricted by various factors, including the accumulation of myeloid-derived suppressor cells (MDSCs). In this study, we determine whether chemotherapeutic drugs that reduce MDSC levels enhance the efficacy of CIK cell therapy in the treatment of solid tumors. Fifty-three patients were included in this study; 17 were diagnosed with metastatic renal cell carcinoma (MRCC), 10 with advanced pancreatic cancer (PC), and 26 with metastatic melanoma (MM). These patients were divided into two groups: CIK cell therapy alone and CIK cell therapy combined with chemotherapy. Combining CIK cell therapy and chemotherapy increased 1-year survival rates and median survival times in MRCC and PC patients, but not in MM patients. The disease control rate did not differ between treatment groups for MRCC or MM patients, but was higher in PC patients receiving combined treatment than CIK cell treatment alone. These data suggest that addition of MDSC-decreasing chemotherapy to CIK cell therapy improves survival in MRCC and PC patients.

  11. In vitro cytotoxicity evaluation of HDAC inhibitor Apicidin in pancreatic carcinoma cells subsequent time and dose dependent treatment.

    PubMed

    Bauden, Monika; Tassidis, Helena; Ansari, Daniel

    2015-07-02

    Apicidin is a potent histone deacetylase inhibitor (HDACI) that selectively binds to histone deacetylases (HDACs) class I and interferes with the deacetylation process, which results in modification of acetylation level of cellular proteins. The aim of the study was to investigate the potential time and dose dependent cytotoxicity of the test compound, Apicidin, in pancreatic cancer cells Capan-1 and Panc-1 as well as estimate maximal tolerable dose (MTD) of the test agent and determine EC50 using four complementary colorimetric cytotoxicity or viability assays. The cells were treated with increasing concentrations of Apicidin (0-5000nM) for 2, 4 and 6h (short term exposure) or 24, 48 and 72h (long term exposure) before conducting cytotoxic analyses with lactate dehydrogenase assay or viability analyses with sulforhodamine B (SRB), methyl tetrazolium (MTT) and crystal violet (CV) assays. In order to investigate whether Apicidin irreversibly affects the cells already during the short term exposure, the medium containing Apicidin was removed and replaced with fresh culturing medium after 6h of treatment. The cells were then incubated for additional 24, 48 or 72h before carrying out the analysis. The results obtained from cytotoxicity and viability assays indicated, that Apicidin was well tolerated by both cell lines at concentrations below 100nM at any given time point and at all applied concentrations during the short term (6h or less) treatment. Continuous prolonged term exposures (48h or greater) of the cells to Apicidin with concentration exceeding 100nM resulted in significantly increasing cytotoxicity and sustained significant loss of cell viability. Moreover, long term exposure of pancreatic cancer cells Capan-1 and Panc-1 to Apicidin concentrations exceeding 100nM showed an initial anti-proliferative effect before cytotoxicity onset. In summary, MTD was exposure time dependent and estimated to 100nM for long term treatment and to at least 5000nM for treatment

  12. Pancreatic Cancer

    MedlinePlus

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  13. Pancreatic pseudocyst

    MedlinePlus

    ... More Acute pancreatitis Chronic pancreatitis Pancreatic abscess Shock Review Date 10/27/2015 Updated by: Subodh K. ... gastroenterologist with Gastrointestinal Specialists of Georgia, Austell, GA. Review provided by VeriMed Healthcare Network. Also reviewed by ...

  14. KiSS‑1‑mediated suppression of the invasive ability of human pancreatic carcinoma cells is not dependent on the level of KiSS‑1 receptor GPR54.

    PubMed

    Wang, Chun-Hui; Qiao, Chong; Wang, Ruo-Chen; Zhou, Wen-Ping

    2016-01-01

    The onset of local invasion and lymphatic metastasis in pancreatic cancer limits survival following surgical intervention and additional therapies. Reduced expression of KiSS‑1 in pancreatic cancer is associated with cancer metastasis. Previous studies have indicated that kisspeptin, the KiSS‑1 peptide, is able to bind to its receptor‑GPR54 (hOT7T175) and suppress the migration of PANC‑1 pancreatic cancer cells. Whether the metastatic suppression of KiSS‑1 is dependent on the levels of GPR54 in pancreatic cancer cell lines remains unclear. Human BxPC‑3 pancreatic carcinoma cells are highly differentiated without exhibiting metastasis, however PANC‑1 pancreatic carcinoma cells are poorly differentiated and exhibit local and lymph node metastasis. Compared with primary cultured trophoblasts, BxPc‑3 and PANC‑1 cells were observed to express low levels of KiSS‑1 mRNA and protein, measured using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. However, greater mRNA and protein expression levels of GPR54 were observed in PANC‑1 cells compared with BxPc‑3 cells. An MTT assay was used to investigate the effect of KiSS‑1 on BxPc‑3 and PANC‑1 cell proliferation. There were no significant differences in proliferation following transfection with KiSS‑1 in BxPc‑3 and PANC‑1 cells compared with the controls (P>0.05). A Transwell assay with chambers coated with Matrigel was used to evaluate the in vitro invasive ability of BxPc‑3 and PANC‑1 cells, with the invasion index of BxPc‑3 and PANC‑1 cells significantly reduced following 48 h of KiSS‑1 overexpression (P<0.05). The mRNA and protein expression levels of KiSS‑1 were significantly increased in BxPc‑3 and PANC‑1 cells 48 h subsequent to transfection with KiSS‑1 (P<0.05), while GPR54 expression was not altered (P>0.05). KiSS‑1 is a metastasis suppressor gene of pancreatic cancer, and this suppression is not dependent on the

  15. KiSS-1-mediated suppression of the invasive ability of human pancreatic carcinoma cells is not dependent on the level of KiSS-1 receptor GPR54

    PubMed Central

    WANG, CHUN-HUI; QIAO, CHONG; WANG, RUO-CHEN; ZHOU, WEN-PING

    2016-01-01

    The onset of local invasion and lymphatic metastasis in pancreatic cancer limits survival following surgical intervention and additional therapies. Reduced expression of KiSS-1 in pancreatic cancer is associated with cancer metastasis. Previous studies have indicated that kisspeptin, the KiSS-1 peptide, is able to bind to its receptor-GPR54 (hOT7T175) and suppress the migration of PANC-1 pancreatic cancer cells. Whether the metastatic suppression of KiSS-1 is dependent on the levels of GPR54 in pancreatic cancer cell lines remains unclear. Human BxPC-3 pancreatic carcinoma cells are highly differentiated without exhibiting metastasis, however PANC-1 pancreatic carcinoma cells are poorly differentiated and exhibit local and lymph node metastasis. Compared with primary cultured trophoblasts, BxPc-3 and PANC-1 cells were observed to express low levels of KiSS-1 mRNA and protein, measured using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. However, greater mRNA and protein expression levels of GPR54 were observed in PANC-1 cells compared with BxPc-3 cells. An MTT assay was used to investigate the effect of KiSS-1 on BxPc-3 and PANC-1 cell proliferation. There were no significant differences in proliferation following transfection with KiSS-1 in BxPc-3 and PANC-1 cells compared with the controls (P>0.05). A Transwell assay with chambers coated with Matrigel was used to evaluate the in vitro invasive ability of BxPc-3 and PANC-1 cells, with the invasion index of BxPc-3 and PANC-1 cells significantly reduced following 48 h of KiSS-1 overexpression (P<0.05). The mRNA and protein expression levels of KiSS-1 were significantly increased in BxPc-3 and PANC-1 cells 48 h subsequent to transfection with KiSS-1 (P<0.05), while GPR54 expression was not altered (P>0.05). KiSS-1 is a metastasis suppressor gene of pancreatic cancer, and this suppression is not dependent on the expression levels of GPR54. Therefore, KiSS-1 is

  16. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  17. Developments in the pathology of penile squamous cell carcinomas.

    PubMed

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

    2010-08-01

    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.

  18. Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer.

    PubMed

    Talamini, G; Bassi, C; Falconi, M; Sartori, N; Salvia, R; Rigo, L; Castagnini, A; Di Francesco, V; Frulloni, L; Bovo, P; Vaona, B; Angelini, G; Vantini, I; Cavallini, G; Pederzoli, P

    1999-07-01

    The aim of this study was to compare alcohol and smoking as risk factors in the development of chronic pancreatitis and pancreatic cancer. We considered only male subjects: (1) 630 patients with chronic pancreatitis who developed 12 pancreatic and 47 extrapancreatic cancers; (2) 69 patients with histologically well documented pancreatic cancer and no clinical history of chronic pancreatitis; and (3) 700 random controls taken from the Verona polling list and submitted to a complete medical check-up. Chronic pancreatitis subjects drink more than control subjects and more than subjects with pancreatic cancer without chronic pancreatitis (P<0.001). The percentage of smokers in the group with chronic pancreatitis is significantly higher than that in the control group [odds ratio (OR) 17.3; 95% CI 12.6-23.8; P<0.001] and in the group with pancreatic carcinomas but with no history of chronic pancreatitis (OR 5.3; 95% CI 3.0-9.4; P<0.001). In conclusion, our study shows that: (1) the risk of chronic pancreatitis correlates both with alcohol intake and with cigarette smoking with a trend indicating that the risk increases with increased alcohol intake and cigarette consumption; (2) alcohol and smoking are statistically independent risk factors for chronic pancreatitis; and (3) the risk of pancreatic cancer correlates positively with cigarette smoking but not with drinking.

  19. Intratumoral α-SMA enhances the prognostic potency of CD34 associated with maintenance of microvessel integrity in hepatocellular carcinoma and pancreatic cancer.

    PubMed

    Wang, Wen-Quan; Liu, Liang; Xu, Hua-Xiang; Luo, Guo-Pei; Chen, Tao; Wu, Chun-Tao; Xu, Yong-Feng; Xu, Jin; Liu, Chen; Zhang, Bo; Long, Jiang; Tang, Zhao-You; Yu, Xian-Jun

    2013-01-01

    Microvessel density (MVD) as an angiogenesis predictor is inefficient per se in cancer prognosis. We evaluated prognostic values of combining intratumoral alpha-smooth muscle actin (α-SMA)-positive stromal cell density and MVD after curative resection in hypervascular hepatocellular carcinoma (HCC) and hypovascular pancreatic cancer (PC). Tissue microarrays were constructed from tumors of 305 HCC and 57 PC patients who underwent curative resection and analyzed for α-SMA and CD34 expression by immunostaining. Prognostic values of these two proteins and other clinicopathological features were examined. Both low α-SMA density and high MVD-CD34 were associated in HCC with the presence of intrahepatic metastasis and microvascular invasion, and they were related to lymph node involvement and microvascular invasion in PC (p<0.05). Although CD34 alone, but not α-SMA, was an independent prognostic factor for overall survival and recurrence-free survival, the combination of low α-SMA and high CD34 was a predictor of worst prognosis for both types of tumors and had a better power to predict patient death and early recurrence (p<0.01). Furthermore, the results show that distribution of most of the α-SMA-positive cells and vascular endothelial cells overlap, showing major colocalization on vascular walls. Poor microvessel integrity, as indicated by high MVD, together with low perivascular α-SMA-positive cell coverage is associated with early recurrence, unfavorable metastasis, and short survival after tumor resection. This finding highlights the significance of vascular quality in tumor progression, which provides an optimized complement to vascular quantity in prognosis of postoperative patients.

  20. Risk of all-type cancer, hepatocellular carcinoma, non-Hodgkin lymphoma and pancreatic cancer in patients infected with hepatitis B virus.

    PubMed

    Andersen, E S; Omland, L H; Jepsen, P; Krarup, H; Christensen, P B; Obel, N; Weis, N

    2015-10-01

    The increased risk of hepatocellular carcinoma (HCC) among patients infected with hepatitis B virus (HBV) is well established; however, long-term risk estimates are needed. Recently, it has been suggested that HBV is associated with non-Hodgkin lymphoma (NHL) and pancreatic cancer (PC). The aim of this Danish nationwide cohort study was to evaluate the association between HBV infection and all-type cancer, HCC, NHL and PC. A cohort of patients infected with HBV (n = 4345) and an age- and sex-matched population-based comparison cohort of individuals (n = 26,070) without a positive test for HBV were linked to The Danish Cancer Registry to compare the risk of all-type cancer, HCC, NHL and PC among the two groups. The median observation period was 8.0 years. Overall, the incidence rate ratio (IRR) for all-type cancer among HBV-infected patients was 1.1 (95% confidence intervals (CI) 0.9-1.3). The IRR of HCC was 17.4 (CI 5.5-54.5), whereas the IRR of PC and NHL was 0.9 (CI 0.3-2.5) and 1.2 (CI 0.4-3.6), respectively. HBV-infected patients had a 10-year risk of 0.24% (Cl 0.12-0.44) for HCC, whereas the comparison cohort had a 10-year risk of 0.03% (Cl 0.02-0.07) for HCC. The risk of all-type cancer, NHL and PC was not higher in the HBV-infected cohort compared to non-HBV infected. We found a 17-fold higher risk of HCC for HBV-infected individuals.

  1. APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-03-16

    Metastatic Malignant Neoplasm in the Brain; Metastatic Solid Neoplasm; Recurrent Colorectal Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Solid Neoplasm; Stage IV Colorectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer; Unresectable Solid Neoplasm

  2. [Biological aspects of pancreatic cancer].

    PubMed

    Tonel, E; Carbone, A; Scirelli, T; Bellone, G; Emanuelli, G

    2005-04-01

    Pancreatic ductal carcinoma still is an aggressive disease with a fatal prognosis due to late diagnosis and resistance to pharmacological and surgical treatments. Molecular investigations of pancreatic cancer are complicated by the restricted accessibility of the organ for biopsies. However, recent studies have indicated that pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. These molecular alterations, including overexpression of receptor-ligand systems, oncogene activation and loss of tumour suppressor genes, leads to a profound disturbance in cell cycle regulation and continuous growth. The molecular findings are now integrated in a pancreatic tumour progression model, with genetically and morphological defined precursor lesions. However, it remains unclear whether the initial target cells of this cancer develop from ductal or acinar cells. This review will present recent emerging questions on the biology of pancreatic cancer with particular emphasis on the cell origin and tumour microenvironment.

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

    SciTech Connect

    Ikeda, Masafumi; Ioka, Tatsuya; Ito, Yoshinori; Yonemoto, Naohiro; Nagase, Michitaka; Yamao, Kenji; Miyakawa, Hiroyuki; Ishii, Hiroshi; Furuse, Junji; Sato, Keiko; Sato, Tosiya; Okusaka, Takuji

    2013-01-01

    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.

  4. Chronic Pancreatitis in Children

    MedlinePlus

    ... Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and Symptoms Staging of Pancreatic Cancer Treatment of Pancreatic Cancer Whipple Procedure Complementary Therapies Pancreatic Cancer Support ...

  5. Acute Pancreatitis in Children

    MedlinePlus

    ... Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and Symptoms Staging of Pancreatic Cancer Treatment of Pancreatic Cancer Whipple Procedure Complementary Therapies Pancreatic Cancer Support ...

  6. Successful treatment of a case with pancreatic neuroendocrine carcinoma with focal hepatoid differentiation: a case report and literature review

    PubMed Central

    Xin, Bao-Bao; Li, Jian-Ang; Han, Xu; Zhao, Jing; Ji, Yuan; Lou, Wen-Hui; Xu, Xue-Feng

    2014-01-01

    A 33-year-old Chinese woman was admitted to our hospital because of an elevated serum alpha-fetoprotein (AFP) level (300 ng/mL) found in a regular medical checkup. Computed tomography imaging of the abdomen revealed a 1.6 × 2.2 cm low-attenuation mass in the head of the pancreas, with no enlarged lymph nodes and no metastatic liver nodules, and a pancreaticoduodenectomy was performed and the tumor was completely removed. The tumor was solid, unencapsulated and poorly demarcated, measuring 2 × 1.4 × 1.8 cm, and the cut surface was grey-yellowish. Histologically, most of the areas of the tumor were composed of small monotonous and round shaped neuroendocrine cells, and approximately 20% of the areas were cells with indistinct cytoplasmic borders, large oval nuclei, prominent nucleoli and abundant eosinophilic cytoplasm, resembling the appearance of HCC. Immunohistochemical stains revealed that the neuroendocrine areas were diffusely positive for chromogranin, and the hepatoid areas showed diffuse and strong positive reaction to AFP. After surgery the AFP level reduced to normal. She received six cycles of postoperative chemotherapy and three years after the surgery was found to have an elevated serum AFP level again which gave rise to the suspicion of tumor recurrence, and a positron emission tomography-computed tomography confirmed the speculation by showing a hypermetabolic lymph node behind the body of the pancreas. She then underwent radiotherapy and the AFP level reduced to normal. Up till now she has survived 46 months since the initial diagnosis. This case and previous cases suggest that the serum AFP could be a useful marker for early detection of the disease, but careful differential diagnosis should be performed, and AFP could also be a marker for evaluation of therapeutic response and recurrence of the AFP-producing hepatoid carcinomas of pancreas. PMID:25419403

  7. Warty Carcinoma Penis: An Uncommon Variant

    PubMed Central

    Ghosh, Arnab; Shrestha, Santosh; Ghartimagar, Dilasma; Narasimhan, Raghavan; Talwar, OP

    2017-01-01

    Penile carcinoma frequency varies widely in different parts of the world and comprises 1–10% of all the malignancies in males. Majority of the cases of penile carcinoma are squamous cell carcinoma of penis comprising 60% to 70% of all cases. Warty carcinoma of penis is an unusual neoplasm and a variant of penile squamous cell carcinoma comprising 5%–10% of all the variants. The other histological variants include basaloid, verrucous, papillary, sarcomatous, mixed, and adenosquamous carcinoma. The various histological entities with an exophytic papillary lesions including warty carcinoma are together referred to as the “verruciform” group of neoplasms. The warty carcinoma has to be differentiated from these lesions and is typically distinguished by histological features of hyperkeratosis, arborescent papillomatosis, acanthosis, and prominent koilocytosis with nuclear pleomorphism. We present a case of 65-year-old male with growth measuring 6 × 4 cm in the penis who underwent total penectomy and was diagnosed as warty carcinoma penis. PMID:28154768

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

    PubMed

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

    2013-07-01

    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-α (TNF‑α), 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-α, 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.

  9. Pancreatic cancer

    MedlinePlus

    ... cancer, cystic pancreatic neoplasms, and other nonendocrine pancreatic tumors. In: Feldman M, Friedman LS, Brandt LJ, ... by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. ...

  10. Pancreatic carcinogenesis: apoptosis and angiogenesis.

    PubMed

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

    2004-04-01

    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.

  11. Evaluation of Matrix Metalloproteinase 7 in Plasma and Pancreatic Juice as a Biomarker for Pancreatic Cancer

    PubMed Central

    Kuhlmann, Koert F.D.; van Till, J.W. Olivier; Boermeester, Marja A.; de Reuver, Philip R.; Tzvetanova, Iva D.; Offerhaus, G. Johan A.; ten Kate, Fiebo J.W.; Busch, Olivier R.C.; van Gulik, Thomas M.; Gouma, Dirk J.; Crawford, Howard C.

    2015-01-01

    Differentiating between periampullary carcinoma and chronic pancreatitis with an inflammatory mass is difficult. Consequently, 6% to 9% of pancreatic resections for suspected carcinoma are done inappropriately for chronic pancreatitis. Here, we test if matrix metalloproteinase 7 (MMP-7), a secreted protease frequently expressed in pancreatic carcinoma, can be measured in plasma, pancreatic, and duodenal juice, and if it can distinguish between periampullary carcinoma and chronic pancreatitis. Ninety-four patients who underwent pancreatic surgery for a (peri)pancreatic neoplasm (n = 63) or chronic pancreatitis (n = 31) were analyzed. Median plasma MMP-7 levels were significantly higher in carcinoma (1.95 ng/mL; interquartile range, 0.81–3.22 ng/mL) compared with chronic pancreatitis and benign disease (0.83 ng/mL; interquartile range, 0.25–1.21 ng/mL; P < 0.01). MMP-7 levels in pancreatic juice were higher, although not significantly, in carcinoma (62 ng/mg protein; interquartile range, 18–241 ng/mg protein) compared with chronic pancreatitis and benign disease (23 ng/mg protein; interquartile range, 8.5–99 ng/mg protein; P = 0.17). MMP-7 levels in duodenal juice were universally low. At an arbitrary cutoff of 1.5 ng/mL in plasma, positive and negative predictive values were 83% and 57%, respectively, values comparable to those of today’s most common pancreatic tumor marker, carbohydrate antigen 19-9 (CA19-9; 83% and 53%, respectively). Positive and negative likelihood ratios for plasma MMP-7 were 3.35 and 0.52, respectively. The area under the receiver operating characteristic curve for MMP-7 was 0.73 (95% confidence interval, 0.63–0.84) and for CA19-9, 0.75 (95% confidence interval, 0.64–0.85). Combined MMP-7 and CA19-9 assessment gave a positive predictive value of 100%. Thus, plasma MMP-7 levels discriminated between patients with carcinoma and those with chronic pancreatitis or benign disease. The diagnostic accuracy of plasma MMP-7 alone is not

  12. Obesity, autophagy and the pathogenesis of liver and pancreatic cancers.

    PubMed

    Aghajan, Mariam; Li, Ning; Karin, Michael

    2012-03-01

    Liver and pancreatic cancers are both highly lethal diseases with limited to no therapeutic options for patients. Recent studies suggest that deregulated autophagy plays a role in the pathogenesis of these diseases by perturbing cellular homeostasis and laying the foundation for disease development. While accumulation of p62 upon impaired autophagy has been implicated in hepatocellular carcinoma, its role in pancreatic ductal adenocarcinoma remains less clear. This review will focus on recent studies illustrating the role of autophagy in liver and pancreatic cancers. The relationships between autophagy, nuclear factor-κB signaling and obesity in hepatocellular carcinoma will be discussed, as well as the dual role of autophagy in pancreatic ductal adenocarcinoma.

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

    PubMed

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

    2010-01-01

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

  14. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  15. Pancreatic neuroendocrine tumors

    PubMed Central

    Sun, Jian

    2017-01-01

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

  16. The Relation of Pancreatic Disease to Weber-Christian Disease

    PubMed Central

    Moore, Sean

    1963-01-01

    A case of acute Weber-Christian disease is reported, in which pancreatitis was accompanied by evidence of dissemination of pancreatic enzymes causing necrosis of fat and vessels. There is clinical and experimental evidence in the literature to suggest that widespread vascular dissemination of lipase occurs in cases of pancreatitis or pancreatic carcinoma. Review of the autopsy literature of cases of Weber-Christian disease shows that a majority had pancreatitis and systemic involvement of fat. A minority showed lesions confined to the panniculus, which tended to ulcerate; these lesions were in other ways not typical of Weber-Christian disease. In this group none had autopsy evidence of pancreatitis. The opinion is expressed that Weber-Christian disease results from disruption of pancreatic tissue and subsequent vascular dissemination of pancreatic enzymes. PMID:20327582

  17. CD14/TLR4 priming potentially recalibrates and exerts anti-tumor efficacy in tumor associated macrophages in a mouse model of pancreatic carcinoma

    PubMed Central

    Prakash, Hridayesh; Nadella, Vinod; Singh, Sandhya; Schmitz-Winnenthal, Hubertus

    2016-01-01

    Pancreatic cancer is the fourth major cause of cancer related deaths in the world and 5 year survival is below 5%. Among various tumor directed therapies, stimulation of Toll-like receptors (TLR) has shown promising effects in various tumor models. However, pancreatic cancer cells frequently express these receptors themselves and their stimulation (TLR 2 and/or 4 particularly) within tumor microenvironment is known to potentially enhance tumor cell proliferation and cancer progression. Consistent stimulation of tumor associated macrophages (TAMs), in particular with tumor derived TLR ligand within the tumor microenvironment promotes cancer related inflammation, which is sterile, non-immunogenic and carcinogenic in nature. In view of this, recalibrating of TAM has the potential to induce immunogenic inflammation. Consistent with this, we provide experimental evidence for the first time in this study that priming of TAMs with TLR4 ligend (LPS) alone or in combination with IFN-γ not only recalibrates pancreatic tumor cells induced M2 polarization, but also confers anti-tumor potential in TAMs. Most interestingly, reduced tumor growth in macrophage depleted animals suggests that macrophage directed approaches are important for the management of pancreatic tumors. PMID:27511884

  18. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  19. Evidence, Mechanism, and Clinical Relevance of the Transdifferentiation from Lung Adenocarcinoma to Squamous Cell Carcinoma.

    PubMed

    Hou, Shenda; Zhou, Shiyu; Qin, Zhen; Yang, Liu; Han, Xiangkun; Yao, Shun; Ji, Hongbin

    2017-03-08

    Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct subtypes of non-small-cell lung carcinoma. Interestingly, approximately 4% to 9% of human non-small-cell lung carcinoma tumors contain mixed adenomatous and squamous pathologies in a single lesion, clinically termed adenosquamous cell carcinoma. More important, these two different pathological components frequently share identical oncogenic mutations, indicative of a potential transition. Indeed, recent data have provided convincing evidence in supporting the ADC to SCC transdifferentiation in lungs. In the liver kinase B1 (official name STK11)-deficient mouse model, lung ADC can progressively transdifferentiate to SCC through pathologically mixed adenosquamous cell carcinoma as the intermediate status. Mechanistic studies further identify essential roles of extracellular matrix remodeling and metabolic reprogramming during this phenotypic transition. Small molecular compounds, including lysyl oxidase inhibitors and reactive oxygen species-inducing reagents such as phenformin, significantly accelerate the transition from lung ADC to SCC and thus confer lung tumors with drug resistance. Consistent with these findings, recent clinical studies have shown that epidermal growth factor receptor-mutant lung ADC can transdifferentiate to SCC in relapsed cancer patients. Together, these data support that this phenotypic transition from lung ADC to SCC might represent a novel mechanism for drug resistance. This review will summarize our current understanding of the transdifferentiation from lung ADC to SCC.

  20. Advances in cryoablation for pancreatic cancer

    PubMed Central

    Luo, Xiao-Mei; Niu, Li-Zhi; Chen, Ji-Bing; Xu, Ke-Cheng

    2016-01-01

    Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. At present, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer. PMID:26811625

  1. Thalidomide in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2013-01-23

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

  2. Chronic Pancreatitis

    PubMed Central

    DiMagno, Matthew J.; DiMagno, Eugene P.

    2012-01-01

    Purpose of review We review important new clinical observations in chronic pancreatitis (CP) reported in 2011. Recent findings Smoking increases the risk of non-gallstone acute pancreatitis (AP) and the progression of AP to CP. Binge drinking during Oktoberfest did not associate with increased hospital admissions for AP. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in CP is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90,000 USP U of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared to endoscopic treatment in patients advanced CP with a dilated main duct +/− pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with CP but ~30% of patients have significant side effects. Summary Patients with non-gallstone related AP or CP of any etiology should cease smoking. Results of this year’s investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in CP, and the mechanisms and treatment of neuropathic pain in CP. PMID:22782018

  3. Chronic pancreatitis.

    PubMed

    Lindley, Keith J

    2006-10-01

    Chronic pancreatitis (CP) is characterised by pancreatic inflammation and fibrosis leading eventually to destruction of pancreatic parenchyma and loss of exocrine and endocrine function. A model of interactions between environmental triggers of pancreatic inflammation and disease susceptibility or modifying genes (including PRSS1, SPINK1 and CFTR) provides a framework within which to understand disease pathogenesis. Early in the disease, when fibrosis is mild and pancreatic damage limited, it is difficult to distinguish CP from recurrent acute pancreatitis (RAP) although it is likely these represent opposite ends of a spectrum of disease with a common aetiology in which CP represents either a later disease stage or disease in individuals predisposed to generate a chronic fibrogenic inflammatory response. Pain is a dominant feature resulting in part from neuroimmune interactions within the pancreas. Diagnosis at an early stage of disease is challenging, though in later stages is dependent upon the demonstration of pancreatic fibrosis and duct ectasia using one or more imaging modalities including transabdominal and endoscopic ultrasound, CT and MRCP or ERCP. Current treatments are largely supportive and reactive. The challenge for pediatricians is to achieve diagnosis at an early stage of the disease and to develop treatments that can alter its natural history.

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

    PubMed Central

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

    2013-01-01

    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

  5. Pancreatic Cysts

    MedlinePlus

    ... fluid can be collected from the cyst for analysis in a laboratory for possible signs of cancer. The characteristics and location of the pancreatic cyst, with your age and sex, can help doctors pinpoint the type of cyst ...

  6. Acute pancreatitis

    MedlinePlus

    ... mg/dL Injury to the pancreas from an accident Other causes include: After certain procedures used to ... pressure Rapid heart rate Rapid breathing (respiratory) rate Lab tests that show the release of pancreatic enzymes ...

  7. Pancreatitis - children

    MedlinePlus

    ... an organ or bone marrow transplant Cystic fibrosis Crohn disease and other disorders when the body's immune system ... lab tests to check the release of pancreatic enzymes. These include tests to check the: Blood amylase ...

  8. Pancreatic abscess

    MedlinePlus

    ... high. Possible Complications Complications may include: Multiple abscesses Sepsis When to Contact a Medical Professional Call your ... 2016:chap 144. Read More Abscess Pancreatic pseudocyst Sepsis Review Date 10/27/2015 Updated by: Subodh ...

  9. Autoimmune pancreatitis

    PubMed Central

    2016-01-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

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

    SciTech Connect

    Geld, Ylanga G. van der; Triest, Baukelien van; Verbakel, Wilko; Soernsen de Koste, John R. van; Senan, Suresh; Slotman, Ben J.; Lagerwaard, Frank J.

    2008-11-15

    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.

  11. Pancreatic Cancer Early Detection Program

    ClinicalTrials.gov

    2014-07-30

    Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

  12. A simian virus 40 large T-antigen segment containing amino acids 1 to 127 and expressed under the control of the rat elastase-1 promoter produces pancreatic acinar carcinomas in transgenic mice.

    PubMed Central

    Tevethia, M J; Bonneau, R H; Griffith, J W; Mylin, L

    1997-01-01

    The simian virus 40 large T antigen induces tumors in a wide variety of tissues in transgenic mice, the precise tissues depending on the tissue specificity of the upstream region controlling T-antigen expression. Expression of mutant T antigens that contain a subset of the protein's activities restricts the spectrum of tumors induced. Others showed previously that expression of a mutant large T antigen containing the N-terminal 121 amino acids (T1-121) under control of the lymphotropic papovavirus promoter resulted in slow-growing choroid plexus tumors, whereas full-length T antigen under the same promoter induced rapidly growing CPR tumors, T-cell lymphomas, and B-cell lymphomas. In those instances, the alteration in tumor induction or progression correlated with inability of the mutant large T antigen to bind the tumor suppressor p53. In the study reported here, we investigated the capacity of an N-terminal T antigen segment (T1-127) expressed in conjunction with small t antigen under control of the rat elastase-1 (E1) promoter to induce pancreatic tumors. The results show that pancreases of transgenic mice expressing T1-127 and small t antigen display acinar cell dysplasia at birth that progresses to neoplasia. The average age to death in these mice is within the range reported for transgenic mice expressing full-length T antigen under control of the E1 promoter. These results indicate that sequestering p53 by binding is not required for the development of rapidly growing acinar cell carcinomas. In addition, we provide evidence that small t antigen is unlikely to be required. Finally, we show that the p53 protein in acinar cell carcinomas is wild type in conformation. PMID:9343166

  13. Efficacy of Immunohistochemical Staining in Differentiating a Squamous Cell Carcinoma in Poorly Differentiated Rectal Cancer: Two Case Reports

    PubMed Central

    Rami, Sairafi; Han, Yoon Dae; Jang, Mi; Cho, Min Soo; Hur, Hyuk; Min, Byung Soh; Lee, Kang Young

    2016-01-01

    A rectal carcinoma, including primary an adenosquamous and a squamous cell carcinoma (SCC), is a very rare disease, accounting for 0.025% to 0.20% of all large-bowel malignant tumors. Because SCCs have a higher mortality than adenosquamous carcinomas, determining whether the primary rectal cancer exhibits an adenomatous component or a squamous component is important. While differentiating between these 2 components, especially in poorly differentiated rectal cancer, is difficult, specific immunohistochemical stains enable accurate diagnoses. Here, we report the use of immunohistochemical stains to distinguish between the adenomatous and the squamous components in 2 patients with low rectal cancer, a 58-year-old man and a 73-year-old woman, who were initially diagnosed using the histopathologic results for a poorly differentiated carcinoma. These data suggest that using these immunohistochemical stains will help to accurately diagnose the type of rectal cancer, especially for poorly differentiated carcinomas, and will provide important information to determine the proper treatment for the patient. PMID:27626026

  14. [Acute pancreatitis].

    PubMed

    Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A

    2014-03-01

    Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.

  15. [Pancreatic ultrasonography].

    PubMed

    Fernández-Rodríguez, T; Segura-Grau, A; Rodríguez-Lorenzo, A; Segura-Cabral, J M

    2015-04-01

    Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%.

  16. Identification of KCa3.1 Channel as a Novel Regulator of Oxidative Phosphorylation in a Subset of Pancreatic Carcinoma Cell Lines

    PubMed Central

    Kovalenko, Ilya; Glasauer, Andrea; Schöckel, Laura; Sauter, Daniel R. P.; Ehrmann, Alexander; Sohler, Florian; Hägebarth, Andrea; Novak, Ivana; Christian, Sven

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) represents the most common form of pancreatic cancer with rising incidence in developing countries and overall 5-year survival rates of less than 5%. The most frequent mutations in PDAC are gain-of-function mutations in KRAS as well as loss-of-function mutations in p53. Both mutations have severe impacts on the metabolism of tumor cells. Many of these metabolic changes are mediated by transporters or channels that regulate the exchange of metabolites and ions between the intracellular compartment and the tumor microenvironment. In the study presented here, our goal was to identify novel transporters or channels that regulate oxidative phosphorylation (OxPhos) in PDAC in order to characterize novel potential drug targets for the treatment of these cancers. We set up a Seahorse Analyzer XF based siRNA screen and identified previously described as well as novel regulators of OxPhos. The siRNA that resulted in the greatest change in cellular oxygen consumption was targeting the KCNN4 gene, which encodes for the Ca2+-sensitive K+ channel KCa3.1. This channel has not previously been reported to regulate OxPhos. Knock-down experiments as well as the use of a small molecule inhibitor confirmed its role in regulating oxygen consumption, ATP production and cellular proliferation. Furthermore, PDAC cell lines sensitive to KCa3.1 inhibition were shown to express the channel protein in the plasma membrane as well as in the mitochondria. These differences in the localization of KCa3.1 channels as well as differences in the regulation of cellular metabolism might offer opportunities for targeted therapy in subsets of PDAC. PMID:27494181

  17. Atypical squamous epithelium in cytologic specimens from the pancreas: cytological differential diagnosis and clinical implications.

    PubMed

    Layfield, L J; Cramer, H; Madden, J; Gopez, E V; Liu, K

    2001-07-01

    Atypical squamous epithelium is an uncommon finding in cytologic specimens obtained from pancreatic lesions. A variety of pathologic conditions can result in the presence of these cells, including primary or metastatic carcinomas, chronic pancreatitis, and squamous metaplasia related to pancreatic or biliary duct stent placement. Primary adenosquamous and squamous-cell carcinomas of the pancreas are rare, representing 3.4% and 1.4 % of pancreatic carcinomas, respectively. Cytologic separation of these malignancies from less ominous metaplasias has immense clinical importance. We reviewed Indiana University Hospital's and Duke University's experiences with atypical squamous epithelium occurring within pancreatic aspirates. Study cases were identified using a computer to search the cytology records of these two institutions. Nine cases with a diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or atypical squamous epithelium were retrieved from the two institutions' Department of Pathology files. One case of pure squamous-cell carcinoma occurred in a patient with a known pulmonary primary; a single case of adenosquamous carcinoma was diagnosed in a patient with a coexistent endometrial primary; a single sample of adenocarcinoma with squamous differentiation was diagnosed in a patient without other known disease; and four primary squamous-cell carcinomas of the pancreas were detected. In addition, a single case of atypical squamous metaplasia associated with a stent was identified, and one case of atypical squamous epithelium associated with chronic pancreatitis was diagnosed. Despite the reactive atypia present in the examples of metaplastic squamous epithelium, separation of these cases from true squamous-cell carcinoma and adenosquamous carcinoma was achievable by cytologic evaluation. No cytologic criteria aided in separating primary pancreatic carcinomas with squamous differentiation from metastatic lesions. In this study, we report our findings in a

  18. Autoimmune pancreatitis mimicking pancreatic tumor

    PubMed Central

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

    2012-01-01

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

  19. A Case of Chronic Calcific Nonalcoholic Pancreatitis

    PubMed Central

    Kangas-Dick, Aaron; Khan, Umair; Awoniyi, Oluwafunbi; Waqar, Shanza; Tun, Nu Nwe; Wong, Cynthia

    2016-01-01

    Tropical Calcific Pancreatitis (TCP) is a type of chronic calcific nonalcoholic pancreatitis. Similar to nonalcoholic chronic pancreatitis, it presents in the second and third decades of life; however this type is reported mostly in the developing tropical and subtropical countries. It is associated with the formation of pancreatic calculi and a high probability of developing insulin-dependent diabetes mellitus. Epidemiologic studies have shown that these patients have an increased risk of developing pancreatic carcinoma. The etiology of TCP remains uncertain, with the current consensus suggesting genetics as well as possible toxicity from consuming large amounts of cassava, a tuber. Definite diagnosis of TCP requires younger age of onset, history of malnutrition, and presence of diabetes mellitus along with extensive pancreatic calcification and ductal calculi. When patients meet most but not all of these conditions the term Idiopathic Chronic Pancreatitis (ICP) is used. This is a case of a 44-year-old man who presented with most features seen in TCP, and however, was diagnosed with ICP. PMID:27957355

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-02-01

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

  2. Carbon-Ion Irradiation Suppresses Migration and Invasiveness of Human Pancreatic Carcinoma Cells MIAPaCa-2 via Rac1 and RhoA Degradation

    SciTech Connect

    Fujita, Mayumi; Imadome, Kaori; Shoji, Yoshimi; Isozaki, Tetsurou; Endo, Satoshi; Yamada, Shigeru; Imai, Takashi

    2015-09-01

    Purpose: To investigate the mechanisms underlying the inhibition of cancer cell migration and invasion by carbon (C)-ion irradiation. Methods and Materials: Human pancreatic cancer cells MIAPaCa-2, AsPC-1, and BxPC-3 were treated by x-ray (4 Gy) or C-ion (0.5, 1, 2, or 4 Gy) irradiation, and their migration and invasion were assessed 2 days later. The levels of guanosine triphosphate (GTP)-bound Rac1 and RhoA were determined by the active GTPase pull-down assay with or without a proteasome inhibitor, and the binding of E3 ubiquitin ligase to GTP-bound Rac1 was examined by immunoprecipitation. Results: Carbon-ion irradiation reduced the levels of GTP-bound Rac1 and RhoA, 2 major regulators of cell motility, in MIAPaCa-2 cells and GTP-bound Rac1 in AsPC-1 and BxPC-3 cells. Proteasome inhibition reversed the effect, indicating that C-ion irradiation induced Rac1 and RhoA degradation via the ubiquitin (Ub)-proteasome pathway. E3 Ub ligase X-linked inhibitor of apoptosis protein (XIAP), which directly targets Rac1, was selectively induced in C-ion–irradiated MIAPaCa-2 cells and coprecipitated with GTP-bound Rac1 in C-ion–irradiated cells, which was associated with Rac1 ubiquitination. Cell migration and invasion reduced by C-ion radiation were restored by short interfering RNA–mediated XIAP knockdown, indicating that XIAP is involved in C-ion–induced inhibition of cell motility. Conclusion: In contrast to x-ray irradiation, C-ion treatment inhibited the activity of Rac1 and RhoA in MIAPaCa-2 cells and Rac1 in AsPC-1 and BxPC-3 cells via Ub-mediated proteasomal degradation, thereby blocking the motility of these pancreatic cancer cells.

  3. Is Pancreatic Cancer Hereditary?

    MedlinePlus

    ... Trials Database Supporting Research Raising Awareness Our Blog Patient Education Pancreas News Basics of Pancreatic Cancer FAQs The ... Detection- Goggins Lab Sol Goldman Center Discussion Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? ...

  4. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as the sudden inflammation ... the incidence of recurrent attacks minimized. Timothy Gardner, MD is Director of Pancreatic Disorders at Dartmouth-Hitchcock ...

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

    PubMed

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

    1994-08-04

    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.

  6. Phage library-screening: a powerful approach for generation of targeting-agents specific for normal pancreatic islet-cells and islet-cell carcinoma in vivo.

    PubMed

    Ueberberg, S; Schneider, S

    2010-02-25

    Phage display technology is a powerful approach for the generation of peptides and antibodies that target specific organ- or tumor-structures. By applying this approach to rats in vivo or freshly isolated rat islets in vitro, we have recently reported the successful isolation of internalizing single-chain antibodies (SCA-antibodies), which are highly specific for the endocrine-cells of a pancreatic islet (either beta- or alpha-cells) both in rodents and in humans. Moreover, others have reported peptides targeting specifically the vascular endothelium of normal or pre-malignant islets or advanced islet-cell tumors. The features of these antibodies and peptides are compatible with a potential use for in vivo delivery of molecular cargos (e.g. imaging agents and therapeutics). Therefore, this article reviews the principles of phage display, provides an overview about agents either specific for the endocrine-cells or the vascular endothelium of islets, discusses methododical key elements for the generation of these ligands and highlights remaining questions and potential future perspectives.

  7. Immune Sculpting of Norepinephrine on MHC-I, B7-1, IDO and B7-H1 Expression and Regulation of Proliferation and Invasion in Pancreatic Carcinoma Cells

    PubMed Central

    Wang, Liancai; Liu, Han; Chen, Xiangli; Zhang, Min; Xie, Keping; Ma, Qingyong

    2012-01-01

    Background The sympathetic neurotransmitter Norepinephrine (NE) contributes to tumorigenesis and cancer progression. This study aims to investigate the role of NE in modulating the immune phenotype and allowing pancreatic carcinoma (PC) cells to escape the immune response. Methods Varied concentrations of NE and interferon-gamma (IFN-γ) were administrated to MIA PaCa-2 and BxPC-3 cell lines for 48 hours. Proliferation and invasion were then investigated using an MTT assay and a membrane invasion culture system respectively. MHC-I, B7-1, IDO and B7-H1 expression were measured using real-time quantitative RT-PCR, western blotting and immunocytochemistry. The synergistic and time-dependent effects of NE/IFN-γ were also investigated. Adrenergic antagonists were used to identify the relevant target receptor of NE. Results The results showed that NE had dose-dependent and time-dependent effects on cell biological processes as well as on the expression of MHC-I, B7-1, IDO and B7-H1. These effects occurred mainly via the β2-adrenergic receptor. Long-term NE treatment was able to antagonize some of the effects of IFN-γ (after 2 weeks of treatment), but NE and IFN-γ had significant synergistic stimulatory effects on IDO and B7-H1 expression. The residual effects on biological activities lasted for 2 weeks, while the immunophenotypic changes decreased at early time points after treatment. Conclusions NE plays important roles in modulating PC cell biological activities and affecting MHC-I, B7-1, IDO and B7-H1 expression in vitro, mainly via the β2-adrenergic receptor (β2-AR) in a time- and dose-dependent fashion. Only at extended treatment durations could NE affect PC cell progression and immune evasion. PMID:23029049

  8. External Beam Radiotherapy Plus 24-Hour Continuous Infusion of Gemcitabine in Unresectable Pancreatic Carcinoma: Long-Term Results of a Phase II Study

    SciTech Connect

    Mattiucci, Gian C.; Morganti, Alessio G.; Valentini, Vincenzo; Ippolito, Edy; Alfieri, Sergio; Antinori, Armando; Crucitti, Antonio; D'Agostino, Giuseppe R.; Di Lullo, Liberato; Luzi, Stefano; Mantini, Giovanna; Smaniotto, Daniela; Doglietto, Gian B.; Cellini, Numa

    2010-03-01

    Purpose: To evaluate the efficacy of gemcitabine-based chemoradiation (CT-RT) in treating patients (pts) affected by locally advanced pancreatic cancers (LAPC). Methods and Materials: Weekly gemcitabine (100 mg/m{sup 2}) was given as a 24-hour infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). After CT-RT, pts received five cycles of sequential chemotherapy with gemcitabine (1000 mg/m{sup 2}; 1, 8, q21). Response rate was assessed according to World Health Organization criteria 6 weeks after the end of CT-RT. Local control (LC), time to progression (TTP), metastases-free survival (MFS), and overall survival (OS) were analyzed by the Kaplan Meier method. Results: Forty pts (male/female 22/18; median age 62 years, range, 36-76) were treated from 2000 to 2005. The majority had T4 tumour (n = 34, 85%), six pts (15%) had T3 tumour. Sixteen pts (40%) were node positive at diagnosis. Grade 3-4 acute toxicity was observed in 21 pts (52.5%). Thirty pts (75%) completed the treatment schedule. A clinical response was achieved in 12 pts (30%). With a median follow-up of 76 months (range, 32-98), 2-year LC was 39.6% (median, 12 months), 2-year TTP was 18.4% (median, 10 months), and 2-year MFS was 29.7% (median, 10 months). Two-year OS (25%; median, 15.5 months) compared with our previous study on 5-fluorouracil-based CT-RT (2.8%) was significantly improved (p <0.001). Conclusions: Gemcitabine CT-RT seems correlated with improved outcomes. Healthier patients who are likely to complete the treatment schedule may benefit most from this therapy.

  9. Pancreatic abscesses.

    PubMed

    Shi, E C; Yeo, B W; Ham, J M

    1984-09-01

    This paper presents the clinical features and problems in the management of 34 patients with pancreatic abscesses. In the majority of patients the abscesses developed following an attack of pancreatitis due to alcohol or gallstones. The abscesses were usually multilocular, and often had spread widely in the retroperitoneal space. Invasion into surrounding viscera or the peritoneal cavity occurred in 12 instances, and eight patients developed major bleeding into the abscess cavity. Obstructive complications (affecting bowel, common bile duct and large veins) occurred in eight patients. Twelve of the 34 patients (35 per cent) died, most deaths being due to failure to control sepsis (seven patients) or to massive bleeding from the abscess cavity (three patients). The mortality of this condition is likely to remain high, but may be reduced by better drainage techniques at the initial exploration. The importance of the infra-mesocolic approach for drainage is emphasized.

  10. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

    PubMed

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

    2017-02-23

    Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  11. Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

    PubMed

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

    The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

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

    PubMed Central

    Wan, Chayan; Cao, Wenqing; Cheng, Cungui

    2014-01-01

    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

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

    PubMed

    Wan, Chayan; Cao, Wenqing; Cheng, Cungui

    2014-01-01

    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.

  14. [Pathologic diagnosis of pancreatic cancer--facts, pitfalls, challenges].

    PubMed

    Zalatnai, A

    2001-09-02

    Discrimination between the well differentiated pancreatic carcinoma and the chronic fibrotizing pancreatitis is one of the most difficult diagnostic problems in the field of pancreatology, and it is also a challenge for the pathologist. The author outlines those objective facts that might lead to diagnostic errors. The two diseases may coexist; on the one hand, malignant tumor can be developed as a complication of a long-standing chronic pancreatitis, while on the other hand, pancreatic carcinoma is frequently accompanied by chronic inflammation. The majority of adenocarcinomas induce a striking desmoplastic stromal reaction, but the chronic pancreatitis is also characterized by a vigorous fibroblast proliferation leading to the possibility of macroscopical misdiagnosis. Microscopically, the pancreatitis can be mistaken for carcinoma, because the actively growing connective tissue irregularly separates the ducts and in addition, the continuous regenerative activity may lead to regressive atypia. For that reason, cytopathologist must evaluate several criteria together, because the nuclear alterations by themselves can be misleading. Although there are some promising new differential diagnostic techniques (apomucins, CAM 17.1, telomerase activity, loss of chromosome Y), so far the most reliable method has been the meticulous evaluation of the cellular and histological findings by the well trained pathologist. To date, molecular pathological methods have shown no advantage in the differential diagnosis.

  15. Application of glycoscience to the early detection of pancreatic cancer.

    PubMed

    Miyoshi, Eiji; Kamada, Yoshihiro

    2016-10-01

    The prognosis of pancreatic cancer is extremely poor compared to other cancers. One of the reasons for this is the difficulty of early diagnosis. Surveillance using cancer biomarkers and image diagnosis can enable early detection and has improved the prognosis of hepatocellular carcinoma in Japan. However, it is very difficult to detect pancreatic cancer at an early stage using cancer biomarkers and image diagnosis alone. Fucosylation is one of the most important types of glycosylation involved in cancer and inflammation. We have developed a novel glycocancer biomarker, fucosylated haptoglobin (Fuc-Hpt), and have investigated its usefulness for the diagnosis of pancreatic cancer over approximately 10 years. Recently, we also found that most pancreatic tissues surrounding pancreatic cancer exhibit chronic pancreatitis with fibrosis and/or fatty degeneration. Certain forms of chronic pancreatitis might indicate high risk for the development of pancreatic cancer. In this review, we provide a historical summary of our research on Fuc-Hpt as a cancer biomarker, and discuss a potential early detection system for pancreatic cancer.

  16. Arterio-Pancreatic Syndrome

    PubMed Central

    Lee, Ser Yee; Ng, Kheng Hong; Sebastian, Mathew George

    2011-01-01

    Acute pancreatitis is a single-organ disorder that has multi-organ sequelae. As a result, it can have varied presentations. Acute pancreatitis presenting as acute limb ischemia is rare. We present a patient with acute pancreatitis presenting with bilateral lower limb ischemia. The episode of acute pancreatitis resolved but the acute lower limb ischemia precipitated as the pancreatitis progressed, and necessitated bilateral above-knee amputations. We review the literature and discuss the pathogenesis of such a phenomenon. PMID:22347150

  17. [Spontaneous peri-pancreatic hematoma associated with celiac trunk stenosis: diagnostic difficulties and therapeutic management].

    PubMed

    El Alaoui, Mounia; Olivié, Damien; Gandon, Yves; Bretagne, Jean-François

    2005-11-01

    We report a case of spontaneous peri-pancreatic hematoma which was associated with a celiac trunk stenosis. Hematoma was probably due to the rupture of a pancreaticoduodenal artery aneurysm. This diagnosis of pancreatic carcinoma, initially retained, illustrates the difficult diagnostic process. Therapeutic modalities for preventing recurrence are discussed.

  18. Advances in the pathology of penile carcinomas.

    PubMed

    Chaux, Alcides; Cubilla, Antonio L

    2012-06-01

    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.

  19. [External pancreatic fistulas management].

    PubMed

    Stepan, E V; Ermolov, A S; Rogal', M L; Teterin, Yu S

    2017-01-01

    The main principles of treatment of external postoperative pancreatic fistulas are viewed in the article. Pancreatic trauma was the reason of pancreatic fistula in 38.7% of the cases, operations because of acute pancreatitis - in 25.8%, and pancreatic pseudocyst drainage - in 35.5%. 93 patients recovered after the treatment. Complex conservative treatment of EPF allowed to close fistulas in 74.2% of the patients with normal patency of the main pancreatic duct (MPD). The usage of octreotide 600-900 mcg daily for at least 5 days to decrease pancreatic secretion was an important part of the conservative treatment. Endoscopic papillotomy was performed in patients with major duodenal papilla obstruction and interruption of transporting of pancreatic secretion to duodenum. Stent of the main pancreatic duct was indicated in patients with extended pancreatic duct stenosis to normalize transport of pancreatic secretion to duodenum. Surgical formation of anastomosis between distal part of the main pancreatic duct and gastro-intestinal tract was carried out when it was impossible to fulfill endoscopic stenting of pancreatic duct either because of its interruption and diastasis between its ends, or in the cases of unsuccessful conservative treatment of external pancreatic fistula caused by drainage of pseudocyst.

  20. MRI of pancreatic metastases from renal cancer

    SciTech Connect

    Kelekis, N.L.; Semelka, R.C.; Siegelman, E.S.

    1996-03-01

    Our goal was to describe the MR features of pancreatic metastases from renal cancer. Five patients with pancreatic metastases from renal cancer were imaged with MR. Imaging was performed on a 1.5 T MR imager using excitation-spoiled fat-suppressed T1-weighted SE images (all patients), T1-weighted spoiled GE images (all patients), T2-weighted fast SE (one patient) and excitation-spoiled fat-suppressed T2-weighted fast SE (one patient) images, serial postgadolinium spoiled GE images (all patients), and postcontrast excitation-spoiled fat-suppressed T1-weighted SE images (two patients). Multiple pancreatic lesions (n = 6) were present in two patients, solitary tumors in two patients, and diffuse micronodular pancreatic enlargement in one patient. All lesions were hypointense compared to normal pancreas on T1-weighted fat-suppressed SE images. Lesions were high in ST on T2-weighted images in two of two patients. All lesions demonstrated enhancement on the immediate postgadolinium spoiled GE images with the smaller tumors (<1.5 cm, three individual and the micronodular tumors) showing diffuse enhancement and the larger tumors (>1.5 cm, five tumors) showing pre-dominantly rim enhancement. Pancreatic metastases from renal cell carcinoma have distinctive MR features that include diffuse enhancement in small lesions and rim enhancement in large lesions on immediate postgadolinium images and high SI on T2-weighted images. 20 refs., 4 figs.

  1. Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma

    PubMed Central

    Han, Xiangkun; Li, Fuming; Fang, Zhaoyuan; Gao, Yijun; Li, Fei; Fang, Rong; Yao, Shun; Sun, Yihua; Li, Li; Zhang, Wenjing; Ma, Huimin; Xiao, Qian; Ge, Gaoxiang; Fang, Jing; Wang, Hongda; Zhang, Lei; Wong, Kwok-kin; Chen, Haiquan; Hou, Yingyong; Ji, Hongbin

    2014-01-01

    Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that reduction of lysyl oxidase (Lox) in Lkb1-deficient lung ADC decreases collagen disposition and triggers extracellular matrix remodelling and upregulates p63 expression, a SCC lineage survival oncogene. Pharmacological Lox inhibition promotes the transdifferentiation, whereas ectopic Lox expression significantly inhibits this process. Notably, ADC and SCC show differential responses to Lox inhibition. Collectively, our findings demonstrate the de novo transdifferentiation of lung ADC to SCC in mice and provide mechanistic insight that may have important implications for lung cancer treatment. PMID:24531128

  2. Spontaneous regression of pancreatic cancer: real or a misdiagnosis?

    PubMed

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

    2012-06-21

    Spontaneous tumor regression has been subject of numerous studies and speculations for many years. This phenomenon is exceptional, but well reported, in some types of tumors, but not in pancreatic cancer. Pancreatic cancer has the worst five-year survival rate of any cancer. Despite numerous molecular studies and clinical approaches, using several mouse models, this cancer responds poorly to the existing chemotherapeutic agents and progress on treatment remains elusive. Although pancreatic cancer tumors seldom undergo spontaneous regression, and some authors take that with skepticism, there are some cases reported in the literature. However, the variability in the description of the reports and technical details could make this process susceptible to misdiagnosis. Distinguishing between different types of pancreatic carcinoma should be taken with caution as they have wide differences in malignant potential. Diseases such as pancreatic benign tumors, insulinomas, or autoimmune pancreatitis could be responsible for this misdiagnosis as a pancreatic cancer. Here we review different cases reported, their clinical characteristics, and possible mechanisms leading to spontaneous regression of pancreatic cancer. We also discuss the possibilities of misdiagnosis.

  3. Strategies for early detection of resectable pancreatic cancer.

    PubMed

    Okano, Keiichi; Suzuki, Yasuyuki

    2014-08-28

    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.

  4. Pancreatic Cancer Stage 3

    MedlinePlus

    ... 3 Description: Stage III pancreatic cancer; drawing shows cancer in the pancreas, common hepatic artery, and portal vein. Also shown ... and superior mesenteric artery. Stage III pancreatic cancer. Cancer ... near the pancreas. These include the superior mesenteric artery, celiac axis, ...

  5. Surgery for pancreatic cancer

    MedlinePlus

    ... medlineplus.gov/ency/article/007649.htm Surgery for pancreatic cancer To use the sharing features on this page, ... surgery are used in the surgical treatment of pancreatic cancer. Whipple procedure: This is the most common surgery ...

  6. Pancreatic pseudocysts and aneurysms

    PubMed Central

    Andrén-Sandberg, Åke

    2010-01-01

    A number of methods are available for the drainage of pancreatic pseudocysts, including percutaneous, endoscopic and open approaches. The author reviewed the most rently reports, and and summarized the latest advances in the pancreatic pseudocysts. PMID:22558566

  7. Pathogenic mechanisms of pancreatitis.

    PubMed

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-02-06

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  8. Pathogenic mechanisms of pancreatitis

    PubMed Central

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-01-01

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  9. Human pancreatic cancer fusion 2 (HPC2) 1-B3: a novel monoclonal antibody to screen for pancreatic ductal dysplasia.

    PubMed

    Morgan, Terry K; Hardiman, Karin; Corless, Christopher L; White, Sandra L; Bonnah, Robert; Van de Vrugt, Henry; Sheppard, Brett C; Grompe, Markus; Cosar, Ediz F; Streeter, Philip R

    2013-01-01

    BACKGROUND.: Pancreatic ductal adenocarcinoma is rarely detected early enough for patients to be cured. The objective of the authors was to develop a monoclonal antibody to distinguish adenocarcinoma and precancerous intraductal papillary mucinous neoplasia (IPMN) from benign epithelium. METHODS.: Mice were immunized with human pancreatic adenocarcinoma cells and monoclonal antibodies were screened against a panel of archived pancreatic tissue sections, including pancreatitis (23 cases), grade 1 IPMN (16 cases), grade 2 IPMN (9 cases), grade 3 IPMN (13 cases), and various grades of adenocarcinoma (17 cases). One monoclonal antibody, human pancreatic cancer fusion 2 (HPC2) 1-B3, which specifically immunostained adenocarcinoma and all grades of IPMN, was isolated. Subsequently, HPC2 1-B3 was evaluated in a retrospective series of 31 fine-needle aspiration (FNA) biopsies from clinically suspicious pancreatic lesions that had long-term clinical follow-up. RESULTS.: HPC2 1-B3 was negative in all 31 cases of chronic pancreatitis that were tested. In contrast, HPC2 1-B3 immunostained the cytoplasm and luminal surface of all 16 well- to moderately differentiated pancreatic ductal adenocarcinomas. It demonstrated only weak focal staining of poorly differentiated carcinomas. All high-grade IPMNs were found to be positive for HPC2 1-B3. The majority of low-grade to intermediate-grade IPMNs were positive (66% of cases). Immunostaining a separate series of pancreatic FNA cell blocks for HPC2 1-B3 demonstrated that the relative risk for detecting at least low-grade dysplasia (2.0 [95% confidence interval, 1.23-3.26]) was statistically significant (P = .002 by the Fisher exact test). CONCLUSIONS.: To reduce the mortality of pancreatic cancer, more effective early screening methods are necessary. The data from the current study indicate that a novel monoclonal antibody, HPC2 1-B3, may facilitate the diagnosis of early pancreatic dysplasia.

  10. Experimental Models of Pancreatitis

    PubMed Central

    Hyun, Jong Jin

    2014-01-01

    Acute pancreatitis is an inflammatory disease characterized by interstitial edema, inflammatory cell infiltration, and acinar cell necrosis, depending on its severity. Regardless of the extent of tissue injury, acute pancreatitis is a completely reversible process with evident normal tissue architecture after recovery. Its pathogenic mechanism has been known to be closely related to intracellular digestive enzyme activation. In contrast to acute pancreatitis, chronic pancreatitis is characterized by irreversible tissue damage such as acinar cell atrophy and pancreatic fibrosis that results in exocrine and endocrine insufficiency. Recently, many studies of chronic pancreatitis have been prompted by the discovery of the pancreatic stellate cell, which has been identified and distinguished as the key effector cell of pancreatic fibrosis. However, investigations into the pathogenesis and treatment of pancreatitis face many obstacles because of its anatomical location and disparate clinical course. Due to these difficulties, most of our knowledge on pancreatitis is based on research conducted using experimental models of pancreatitis. In this review, several experimental models of pancreatitis will be discussed in terms of technique, advantages, and limitations. PMID:24944983

  11. Case report. Acinar cell carcinoma with fatty change arising from the pancreas.

    PubMed

    Chung, W-S; Park, M-S; Kim, D W; Kim, K W

    2011-12-01

    Acinar cell carcinoma of the pancreas is a rare malignant tumour developing from acinar cells, accounting for approximately 1% of pancreatic exocrine tumours. We experienced a case of an acinar cell carcinoma with fatty change. To the best of our knowledge, this is the first case report of an acinar cell carcinoma with fatty change in the clinical literature.

  12. Chronic pancreatitis: relation to acute pancreatitis and pancreatic cancer.

    PubMed

    Uomo, G; Rabitti, P G

    2000-01-01

    The relationship between chronic pancreatitis (CP) and other pancreatic diseases, such as acute pancreatitis (AP) and pancreatic cancer (PK), remains a fairly debated question. The progression from alcoholic AP to CP is controversial, and some long-term epidemiological studies suggest that alcoholic CP might be the result of recurrent alcoholic AP (necrosis-fibrosis sequence) and a subgroup of alcoholics may present recurrent AP without progression to CP. Other predisposing factors (genetic, nutritional, environmental) seems to be important in inducing different outcomes of pancreatic damage due to alcohol. However, recurrent episodes of AP are clearly involved in pathophysiology of CP in patients with hereditary pancreatitis. A relationship between CP and subsequent PK development has long been suspected, but we actually don't know whether this association is direct or is the result of confounding factors, such as alcohol intake or cigarette smoking. Many issues should be considered as indicators of a causal association, and several of them are not fulfilled. Nonetheless, epidemiological studies (case-control or cohort studies) showed that the risk of PK is increased in patients with CP; the risk is significantly higher in tropical calcifying CP and hereditary pancreatitis. Studies on growth factors, oncogenes, tumor-suppressor genes, and angiogenesis suggest that the sequence PC-KP is plausible from the biological standpoint.

  13. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    PubMed Central

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J.-Matthias

    2017-01-01

    Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes. PMID:28241470

  14. Serological characteristics of autoimmune pancreatitis and its differential diagnosis from pancreatic cancer by using a combination of carbohydrate antigen 19-9, globulin, eosinophils and hemoglobin.

    PubMed

    Yan, Tianlian; Ke, Yini; Chen, Yi; Xu, Chengfu; Yu, Chaohui; Li, Youming

    2017-01-01

    Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis, which may be misdiagnosed as pancreatic carcinoma. This study aims to verify new biomarkers for AIP and propose a serological pattern to differentiate AIP from pancreatic adenocarcinoma with routinely performed tests. In this study, data of serum samples were collected and compared between 25 patients with AIP and 100 patients with pancreatic carcinoma. Receiver operating characteristic analysis and logistic regression was performed to evaluate the diagnostic effect of serum parameters in differentiating AIP from pancreatic carcinoma alone or in combination. Among several serum markers observed in the two groups, carbohydrate antigen 19-9 (Ca19-9), globulin, eosinophils and hemoglobin were selected as the independent markers. Serum levels of Globulin, Eosinophil percentage in AIP group were significantly higher than in pancreatic cancer group (P<0.05), while hemoglobin and tumor marker CA19-9 levels were lower (P <0.05). The combination of these markers identified patients with AIP with 92% sensitivity and 79% specificity, which indicated relatively high diagnostic value. Elevated serum eosinophils, globulin, together with decreased hemoglobin level can be used as a preoperative indicator for AIP and can help to initiate diagnosis of AIP in time.

  15. Serological characteristics of autoimmune pancreatitis and its differential diagnosis from pancreatic cancer by using a combination of carbohydrate antigen 19-9, globulin, eosinophils and hemoglobin

    PubMed Central

    Chen, Yi; Xu, Chengfu; Yu, Chaohui; Li, Youming

    2017-01-01

    Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis, which may be misdiagnosed as pancreatic carcinoma. This study aims to verify new biomarkers for AIP and propose a serological pattern to differentiate AIP from pancreatic adenocarcinoma with routinely performed tests. In this study, data of serum samples were collected and compared between 25 patients with AIP and 100 patients with pancreatic carcinoma. Receiver operating characteristic analysis and logistic regression was performed to evaluate the diagnostic effect of serum parameters in differentiating AIP from pancreatic carcinoma alone or in combination. Among several serum markers observed in the two groups, carbohydrate antigen 19–9 (Ca19-9), globulin, eosinophils and hemoglobin were selected as the independent markers. Serum levels of Globulin, Eosinophil percentage in AIP group were significantly higher than in pancreatic cancer group (P<0.05), while hemoglobin and tumor marker CA19-9 levels were lower (P <0.05). The combination of these markers identified patients with AIP with 92% sensitivity and 79% specificity, which indicated relatively high diagnostic value. Elevated serum eosinophils, globulin, together with decreased hemoglobin level can be used as a preoperative indicator for AIP and can help to initiate diagnosis of AIP in time. PMID:28369140

  16. Pancreatic Cancer Genetics

    PubMed Central

    Amundadottir, Laufey T.

    2016-01-01

    Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, 4]. The vast majority of tumors arise in the exocrine pancreas, with pancreatic ductal adenocarcinoma (PDAC) accounting for approximately 95% of tumors. Tumors arising in the endocrine pancreas (pancreatic neuroendocrine tumors) represent less than 5% of all pancreatic tumors [5]. Smoking, type 2 diabetes mellitus (T2D), obesity and pancreatitis are the most consistent epidemiological risk factors for pancreatic cancer [5]. Family history is also a risk factor for developing pancreatic cancer with odds ratios (OR) ranging from 1.7-2.3 for first-degree relatives in most studies, indicating that shared genetic factors may play a role in the etiology of this disease [6-9]. This review summarizes the current knowledge of germline pancreatic cancer risk variants with a special emphasis on common susceptibility alleles identified through Genome Wide Association Studies (GWAS). PMID:26929738

  17. Inherited pancreatic cancer syndromes.

    PubMed

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

    2012-01-01

    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.

  18. Metastatic pancreatic cancer presenting as linitis plastica of the stomach.

    PubMed

    Garg, Shivani; Mulki, Ramzi; Sher, Daniel

    2016-03-08

    Metastatic disease from pancreatic carcinoma involving the stomach is an unusual event, and the pattern of spread in the form of linitis plastica, to our knowledge, has not been reported previously. Local recurrence after curative resection for pancreatic cancer is the most common pattern of disease. We report a case of metastatic pancreatic adenocarcinoma presenting as linitis plastica of the stomach 4 years after curative resection. A 52-year-old man presented with epigastric pain and melaena 4 years after undergoing a Whipple's procedure for a poorly-differentiated pancreatic adenocarcinoma, stage IB; T2N0M0. CT imaging of the abdomen revealed thickening of the gastric wall, and subsequent oesophagogastroduodenoscopy (OGD) revealed diffuse friable erythaematous tissue. The biopsy specimen obtained during the OGD revealed a poorly differentiated adenocarcinoma, with similar appearance to the prior specimen obtained from the pancreas.

  19. Pancreatic carcinosarcoma with rare long-term survival

    PubMed Central

    Jia, Zhe; Zhang, Ke; Huang, RongHai; Zhou, XinGang; Jiang, Li

    2017-01-01

    Abstract Patient concerns: We report a rare case of pancreatic carcinosarcoma involving a 44-year-old woman. The patient complained of discomfort associated with the upper abdomen and jaundice of skin and sclera for 1 week. Diagnoses: After hospitalization, relevant examinations were completed. The disease was diagnosed as carcinoma of the pancreatic head. Interventions: Whipple procedure was conducted in May 2013. Intraoperative exploration indicated 2 components of the tumor: a fish-shaped gray matter and a hard structure similar to cancellous bone. Histopathological examination showed adenocarcinoma and osteosarcoma. After surgery, the patient received 8 cycles of chemotherapy with gemcitabine and raltitrexed. Outcomes: Previous studies indicated poor prognosis for pancreatic carcinosarcoma. However, our patient survived for 31 months with no recurrence till date. Lessons subsections: Coexistence of pancreatic adenocarcinoma and osteosarcoma is very rare. Our case was also an exception in manifesting longer survival than expected. PMID:28121946

  20. Vitamin D Receptor Signaling and Pancreatic Cancer Cell EMT

    PubMed Central

    Li, Zhiwei; Guo, Junli; Xie, Keping; Zheng, Shaojiang

    2016-01-01

    Pancreatic ductal adenocarcinoma remains one of the most lethal of human malignancies. Even in patients who undergo resection, long-term survival rates remain extremely low. A major contributor to the aggressiveness of pancreatic ductal adenocarcinoma is epithelial-to-mesenchymal transition (EMT), a physiologic process of morphological and genetic changes in carcinoma cells from an epithelial phenotype to a mesenchymal phenotype, which is the basis of the high metastatic potential of pancreatic cancer cells. EMT is triggered by various tumor microenvironmental factors, including cytokines, growth factors, and chemotherapeutic agents. This review highlights the growing evidence of the effect of EMT on pancreatic cancer progression, focusing on the interaction of EMT with other pathways central to cancer progression, especially vitamin D receptor signaling. Studies of the signaling pathways that lead to the inactivation of EMT programs during these disease processes are providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions. PMID:25506892

  1. Congenital hepatic artery aneurysm simulating pancreatic carcinoma

    SciTech Connect

    Gavin, P.M.; Matalon, T.A.S.; Petasnick, J.P.; Roseman, D.L.

    1984-09-01

    The authors report a case of a hepatic artery aneurysm that simulated a mass in the head of the pancreas. The correct diagnosis was made preoperatively based on several findings: curvilinear calcification within the mass on CT, a well-defined crystic collection on ultrasound, absence of biliary duct dilatation or jaundice, and a presence of other aneurysms.

  2. Salivary duct carcinoma: the predominance of apocrine morphology, prevalence of histologic variants, and androgen receptor expression.

    PubMed

    Williams, Lindsay; Thompson, Lester D R; Seethala, Raja R; Weinreb, Ilan; Assaad, Adel M; Tuluc, Madalina; Ud Din, Nasir; Purgina, Bibianna; Lai, Chi; Griffith, Christopher C; Chiosea, Simion I

    2015-05-01

    Salivary duct carcinoma (SDC) is a prototypic aggressive salivary gland carcinoma. Our aim is to determine the prevalence of histologic variants (micropapillary, basal-like) and androgen receptor (AR) expression in a large multi-institutional series of SDC. AR status was determined by immunohistochemistry (IHC). Most SDCs were characterized by an apocrine phenotype and AR expression. Cases with a nonapocrine phenotype and AR-negative status were studied by additional IHC and fluorescence in situ hybridization for ETV6 or MYB/NFIB. The diagnosis of SDC was confirmed in 187 of 199 (94%) cases. Variant morphologies were identified in 12 cases: micropapillary (n=6), sarcomatoid (n=3), mucinous (n=2), and basal-like (n=1). AR IHC was performed in 183 cases, of which 179 (97.8%) showed AR expression. On the basis of morphologic appearance and results of additional studies, 12 cases were reclassified as squamous cell carcinoma (SCC) (n=4), epithelial-myoepithelial carcinoma with high-grade transformation (HGT) (n=2), myoepithelial carcinoma (n=2), mammary analogue secretory carcinoma, high grade (ETV6 translocated; n=1), adenoid cystic carcinoma with HGT (n=1), acinic cell carcinoma with HGT (n=1), and adenosquamous carcinoma (n=1). AR-negative SDC is extremely rare, and the majority of such cases are more accurately classified as other entities. HGTs of other salivary carcinomas and squamous cell carcinoma are the most common mimics of SDC. SDCs with variant morphologies still show at least a minor component of conventional apocrine appearance. Thus, apocrine morphology defines SDC.

  3. CT features of nonfunctioning islet cell carcinoma

    SciTech Connect

    Eelkema, E.A.; Stephens, D.H.; Ward, E.M.; Sheedy, P.F. II

    1984-11-01

    To determine the computed tomographic (CT) characteristics of nonfunctioning islet cell carcinoma of the pancreas, the CT scans of 27 patients with that disease were reviewed. The pancreatic tumor was identified as a mass in 26 patients (96%) Of the 25 tumors evaluated with contrast enhancement, 20 became partially diffusely hyperdense relative to nearby normal pancreatic tissue. Hepatic metastases were identified in 15 patients (56%), regional lymphadenopathy in 10 (37%), atrophy of the gland proximal to the tumor in six (22%), dilatation of the biliary ducts in five (19%), and dilatation of the pancreatic duct in four (15%). The CT appearances of the nonfunctioning islet cell tumors were compared with those of 100 ordinary (ductal) pancreatic adenocarcinomas. Although the two types of tumors were sometimes indistinguishable, features found to be more characteristic of islet cell carcinoma included a pancreatic mass of unusually large size, calcification within the tumor, and contrast enhancement of either the primary tumor or hepatic metastases. Involvement of the celiac axis or proximal superior mesenteric artery was limited to ductal carcinoma.

  4. Pancreatic Cancer Stage 2A

    MedlinePlus

    ... 2A Description: Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown. Stage IIA pancreatic cancer. Cancer has spread to nearby tissue and organs ...

  5. Pancreatic Cancer Stage 2B

    MedlinePlus

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  6. Prostaglandin E2 activates the mTORC1 pathway through an EP4/cAMP/PKA- and EP1/Ca2+-mediated mechanism in the human pancreatic carcinoma cell line PANC-1.

    PubMed

    Chang, Hui-Hua; Young, Steven H; Sinnett-Smith, James; Chou, Caroline Ei Ne; Moro, Aune; Hertzer, Kathleen M; Hines, Oscar Joe; Rozengurt, Enrique; Eibl, Guido

    2015-11-15

    Obesity, a known risk factor for pancreatic cancer, is associated with inflammation and insulin resistance. Proinflammatory prostaglandin E2 (PGE2) and elevated insulin-like growth factor type 1 (IGF-1), related to insulin resistance, are shown to play critical roles in pancreatic cancer progression. We aimed to explore a potential cross talk between PGE2 signaling and the IGF-1/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway in pancreatic cancer, which may be a key to unraveling the obesity-cancer link. In PANC-1 human pancreatic cancer cells, we showed that PGE2 stimulated mTORC1 activity independently of Akt, as evaluated by downstream signaling events. Subsequently, using pharmacological and genetic approaches, we demonstrated that PGE2-induced mTORC1 activation is mediated by the EP4/cAMP/PKA pathway, as well as an EP1/Ca(2+)-dependent pathway. The cooperative roles of the two pathways were supported by the maximal inhibition achieved with the combined pharmacological blockade, and the coexistence of highly expressed EP1 (mediating the Ca(2+) response) and EP2 or EP4 (mediating the cAMP/PKA pathway) in PANC-1 cells and in the prostate cancer line PC-3, which also robustly exhibited PGE2-induced mTORC1 activation, as identified from a screen in various cancer cell lines. Importantly, we showed a reinforcing interaction between PGE2 and IGF-1 on mTORC1 signaling, with an increase in IL-23 production as a cellular outcome. Our data reveal a previously unrecognized mechanism of PGE2-stimulated mTORC1 activation mediated by EP4/cAMP/PKA and EP1/Ca(2+) signaling, which may be of great importance in elucidating the promoting effects of obesity in pancreatic cancer. Ultimately, a precise understanding of these molecular links may provide novel targets for efficacious interventions devoid of adverse effects.

  7. TLR9 ligation in pancreatic stellate cells promotes tumorigenesis

    PubMed Central

    Zambirinis, Constantinos P.; Levie, Elliot; Nguy, Susanna; Avanzi, Antonina; Barilla, Rocky; Xu, Yijie; Seifert, Lena; Daley, Donnele; Greco, Stephanie H.; Deutsch, Michael; Jonnadula, Saikiran; Torres-Hernandez, Alejandro; Tippens, Daniel; Pushalkar, Smruti; Eisenthal, Andrew; Saxena, Deepak; Ahn, Jiyoung; Hajdu, Cristina; Engle, Dannielle D.; Tuveson, David

    2015-01-01

    Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis. PMID:26481685

  8. TLR9 ligation in pancreatic stellate cells promotes tumorigenesis.

    PubMed

    Zambirinis, Constantinos P; Levie, Elliot; Nguy, Susanna; Avanzi, Antonina; Barilla, Rocky; Xu, Yijie; Seifert, Lena; Daley, Donnele; Greco, Stephanie H; Deutsch, Michael; Jonnadula, Saikiran; Torres-Hernandez, Alejandro; Tippens, Daniel; Pushalkar, Smruti; Eisenthal, Andrew; Saxena, Deepak; Ahn, Jiyoung; Hajdu, Cristina; Engle, Dannielle D; Tuveson, David; Miller, George

    2015-11-16

    Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis.

  9. Hypermutation In Pancreatic Cancer.

    PubMed

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

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

    ClinicalTrials.gov

    2016-12-07

    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

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

    PubMed

    Chaux, Alcides; Cubilla, Antonio L

    2012-05-01

    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.

  12. Tris DBA palladium is highly effective against growth and metastasis of pancreatic cancer in an orthotopic model

    PubMed Central

    Díaz, Begoña; Ostapoff, Katherine T.; Toombs, Jason E.; Lo, Jason; Bonner, Michael Y.; Curatolo, Adam; Adsay, Volkan; Brekken, Rolf A.; Arbiser, Jack L.

    2016-01-01

    Pancreatic carcinoma ranks among the most lethal of human cancers. Besides late detection, other factors contribute to its lethality, including a high degree of chemoresistance, invasion, and distant metastases. Currently, the mainstay of therapy involves resection of local disease in a minority of patients (Whipple procedure) and systemic gemcitabine. While systemic chemotherapy has some benefit, even with optimal treatment, the five year survival after diagnosis is dismal. Thus, treatment of pancreatic carcinoma remains a tremendous unmet need. The organometallic compound tris DBA palladium is a potent inhibitor of N-myristoyltransferase 1 (NMT1), an enzyme that catalyzes the transfer of myristate to protein substrates. This compound is highly effective in vivo against murine models of melanoma with both mutant and wild type b-RAF genotypes. Based upon the signaling similarities between melanoma and pancreatic carcinoma, we evaluated the efficacy of tris DBA palladium in vitro and in vivo against pancreatic carcinoma. We found that tris DBA palladium decreased proliferation and colony formation of pancreatic cancer cells in vitro. In an orthotopic mouse model, tris DBA palladium was highly active in inhibiting growth, ascites production, and distant metastases in vivo. Furthermore, tris DBA palladium impaired chemotaxis and inhibited cilia formation in Pan02 cells in a NMT1-dependent manner. We propose that NMT1 is a novel regulator of cilia formation and tris DBA palladium a novel inhibitor of cilia formation and metastasis in pancreatic cancer. Thus, further evaluation of tris DBA palladium for the treatment of pancreatic cancer is warranted. PMID:27438140

  13. Lymphoplasmacytic sclerosing pancreatitis (autoimmune pancreatitis): evaluation with multidetector CT.

    PubMed

    Kawamoto, Satomi; Siegelman, Stanley S; Hruban, Ralph H; Fishman, Elliot K

    2008-01-01

    Lymphoplasmacytic sclerosing pancreatitis is a form of chronic pancreatitis characterized by a mixed inflammatory infiltrate that centers on the pancreatic ducts. It is a cause of benign pancreatic disease that can clinically mimic pancreatic cancer. Preoperative detection of lymphoplasmacytic sclerosing pancreatitis is important because patients usually respond to steroid therapy. Patients with lymphoplasmacytic sclerosing pancreatitis are often referred for computed tomography (CT) when they are suspected of having a pancreatic or biliary neoplasm; therefore, it is important to search for potential findings suggestive of lymphoplasmacytic sclerosing pancreatitis when typical findings of a pancreatic or biliary neoplasm are not found. Typical CT findings include diffuse or focal enlargement of the pancreas without dilatation of the main pancreatic duct. Focal enlargement is most commonly seen in the head of the pancreas, and the involved pancreas on contrast material-enhanced CT images may be iso-attenuating relative to the rest of the pancreas, or hypo-attenuating, especially during the early postcontrast phase. Thickening and contrast enhancement of the wall of the common bile duct and gallbladder may reflect inflammatory infiltrate and fibrosis associated with lymphoplasmacytic sclerosing pancreatitis. There are several features seen at CT that may help to differentiate lymphoplasmacytic sclerosing pancreatitis from pancreatic cancer, such as diffuse enlargement of the pancreas with minimal peripancreatic stranding in patients with obstructive jaundice, an absence of significant pancreatic atrophy, and an absence of significant main pancreatic duct dilatation. When these findings are encountered, clinical, other imaging, and serologic data should be evaluated.

  14. Green Tea Epigallocatechin Gallate Exhibits Anticancer Effect in Human Pancreatic Carcinoma Cells via the Inhibition of Both Focal Adhesion Kinase and Insulin-Like Growth Factor-I Receptor

    PubMed Central

    Vu, Hoang Anh; Beppu, Yuuichi; Chi, Hoang Thanh; Sasaki, Kousuke; Yamamoto, Hideaki; Xinh, Phan Thi; Tanii, Takashi; Hara, Yukihiko; Watanabe, Toshiki; Sato, Yuko; Ohdomari, Iwao

    2010-01-01

    The exact molecular mechanism by which epigallocatechin gallate (EGCG) suppresses human pancreatic cancer cell proliferation is unclear. We show here that EGCG-treated pancreatic cancer cells AsPC-1 and BxPC-3 decrease cell adhesion ability on micro-pattern dots, accompanied by dephosphorylations of both focal adhesion kinase (FAK) and insulin-like growth factor-1 receptor (IGF-1R) whereas retained the activations of mitogen-activated protein kinase and mammalian target of rapamycin. The growth of AsPC-1 and BxPC-3 cells can be significantly suppressed by EGCG treatment alone in a dose-dependent manner. At a dose of 100 μM which completely abolishes activations of FAK and IGF-1R, EGCG suppresses more than 50% of cell proliferation without evidence of apoptosis analyzed by PARP cleavage. Finally, the MEK1/2 inhibitor U0126 enhances growth-suppressive effect of EGCG. Our data suggests that blocking FAK and IGF-1R by EGCG could prove valuable for targeted therapy, which can be used in combination with other therapies, for pancreatic cancer. PMID:21318151

  15. Non-functioning Well Differentiated Endocrine Carcinoma of the Pancreas

    PubMed Central

    Terada, Tadashi

    2009-01-01

    The author reports a typical but rare case of non-functioning well differentiated endocrine carcinoma of the pancreas. A 67-year-old man was admitted to our hospital because of abdominal pain. No hormone-related symptoms were recognized. He has no familiar history of pancreatic neoplasms. Various imaging modalities including US, CT and MRI revealed a tumor of the pancreatic body. Distal pancreatectomy and splenectomy were performed. A solid well demarcated tumor was present in the pancreatic body. Peripancreatic lymph nodes showed marked swelling suggestive of metastases. Immunohistyochemically, tumor cells were positive for cytokeratin, synaptophysin, neuron-specific enolase, and CD56; they were negative for chromogranin, gastrin, glucagon, somatostatin, pancreatic polypeptide, and vasoactive intestinal polypeptide. The pathological diagnosis was non-functioning well differentiated endocrine carcinoma of the pancreas. PMID:27990210

  16. Lymphoplasmacytic sclerosing pancreatitis.

    PubMed

    Plaza, Jose Antonio; Colonna, Jorge; Vitellas, Kenneth M; Frankel, Wendy L

    2005-10-01

    Lymphoplasmacytic sclerosing pancreatitis is a rare entity that has been described under many different names and constitutes a diagnostic challenge as it may simulate a neoplastic process. Herein, we report a case of a 61-year-old woman who presented to our institution complaining of left flank pain and was found to have normal levels of amylase and lipase. An abdominal magnetic resonance image showed thickening of the pancreatic tail and compression of the pancreatic duct. The radiographic differential included both chronic pancreatitis and a neoplastic process. She underwent an exploratory laparotomy, during which a pancreatectomy and splenectomy were performed. Grossly, the pancreas contained a yellowish white, firm homogeneous mass measuring 6.5 x 3.3 x 2.9 cm involving the entire pancreatic tail and hilum of the spleen. Histologically, pancreatic sections showed extensive fibrosis admixed with an inflammatory infiltrate. This infiltrate was composed mainly of lymphocytes with multiple germinal centers, as well as plasma cells and eosinophils that surrounded pancreatic ducts and extended into the peripancreatic adipose tissue. No malignancy was identified, and the process was diagnosed as lymphoplasmacytic sclerosing pancreatitis.

  17. Embelin suppresses pancreatic cancer growth by modulating tumor immune microenvironment.

    PubMed

    Marsh, Justine L; Jackman, Chris P; Tang, Su-Ni; Shankar, Sharmila; Srivastava, Rakesh K

    2014-01-01

    Since pancreatic carcinoma is largely refractory to conventional therapies, development of novel agents is required for the effective treatment of pancreatic cancer. The objective of this paper was to examine the molecular mechanisms by which embelin inhibited human pancreatic cancer growth in mice by modulating tumor immune microenvironment. Embelin inhibited PANC-1 tumor growth, angiogenesis, and metastasis which were associated with suppression of Akt and Sonic Hedgehog (Shh) pathways. Embelin inhibited the expression of Bcl-2, cyclin D1, CDK2 and CDK6, IL-6 and IL-8, and induced the expression of Bax in tumor tissues. Embelin also reversed epithelial-mesenchymal transition by up-regulating E-cadherin and inhibiting the expression of Snail, Slug and Zeb1. Embelin inhibited pancreatic cancer growth in Kras(G12D) mice by modulating tumor immune microenvironment where CTL, NKT, γδT, NK, and IFNγ (Th1 type) cells were up-regulated, and Th17, PMN-MDSC, IL-6 and IL-8 (Th2 type) immune cells were inhibited. These data suggest that embelin can inhibit pancreatic cancer growth by modulating tumor immune microenvironment and Akt and Shh pathways, and inhibiting inflammation. Embelin may offer therapeutic benefits for the treatment and/or prevention of pancreatic cancer.

  18. Review of idiopathic pancreatitis

    PubMed Central

    Lee, Jason Kihyuk; Enns, Robert

    2007-01-01

    Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications, infections, toxins, autoimmune disorders, vascular causes, and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review, areas of controversies are highlighted. PMID:18081217

  19. [Pancreatic cancer stem cell].

    PubMed

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2015-05-01

    Prognosis of pancreatic cancer remains dismal due to the resistance against conventional therapies. Metastasis and massive invasion toward surrounding organs hamper radical resection. Small part of entire cancer cells reveal resistance against chemotherapy or radiotherapy, increased tumorigenicity and migratory phenotype. These cells are called as cancer stem cells, as a counter part of normal stem cells. In pancreatic cancer, several cancer stem cell markers have been identified, which enabled detailed characterization of pancreatic cancer stem cells. Recent researches clarified that conventional chemotherapy itself could increase cancer cells with stem cell-phenotype, suggesting the necessity of cancer stem cell-targeting therapy. Based on these observations, pancreatic cancer stem cell-targeting therapies have been tested, which effectively eliminated cancer stem cell fraction and attenuated cancer progression in experimental models. Clinical efficacy of these therapies need to be evaluated, and cancer stem cell-targeting therapy will contribute to improve the prognosis of pancreatic cancer.

  20. Temsirolimus in Treating Patients With Metastatic or Locally Advanced Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2015-02-05

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

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

    PubMed Central

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

    1996-01-01

    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). Images Figure 2 PMID:8980403

  2. The role of positron emission tomography in the detection of pancreatic disease

    SciTech Connect

    Syrota, A.; Duquesnoy, N.; Paraf, A.; Kellershohn, C.

    1982-04-01

    Positron emission tomography (PET) was used to assess possible pancreatic disease in 100 patients. Following injection of 10-15 mCi (370-740 MBq) of /sup 11/C-L-methionine, 4-12 transverse sections 2 cm thick were obtained. In 85 patients with a definite diagnosis (45 normal, 9 acute pancreatitis, 18 chronic pancreatitis, and 13 cancer), PET showed a sensitivity of 85.0%, a specificity of 97.8%, and an accuracy of 91.8%, higher than with transmission computed tomography (CT) or ultrasonography, despite relatively low spatial resolution; this can be explained by the fact that exocrine pancreatic function was altered prior to morphological change. In 22 normal subjects, 0.011 +/- 0.003% (mean +/- S.D.) of injected /sup 11/C was found in 1 ml of liver tissue and 0.015 +/- 0.005% in 1 ml of pancreatic tissue; the pancreas-to-liver concentration ratio was 1.3 +/- 0.4. Hepatic /sup 11/C concentration was identical in the four groups of patients. Pancreatic uptake of /sup 11/C-L-methionine was significantly lower in patients with chronic pancreatitis (n = 13) and pancreatic carcinoma (n = 10) (p <0.001); however, it was not possible to distinguish cancer from chronic pancreatitis because the same functional alteration occurred in both.

  3. The role of positron emission tomography in the detection of pancreatic disease

    SciTech Connect

    Syrota, A.; Duquesnoy, N.; Paraf, A.; Kellershohn, C.

    1982-04-01

    Positron emission tomography (PET) was used to assess possible pancreatic disease in 100 patients. Following injection of 10-15 mCi (370-740 MBq) of 11C-L-methionine, 4-12 transverse sections 2 cm thick were obtained. In 85 patients with a definite diagnosis (45 normal, 9 acute pancreatitis, 18 chronic pancreatitis, and 13 cancer), PET showed a sensitivity of 85.0%, a specificity of 97.8%, and an accuracy of 91.8%, higher than with transmission computed tomography (CT) or ultrasonography, despite relatively low spatial resolution; this can be explained by the fact that exocrine pancreatic function was altered prior to morphological change. In 22 normal subjects, 0.011 +/- 0.003% (mean +/- S.D). of injected 11C was found in 1 ml of liver tissue and 0.015 +/- 0.005% in 1 ml of pancreatic tissue; the pancreas-to-liver concentration ratio was 1.3 +/- 0.4. Hepatic 11C concentration was identical in the four groups of patients. Pancreatic uptake of 11C-L-methionine was significantly lower in patients with chronic pancreatitis (n . 13) and pancreatic carcinoma (n . 10) (p less than 0.001); however, it was not possible to distinguish cancer from chronic pancreatitis because the same functional alteration occurred in both.

  4. Pancreatic tuberculosis with acquired immunodeficiency syndrome: a case report and systematic review.

    PubMed

    Meesiri, Somchai

    2012-02-21

    Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or pseudocysts. Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass. The patient was diagnosed with pancreatic TB and acquired immunodeficiency syndrome, and was treated with antituberculous drugs and percutaneous catheter drainage without a laparotomy. The clinical presentation, radiographic investigation and management of pancreatic TB are summarized in this paper to emphasize the importance of considering this rare disease in the differential diagnosis of pancreatic masses concomitant with human immunodeficiency virus infection. I also emphasize the need for both histopathological and microbiological diagnosis via fine-needle aspiration.

  5. Molecular imaging of late somatostatin receptor-positive metastases of renal cell carcinoma in the pancreas by 68Ga DOTATOC PET/CT: a rare differential diagnosis to multiple primary pancreatic neuroendocrine tumors.

    PubMed

    Peter, Luisa; Sänger, Jörg; Hommann, Merten; Baum, Richard Paul; Kaemmerer, Daniel

    2014-08-01

    Ga somatostatin receptor PET/CT, currently the most sensitive imaging modality for well-differentiated neuroendocrine tumors, is based on the molecular imaging of somatostatin receptors (SSTRs) that are expressed in different tumor entities such as neuroendocrine neoplasms, lymphomas, meningiomas, or renal cell cancer (RCC). Most neuroendocrine neoplasms show a high expression of SSTR subtypes 2A and 5, whereas the overexpression of SSTR2A in RCC is mainly seen in peritumoral vessels. Here we report a case with strongly SSTR-positive pancreatic lesions detected by Ga DOTATOC PET/CT, which histologically turned out to be ultralate metastases of a RCC.

  6. Epidemiology of pancreatic cancer

    PubMed Central

    Ilic, Milena; Ilic, Irena

    2016-01-01

    Cancer of the pancreas remains one of the deadliest cancer types. Based on the GLOBOCAN 2012 estimates, pancreatic cancer causes more than 331000 deaths per year, ranking as the seventh leading cause of cancer death in both sexes together. Globally, about 338000 people had pancreatic cancer in 2012, making it the 11th most common cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends for pancreatic cancer incidence and mortality varied considerably in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. The overall five-year survival rate is about 6% (ranges from 2% to 9%), but this vary very small between developed and developing countries. To date, the causes of pancreatic cancer are still insufficiently known, although certain risk factors have been identified, such as smoking, obesity, genetics, diabetes, diet, inactivity. There are no current screening recommendations for pancreatic cancer, so primary prevention is of utmost importance. A better understanding of the etiology and identifying the risk factors is essential for the primary prevention of this disease. PMID:27956793

  7. Pancreatic groove cancer

    PubMed Central

    Ku, Yuan-Hao; Chen, Shih-Chin; Shyr, Bor-Uei; Lee, Rheun-Chuan; Shyr, Yi-Ming; Wang, Shin-E.

    2017-01-01

    Abstract Pancreatic groove cancer is very rare and can be indistinguishable from groove pancreatitis. This study is to clarify the characteristics, clinical features, managements, and survival outcomes of this rare tumor. Brief descriptions were made for each case of pancreatic groove cancer encountered at our institute. Individualized data of pancreatic groove cancer cases described in the literature were extracted and added to our database to expand the study sample size for a more complete analysis. A total of 33 patients with pancreatic groove cancer were included for analysis, including 4 cases from our institute. The median tumor size was 2.7 cm. The most common symptom was nausea or vomiting (89%), followed by jaundice (67%). Duodenal stenosis was noted by endoscopy in 96% of patients. The histopathological examination revealed well differentiated tumor in 43%. Perineural invasion was noted in 90%, and lymphovascular invasion and lymph node involvement in 83%. Overall 1-year survival rate was 93.3%, and 3- or 5-year survival rate was 62.2%, with a median survival of 11.0 months. Survival outcome for the well-differentiated tumors was better than those of the moderate/poorly differentiated ones. Early involvement of duodenum causing vomiting is often the initial presentation, but obstructive jaundice does not always happen until the disease progresses. Tumor differentiation is a prognostic factor for survival outcome. The possibility of pancreatic groove cancer should be carefully excluded before making the diagnosis of groove pancreatitis for any questionable case. PMID:28079795

  8. Pathophysiology of acute pancreatitis.

    PubMed

    Bhatia, Madhav; Wong, Fei Ling; Cao, Yang; Lau, Hon Yen; Huang, Jiali; Puneet, Padmam; Chevali, Lakshmi

    2005-01-01

    Acute pancreatitis is a common clinical condition. It is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction. If this inflammatory reaction is marked, it leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and the resultant MODS. At the same time, recent research has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In this review, we will discuss about our current understanding of the pathophysiology of acute pancreatitis.

  9. Pancreatitis following liver transplantation.

    PubMed

    Alexander, J A; Demetrius, A J; Gavaler, J S; Makowka, L; Starzl, T E; Van Thiel, D H

    1988-06-01

    Since 1981, when the liver transplantation program was initiated at the University of Pittsburgh, we have been impressed with the prevalence of pancreatitis occurring following liver transplantation in patients transplanted for hepatitis B-related liver disease. To either confirm this clinical impression or refute it, the records of the 27 HbsAg+ patients and those of an additional 24 HbsAg- but HbcAb and/or HbsAb+ patients who underwent orthotopic liver transplantation were reviewed to determine the prevalence of clinical pancreatitis and hyperamylasemia (biochemical pancreatitis) following liver transplantation (OLTx). Post-OLTx hyperamylasemia occurred significantly more frequently in HbsAg+ patients (6/27) than it did in the HbsAg- patients (0/24) (P less than 0.05). More importantly, clinical pancreatitis occurred in 14% (4/27) of the HbsAg+ patients and 0% (0/24) of the HbsAg- patients. Interestingly, in each case, the pancreatitis was associated with the occurrence of acute hepatitis B infection of the allograft. Based upon these data, we conclude that pancreatitis occurring after liver transplantation is more common in patients transplanted for active viral liver disease caused by hepatitis B than in those with inactive viral liver disease. These observations suggest that pancreatitis occurring in, at least some cases following liver transplantation for viral liver disease, may result from hepatitis B virus infection of the pancreas.

  10. Diagnosis of autoimmune pancreatitis.

    PubMed

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

    2014-11-28

    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).

  11. Pleuropulmonary complications of pancreatitis

    PubMed Central

    Kaye, Michael D.

    1968-01-01

    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

  12. Sister Mary Joseph's nodule as initial pancreatic cancer manifestation.

    PubMed

    Vallejo Bernad, Cristina; Casamayor Franco, María Carmen; Hakim Alonso, Sofía

    2017-02-01

    We report the case of an 85-year-old female patient who presented with umbilical pain associated with an indurated growth, the whole being apparently consistent with incarcerated umbilical hernia, which prompted an urgent surgical procedure for its removal. The pathology study revealed dermal infiltration by a malignancy. Gland tumor cells expressed an immunohistochemical profile initially consistent with a pancreatic origin. In view of these findings a CT scan was performed, which revealed a pancreatic tail tumor as well as multiple hepatic metastasis. Skin metastasis is a rare sign usually reflecting a carcinoma of unknown origin. Umbilical skin metastasis, called Sister Mary Joseph´s nodule, reflect an intra-abdominal tumor, being pancreatic cancer strange.

  13. PKD signaling and pancreatitis

    PubMed Central

    Yuan, Jingzhen; Pandol, Stephen J.

    2016-01-01

    Background Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. Methods This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Results Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. Conclusions These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID:26879861

  14. Magnetic resonance imaging findings of undifferentiated carcinoma with osteoclast-like giant cells of pancreas.

    PubMed

    Yang, Kyung Yoon; Choi, Joon-Il; Choi, Moon Hyung; Park, Michael Yong; Rha, Sung Eun; Byun, Jae Young; Jung, Eun Sun; Lall, Chandana

    2016-01-01

    Undifferentiated carcinoma with osteoclast-like giant cells is a rare pancreatic and periampullary neoplasm with less than 50 cases reported in the literature. Pathologically, this tumor mimics a giant cell tumor in bones. We report a case of undifferentiated carcinoma with osteoclast-like giant cells in a 55-year-old man presenting as a pancreatic mass with associated regional and distant lymphadenopathy. On T1- and T2-weighted images, the mass shows dark signal intensity which was atypical for a pancreatic adenocarcinoma.

  15. Can Pancreatic Cancer Be Found Early?

    MedlinePlus

    ... Team About Pancreatic Cancer? Pancreatic Cancer Early Detection, Diagnosis, and Staging Can Pancreatic Cancer Be Found Early? Pancreatic cancer is hard to find early. The pancreas is deep inside the body, so early tumors ...

  16. Recurrent acute pancreatitis.

    PubMed

    Khurana, Vishal; Ganguly, Ishita

    2014-09-28

    Recurrent acute pancreatitis (RAP) is commonly encountered, but less commonly understood clinical entity, especially idiopathic RAP, with propensity to lead to repeated attacks and may be chronic pancreatitis if attacks continue to recur. A great number of studies have been published on acute pancreatitis, but few have focused on RAP. Analysing the results of clinical studies focusing specifically on RAP is problematic in view due to lack of standard definitions, randomised clinical trials, standard evaluation protocol used and less post intervention follow-up duration. With the availability of newer investigation modalities less number of etiologies will remains undiagnosed. This review particularly is focused on the present knowledge in understanding of RAP.

  17. [Primary pancreatic plasmacytoma].

    PubMed

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

    2014-01-01

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

  18. Pancreatic Cancer Epidemiology, Detection, and Management

    PubMed Central

    Zhang, Qiubo; Zeng, Linjuan; Chen, Yinting; Lian, Guoda; Qian, Chenchen; Chen, Shaojie; Li, Jiajia; Huang, Kaihong

    2016-01-01

    PC (pancreatic cancer) is the fourth most common cause of death due to cancer worldwide. The incidence and mortality rates have been increasing year by year worldwide, and this review has analyzed the most recent incidence and mortality data for pancreatic cancer occurrence in China. Several possible risk factors have been discussed here, involving known established risk factors and novel possible risk factors. The development of this cancer is a stepwise progression through intraepithelial neoplasia to carcinoma. Though early and accurate diagnosis is promising based on a combination of recent techniques including tumor markers and imaging modalities, lacking early clinical symptoms makes the diagnosis late. Correct staging is critical because treatment is generally based on this parameter. Treatment options have improved throughout the last decades. However, surgical excision remains the primary therapy and efficacy of conventional chemoradiotherapy for PC is limited. Recently, some novel new therapies have been developed and will be applied in clinics soon. This review will provide an overview of pancreatic cancer, including an understanding of the developments and controversies. PMID:26941789

  19. GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas.

    PubMed

    Davis, Drew G; Siddiqui, Momin T; Oprea-Ilies, Gabriela; Stevens, Keith; Osunkoya, Adeboye O; Cohen, Cynthia; Li, Xiaoxian Bill

    2016-01-01

    GATA-3, a member of the GATA family of zinc-finger DNA binding proteins, and FOXA1, a member of the forkhead transcription factor family, are both associated with estrogen receptor expression. Both GATA-3 and FOXA1 are useful markers for breast carcinoma, but their expression in the different breast cancer subtypes and other neoplasms has not been thoroughly evaluated. We examined the expression of GATA-3 and FOXA1 in estrogen receptor-positive, Her2/neu-positive, and triple-negative breast carcinomas as well as in 10 other common carcinomas, including hepatocellular, colonic, pancreatic, gastric, endometrial (endometrioid), lung, prostatic, renal cell, urothelial, and ovarian serous carcinomas. Primary and metastatic melanomas and mesotheliomas were also evaluated. GATA-3 and FOXA1 staining of estrogen receptor-positive breast carcinomas was seen in 96.6% and 96.2%, respectively. In triple-negative breast carcinomas, GATA-3 and FOXA1 staining was seen in 21.6% and 15.9%, respectively. Among the other tumors, GATA-3 staining was only seen in urothelial carcinoma (70.9%) and FOXA1 staining was only seen in prostatic (87.5%), urothelial (5.1%) carcinomas, and mesotheliomas (40.0%). In conclusion, GATA-3 and FOXA1 are excellent breast carcinoma markers; however, their utility is limited in the triple-negative subtype. The utility of FOXA1 in diagnosing prostatic carcinoma and mesothelioma warrants further investigation.

  20. Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets

    PubMed Central

    Witkiewicz, Agnieszka K.; McMillan, Elizabeth A.; Balaji, Uthra; Baek, GuemHee; Lin, Wan-Chi; Mansour, John; Mollaee, Mehri; Wagner, Kay-Uwe; Koduru, Prasad; Yopp, Adam; Choti, Michael A.; Yeo, Charles J.; McCue, Peter; White, Michael A.; Knudsen, Erik S.

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and insights into both disease etiology and targeted intervention are needed. A total of 109 micro-dissected PDA cases were subjected to whole-exome sequencing. Microdissection enriches tumour cellularity and enhances mutation calling. Here we show that environmental stress and alterations in DNA repair genes associate with distinct mutation spectra. Copy number alterations target multiple tumour suppressive/oncogenic loci; however, amplification of MYC is uniquely associated with poor outcome and adenosquamous subtype. We identify multiple novel mutated genes in PDA, with select genes harbouring prognostic significance. RBM10 mutations associate with longer survival in spite of histological features of aggressive disease. KRAS mutations are observed in >90% of cases, but codon Q61 alleles are selectively associated with improved survival. Oncogenic BRAF mutations are mutually exclusive with KRAS and define sensitivity to vemurafenib in PDA models. High-frequency alterations in Wnt signalling, chromatin remodelling, Hedgehog signalling, DNA repair and cell cycle processes are observed. Together, these data delineate new genetic diversity of PDA and provide insights into prognostic determinants and therapeutic targets. PMID:25855536

  1. Painless acute pancreatitis associated with sorafenib treatment: a case report.

    PubMed

    Kobayashi, Yasuyuki; Kanemitu, Toshiyuki; Kamoto, Akihito; Satoh, Mototaka; Mori, Naoki; Sekii, Kenichiro; Yoshioka, Toshiaki; Itatani, Hiroaki; Fujimoto, Takashi

    2011-06-01

    Sorafenib is a multikinase inhibitor that is used for the treatment of metastatic renal-cell carcinoma. We report the case of a patient with painless acute pancreatitis associated with sorafenib treatment. The patient was a 71-year-old man who had undergone surgery for left renal carcinoma and tumor thrombus in the inferior vena cava and right atrium (IVC-RA). After a follow-up period of 3 years, he developed right adrenal metastasis and received interferon (IFN)-alpha treatment. One year later, progression of the adrenal metastasis was observed, and he was admitted to a hospital for treatment with sorafenib, which was administered at a dose of 800 mg/day. Two weeks later, he developed painless acute pancreatitis associated with sorafenib treatment. Thereafter, sorafenib treatment was discontinued, and he was treated with conservative therapy. Three weeks later, he was discharged. Even though painless acute pancreatitis associated with sorafenib treatment is rare, the possible development of painless acute pancreatitis in patients undergoing sorafenib treatment must be kept in mind.

  2. FDG-PET evaluation of indeterminate pancreatic masses

    SciTech Connect

    Ho, Chi-Lai; Dehdashti, Farrokh; Griffeth, L.K.

    1996-05-01

    The purpose of this study was to assess the-ability of PET with 2-[{sup 18}F]fluoro-2-deoxy-D-glucose (FDG) to differentiate benign from malignant pancreatic masses in patients with indeterminate findings on CT. We performed FDG-PET on 12 patients with indeterminate mass lesions and 2 patients with CT findings typical for malignancy. Eight were found to have pancreatic carcinoma and six had benign lesions. The final diagnosis was histopathologically confirmed in all patients but two with a presumed diagnosis of focal pancreatitis based on stable clinical follow-up for at least 12 months. Lesion uptake of FDG was evaluated qualitatively and semi-quantitatively by determination of the standardized uptake value (SUV). With use of a 2.5 cutoff value for SUV, all eight malignant and four of six benign lesions were correctly categorized. Qualitative evaluation gave the same results. The two false-positive lesions had elevated SUV values of 3.4 and 3.8, respectively. Our results indicate that FDG-PET has potential value for assessing patients with CT findings that are indeterminate for pancreatic carcinoma. FDG-PET may obviate invasive diagnostic procedures in many patients with benign disease. 36 refs., 2 figs., 1 tab.

  3. [Experimental models of acute pancreatitis].

    PubMed

    Ceranowicz, Piotr; Cieszkowski, Jakub; Warzecha, Zygmunt; Dembiński, Artur

    2015-02-21

    Acute pancreatitis is a severe disease with high mortality. Clinical studies can bring some data about etiology, pathogenesis and the course of acute pancreatitis. However, studies concerning early events of this disease and the new concepts of treatment cannot be performed on humans, due to ethical reasons. Animal models of acute pancreatitis have been developed to solve this problem. This review presents currently used experimental models of acute pancreatitis, their properties and clinical relevance. Experimental models of acute pancreatitis can be divided into in vivo (non-invasive and invasive) and ex vivo models. The onset, development, severity and extent of acute pancreatitis, as well as the mortality, vary considerably between these different models. Animal models reproducibly produce mild, moderate or severe acute pancreatitis. One of the most commonly used models of acute pancreatitis is created by administration of supramaximal doses of cerulein, an analog of cholecystokinin. This model produces acute mild edematous pancreatitis in rats, whereas administration of cerulein in mice leads to the development of acute necrotizing pancreatitis. Acute pancreatitis evoked by retrograde administration of sodium taurocholate into the pancreatic duct is the most often used model of acute severe necrotizing pancreatitis in rats. Ex vivo models allow to eliminate the influence of hormonal and nervous factors on the development of acute pancreatitis.

  4. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez Muñoz, J Enrique

    2015-09-01

    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 treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis. The multimodal dynamic endoscopic ultrasound-guided secretin-stimulated evaluation of the pancreas provides relevant morphological and functional information for the diagnosis of chronic pancreatitis at early stages. Extracorporeal shock wave lithotripsy in patients with calcifying pancreatitis and endoscopic pancreatic stent placement are effective alternatives for pain therapy in patients with chronic pancreatitis. Presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significantly increase of mortality rate. Despite that, pancreatic enzyme replacement therapy is not prescribed in the majority of patients with pancreatic exocrine insufficiency, or it is prescribed at a low dose. The newly developed and commercialized needles for endoscopic ultrasound-guided pancreatic biopsy are effective in retrieving appropriate tissue samples for the histological diagnosis of autoimmune pancreatitis. Maintenance therapy with azathioprine is effective and safe to prevent relapses in patients with autoimmune pancreatitis.

  5. Solid type clear cell carcinoma of the pancreas: differential diagnosis of an unusual case and review of the literature.

    PubMed

    Loos, Martin; Bergmann, Frank; Bauer, Andrea; Hoheisel, Jörg D; Esposito, Irene; Kleeff, Jörg; Schirmacher, Peter; Büchler, Markus W; Klöppel, Günter; Friess, Helmut

    2007-06-01

    Pancreatic neoplasms have been reliably classified on the basis of their histopathology and immunophenotype. In this study, we report on a pancreatic tumor whose phenotype and genotype could not be assigned to any known tumor entity. The tumor was observed in the pancreatic head of a 54-year-old woman. It was found to be a solid infiltrating carcinoma with abundant clear cells. Apart from cytokeratin, the tumor cells expressed vimentin, S100, and MUC-1. DNA microarray analysis revealed a transcription profile clearly differing from that of normal pancreatic tissue and pancreatic ductal adenocarcinoma. Despite metastatic behavior, the tumor displayed a more favorable course than conventional pancreatic ductal adenocarcinoma. We suggest that this tumor be called solid type clear cell carcinoma of the pancreas.

  6. A case of mixed adenoneuroendocrine carcinoma of the pancreas

    PubMed Central

    Murata, Masaru; Takahashi, Hidekazu; Yamada, Moyuru; Song, Misa; Hiratsuka, Masahiro

    2017-01-01

    Abstract Rationale: Tumors with multiple histological features, such as adenocarcinomas and neuroendocrine carcinomas, were included as a new category of neuroendocrine carcinomas in the 2010 World Health Organization classification. We recently experienced a rare case of a pancreatic carcinoma with both adenocarcinoma and neuroendocrine carcinoma components, a so-called mixed adenoneuroendocrine carcinoma. Patient concerns and diagnosis: A 66-year-old man was referred to our hospital with obstructive jaundice. Contrast-enhanced computed tomography images indicated a tumor located at the pancreatic head measuring 3.0 × 2.5 cm in diameter and invading the common bile duct. Cytological examination of the bile juice obtained by endoscopic retrograde cholangiopancreatography revealed adenocarcinoma cells. Pancreaticoduodenectomy was performed safely as radical resection. Interventions: Microscopically, the resected tumor consisted of tightly intermingled adenocarcinoma and neuroendocrine carcinoma components. On the immunohistochemical examination, p53 was ubiquitously positive in both components, whereas chromogranin A, synaptophysin and neuron-specific enolase, neuroendocrine markers, were limited to the neuroendocrine carcinoma component. Outcomes: Thus, such features of both adenocarcinoma and neuroendocrine carcinoma observed microscopically and immunohistochemically seemed to indicate a composite tumor. Lessons: The findings of this case suggest that adenocarcinoma and neuroendocrine carcinoma may be derived from a single cancer stem cell. PMID:28248881

  7. Pancreatic Islet Transplantation

    MedlinePlus

    ... allo-transplantation?" For each pancreatic islet allo-transplant infusion, researchers use specialized enzymes to remove islets from ... in a lab. Transplant patients typically receive two infusions with an average of 400,000 to 500, ...

  8. Surgery for Pancreatic Cancer

    MedlinePlus

    ... the abdomen. The surgeon can look at the pancreas and other organs for tumors and take biopsy ... pancreatic cancers appear to be confined to the pancreas at the time they are found. Even then, ...

  9. Chronic Pancreatitis in Children

    MedlinePlus

    ... years to appear, but this, too, is highly variable; some patients with chronic pancreatitis will develop diabetes ... of modifying factors include other genes or environmental variables, which is a term that scientists use to ...

  10. Pancreatic exocrine function testing

    SciTech Connect

    Goff, J.S.

    1981-11-01

    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.

  11. Pancreatic Cancer Risk Factors

    MedlinePlus

    ... age at the time of diagnosis is 71. Gender Men are slightly more likely to develop pancreatic ... would like to unsubscribe/opt out from our communications, please follow this link: http://www.cancer.org/ ...

  12. Pathology and genetics of pancreatic neoplasms with acinar differentiation.

    PubMed

    Wood, Laura D; Klimstra, David S

    2014-11-01

    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/β-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.

  13. [Management of postoperative pancreatic fistula].

    PubMed

    Hackert, T; Büchler, M W

    2015-06-01

    The occurrence of a postoperative pancreatic fistula is one of the most important complications following pancreatic resections. The frequency of this complication varies between 3 % after pancreatic head resection and up to 35 % following distal pancreatectomy. In 2005, the international definition of postoperative pancreatic fistula was standardized according to the approach of the International Study Group of Pancreatic Surgery (ISGPS) including an A-C grading system of the severity. Consequently, results from different studies have become comparable and the historically reported fistula rates can be evaluated more critically. The present review summarises the currently available data on incidence, risk factors, fistula-associated complications and management of postoperative pancreatic fistula.

  14. Arsenic-Induced Pancreatitis

    PubMed Central

    Connelly, Sean; Zancosky, Krysia; Farah, Katie

    2011-01-01

    The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide has brought about tremendous advancement in the treatment of acute promyelocytic myelogenous leukemia (APML). In most instances, the benefits of these treatments outweigh the risks associated with their respective safety profiles. Although acute pancreatitis is not commonly associated with arsenic toxicity, it should be considered as a possible side effect. We report a case of arsenic-induced pancreatitis in a patient with APML. PMID:22606427

  15. Hereditary pancreatitis: current perspectives.

    PubMed

    Raphael, Kara L; Willingham, Field F

    2016-01-01

    Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy.

  16. Expression of RUNX3 gene in pancreatic adenocarcinoma and its clinical significance.

    PubMed

    Xue, L-N; Bai, F H; Wang, X-Y; Lin, M; Tan, Y; Yao, X-Y; Xu, K-Q

    2014-05-23

    We investigated the clinical significance of RUNX3 gene expression in human pancreatic carcinoma. Five samples of pancreatic tissues and 30 samples of pancreatic cancer tissues and paracancerous tissues were collected. RUNX3 expression was detected by real-time PCR and immunohistochemistry. The relationships between clinicopathological findings and the expression of RUNX3 were analyzed. The relative quantification level of RUNX3 mRNA expression in human pancreatic carcinoma tissues and paracancerous tissues was 2.60 (0.42-12.82) and 1.02 (0.19-3.58), respectively (P < 0.05). The percentage of positive cells expressing RUNX3 protein in human pancreatic tissues and paracancerous tissues was 45.5 ± 26.2 and 6.9 ± 6.0%, respectively (P < 0.01). The high RUNX3 group (N = 9) with 45.5% or more of the cancer cells staining for RUNX3 and the low RUNX3 group (N = 21) with less than 45.5% cancer cells staining for RUNX3. Low expression of RUNX3 correlated significantly with an advanced TNM stage (χ(2) = 6.897, P = 0.045), lymph node metastasis (χ(2) = 4.739, P = 0.029) and neural invasion (χ(2) = 5.44, P = 0.020). On the other hand, no association could be found between RUNX3 expression and clinicopathological variables including age, gender, tumor location, tumor size, tumor differentiation or the serum concentration of CEA and CA199. The expression of RUNX3 in pancreatic cancer tissues was obviously higher than that in the paracancerous tissues. Low expression of RUNX3 may have an important role in aggressiveness, lymph node metastasis and neural invasion in pancreatic cancer. In pancreatic carcinoma tissues, low expression of RUNX3 may indicate a poor prognosis.

  17. Anaplastic Carcinoma Possibly Arising from a Heterotopic Pancreas.

    PubMed

    Adachi, Yasushi; Mita, Hiroaki; Takahashi, Hideaki; Akino, Kimishige; Kikuchi, Takefumi; Ishii, Yoshifumi; Endo, Takao

    2015-01-01

    Anaplastic carcinoma is a rare pancreatic cancer, and the malignant transformation of a heterotopic pancreas is also rare. We herein report a case of an elderly woman with a mass of unknown origin in the abdominal cavity. Computed tomography identified the extent of the tumor but not the organ of origin. The abdominal tumor eventually metastasized to the liver and lung. An autopsy and immunohistochemical examination revealed an anaplastic carcinoma possibly originating in an ectopic pancreas.

  18. Nanog Predicts Poor Prognosis in Human Pancreatic Cancer and Is Downregulated by QingyihuaJi Formula in Pancreatic Cancer Stem Cells

    PubMed Central

    Song, Libin; Dong, Lei; Weng, Lao I.; Wang, Peng; Hua, Yongqiang

    2016-01-01

    Qingyihuaji formula (QYHJ), confirmed efficacious in a series of clinical trials, has been applied to human pancreatic carcinoma treatment in Shanghai Cancer Center for years. Recent evidence highlighted that pluripotent stem cells transcription factor Nanog plays a pivotal role in carcinogenesis. However, there is little published information regarding the underlying clinical significance and mechanisms of transcription factor Nanog in pancreatic cancer. In this study, our results indicated that Nanog is overexpressed in human pancreatic cancer stem cells and downregulated by QYHJ, which may contribute to explain the clinical effectiveness of QYHJ and provide advanced pancreatic cancer patients with a new therapeutic option, supporting our hypothesis that the degradation pathway is another mechanism by which QYHJ affects Nanog expression. PMID:27829864

  19. Atezolizumab and Bevacizumab in Treating Patients With Recurrent, Persistent, or Metastatic Cervical Cancer

    ClinicalTrials.gov

    2017-03-08

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  20. [Acute pancreatitis due to lupus].

    PubMed

    Hani, Mohamed Aziz; Guesmi, Fethi; Ben Achour, Jamel; Zribi, Riadh; Bouasker, Ibtissem; Zoghlami, Ayoub; Najah, Nabil

    2004-02-01

    Among digestive clinical presentations of systemic lupus erythematosus, acute pancreatitis remains a serious affection with very poor prognosis. To date, pathogenesis is still unclear. We report two cases of fatal acute pancreatitis related to systemic lupus erythematosus.

  1. Metabolic pancreatitis: Etiopathogenesis and management

    PubMed Central

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

    2013-01-01

    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

  2. Surgery for pancreatic cancer -- discharge

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000820.htm Surgery for pancreatic cancer - discharge To use the sharing features on this ... References Claudius C, Lillemoe KD. Palliative Therapy for Pancreatic Cancer. In: Cameron JL, Cameron AM, eds. Current Surgical ...

  3. Genetics Home Reference: hereditary pancreatitis

    MedlinePlus

    ... HEREDITARY Sources for This Page Greer JB, Whitcomb DC. Inflammation and pancreatic cancer: an evidence-based review. ... J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP; European Registry of Hereditary Pancreatitis and ...

  4. Nutrition, Inflammation, and Acute Pancreatitis

    PubMed Central

    Petrov, Max

    2013-01-01

    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

  5. Hepatobiliary and pancreatic ascariasis

    PubMed Central

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-01-01

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease. PMID:27672273

  6. Chronic pancreatitis in dogs.

    PubMed

    Watson, Penny

    2012-08-01

    Chronic pancreatitis used to be considered uncommon in dogs, but recent pathological and clinical studies have confirmed that it is in fact a common and clinically significant disease. Clinical signs can vary from low-grade recurrent gastrointestinal signs to acute exacerbations that are indistinguishable from classical acute pancreatitis. Chronic pancreatitis is a significant cause of chronic pain in dogs, which must not be underestimated. It also results in progressive impairment of endocrine and exocrine function and the eventual development of diabetes mellitus or exocrine pancreatic insufficiency or both in some affected dogs at end stage. The etiology is unknown in most cases. Chronic pancreatitis shows an increased prevalence in certain breeds, and recent work in English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed. The histological and clinical appearance is different in different breeds, suggesting that etiologies may also be different. Diagnosis is challenging because the sensitivities of the available noninvasive tests are relatively low. However, with an increased index of suspicion, clinicians will recognize more cases that will allow them to institute supportive treatment to improve the quality of life of the patient.

  7. Hepatobiliary and pancreatic ascariasis.

    PubMed

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-09-07

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease.

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

    ClinicalTrials.gov

    2016-12-09

    Estrogen Receptor-positive Breast Cancer; Gastrinoma; Glucagonoma; HER2-negative Breast Cancer; Insulinoma; Mucositis; Oral Complications; Pancreatic Polypeptide Tumor; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Islet Cell Carcinoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Renal Cell Cancer

  9. An innovative strategy for the identification and 3D reconstruction of pancreatic cancer from CT images.

    PubMed

    Marconi, S; Pugliese, L; Del Chiaro, M; Pozzi Mucelli, R; Auricchio, F; Pietrabissa, A

    2016-09-01

    We propose an innovative tool for Pancreatic Ductal AdenoCarcinoma 3D reconstruction from Multi-Detector-Computed Tomography. The tumor mass is discriminated from health tissue, and the resulting segmentation labels are rendered preserving information on different hypodensity levels. The final 3D virtual model includes also pancreas and main peri-pancreatic vessels, and it is suitable for 3D printing. We performed a preliminary evaluation of the tool effectiveness presenting ten cases of Pancreatic Ductal AdenoCarcinoma processed with the tool to an expert radiologist who can correct the result of the discrimination. In seven of ten cases, the 3D reconstruction is accepted without any modification, while in three cases, only 1.88, 5.13, and 5.70 %, respectively, of the segmentation labels are modified, preliminary proving the high effectiveness of the tool.

  10. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis

    PubMed Central

    Xue, Jing; Sharma, Vishal; Hsieh, Michael H.; Chawla, Ajay; Murali, Ramachandran; Pandol, Stephen J.; Habtezion, Aida

    2015-01-01

    Chronic pancreatitis (CP) is a progressive and irreversible inflammatory and fibrotic disease with no cure. Unlike acute pancreatitis, we find that alternatively activated macrophages (AAMs) are dominant in mouse and human CP. AAMs are dependent on IL-4 and IL-13 signaling and we show that mice lacking IL-4Rα, myeloid specific IL-4Rα, and IL-4/IL-13 were less susceptible to pancreatic fibrosis. Furthermore, we demonstrate that mouse and human pancreatic stellate cells (PSCs) are a source of IL-4/IL-13. Notably, we show that pharmacologic inhibition of IL-4/IL-13 in human ex-vivo studies as well as in established mouse CP decreases pancreatic AAMs and fibrosis. We identify a critical role for macrophages in pancreatic fibrosis and in turn PSCs as important inducers of macrophage alternative activation. Our study challenges and identifies pathways involved in cross talk between macrophages and PSCs that can be targeted to reverse or halt pancreatic fibrosis progression. PMID:25981357

  11. Histological subtypes of oral non-tonsillar squamous cell carcinoma in dogs.

    PubMed

    Nemec, A; Murphy, B; Kass, P H; Verstraete, F J M

    2012-01-01

    Several histological subtypes and grades of oral squamous cell carcinoma (SCC) are described in human literature and these subtypes have distinct morphological features and biological behaviour. This retrospective study (1990-2010) included 84 dogs diagnosed with SCC of the oral cavity and oropharynx, excluding the tonsils. Sixty-nine of the SCCs (82.1%) were further diagnosed as conventional SCC (CSCC) (33 [47.8%] well-differentiated, 31 [44.9%] moderately-differentiated and five [7.3%] poorly-differentiated), five (5.95%) each as papillary SCC and basaloid SCC, three (3.6%) as adenosquamous carcinoma and two (2.4%) as spindle cell carcinoma. Compared with the general hospital population, neutered female dogs, dogs aged 10 to <15 years, English springer spaniels and Shetland sheepdogs were overrepresented. The majority (78.1%) of SCCs were proliferative with or without associated ulceration, although no significant association was observed between the gross appearance and different SCC subtypes. 71.4% of SCCs were located in dentate jaws; however, well-differentiated CSCC more often affected the tongue and other non-dentate mucosal surfaces (P=0.0022). No significant association was found between any of the SCC subtypes and tumour-associated inflammation (TAI), perineural and lymphovascular invasion (PNI, LVI), or between gross appearance of the tumour and tumour location, PNI, LVI or TAI or PNI, LVI, TAI and tumour location.

  12. Squamous Cell Carcinoma of Pancreas: Mystery and Facts.

    PubMed

    Raghavapuram, Saikiran; Vaid, Arjun; Rego, Rayburn F

    2015-08-01

    Squamous cell carcinoma of the pancreas is very rare as pancreas does not have any squamous cells. Only a few cases have been reported in the literature so far. We describe such a case where in the patient presented with painless jaundice. CT and EUS confirmed the pancreatic mass biopsy of which showed squamous cell cancer.

  13. Incidental isolated pancreatic hydatid cyst.

    PubMed

    Kısaoğlu, Abdullah; Özoğul, Bünyami; Atamanalp, Sabri Selçuk; Pirimoğlu, Berhan; Aydınlı, Bülent; Korkut, Ercan

    2015-03-01

    Isolated pancreatic hydatid cysts are a rare parasitic disease even in endemic areas. It is difficult to discriminate primary pancreatic hydatid cysts from other cystic and solid lesions of the pancreas. This is a case report of an incidental isolated pancreatic hydatid cyst. A heterogeneous cystic lesion in the body of the pancreas was identified on magnetic resonance imaging of a patient previously diagnosed patient with cholelithiasis, and because of the malignant possibility of the lesion, splenectomy with distal pancreatectomy and cholecystectomy was performed. The histopathologic diagnosis was reported as a hydatid cyst. Pancreatic hydatid cysts should be kept in mind in the differential diagnosis of pancreatic pseudocysts and cystic malignancies.

  14. Incorporation of (/sup 35/S)sulfate in normal and neoplastic rat pancreatic acinar cells in relationship to cytodifferentiation

    SciTech Connect

    Kanwar, Y.S.; Rao, M.S.; Longnecker, D.S.; Reddy, J.K.

    1984-11-01

    The rates of (/sup 35/S)sulfate incorporation in highly differentiated acinar cells from normal pancreas, moderately differentiated cells of nafenopin-induced transplantable pancreatic carcinoma, and poorly differentiated cells from azaserine-induced transplantable pancreatic carcinoma were examined in an attempt to determine if sulfation is a property of acinar cells with well-developed secretory granules. The cells were dissociated, pulsed with (/sup 35/S)sulfate (specific activity, approximately 1000 Ci/mmol) for 10 and 60 min, and chased with medium containing 100 X excess of cold inorganic sulfate for 0, 15, 60, and 120 min. The cells were then processed for determining their pool size and light and electron microscopic autoradiography. No significant differences among their pool sizes were observed. However, the light microscopic autoradiograms revealed the (/sup 35/S)sulfate incorporation as follows: azaserine-induced transplantable pancreatic carcinoma greater than nafenopin-induced transplantable pancreatic carcinoma greater than normal pancreas. Electron microscopic autoradiograms revealed similar trends. The grain densities (concentration of radiation) were highest in the Golgi regions immediately postpulse (0 min) and gradually shifted toward the secretory granules over a 120-min period. In addition, the grain density values of the secretory granule-rich cells of nafenopin-induced transplantable pancreatic carcinoma were relatively similar to the cells of normal pancreas, whereas the grain density values of secretory granule-deficient cells from this tumor were similar to those of poorly differentiated neoplastic cells of azaserine-induced transplantable pancreatic carcinoma. These results show that poorly differentiated neoplastic cells incorporate more (/sup 35/S)sulfate than do the well-differentiated cells, but the reasons for this unexpected differential incorporation are at present unknown.

  15. The Wnt/β-catenin signaling pathway mechanism for pancreatic cancer chemoresistance in a three-dimensional cancer microenvironment

    PubMed Central

    Zhang, Qiang; Meng, Xing-Kai; Wang, Wan-Xiang; Zhang, Rui-Ming; Zhang, Tong; Ren, Jian-jun

    2016-01-01

    β-catenin is a key protein that is encoded by the CTNNB1 gene in the Wnt signaling pathway. This study investigated the associations between β-catenin expression and implications for the efficacy of gemcitabine on pancreatic cancer cells in a three-dimensional (3-D) cancer microenvironment. For low β-catenin expression pancreatic carcinoma cells, the inhibition rates (IRs) for low, middle, and high doses of gemcitabine were 0.615 ± 0.079, 0.691 ± 0.093, and 0.765 ± 0.061, respectively. For the high β-catenin expression pancreatic carcinoma cells, the IRs for the same doses were 0.325 ± 0.072, 0.453 ± 0.075, and 0.537 ± 0.056, respectively. Additionally, the evaluation of β-catenin immunoreactivity in 31 pancreatic cancer patients revealed that the low β-catenin protein expression group had significantly longer overall survival (OS) and disease free survival (DFS) than the high β-catenin protein group (P < 0.05). Overall, β-catenin protein expression levels were significantly correlated to gemcitabine sensitivity in seven pancreatic carcinoma cell lines in the 3-D cancer microenvironment. These data suggest that large-scale clinical studies are warranted to assess the role of the Wnt/β-catenin signaling pathway on β-catenin protein expression and chemosensitivity to gemcitabine in pancreatic cancer. PMID:27830034

  16. Hypertriglyceridaemia-induced pancreatitis.

    PubMed

    Weston, Natasha; Fernando, Upul; Baskar, Varadarajan

    2013-02-27

    Hypertriglyceridaemia is the third most common cause of acute pancreatitis but is relatively rare and therefore requires a high level of clinical suspicion to be diagnosed. We discuss the case of a 46-year-old man who initially presented to the accident and emergency department with suspected first presentation of diabetic ketoacidosis (DKA) and a normal amylase but who did not respond to DKA treatment. Further history revealed significant cardiovascular risk factors, examination showed an evidence of hyperlipidaemia and investigations revealed acute pancreatitis secondary to hypertriglyceridaemia. We discuss the causes of hypertriglyceridaemia, the difficulty in differentiating primary versus secondary hypertriglyceridaemia, possible pathogenesis and current evidence-based treatments.

  17. Enzymatic Debridement in Necrotizing Pancreatitis

    PubMed Central

    Cakir, Murat; Tekin, Ahmet; Kucukkartallar, Tevfik; Vatansev, Husamettin; Kartal, Adil

    2015-01-01

    Multiple organ failure and pancreatic necrosis are the factors that determine prognosis in acute pancreatitis attacks. We investigated the effects of collagenase on the debridement of experimental pancreatic necrosis. The study covered 4 groups; each group had 10 rats. Group I was the necrotizing pancreatitis group. Group II was the collagenase group with pancreatic loge by isotonic irrigation following necrotizing pancreatitis. Group III was the collagenase group with pancreatic loge following necrotizing pancreatitis. Group IV was the intraperitoneal collagenase group following necrotizing pancreatitis. The progress of the groups was compared hematologically and histopathologically. There was no difference among the groups regarding the levels of leukocyte, hemogram, and urea. The differences in AST levels between Group I and II; and differences in glucose, calcium, LDH, AST, and amylase between Group II and III; between Group II and IV; between Group I and III; and between Group I and IV were statistically significant (P < 0.05). There were statistically significant differences between Group II and III, and Group II and IV regarding edema, acinar necrosis, inflammatory cell infiltration, hemorrhage, and fat necrosis (P < 0.05). In conclusion, the collagenase preparation used in this experimental pancreatitis model was found to be effective in the debridement of pancreatic necrosis. PMID:26011212

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

    ClinicalTrials.gov

    2014-10-09

    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

  19. Pancreatic disorders in inflammatory bowel disease

    PubMed Central

    Antonini, Filippo; Pezzilli, Raffaele; Angelelli, Lucia; Macarri, Giampiero

    2016-01-01

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn’s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD. PMID:27574565

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

    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.

  1. Arterial complication of irreversible electroporation procedure for locally advanced pancreatic cancer

    PubMed Central

    Ekici, Yahya; Tezcaner, Tugan; Aydın, Hüseyin Onur; Boyvat, Fatih; Moray, Gökhan

    2016-01-01

    Irreversible electroporation (IRE) is a non-thermal ablation technique used especially in locally advanced pancreatic carcinomas that are considered surgically unresectable. We present the first case of acute superior mesenteric artery (SMA) occlusion secondary to pancreatic IRE procedure that has not been reported before in the literature. A 66-year-old man underwent neoadjuvant chemoradiotherapy for locally advanced pancreatic ductal adenocarcinoma. IRE procedure was applied to the patient during laparotomy under general anesthesia. After finishing the procedure, an acute intestinal ischemia was detected. A conventional vascular angiography was performed and a metallic stent was successfully placed to the SMA and blood flow was maintained. It is important to be careful in such cases of tumor involvement of SMA when evaluating for IRE procedure of pancreatic tumor. PMID:27795815

  2. Precursor lesions for sporadic pancreatic cancer: PanIN, IPMN, and MCN.

    PubMed

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

    2014-01-01

    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.

  3. p53 tumour suppressor gene expression in pancreatic neuroendocrine tumour cells.

    PubMed Central

    Bartz, C; Ziske, C; Wiedenmann, B; Moelling, K

    1996-01-01

    Neuroendocrine pancreatic tumours grow slower and metastasise later than ductal and acinar carcinomas. The expression of the p53 tumour suppressor gene in pancreatic neuroendocrine tumour cells is unknown. Pancreatic neuroendocrine cell lines (n = 5) and human tumour tissues (n = 19) were studied for changed p53 coding sequence, transcription, and translation. Proliferative activity of tumour cells was determined analysing Ki-67 expression. No mutation in the p53 nucleotide sequence of neuroendocrine tumour cell was found. However, an overexpression of p53 could be detected in neuroendocrine pancreatic tumour cell lines at a protein level. As no p53 mutations were seen, it is suggested that post-translational events can also lead to an overexpression of p53. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8675094

  4. Hepatocellular carcinoma.

    PubMed

    Macdonald, G A

    1999-05-01

    Hepatitis C infection is associated with the development of hepatocellular carcinoma, and progress has been made in a number of areas. Transgenic mice lines expressing the hepatitis C core protein develop hepatic steatosis, adenomas, and hepatocellular carcinomas, with no significant hepatitis or fibrosis. This implies that hepatitis C can lead directly to malignant transformation. A new lesion, irregular regeneration, has been described in chronic hepatitis C infection and is associated with a 15-fold increase in the relative risk of developing hepatocellular carcinoma. A minority of patients with hepatitis C-related hepatocellular carcinoma have intense lymphocytic infiltration of the cancer, a feature associated with a better prognosis. Several studies have confirmed the association between large cell dysplasia and hepatocellular carcinoma. However, large cell dysplasia may not be a premalignant lesion and instead may be a marker for premalignant alterations elsewhere in the liver. Oral contraceptives previously have been linked to an increased risk of hepatocellular carcinoma. A large multicenter European case-control study has shown minimal increased risk of hepatocellular carcinoma with use of steroidal contraception. Tamoxifen had shown promise in the management of advanced hepatocellular carcinoma. However, a randomized placebo-controlled study of 477 patients with hepatocellular carcinoma found no benefit from tamoxifen. In a preliminary study, however, octreotide has shown improved survival and quality of life in patients with advanced hepatocellular carcinoma. Finally, interferon treatment continues to be linked to a reduced risk of hepatocellular carcinoma in patients with hepatitis C. These studies generally are not randomized, and a randomized prospective study is required to address this issue.

  5. [Rare forms of the ductal carcinoma of the pancreas].

    PubMed

    Setdikova, G R; Filippova, E M; Paklina, O V; Kriger, A G; Chekmareva, I A; Gorin, D S; Berelavichus, S V; Bedin, V V; Tavobilov, M M

    2013-01-01

    Clinical cases of patients with rare forms of ductal pancreatic carcinoma are described. Difficulties of preoperative radiologic verification of ostheoclast-like giantcell tumor and cricoids-cell carcinoma of the pancreas are described. Morphologigic and immunohistochemical features of these tumors are highlighted. One of the clinical cases demonstrate the aggressive tumor behavior, led to liver metastases 4 months after the radical operation. Literature review highlights historical aspects and the state-of-art of diagnostics and treatment of rare forms of the ductal carcinoma of the pancreas.

  6. Endoscopic ultrasound in the diagnosis and management of carcinoma pancreas

    PubMed Central

    Puri, Rajesh; Manrai, Manish; Thandassery, Ragesh Babu; Alfadda, Abdulrahman A

    2016-01-01

    Endoscopic ultrasound (EUS) has become an important component in the diagnosis and treatment of carcinoma pancreas. With the advent of advanced imaging techniques and tissue acquisition methods the role of EUS is becoming increasingly important. Small pancreatic tumors can be reliably diagnosed with EUS. EUS guided fine needle aspiration establishes diagnosis in some cases. EUS plays an important role in staging of carcinoma pancreas and in some important therapeutic methods that include celiac plexus neurolysis, EUS guided biliary drainage and drug delivery. In this review we attempt to review the role of EUS in diagnosis and management of carcinoma pancreas. PMID:26839647

  7. Endoscopic ultrasound in the diagnosis and management of carcinoma pancreas.

    PubMed

    Puri, Rajesh; Manrai, Manish; Thandassery, Ragesh Babu; Alfadda, Abdulrahman A

    2016-01-25

    Endoscopic ultrasound (EUS) has become an important component in the diagnosis and treatment of carcinoma pancreas. With the advent of advanced imaging techniques and tissue acquisition methods the role of EUS is becoming increasingly important. Small pancreatic tumors can be reliably diagnosed with EUS. EUS guided fine needle aspiration establishes diagnosis in some cases. EUS plays an important role in staging of carcinoma pancreas and in some important therapeutic methods that include celiac plexus neurolysis, EUS guided biliary drainage and drug delivery. In this review we attempt to review the role of EUS in diagnosis and management of carcinoma pancreas.

  8. A case of undifferentiated carcinoma of the pancreas mimicking main-duct intraductal papillary mucinous neoplasm (IPMN).

    PubMed

    Kawai, Yuichi; Nakamichi, Rei; Kamata, Noriko; Miyake, Hideo; Fujino, Masahiko; Itoh, Shigeki

    2015-03-01

    We report here a rare case of undifferentiated carcinoma of the pancreas mimicking main-duct intraductal papillary mucinous neoplasm. In an 80-year-old woman, an approximately 8-mm papillary mass was incidentally detected at the downstream edge of a dilatated main pancreatic duct lumen on CT and MRI. Main pancreatic duct dilatation in the pancreatic body and tail and parenchymal atrophy were observed in the upstream of the mass. Histopathologically, the tumor protruded into the downstream edge of the dilatated main pancreatic duct lumen in the pancreatic body. The tumor cells had highly atypical nuclei and abundant polymorphic structures, and showed positive staining for granulocyte colony-stimulating factor, which led to the diagnosis of undifferentiated carcinoma. A total of 13 cases of undifferentiated carcinoma with intraductal tumor growth have been reported to date. The case report by Bergmann et al. has been the smallest in histopathological specimen, and the present case is the smallest in size detected by radiological images. Since early undifferentiated carcinoma of the pancreas can resemble those of main-duct intraductal papillary mucinous neoplasm in cross-sectional images, we have to consider undifferentiated carcinoma in the differential diagnosis of the solitary and papillary mass with low contrast enhancement in early phase in the main pancreatic duct.

  9. Childhood Carcinoma.

    PubMed

    Vargas, Sara O

    2010-09-01

    Carcinoma in children differs from that occurring in adults. It is far rarer and represents only a small fraction of all pediatric cancer diagnoses. Pediatric sarcomas were among the first tumors in which recurrent chromosomal aberrations were discovered. Once defined, these recurrent aberrations, many of them translocations, became incorporated into the pathologist's diagnostic armamentarium. In the past several years, defining chromosomal rearrangements have been identified in pediatric carcinomas as well, and this has become a new frontier in pathologic diagnosis. This article provides an overview of pediatric carcinoma as well as a detailed review of selected types of carcinoma that in particular can present diagnostic difficulty to the practicing pathologist and illustrate new and emerging concepts in pediatric carcinoma.

  10. GSH2 promoter methylation in pancreatic cancer analyzed by quantitative methylation-specific polymerase chain reaction

    PubMed Central

    GAO, FEI; HUANG, HAO-JIE; GAO, JUN; LI, ZHAO-SHEN; MA, SHU-REN

    2015-01-01

    Tumor suppressor gene silencing via promoter hypermethylation is an important event in pancreatic cancer pathogenesis. Aberrant DNA hypermethylation events are highly tumor specific, and may provide a diagnostic tool for pancreatic cancer patients. The objective of the current study was to identify novel methylation-related genes that may potentially be used to establish novel therapeutic and diagnostic strategies against pancreatic cancer. The methylation status of the GS homeobox 2 (GSH2) gene was analyzed using the sodium bisulfite sequencing method. The GSH2 methylation ratio was examined in primary carcinomas and corresponding normal tissues derived from 47 patients with pancreatic cancer, using quantitative methylation-specific polymerase chain reaction. Methylation ratios were found to be associated with the patient's clinicopathological features. GSH2 gene methylation was detected in 26 (55.3%) of the 47 pancreatic cancer patients, indicating that it occurs frequently in pancreatic cancer. A significant association with methylation was observed for tumor-node-metastasis stage (P=0.031). GSH2 may be a novel methylation-sensitive tumor suppressor gene in pancreatic cancer and may be a tumor-specific biomarker of the disease. PMID:26171036

  11. Early pancreatic panniculitis associated with HELLP syndrome and acute fatty liver of pregnancy.

    PubMed

    Kirkland, Eugene B; Sachdev, Reena; Kim, Jinah; Peng, David

    2011-10-01

    Pancreatic panniculitis represents a rare cutaneous disorder most commonly associated with acute or chronic pancreatitis or pancreatic carcinoma. We describe a case of a 17-year-old woman who presented with a 2-day history of erythematous patches involving her bilateral knees and tender, scattered red-brown nodules involving her bilateral anterior shins. She was seen during a hospitalization for emergent cesarean section and her hospital course was complicated by HELLP syndrome (defined by the presence of hemolysis, elevated liver enzymes, low platelet count), acute fatty liver of pregnancy and pancreatitis. The characteristic histopathologic findings, including ghost cells, fat necrosis and granular basophilic material with dystrophic calcification, appear in later lesions. In early lesions, as was shown in this case, a neutrophilic subcutaneous infiltrate raises a differential diagnosis including infection, subcutaneous Sweet's syndrome or atypical erythema nodosum. To our knowledge, this represents the first report of pancreatic panniculitis in association with HELLP syndrome and acute fatty liver of pregnancy. Early recognition is critical, as skin lesions may precede the development of pancreatitis. Often, as in our case, the effects of pancreatitis may be life threatening.

  12. Diabetes and pancreatic cancer.

    PubMed

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

    2014-07-28

    Research suggests a possible link between type 2 diabetes and several malignancies. Animal models have shown that hyperinsulinemic state underlying diabetes promotes tumor formation through stimulation of insulin-IGF-1 pathway; a possible role of inflammation is also proposed. One such link which has been under considerable study for years is that between diabetes and pancreatic cancer. Although epidemiological evidence points towards a reciprocal link between the two, the cause-effect relationship still remains unclear. This link was the subject of a large German epidemiological study presented at the American Society of Clinical Oncology Annual Meeting 2014 (Abstract #1604), which underscored the link between diabetes and some cancers. Schmidt et al. performed a retrospective database analysis over a 12 year period and reported an increased risk of certain types of cancer in diabetic patients. The most significant association (HR 2.17) was found for pancreatic cancer. Given the high mortality of pancreatic cancer, prevention through timely screening could play an important role in improving prognosis. Older subjects with recent-onset diabetes represent a high-risk group and hence are potential targets for pancreatic cancer screening thereby enabling its early diagnosis at a curable stage.

  13. Pancreatic Cancer Stage 4

    MedlinePlus

    ... lung, liver, and peritoneal cavity. An inset shows cancer cells spreading from the pancreas, through the blood and lymph system, to another ... abdomen that contains the intestines, stomach, and liver). Cancer may also have spread to ... pancreas or to lymph nodes. Stage IV pancreatic cancer. ...

  14. What Are the Key Statistics about Pancreatic Cancer?

    MedlinePlus

    ... Cancer Research? Pancreatic Cancer About Pancreatic Cancer Key Statistics for Pancreatic Cancer How common is pancreatic cancer? ... can be affected by certain risk factors . For statistics related to survival, see Pancreatic Cancer Survival Rates ...

  15. Undifferentiated Carcinoma with Osteoclast-Like Giant Cells of the Pancreas in a Patient with New Diagnosis of Follicular Non-Hodgkin's Lymphoma.

    PubMed

    Shah, Apeksha; Khurana, Tanvi; Freid, Lauren; Siddiqui, Ali A

    2014-01-01

    Pancreatic tumors with osteoclast-like giant cells are rare, with only 50 cases published to date. We report a case of a 67-year-old male with a new diagnosis of follicular non-Hodgkin's lymphoma with an incidental pancreatic body mass on abdominal imaging. Cytology from the pancreatic mass obtained via endoscopic ultrasound-directed fine-needle aspiration (EUS-FNA) revealed an undifferentiated carcinoma with osteoclast-like giant cells.

  16. Delayed internal pancreatic fistula with pancreatic pleural effusion postsplenectomy

    PubMed Central

    Jin, Shu-Guang; Chen, Zhe-Yu; Yan, Lu-Nan; Zeng, Yong

    2010-01-01

    The occurrence of pancreatic pleural effusion, secondary to an internal pancreatic fistula, is a rare clinical syndrome and diagnosis is often missed. The key to the diagnosis is a dramatically elevated pleural fluid amylase. This pancreatic pleural effusion is also called a pancreatic pleural fistula. It is characterized by profuse pleural fluid and has a tendency to recur. Here we report a case of delayed internal pancreatic fistula with pancreatic pleural effusion emerging after splenectomy. From the treatment of this case, we conclude that the symptoms and signs of a subphrenic effusion are often obscure; abdominal computed tomography may be required to look for occult, intra-abdominal infection; and active conservative treatment should be carried out in the early period of this complication to reduce the need for endoscopy or surgery. PMID:20845520

  17. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis

    PubMed Central

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

    2016-01-01

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

  18. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis.

    PubMed

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

    2016-03-11

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

  19. Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

    ClinicalTrials.gov

    2016-10-18

    Pancreatic Ductal Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  20. Follicular Pancreatitis: A Distinct Form of Chronic Pancreatitis - An Additional Mimic of Pancreatic Neoplasms

    PubMed Central

    Gupta, Rajib K; Xie, Bill H; Patton, Kurt T; Lisovsky, Mikhail; Burks, Eric; Behrman, Stephen W; Klimstra, David; Deshpande, Vikram

    2016-01-01

    Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis. Immunohistochemistry for Bcl-2, CD21, kappa and lambda light chains as well as IgG4 and IgG were performed. We found a total of six patients (male:female = 2:1, mean age = 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis while two presented with abdominal pain, fatigue and elevated liver enzymes. On imaging, three patients had a discrete solid mass while 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatic portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2 negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis or granulocytic epithelial lesions. IgG4/IgG ratio was <40% in all 6 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers. PMID:26563969

  1. Acute Pancreatitis after Kidney Transplantation

    PubMed Central

    Tabakovic, Mithat; Salkic, Nermin N.; Bosnjic, Jasmina; Alibegovic, Ervin

    2012-01-01

    Acute pancreatitis is a rare but life-threatening complication in patients with transplanted kidney. The incidence of acute pancreatitis after kidney transplantation ranges from 2% to 7%, with mortality rate between 50 and 100%. We report a case of a female patient aged 46 years, developing an interstitial acute pancreatitis 8 years following a renal transplantation. The specific aethiological factor was not clearly established, although possibility of biliary pancreatitis with spontaneous stone elimination and/or medication-induced pancreatitis remains the strongest. Every patient after renal transplantation with an acute onset of abdominal pain should be promptly evaluated for presence of pancreatitis with a careful application of the most appropriate diagnostic procedure for each individual patient. PMID:23259142

  2. Hepatocellular carcinoma

    SciTech Connect

    Nakashima, T.; Kojiro, M.

    1986-01-01

    With the remarkable recent diagnostic and therapeutic advances and the discovery of a possible pathogenetic role of hepatitis B virus, the study and treatment of hepatocellular carcinoma are entering a new era. Parallel developments in the pathological study of this malignancy are also to be expected. To coincide with this new era, this book presents the authors' accumulated pathomorphological knowledge of hepatocellular carcinoma. The detailed coverage is based on the examination findings of 439 cases of hepatocellular carcinoma autopsied at the authors' department in the last twenty years.

  3. Role of the preoperative usefulness of the pathological diagnosis of pancreatic diseases

    PubMed Central

    Matsumoto, Kazuya; Takeda, Yohei; Onoyama, Takumi; Kawata, Soichiro; Kurumi, Hiroki; Ueki, Masaru; Miura, Norimasa; Isomoto, Hajime

    2016-01-01

    Pancreatic cancer is the fifth leading cause of cancer death and has the lowest survival rate of any solid cancer. Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is currently capable of providing a cytopathological diagnosis of pancreatic malignancies with a higher diagnostic power, with a sensitivity and specificity of 85%-89% and 98%-99%, compared to pancreatic juice cytology (PJC), whose sensitivity and specificity are only 33.3%-93% and 83.3%-100%. However, EUS-FNA is not effective in the cases of carcinoma in situ and minimally invasive carcinoma because both are undetectable by endoscopic ultrasonography, although PJC is able to detect them. As for the frequency of complications such as post endoscopic retrograde cholangiopancreatography pancreatitis, EUS-FNA is safer than PJC. To diagnose pancreatic cancer appropriately, it is necessary for us to master both procedures so that we can select the best methods of sampling tissues while considering the patient’s safety and condition. PMID:27672423

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

    PubMed

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

    2015-04-01

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

  5. [Latest advances in acute pancreatitis].

    PubMed

    de-Madaria, Enrique

    2015-09-01

    The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition.

  6. [Exocrine pancreatic insufficiency (author's transl)].

    PubMed

    Götze, H

    1980-12-01

    Exocrine pancreatic insufficiency usually does not develop before reduction of enzyme output by more than 90%. Patients with pancreatic insufficiency have a ravenous appetite but fail to thrive from malnutrition. The caloric deprivation is primarily due to fat malabsorption, recognized by the passage of bulky foul smelling greasy stools. Several isolated enzyme deficiencies can be separated from diseases with generalised pancreatic insufficiency. Under replacement therapy with pancreatic enzyme supplements most patients improve and gain weight, although fat and bile acid malabsorption are not abolished.

  7. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez-Muñoz, J Enrique

    2013-10-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern knowledge of the etiopathogenesis of the disease, the pharmacological treatment of pain, and knowledge of the natural history of autoimmune pancreatitis. New evidence supports the relatively low prevalence of chronic alcoholic pancreatitis, and the role of tobacco in triggering the etiopathogenic mechanisms of chronic pancreatitis is better understood. Some studies have identified certain factors that are associated with having a positive genetic test in adults with chronic idiopathic pancreatitis, which should help to select those patients who should undergo genetic studies. Antioxidant therapy has been shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Finally, the development of exocrine and endocrine pancreatic insufficiency is a very common finding during the long-term follow-up of patients with autoimmune pancreatitis. Smoking also seems to play a role in this type of pancreatitis.

  8. Acute pancreatitis: The stress factor

    PubMed Central

    Binker, Marcelo G; Cosen-Binker, Laura I

    2014-01-01

    Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications. Etiologies of pancreatitis vary, with gallstones accounting for the majority of all cases, followed by alcohol. Other causes of pancreatitis include trauma, ischemia, mechanical obstruction, infections, autoimmune, hereditary, and drugs. The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion, intracellular activation of proteases, and generation of inflammatory mediators. Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells, whose systemic action ultimately determined the severity of the disease. Indeed, severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome, characterized by a progressive physiologic failure of several interdependent organ systems. Stress occurs when homeostasis is threatened, and stressors can include physical or mental forces, or combinations of both. Depending on the timing and duration, stress can result in beneficial or harmful consequences. While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis, the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention. This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis. PMID:24914340

  9. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez-Muñoz, J Enrique

    2014-09-01

    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.

  10. Adrenocortical carcinoma

    MedlinePlus

    ... Adrenocortical carcinoma (ACC) is a cancer of the adrenal glands . The adrenal glands are two triangle-shaped glands. One gland is ... unknown. Symptoms Symptoms of increased cortisol or other adrenal gland hormones may include: Fatty, rounded hump high on ...

  11. Basal Cell Carcinoma

    MedlinePlus

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  12. MicroRNA-1291 targets the FOXA2-AGR2 pathway to suppress pancreatic cancer cell proliferation and tumorigenesis

    PubMed Central

    Qiu, Jing-Xin; Kim, Edward J.; Yu, Ai-Ming

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Better understanding of pancreatic cancer biology may help identify new oncotargets towards more effective therapies. This study investigated the mechanistic actions of microRNA-1291 (miR-1291) in the suppression of pancreatic tumorigenesis. Our data showed that miR-1291 was downregulated in a set of clinical pancreatic carcinoma specimens and human pancreatic cancer cell lines. Restoration of miR-1291 expression inhibited pancreatic cancer cell proliferation, which was associated with cell cycle arrest and enhanced apoptosis. Furthermore, miR-1291 sharply suppressed the tumorigenicity of PANC-1 cells in mouse models. A proteomic profiling study revealed 32 proteins altered over 2-fold in miR-1291-expressing PANC-1 cells that could be assembled into multiple critical pathways for cancer. Among them anterior gradient 2 (AGR2) was reduced to the greatest degree. Through computational and experimental studies we further identified that forkhead box protein A2 (FOXA2), a transcription factor governing AGR2 expression, was a direct target of miR-1291. These results connect miR-1291 to the FOXA2-AGR2 regulatory pathway in the suppression of pancreatic cancer cell proliferation and tumorigenesis, providing new insight into the development of miRNA-based therapy to combat pancreatic cancer. PMID:27322206

  13. Thromboembolism and pancreatic cancer.

    PubMed

    De Souza, Andre Luiz; Saif, Muhammad Wasif

    2014-07-28

    Venous thromboembolism (VTE) is a frequent event in the clinical course of patients with exocrine pancreatic cancer; studies have been designed to evaluate the role of prophylactic anticoagulation in this ominous disease. Searching for the molecular basis of thrombosis in cancer, Bozkurt et al. present in the Abstract #e22049 the result of their investigation on the frequency of inherited and carcinogenesis-acquired proteins in oncologic patients with and without venous thromboembolism. From the bedside, Muñoz Martin et al. present in the Abstract #e15187 their work on the incidence of venous thromboembolism in patients with exocrine pancreatic cancer and the role of the established Khorana score in predicting symptomatic and incidental venous thromboembolism. At last, Cella et al. in the Abstract #e20625 expand the predictor landscape from the Khorana score to other risk factors for venous thromboembolism, refining the selection of oncologic patients who can benefit from prophylactic anticoagulation.

  14. Squamous Cell Carcinoma of the Pancreas in a Patient with Germline BRCA2 Mutation-Response to Neoadjuvant Radiochemotherapy

    PubMed Central

    Schultheis, Anne M.; Nguyen, Gia Phuong; Ortmann, Monika; Kruis, Wolfgang; Büttner, Reinhard; Schildhaus, Hans-Ulrich; Markiefka, Birgid

    2014-01-01

    Primary squamous cell carcinoma of the pancreas is a rare malignant neoplasia, accounting for approximately 0.5–2% of all malignant pancreatic tumors. These lesions are characterized by poor prognosis. Here we report on a case of a 57-year-old female patient with known BRCA2 germline mutation presenting with primary squamous cell carcinoma of the pancreas as the only malignancy. The tumor was locally advanced at the first presentation but responded almost completely to neoadjuvant radio-chemotherapy. Our case highlights the facts (i) that pancreatic carcinomas belong to the tumor spectrum of patients with the BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) and (ii) that tumors of the pancreas can represent the first or even the only manifestation of HBOC. Furthermore, this case of a nonkeratinizing squamous cell carcinoma indicates that HBOC-associated carcinomas of the pancreas might be characterized by a broader morphological spectrum than was previously thought. Since BRCA mutations cause deficiency of DNA double-strand breakage repair in tumors, neoadjuvant treatment regimens might become a reasonable option in HBOC-associated pancreatic carcinomas. To our knowledge, this is the first reported case of a primary pancreatic squamous cell carcinoma in a patient with this particular genetic background of BRCA2-associated HBOC. PMID:24959366

  15. Traumatic pancreatic pseudocysts.

    PubMed

    Popoola, D; Lou, M A; Sims, E H

    1983-05-01

    At the Martin Luther King, Jr, General Hospital in Los Angeles, during the period from June 1972 to April 1981, seven patients underwent surgery for traumatic pancreatic pseudocysts. The overall average age was 28 and the average hospital stay was 31 days. Ultrasound was the most useful test for diagnosis and follow-up. Preoperatively, serum amylases were not consistently elevated. Overall recurrences and complications totaled 57 percent. There were no deaths. The authors consider a large cystogastrostomy the treatment of choice for mature cysts that are satisfactorily adherent to the stomach. The second preference is a Roux-en-Y cystojejunostomy. External drainage was employed for acute cysts that required drainage. A distal pancreatectomy was performed for patients with small pancreatic tail pseudocysts. Patients who underwent acute drainage were usually drained externally and had a poorer outcome than patients who were operated on later with internal drainage. When compared with another group of 15 alcoholic patients who were operated on for pancreatic pseudocysts, patients with traumatic pseudocysts had a poorer outcome.

  16. Resection of Late Pulmonary Metastases from Pancreatic Adenocarcinoma: Is Surgery an Option?

    PubMed

    Brieau, Bertrand; Barret, Maximilien; Rouquette, Alexandre; Dréanic, Johann; Brezault, Catherine; Regnard, Jean François; Coriat, Romain

    2015-01-01

    Patients with recurrences from pancreas adenocarcinoma have a poor survival rate despite new chemotherapy treatment options. Recurrences are mainly hepatic metastases or peritoneal dissemination and surgical treatment is not recommended. Late and single metachronous pulmonary recurrences are uncommon and may mimic primary lung carcinoma. We report two patients with late and unique pulmonary metastasis from pancreatic cancer. These two patients underwent surgical resection; three and five years later, they did not experience recurrences. Cases called for a surgical approach in late and unique pulmonary metastases from pancreatic cancer, and paved the way for a prolonged chemotherapy free period.

  17. Clinicoradiological appraisal of ‘paraduodenal pancreatitis’: Pancreatitis outside the pancreas!

    PubMed Central

    Arora, Ankur; Rajesh, S; Mukund, Amar; Patidar, Yashwant; Thapar, Shalini; Arora, Asit; Bhatia, Vikram

    2015-01-01

    Purpose: Paraduodenal pancreatitis (PP) is a unique form of focal chronic pancreatitis that selectively involves the duodenum and aberrant pancreatic tissue located near the minor papilla (beyond the pancreas proper). The pseudotumoral nature of the disease often generates considerable clinical quandary and patient apprehension, and therefore merits a better understanding. The present study appraises the clinicoradiological manifestations of PP in 33 patients. Materials and Methods: Clinical, laboratory, and radiological manifestations of 33 patients of PP treated in gastroenterology/hepatology and hepato-pancreatico-biliary surgery units during June 2010-August 2014 were retrospectively reviewed. Results: All patients were young to middle-aged men (100%) with history of alcohol abuse (93.9%) and/or smoking (42.4%), who presented either with acute or gradually worsening abdominal pain (90.9%). Pancreatic enzymes and serum tumor markers remained normal or were mildly/transiently elevated. Cystic variant was detected in 57.6% (solid in 42.4%); the disease remained confined to the groove/duodenum (pure form) in 45.4%. Medial duodenal wall thickening with increased enhancement was seen in 87.87 and 81.81%, respectively, and duodenal/paraduodenal cysts were seen in 78.78%. Pancreatic calcifications and biliary stricture were seen 27.3% patients. Peripancreatic arteries were neither infiltrated nor encased. Conclusion: PP has a discrete predilection for middle-aged men with history of longstanding alcohol abuse and/or smoking. Distinguishing imaging findings include thickening of the pancreatic side of duodenum exhibiting increased enhancement with intramural/paraduodenal cysts. This may be accompanied by plate-like scar tissue in the groove region, which may simulate groove pancreatic carcinoma. However, as opposed to carcinoma, the peripancreatic arteries are neither infiltrated nor encased, rather are medially displaced. PMID:26288527

  18. 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

    2014-06-10

    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

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

    ClinicalTrials.gov

    2014-12-29

    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

  20. Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2014-09-22

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer

  1. Trebananib in Treating Patients With Persistent or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-02-10

    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

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

    ClinicalTrials.gov

    2016-10-26

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

  3. Groove Pancreatitis: A Rare form of Chronic Pancreatitis

    PubMed Central

    Jani, Bharivi; Rzouq, Fadi; Saligram, Shreyas; Nawabi, Atta; Nicola, Marian; Dennis, Katie; Ernst, Carly; Abbaszadeh, Ali; Bonino, John; Olyaee, Mojtaba

    2015-01-01

    Context: Groove pancreatitis is a rare form of chronic pancreatitis affecting the “groove” of the pancreas among the pancreatic head, duodenum, and common bile duct. The exact cause is unknown, although there are associations with long-term alcohol abuse, smoking, peptic ulcer disease, heterotopic pancreas, gastric resection, biliary disease, and anatomical or functional obstruction of the minor papilla. The diagnosis can be challenging. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography are the preferred imaging modalities. The treatment of choice is conservative although surgical intervention can sometimes be required. Case Report: A 57-year-old male with a history of human immunodeficiency virus and hepatitis B presented with 4 days of epigastric pain. Abdominal exam revealed absent bowel sounds and epigastric tenderness. He had a creatinine of 1.72 mg/dL, potassium of 2.9 mmol/L, and a normal lipase level of 86 U/L. Liver enzymes and total bilirubin were normal. Computed tomography abdomen showed high-grade obstruction of the second portion of the duodenum without any obvious mass. An esophagogastroduodenoscopy showed a mass at the duodenal bulb causing luminal narrowing, with biopsies negative for malignancy. Magnetic resonance imaging revealed a mass in the region of the pancreatic head and descending duodenum. EUS revealed a 3 cm mass in the region of pancreatic head with irregular borders and no vascular invasion. Fine needle aspiration (FNA) was nondiagnostic. The patient then underwent a Whipple's procedure. Pathology of these specimens was negative for malignancy but was consistent with para-duodenal or groove pancreatitis. Conclusion: The low incidence of groove pancreatitis is partly due to lack of familiarity with the disease. Groove pancreatitis should be considered in the differential for patients presenting with pancreatic head lesions and no cholestatic jaundice, especially when a duodenal obstruction is present, and

  4. Acute pancreatitis in patients with pancreatic cancer

    PubMed Central

    Li, Shaojun; Tian, Bole

    2017-01-01

    Abstract Acute pancreatitis (AP) is a rare manifestation of pancreatic cancer (PC). The relationship between AP and PC remains less distinct. From January 2009 to November 2015, 47consecutive patients with PC who presented with AP were reviewed for this study. Clinical features, clinicopathologic variables, postoperative complications, and follow-up evaluations of patients were documented in detail from our database. In order to identify cutoff threshold time for surgery, receiver operating curve (ROC) was built according to patients with or without postoperative complications. Cumulative rate of survival was calculated by using the Kaplan–Meier method. The study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of West China Hospital. This study included 35 men (74.5%) and 12 women (25.5%) (mean age: 52 years), with a median follow-up of 40 months. AP was clinically mild in 45 (95.7%) and severe in 2 (4.3%). The diagnosis of PC was delayed by 2 to 660 days (median 101 days). Thirty-nine (83.0%) cases underwent surgery. Eight (17.0%) cases performed biopsies only. Of 39 patients, radical surgery was performed in 32 (82.1%) cases and palliative in 7 (19.9%) cases. Two (8.0%) patients were needed for vascular resection and reconstruction. Postoperative complications occurred in 12 (30.8%) patients. About 24.5 days was the best cutoff point, with an area under curve (AUC) of 0.727 (P = 0.025, 95% confidence interval: 0.555–0.8999). The survival rate of patients at 1 year was 23.4%. The median survival in patients with vascular resection and reconstruction was 18 months, compared with 10 months in patients without vascular resection (P = 0.042). For the primary stage (T), Tix was identified in 3 patients, the survival of whom were 5, 28, 50 months, respectively. And 2 of them were still alive at the follow-up period. The severity of AP was mainly mild. Surgical intervention after 24.5 days may benefit for

  5. Acute pancreatitis as a complication of trans-arterial chemoembolization of hepatocellular cancer—case report and review of literature

    PubMed Central

    Brown, Mathew; Agrawal, Sangeeta; Short, Robert F.

    2017-01-01

    Transarterial chemoembolization (TACE) is a therapeutic procedure often performed for hepatocellular carcinoma (HCC). Local complications, though generally uncommon, can arise from arterial ischemia and local cytotoxicity from the chemotherapeutic delivery. We present a case of acute pancreatitis as a rare complication of the TACE procedure along with a review of literature of this uncommon adverse effect. PMID:28280633

  6. Canagliflozin-Associated Acute Pancreatitis.

    PubMed

    Verma, Rajanshu

    2016-01-01

    Canagliflozin is a new drug in class of sodium-glucose cotransporter 2 inhibitors used for treatment of type 2 diabetes mellitus. We describe a patient who developed moderately severe acute pancreatitis as an untoward consequence after being initiated on this drug. To the best of our knowledge, this is the first reported case of canagliflozin-associated acute pancreatitis in clinical literature.

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

    PubMed Central

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

    2012-01-01

    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

  8. Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer

    PubMed Central

    Scaiewicz, V.; Sorin, V.; Fellig, Y.; Birman, T.; Mizrahi, A.; Galula, J.; Abu-lail, R.; Shneider, T.; Ohana, P.; Buscail, L.; Hochberg, A.; Czerniak, A.

    2010-01-01

    Pancreatic cancer is the eighth most common cause of death from cancer in the world, for which palliative treatments are not effective and frequently accompanied by severe side effects. We propose a DNA-based therapy for pancreatic cancer using a nonviral vector, expressing the diphtheria toxin A chain under the control of the H19 gene regulatory sequences. The H19 gene is an oncofetal RNA expressed during embryo development and in several types of cancer. We tested the expression of H19 gene in patients, and found that 65% of human pancreatic tumors analyzed showed moderated to strong expression of the gene. In vitro experiments showed that the vector was effective in reducing Luciferase protein activity on pancreatic carcinoma cell lines. In vivo experiment results revealed tumor growth arrest in different animal models for pancreatic cancer. Differences in tumor size between control and treated groups reached a 75% in the heterotopic model (P = .037) and 50% in the orthotopic model (P = .007). In addition, no visible metastases were found in the treated group of the orthotopic model. These results indicate that the treatment with the vector DTA-H19 might be a viable new therapeutic option for patients with unresectable pancreatic cancer. PMID:21052499

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

    PubMed

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

    2012-01-01

    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.

  10. Moesin-dependent cytoskeleton remodelling is associated with an anaplastic phenotype of pancreatic cancer.

    PubMed

    Abiatari, Ivane; Esposito, Irene; Oliveira, Tiago De; Felix, Klaus; Xin, Hong; Penzel, Roland; Giese, Thomas; Friess, Helmut; Kleeff, Jörg

    2010-05-01

    Cell motility is controlled by the dynamic cytoskeleton and its related proteins, such as members of the ezrin/radixin/moesin (ERM) family, which act as signalling molecules inducing cytoskeleton remodelling. Although ERM proteins have been identified as important factors in various malignancies, functional redundancy between these proteins has hindered the dissection of their individual contribution. The aim of the present study was to analyse the functional role of moesin in pancreatic malignancies. Cancer cells of different malignant lesions of human and transgenic mice pancreata were evaluated by immunohistochemistry. For functional analysis, cell growth, adhesion and invasion assays were carried out after transient and stable knock-down of moesin expression in pancreatic cancer cells. In vivo tumourigenicity was determined using orthotopic and metastatic mouse tumour models. We now show that moesin knock-down increases migration, invasion and metastasis and influences extracellular matrix organization of pancreatic cancer. Moesin-regulated migratory activities of pancreatic cancer cells were in part promoted through cellular translocation of beta-catenin, and re-distribution and organization of the cytoskeleton. Analysis of human and different transgenic mouse pancreatic cancers demonstrated that moesin is a phenotypic marker for anaplastic carcinoma, suggesting that this ERM protein plays a specific role in pancreatic carcinogenesis.

  11. PERIOD1 is an anti-apoptotic factor in human pancreatic and hepatic cancer cells.

    PubMed

    Sato, Fuyuki; Nagata, Chihiro; Liu, Yang; Suzuki, Takahiro; Kondo, Jun; Morohashi, Satoko; Imaizumi, Tadaatsu; Kato, Yukio; Kijima, Hiroshi

    2009-12-01

    PERIOD1 (PER1) is a clock gene. We examined the effect of knockdown of PER1 on apoptosis in pancreatic cancer (MIA PaCa-2 and PANC-1) and hepatocellular carcinoma (HepG2) cells. Transfection of siRNA against PER1 into these cells increased the cleaved forms of caspases and poly-ADP-ribose-polymerase and induced apoptosis in all three cell lines. In the two pancreatic cancer cell lines, PER1 knockdown resulted in upregulation of Bax and downregulation of Bcl-2. Expression of p53 was not altered in the two pancreatic cancer cell lines containing mutated p53, but was upregulated in the HepG2 cells containing wild-type p53. Cell proliferation of MIA PaCa-2 and HepG2 was inhibited by PER1 knockdown. We also examined, by immunohistochemical staining, the expression of PER1 in pancreatic cancer tissue and found that PER1 was strongly expressed in pancreatic cancer cells. These results indicate that PER1 acts as an anti-apoptotic factor in pancreatic cancer cells.

  12. Cystic dystrophy of the duodenal wall is not always associated with chronic pancreatitis

    PubMed Central

    Pezzilli, Raffaele; Santini, Donatella; Calculli, Lucia; Casadei, Riccardo; Morselli-Labate, Antonio Maria; Imbrogno, Andrea; Fabbri, Dario; Taffurelli, Giovanni; Ricci, Claudio; Corinaldesi, Roberto

    2011-01-01

    Cystic dystrophy of the duodenal wall is a rare form of the disease which was described in 1970 by French authors who reported the presence of focal pancreatic disease localized in an area comprising the C-loop of the duodenum and the head of the pancreas. German authors have defined this area as a “groove”. We report our recent experience on cystic dystrophy of the paraduodenal space and systematically review the data in the literature regarding the alterations of this space. A MEDLINE search of papers published between 1966 and 2010 was carried out and 59 papers were considered for the present study; there were 19 cohort studies and 40 case reports. The majority of patients having groove pancreatitis were middle aged. Mean age was significantly higher in patients having groove carcinoma. The diagnosis of cystic dystrophy of the duodenal wall can now be assessed by multidetector computer tomography, magnetic resonance imaging and endoscopic ultrasonography. These latter two techniques may also add more information on the involvement of the remaining pancreatic gland not involved by the duodenal malformation and they may help in differentiating “groove pancreatitis” from “groove adenocarcinoma”. In conclusion, chronic pancreatitis involving the entire pancreatic gland was present in half of the patients with cystic dystrophy of the duodenal wall and, in the majority of them, the pancreatitis had calcifications. PMID:22110260

  13. Somatostatin therapy of acute experimental pancreatitis.

    PubMed Central

    Lankisch, P G; Koop, H; Winckler, K; Fölsch, U R; Creutzfeldt, W

    1977-01-01

    Because somatostatin (SRIF) reduces exocrine pancreatic secretion, its effect on acute pancreatitis was investigated in rats. Linear SRIF reduced serum amylase and lipase but had no effect on pancreatic necrosis, oedema, leucocyte infiltration, and enzyme content. The mortality rate was not reduced. These results do not recommend the use of SRIF in the treatment of acute pancreatitis. PMID:604191

  14. [Therapeutic attitude in acute necrotizing pancreatitis].

    PubMed

    Leşe, Mihaela; Pop, C; Naghi, Ildiko; Mureşan, Lavinia

    2002-01-01

    The necrosectomy, celiostomy and pancreatic drainage represent the surgical treatment of choice in necrotizing pancreatitis. We present the clinical observation of a patient 59 years old operated in surgical service of Baia Mare for acute necrotizing pancreatitis, discussing the moment of operation, tips of operations, postoperative complications as well as our experience in acute grave pancreatitis treatment.

  15. Proteomics studies of pancreatic cancer

    PubMed Central

    Chen, Ru; Pan, Sheng; Aebersold, Ruedi; Brentnall, Teresa A.

    2008-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States, with 4% survival 5 years after diagnosis. Biomarkers are desperately needed to improve earlier, more curable cancer diagnosis and to develop new effective therapeutic targets. The development of quantitative proteomics technologies in recent years offers great promise for understanding the complex molecular events of tumorigenesis at the protein level, and has stimulated great interest in applying the technology for pancreatic cancer studies. Proteomic studies of pancreatic tissues, juice, serum/plasma, and cell lines have recently attempted to identify differentially expressed proteins in pancreatic cancer to dissect the abnormal signaling pathways underlying oncogenesis, and to detect new biomarkers. It can be expected that the continuing evolution of proteomics technology with better resolution and sensitivity will greatly enhance our capability in combating pancreatic cancer. PMID:18633454

  16. Autoimmune pancreatitis: a surgical dilemma.

    PubMed

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

    2014-12-01

    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.

  17. [Surgical management of chronic pancreatitis].

    PubMed

    Regimbeau, Jean-Marc; Dumont, Frédéric; Yzet, Thierry; Chatelain, Denis; Bartoli, Eacute Ric; Brazier, Franck; Bréhant, Olivier; Dupas, Jean-Louis; Mauvais, François; Delcenserie, Richard

    2007-01-01

    Surgical indications for chronic pancreatitis can be schematically separated into five main groups: pain, effects of fibrosis on adjacent organs, the consequences of main pancreatic duct rupture above an obstruction, and suspected cancer. Finally surgery is also indicated in patients who cannot undergo endoscopic procedures (no accessible papilla) or who have too recently undergone this procedure. Surgical procedures include derivation (pancreatic, cystic, biliary) or mixed procedures combining derivation/resection or pancreatic resection. Finally splanchnicectomy can be discussed. Whatever the indication, surgical treatment must meet several goals: the approach to surgery must be multidisciplinary, surgery must be associated with low morbidity and mortality, preserve as much endocrine function as possible, improve quality of life, and be evaluated in the long term, as well as prospectively if possible. We clarify some important points about the management of patients with chronic pancreatitis before discussing the various treatments in detail.

  18. [Diabetes mellitus in acute pancreatitis].

    PubMed

    Díaz-Rubio, José Luis; Torre-Delgadillo, Aldo; Robles-Díaz, Guillermo

    2002-01-01

    Exocrine and endocrine components of pancreas are interrelated anatomically and functionally. Exocrine pancreatic dysfunction often accompanies endocrine pancreatic impairment and vice versa. Diabetes mellitus resulting from alterations of exocrine pancreas, such as acute or chronic pancreatitis, is known as pancreatic diabetes. Hyperglycemia during acute pancreatitis (AP) can be due to abnormalities in insulin secretion, increase in counterregulatory hormones release, or decrease in glucose utilization by peripheral tissues. Causal association is suggested between diabetic ketoacidosis and AP and is attributed to alternation in metabolism of triglycerides. High blood glucose levels are associated with severe AP and constitute factor of worst prognosis. Some patients are discharged with diabetes after AP episode, while others develop diabetes during first year of follow-up. Origin and frequency of glycemic abnormalities associated with AP have not been settled yet accurately. Also, predictive factors for diabetes development and persistence after AP have not been recognized to date.

  19. Blood tests for acute pancreatitis

    PubMed Central

    Basnayake, Chamara; Ratnam, Dilip

    2015-01-01

    Summary The diagnosis of acute pancreatitis requires the presence of at least two of the three diagnostic criteria – characteristic abdominal pain, elevated serum amylase or lipase, and radiological evidence of pancreatitis. Serum concentrations of amylase and lipase rise within hours of the pancreatic injury. A threshold concentration 2–4 times the upper limit of normal is recommended for diagnosis. Serum lipase is now the preferred test due to its improved sensitivity, particularly in alcohol-induced pancreatitis. Its prolonged elevation creates a wider diagnostic window than amylase. Neither enzyme is useful in monitoring or predicting the severity of an episode of pancreatitis in adults. New biomarkers including trypsinogen and elastase have no significant advantage over amylase or lipase. PMID:26648641

  20. New developments in pancreatic cancer.

    PubMed

    Greer, Julia B; Brand, Randall E

    2011-04-01

    Pancreatic adenocarcinoma presents in an advanced stage and has a dismal prognosis. Extensive recent research efforts have provided us with greater insight into the etiology of pancreatic cancer and have also improved our means of prognostication. Molecular analysis demonstrated that specific pathways involved in pancreatic carcinogenesis are perhaps more valuable to study than single genetic aberrations. Previous risk factors, including family history, body mass index, and current cigarette smoking, were validated and novel risks, such as ABO blood group alleles, were identified. Similar to other illnesses, combinations of healthful habits, such as not smoking, adhering to a Mediterranean dietary pattern, and engaging in physical activity, may decrease pancreatic cancer risk. Finally, CA 19-9 levels, the presence of diabetes mellitus, and a six-gene signature provided critical information regarding survival that could help guide treatment of individuals diagnosed with pancreatic adenocarcinoma.

  1. Alcohol consumption on pancreatic diseases.

    PubMed

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

    2013-02-07

    Although the association between alcohol and pancreatic diseases has been recognized for a long time, the impact of alcohol consumption on pancreatitis and pancreatic cancer (PC) remains poorly defined. Nowadays there is not consensus about the epidemiology and the beverage type, dose and duration of alcohol consumption causing these diseases. The objective of this study was to review the epidemiology described in the literature for pancreatic diseases as a consequence of alcoholic behavior trying to understand the association between dose, type and frequency of alcohol consumption and risk of pancreatitis and PC. The majority of the studies conclude that high alcohol intake was associated with a higher risk of pancreatitis (around 2.5%-3% between heavy drinkers and 1.3% between non drinkers). About 70% of pancreatitis are due to chronic heavy alcohol consumption. Although this incidence rate differs between countries, it is clear that the risk of developing pancreatitis increases with increasing doses of alcohol and the average of alcohol consumption vary since 80 to 150 g/d for 10-15 years. With regard to PC, the role of alcohol consumption remains less clear, and low to moderate alcohol consumption do not appear to be associated with PC risk, and only chronic heavy drinking increase the risk compared with lightly drinkers. In a population of 10%-15% of heavy drinkers, 2%-5% of all PC cases could be attributed to alcohol consumption. However, as only a minority (less than 10% for pancreatitis and 5% for PC) of heavily drinkers develops these pancreatic diseases, there are other predisposing factors besides alcohol involved. Genetic variability and environmental exposures such as smoking and diet modify the risk and should be considered for further investigations.

  2. The clinical significance of pancreatic steatosis.

    PubMed

    Smits, Mark M; van Geenen, Erwin J M

    2011-03-01

    More research is now focused on pancreatic steatosis. Multiple definitions, clinical associations and synonyms for pancreatic steatosis are described in the literature and can be confusing. The integration and comparison of several studies concerning this topic is therefore challenging. In the past, pancreatic steatosis was considered an innocuous condition, a bystander of many underlying diseases (such as congenital syndromes, hemochromatosis and viral infection). However, evidence that pancreatic steatosis (strongly associated with obesity and the metabolic syndrome) has a role in type 2 diabetes mellitus, pancreatic exocrine dysfunction, acute pancreatitis, pancreatic cancer and the formation of pancreatic fistula after pancreatic surgery is emerging. This Review focuses on the different etiological factors and the clinical consequences of pancreatic steatosis.

  3. Hereditary pancreatic cancer: a clinical perspective.

    PubMed

    Greer, Julia B; Lynch, Henry T; Brand, Randall E

    2009-01-01

    Pancreatic cancer is an extraordinarily deadly disease and is responsible for over 220,000 deaths worldwide each year. One of the greatest risk factors for developing pancreatic cancer is a positive family history. Hereditary pancreatitis patients have a greatly elevated pancreatic cancer risk and individuals with cystic fibrosis may rarely develop this cancer, but often at very young ages. Various genetically linked cancer syndromes have been associated with pancreatic cancer in mutation-positive family members. Finally, familial pancreatic cancer-defined as families with two or more first-degree relatives who have pancreatic cancer but do not have a known cancer syndrome-is a known entity whose disease-causing mutation remains unidentified. This article describes research to date on hereditary pancreatic cancer, addresses how best clinicians should recognise hereditary forms of pancreatic cancer and explains the emotional burden of discovering a potentially lethal mutation. Many controversies and unanswered questions in hereditary pancreatic cancer remain.

  4. High risk of acute pancreatitis after endoscopic ultrasound-guided fine needle aspiration of side branch intraductal papillary mucinous neoplasms

    PubMed Central

    Siddiqui, Ali A.; Shahid, Haroon; Shah, Apeksha; Khurana, Tanvi; Huntington, William; Ghumman, Saad S.; Loren, David E.; Kowalski, Thomas E.; Laique, Sobia; Hayat, Umar; Eloubeidi, Mohamad A.

    2015-01-01

    Background and Objectives: Data on the risk of acute pancreatitis following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cystic lesions are limited. The aim of our study was to evaluate the frequency of acute pancreatitis after EUS-FNA of pancreatic cysts and solid lesions, and determine whether there was a difference in pancreatitis risk in patients with side branch intraductal papillary mucinous neoplasms (SB-IPMN). Patients and Methods: A retrospective review of patients who underwent EUS-FNA of pancreatic cysts and solid lesions was performed. The primary outcome measure was development of acute pancreatitis after EUS-FNA. Factors associated with acute pancreatitis were examined by statistical analysis to determine independent predictors of acute pancreatitis. Statistical significance was determined at a P ≤ 0.05. Results: We identified 186 patients with pancreatic cystic lesions and 557 with solid lesions in which EUS-FNA was performed. The median size of the cysts was 19 mm (range: 10-66 mm). There were 37 IPMNs, 33 mucinous cystic neoplasms, 58 serous cysts and 46 pseudocysts and 12 solid-cystic ductal carcinomas. The majority of patients (75%) with solid lesions were diagnosed with adenocarcinoma. Patients with pancreatic cysts had a statistically greater frequency of developing pancreatitis after EUS-FNA when compared to those with solid lesions (2.6% vs. 0.36% respectively; P = 0.13). In patients with cysts, there were no statistically significant differences between the two groups (with and without pancreatitis) with regard to a cyst location, size of the cyst, and number of needle passes or trainee involvement. Patients with SB-IPMN had a statistically higher frequency of pancreatitis after EUS-FNA compared to those with other cyst types (8% vs. 1.3% respectively; odds ratio = 6.4, 95% confidence intervals = 1.0-40.3, P = 0.05). Discussion: Patients with SB-IPMN are at a higher risk of developing acute pancreatitis after

  5. Minimally invasive treatment of infected pancreatic necrosis

    PubMed Central

    Cebulski, Włodzimierz; Słodkowski, Maciej; Krasnodębski, Ireneusz W.

    2014-01-01

    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. PMID:25653725

  6. Venous complications of pancreatitis: a review.

    PubMed

    Aswani, Yashant; Hira, Priya

    2015-01-31

    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.

  7. [Ultrasonography of pancreatic neoplasms].

    PubMed

    Innocenti, P; Falchini, M; Stecco, A

    1999-01-01

    Pancreatic tumors are the fourth cause of death in Occident: the 5-year-survival rate is less than 5% because of diagnostic difficulties, low clinical expression at early stage, and complexity of the surgical treatment. The role of ultrasound (US) is in early diagnosis, because also in early cancer there could be lymphatic spread or peritoneal involvement. There are multiple modalities to study the pancreas with US: abdominal US, "contact" US (endosonography and intra-operative or laparoscopic US). The first is not invasive, cheap but limited by extrinsic and intrinsic factors, the latter are respectively characterized by high cost, and need of endoscopic specialists for endosonography, the complementarity to laparoscopy or surgery for the laparoscopic/intraoperative US. Abdominal US is the first diagnostic step for the pancreas, but it is not affordable in 15-25% of patients, because of meteorism. In all the other cases, it represents the pancreas with a good contrast between the normal parenchyma and tumoral tissues. Abdominal US, together with biopsy, can define the resectability. Ecoendoscopy is actually dedicated to small tumors staging, but recent studies demonstrate the same results achieved by spiral TC. Laparoscopic US is a second step imaging in patients already selected for surgery. The first finality in US evaluation of tumor masses is early diagnosis of pancreatic cancer; it can give to some of these patients the opportunity of undergoing to surgical treatment. This could be achieved by a proper use of the moititude of ultrasonic abdominal explorations that are requested in daily practice. US, together with CT and MR, can define the resectability of the tumor, with further supplementar evaluation by mean of laparoscopic US. Intraoperative US is now indicated for planning and guiding the surgeon in resection of the pancreatic cancer.

  8. Screening for Pancreatic Cancer.

    PubMed

    Ngamruengphong, Saowanee; Canto, Marcia Irene

    2016-12-01

    Pancreatic cancer (PC) is a highly fatal disease that can only be cured by complete surgical resection. However, most patients with PC have unresectable disease at the time of diagnosis, highlighting the need to detect PC and its precursor lesions earlier in asymptomatic patients. Screening is not cost-effective for population-based screening of PC. Individuals with genetic risk factors for PC based on family history or known PC-associated genetic syndromes, however, can be a potential target for PC screening programs. This article provides an overview of the epidemiology and genetic background of familial PC and discusses diagnostic and management approaches.

  9. Segmental pancreatic autotransplantation for chronic pancreatitis. A preliminary report

    SciTech Connect

    Rossi, R.L.; Braasch, J.W.; O'Bryan, E.M.; Watkins, E. Jr.

    1983-03-01

    A patient who underwent 95% pancreatectomy with autotransplantation of the body and tail of the gland to the femoral area for chronic pancreatitis is presented. The pain resolved, and the patient's blood glucose level remained within normal limits. High levels of insulin were found in the iliac vein on the transplanted side. Patency of the graft was demonstrated by technetium scan and arteriography and followed by a color-coded Doppler imaging system. Segmental pancreatic autotransplantation offers a method of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis.

  10. [Anatomy of the pancreatic nerve plexuses and significance of their dissection].

    PubMed

    Kimura, Wataru; Watanabe, Toshihiro

    2011-05-01

    Although various therapeutic modalities for carcinoma of the pancreas are available, curative resection is the most important. Thus, the aim of surgery for carcinoma of the pancreas is local complete resection of the carcinoma. All of the important pancreaticoduodenal arcades of arteries, veins, and nerves are situated on the fusion fascia of Treits. The pancreatic parenchyma, extrapancreatic nerve plexuses, superior mesenteric artery (SMA), and portal vein are also covered within the fusion fascia and exist in the same area. Carcinoma of the head of the pancreas invades through the pancreatic parenchyma, following the arteries, veins, and especially nerves between the parenchyma and fusion fascia, and then spreads horizontally toward the SMA or celiac axis. The entire dissected end of the nerve plexus should be investigated during surgery using frozen specimens and confirmed to be negative for cancer. If the dissected end is positive for cancer, additional resection of the nerve plexus should be performed to achieve curative resection. It is not possible to investigate thoroughly whether the dissected end of the nerve plexus is positive or negative for carcinoma after surgery, since the end may be long and some specimens may be deformed by formalin fixation; thus it is difficult to identify the true surgically dissected end. The pancreaticoduodenal artery arises from the left side of the SMA and divides into two arteries: jejunal artery 1; and the inferior pancreaticoduodenal artery (IPDA), which runs behind and transversely to the right of both the anterior and posterior IPDA. A common origin of the anterior and posterior IPDA is found in 80% of cases. The postoperative course of patients with pancreatic head carcinoma with invasion of the perineural plexuses immediately behind the SMA is not as good as in that of patients without cancerous invasion, even if additional resection is performed so that the dissected end is confirmed to be negative during surgery

  11. Current and Future Trends in Early Detection of Pancreatic Cancer: Molecular Targets and PET Probes.

    PubMed

    Alauddin, Mian M; De Palatis, Louis

    2015-01-01

    Early detection of pancreatic cancer has been a long-standing challenge in determining prognosis and management of the deadly disease. Although the incidence of pancreatic cancer is low (2% of all malignancies), it is the fourth leading cause of deaths attributable to cancer in the U.S. A major cause for the high mortality rate, which exceeds 85%, is the difficulty in diagnosing the disease early in its development. The relative lack of reliable diagnostic tools to screen patients who are asymptomatic prior to the aggressive progression of disease has been the primary contributing factor in the high mortality rate in this patient population. Indeed, 80-90% of patients with pancreatic cancer have relatively small unresectable tumors at the time of diagnosis. Therefore, there is an unmet need for a highly sensitive diagnostic imaging modality to detect early-stage pancreatic cancer, as this may save the lives of many thousands of patients. Many literature reviews have been published on various aspects of pancreatic cancer, including biology, screening, and therapy; however, limited information is available on early detection, especially the use of highly sensitive modalities such as positron emission tomography (PET). Current [(18)F]FDG/PET imaging combined with CT (PET/CT) lacks the necessary sensitivity and specificity for detection of small lesions (~2-3 mm) of pancreatic cancer that may be resectable and curable. Furthermore, accumulation of [(18)F]FDG in inflammatory tissue is a major problem; therefore, an appropriate PET tracer that is both highly sensitive and specific for carcinoma is necessary for PET imaging of early stage pancreatic cancer. This review focuses on early detection of pancreatic cancer by PET, including new targets and the development and application of new PET tracers.

  12. Preclinical validation of AXL receptor as a target for antibody-based pancreatic cancer immunotherapy

    PubMed Central

    Leconet, Wilhem; Larbouret, Christel; Chardès, Thierry; Thomas, Gaëlle; Neiveyans, Madeline; Busson, Muriel; Jarlier, Marta; Radosevic-Robin, Nina; Pugnière, Martine; Bernex, Florence; Penault-Llorca, Frédérique; Pasquet, Jean-Max; Pèlegrin, André; Robert, Bruno

    2014-01-01

    AXL receptor tyrosine kinases is implicated in proliferation and invasion of many cancers, particularly in pancreatic ductal adenocarcinoma (PDAC), for which new therapeutic options are urgently required. We investigated whether inhibition of AXL activity by specific monoclonal antibodies (mAbs) is efficient in limiting proliferation and migration of pancreatic cancer cells. Expression of AXL was evaluated by immunohistochemistry in 42 PDAC. The AXL role in oncogenesis was studied using the short hairpin RNA approach in a pancreatic carcinoma cell line. We further generated anti-human AXL mAbs and evaluated their inhibitory effects and the AXL downstream signaling pathways first in vitro, in a panel of pancreatic cancer cell lines and then in vivo, using subcutaneous or orthotopic pancreatic tumor xenografts. AXL receptor was found expressed in 76% (32/42) of PDAC and was predominantly present in invasive cells. The AXL-knockdown Panc-1 cells decreased in vitro cell migration, survival and proliferation, and reduced in vivo tumor growth. Two selected anti-AXL mAbs (D9 and E8), which inhibited phosphorylation of AXL and of its downstream target AKT without affecting GAS6 binding, induced down-expression of AXL by internalization, leading to an inhibition of proliferation and migration in the four pancreatic cancer cell lines studied. In vivo, treatment by anti-AXL mAbs significantly reduced growth of both subcutaneous and orthotopic pancreatic tumor xenografts independently of their KRAS mutation status. Our in vitro and preclinical in vivo data demonstrate that anti-human AXL mAbs could represent a new approach to the pancreatic cancer immunotherapy. PMID:24240689

  13. Role of 18F-FDG PET/CT in the management of a case of autoimmune pancreatitis with extrapancreatic manifestations.

    PubMed

    Santhosh, Sampath; Bhattacharya, Anish; Harisankar, Chidambaram Natarajan Balasubramanian; Kochhar, Rakesh; Mittal, Bhagwant Rai

    2013-11-01

    Autoimmune pancreatitis and pancreatic cancer share many clinical features like advanced age, painless jaundice, weight loss, and elevated serum levels of CA 19-9. The authors report a 58-year-old male patient provisionally diagnosed with periampullary carcinoma on the basis of ultrasonography and serological markers and planned for Whipple resection. (18)F-FDG PET/CT findings were suggestive of autoimmune pancreatitis, subsequently confirmed on cytological diagnosis. The follow-up PET/CT scan after 1 week of steroid therapy showed regression of FDG uptake in most of the lesions with appearance of salivary gland uptake.

  14. EBV-associated lymphoepithelioma-like carcinoma of the pancreas: Case report with targeted sequencing analysis.

    PubMed

    Samdani, Rashmi T; Hechtman, Jaclyn F; O'Reilly, Eileen; DeMatteo, Ronald; Sigel, Carlie S

    2015-01-01

    Lymphoepithelioma-like carcinomas are distinctive epithelial derived malignant neoplasms that have a syncytial growth pattern and lymphoid stroma. The majority of tumors with this appearance are Epstein Barr virus (EBV)-associated. We report a patient with a clinical presentation concerning for lymphoma who was diagnosed with an EBV-associated pancreatic carcinoma with a lymphoepithelioma-like pattern. Targeted sequencing analysis showed a molecular profile distinct from conventional ductal adenocarcinoma of the pancreas.

  15. Redox signaling in acute pancreatitis

    PubMed Central

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-01-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551

  16. Redox signaling in acute pancreatitis.

    PubMed

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-08-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF-VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  17. [Pancreatic cancer in a patient with congenital agenesis of the dorsal pancreas].

    PubMed

    Oki, Yusuke; Onoyama, Hirohiko; Nikaido, Mitsuhiro; Iinuma, Shoji; Endo, Koji; Tomita, Yumi; Mizuno, Katsuhiko; Yasui, Hiroshi

    2013-06-01

    A 65-year-old man with back pain showed a hypovascular lesion of the head of the pancreas on dynamic computed tomography and abdominal ultrasonography. The distal portion of the pancreas was not visible. Endoscopic retrograde cholangiopancreatography revealed pancreatic duct obstruction, and the duodenal minor papilla was not visible. Therefore, we diagnosed the patient's condition as stage IVa pancreatic cancer with congenital agenesis of the dorsal pancreas. The patient underwent successful chemotherapy with 3 courses of gemcitabine and S-1, which was followed by pancreaticoduodenectomy. Pathological staging revealed invasive ductal carcinoma, pT3, pN0, pM0, stage III. We report a rare case of pancreatic cancer with congenital agenesis of the dorsal pancreas.

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

    PubMed

    Leffler, J; Dvorák, J

    1998-08-01

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

  19. Necrotizing pancreatitis: challenges and solutions

    PubMed Central

    Bendersky, Victoria A; Mallipeddi, Mohan K; Perez, Alexander; Pappas, Theodore N

    2016-01-01

    Acute pancreatitis is a common disease that can progress to gland necrosis, which imposes significant risk of morbidity and mortality. In general, the treatment for pancreatitis is a supportive therapy. However, there are several reasons to escalate to surgery or another intervention. This review discusses the pathophysiology as well as medical and interventional management of necrotizing pancreatitis. Current evidence suggests that patients are best served by delaying interventions for at least 4 weeks, draining as a first resort, and debriding recalcitrant tissue using minimally invasive techniques to promote or enhance postoperative recovery while reducing wound-related complications. PMID:27826206

  20. Recent Progress in Pancreatic Cancer

    PubMed Central

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

    2013-01-01

    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

  1. Pancreatic infection with Candida parapsilosis.

    PubMed

    Ibáñez, R; Serrano-Heranz, R

    1999-01-01

    Candida species other than C. albicans have been implicated as pathogens in intravascular (bloodstream, intravascular devices, endocarditis) and extravascular (arthritis, osteomielitis, endophtalmitis) infections. C. parapsilosis, however, is rarely implicated in intra-abdominal infections (peritonitis during peritoneal dialysis, complicating surgery or solid-organ transplantation). We describe a case of a 48-y-old male with acute pancreatitis who had a pancreatic abscess produced by primary C. parapsilosis infection. Although he received adequate treatment with antifungal medication and surgical drainage, the outcome was fatal. Because the clinical findings are indistinguishable from bacterial abscesses, Candida species should be considered in cases of complicated pancreatitis, in order to establish a prompt adequate treatment.

  2. Leptomeningeal carcinomatosis as primary manifestation of pancreatic cancer.

    PubMed

    Trinh, Victoria T; Medina-Flores, Rafael; Chohan, Muhammad O

    2016-08-01

    Leptomeningeal carcinomatosis (LMC) is a rare complication of cancer that often presents at an advanced stage after obvious metastasis of a primary cancer or locally advanced disease. We present an uncommon case of LMC secondary to pancreatic carcinoma presenting with headache, unilateral VII nerve palsy, and lower extremity weakness. Initial cerebrospinal fluid (CSF) studies were concerning for chronic aseptic meningitis but negative for malignant cells; the diagnosis of tuberculous meningitis was erroneously evoked. Three lumbar punctures were required to capture malignant cells. The diagnosis of LMC was based on CSF examination with cytology/immunohistochemistry and leptomeningeal enhancement on MRI. Post mortem autopsy revealed advanced and diffusely metastatic pancreatic adenocarcinoma. This patient demonstrates that solid tumors can present with leptomeningeal spread that often confuses the treating physician. Fungal or tuberculous meningitis can mimic LMC in the absence of neoplastic signs and negative CSF cytology. This event is exceedingly rare in pancreatic cancer. If the index of suspicion is high, repeat CSF sampling can increase the sensitivity of detection of malignant cells and thus result in the correct diagnosis.

  3. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

    PubMed Central

    Gilliland, Taylor M.; Villafane-Ferriol, Nicole; Shah, Kevin P.; Shah, Rohan M.; Tran Cao, Hop S.; Massarweh, Nader N.; Silberfein, Eric J.; Choi, Eugene A.; Hsu, Cary; McElhany, Amy L.; Barakat, Omar; Fisher, William; Van Buren, George

    2017-01-01

    Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3) enteral nutrition (EN) should be preferred as a nutritional intervention over total parenteral nutrition (TPN) postoperatively; and, (4) a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate

  4. Magnetic resonance imaging of pancreatitis: An update

    PubMed Central

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

    2014-01-01

    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

  5. Radio sensitizing effect of aloe polysaccharide on pancreatic cancer bxpc-3 cells.

    PubMed

    Xu, Chunjin; Xu, Feng

    2016-07-01

    The roles of autophagy in pancreatic cancers are complex and may differ depending on tumor type or context. This study aimed to investigate if aloe polysaccharide can be used as a radio-sensitizing chemical to induce autophagy in pancreatic cancer cells. Pancreatic carcinoma BxPC-3 cells were divided into four groups: A control group, an aloe polysaccharide only group, a radiation only group and a radiation combined with aloe polysaccharide group (combination group). Transmission electron microscopy was used to observe ultra structural changes of autophagosomes in each cell group. The mRNA expressions of ULK1, GABARAPL1, BECN1, and BCL-2 were detected by real-time PCR. Autophagosomes or autophagolysosomes were observed in all experimental groups except the control group. Compared with the control group, ULK1 mRNA expression was up-regulated and BECN1 and BCL-2 mRNA expression were down-regulated in all groups (P<0.05); changes in expression were most obvious in the combination group (P<0.05). GABARAPL1 mRNA expression was up-regulated in the combination group (P<0.05), but had no significant changes among other groups. In brief, aloe polysaccharide induces autophagy in pancreatic carcinoma BxPC-3 cells both alone and in concert with radiation. Autophagic cell death may be one of the mechanisms producing a radiosensitizing effect.

  6. Simultaneous occurrence of autoimmune pancreatitis and pancreatic cancer in patients resected for focal pancreatic mass

    PubMed Central

    Macinga, Peter; Pulkertova, Adela; Bajer, Lukas; Maluskova, Jana; Oliverius, Martin; Smejkal, Martin; Heczkova, Maria; Spicak, Julius; Hucl, Tomas

    2017-01-01

    AIM To assess the occurrence of autoimmune pancreatitis (AIP) in pancreatic resections performed for focal pancreatic enlargement. METHODS We performed a retrospective analysis of medical records of all patients who underwent pancreatic resection for a focal pancreatic enlargement at our tertiary center from January 2000 to July 2013. The indication for surgery was suspicion of a tumor based on clinical presentation, imaging findings and laboratory evaluations. The diagnosis of AIP was based on histology findings. An experienced pathologist specialized in pancreatic disease reviewed all the cases and confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The histological diagnosis of AIP was set according to the international consensus diagnostic criteria. RESULTS Two hundred ninety-five pancreatic resections were performed in 201 men and 94 women. AIP was diagnosed in 15 patients (5.1%, 12 men and 3 women) based on histology of the resected specimen. Six of them had AIP type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma (PC) was also present in six patients with AIP (40%), all six were men. Patients with AIP + PC were significantly older (60.5 vs 49 years of age, P = 0.045), more likely to have been recently diagnosed with diabetes (67% vs 11%, P = 0.09), and had experienced greater weight loss (15.5 kg vs 8.5 kg, P = 0.03) than AIP patients without PC. AIP was not diagnosed in any patients prior to surgery; however, the diagnostic algorithm was not fully completed in every case. CONCLUSION The possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP does not rule out simultaneous presence of PC.

  7. Pancreatic stellate cell: Pandora's box for pancreatic disease biology

    PubMed Central

    Bynigeri, Ratnakar R; Jakkampudi, Aparna; Jangala, Ramaiah; Subramanyam, Chivukula; Sasikala, Mitnala; Rao, G Venkat; Reddy, D Nageshwar; Talukdar, Rupjyoti

    2017-01-01

    Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin. PSCs maintain their activated phenotype via an autocrine loop involving different cytokines and contribute to progressive fibrosis in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). Several pathways (e.g., JAK-STAT, Smad, Wnt signaling, Hedgehog etc.), transcription factors and miRNAs have been implicated in the inflammatory and profibrogenic function of PSCs. The role of PSCs goes much beyond fibrosis/desmoplasia in PDAC. It is now shown that PSCs are involved in significant crosstalk between the pancreatic cancer cells and the cancer stroma. These interactions result in tumour progression, metastasis, tumour hypoxia, immune evasion and drug resistance. This is the rationale for therapeutic preclinical and clinical trials that have targeted PSCs and the cancer stroma. PMID:28210075

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

    ClinicalTrials.gov

    2014-10-07

    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

  9. 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.

  10. Evaluating steatosis in pancreatic transplant.

    PubMed

    Verma, Aneesha Ratan; Papalois, Vassilios

    2011-06-01

    Pancreatic transplant remains the only treatment that cures insulin-dependent diabetes mellitus. It is recognized by transplant surgeons that donor pancreases with excessive fat infiltration have a poorer clinical outcome, resulting in significant recipient morbidity and mortality. However, no objective measure of pancreatic fat infiltration exists, and no study has been done that correlates the level of fat infiltration with clinical outcome. There have been significant radiologic advances that allow assessment of fat content of organs, and these could be used to accurately quantify the extent of pancreatic fat infiltration. We reviewed the literature regarding pancreatic steatosis, and examined ways in which the level of steatosis could be objectively measured before transplant, thereby improving clinical outcome.

  11. Chronic pancreatitis and cystic fibrosis

    PubMed Central

    Witt, H

    2003-01-01

    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

  12. Listeria Vaccines for Pancreatic Cancer

    DTIC Science & Technology

    2013-10-01

    AD_________________ Award Number: W81XWH-12-1-0411 TITLE: Listeria vaccines for pancreatic cancer...29September2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Listeria vaccines for pancreatic cancer 5b. GRANT NUMBER W81XWH-12-1-0411 5c...explored the capacity of Listeria vaccines to induce anti-tumor T cell immunity in the KPC model. We have found that Listeria vaccines produce

  13. Pancreatic cancer, inflammation, and microbiome.

    PubMed

    Zambirinis, Constantinos P; Pushalkar, Smruti; Saxena, Deepak; Miller, George

    2014-01-01

    Pancreatic cancer is one of the most lethal cancers worldwide. No effective screening methods exist, and available treatment modalities do not effectively treat the disease. Inflammatory conditions such as pancreatitis represent a well-known risk factor for pancreatic cancer development. Yet only in the past 2 decades has pancreatic cancer been recognized as an inflammation-driven cancer, and the precise mechanisms underlying the pathogenic role of inflammation are beginning to be explored in detail. A substantial amount of preclinical and clinical evidence suggests that bacteria are likely to influence this process by activating immune receptors and perpetuating cancer-associated inflammation. The recent explosion of investigations of the human microbiome have highlighted how perturbations of commensal bacterial populations can promote inflammation and promote disease processes, including carcinogenesis. The elucidation of the interplay between inflammation and microbiome in the context of pancreatic carcinogenesis will provide novel targets for intervention to prevent and treat pancreatic cancer more efficiently. Further studies toward this direction are urgently needed.

  14. Pancreatic cancer chemoradiotherapy.

    PubMed

    Brunner, Thomas B; Seufferlein, Thomas

    2016-08-01

    Pancreatic cancer is the most lethal gastrointestinal tumour. Chemotherapy is the mainstay of therapy in the majority of the patients whereas resection is the only chance of cure but only possible in 15-20% of all patients. The integration of radiotherapy into multimodal treatment concepts is heavily investigated. It is now commonly accepted that induction chemotherapy should precede radiotherapy. When fractionated conventionally it should be given as chemoradiotherapy. Recently, stereotactic body radiotherapy emerged as an alternative, but will have to be carefully investigated in clinical trials. This review aims to give an overview of radiotherapeutic strategies with a focus on the latest developments in the field in the context of chemotherapy and surgery.

  15. Pancreatic cancer stem cells.

    PubMed

    Zhu, Ya-Yun; Yuan, Zhou

    2015-01-01

    Studies are emerging in support of the cancer stem cells (CSCs) theory which considers that a tiny subset of cancer cells is exclusively responsible for the initiation and malignant behavior of a cancer. This cell population, also termed CSCs, possesses the capacity both to self-renew, producing progeny that have the identical tumorigenic potential, and to differentiate into the bulk of cancer cells, helping serve the formation of the tumor entities, which, altogether, build the hierarchically organized structure of a cancer. In this review, we try to articulate the complicated signaling pathways regulating the retention of the characteristics of pancreatic CSCs, and in the wake of which, we seek to offer insights into the CSCs-relevant targeted therapeutics which are, in the meantime, confronted with bigger challenges than ever.

  16. Ampullary carcinoma in a patient with agenesis of the dorsal pancreas: a case report.

    PubMed

    Mistry, Jitendra H; Yadav, Amitabh; Nundy, Samiran

    2015-04-01

    The most common congenital anomaly of the pancreas is pancreatic divisum (Tadokoro et al. in Anat Res Int 2011:1-7, 2011). Agenesis of the dorsal pancreas is extremely rare (Schnedl et al. in World J Gastroenterol 15(3):376-377, 2009). We are reporting a case of agenesis of dorsal pancreas presented with ampullary carcinoma.

  17. Nasopharyngeal carcinoma

    SciTech Connect

    Ho, J.H.C.

    1985-07-01

    In this editorial comment, the author presents a review of recent achievements in the diagnosis and treatment of squamous cell carcinoma of the nasopharynx. The value of the use of CT scans for differentiating between cranial nerve involvement by recurring tumors and irradiation neuropathy, and between temporal lobe irradiation encephalopathy and other nonneoplastic neurologic disorders and meningeal metastasis is discussed. Magnetic resonance imaging is said to be superior to CT for finding soft tissue involvement or abnormalities in the brain. 13 references.

  18. Adrenocortical Carcinoma

    PubMed Central

    Kim, Alex C.; Sabolch, Aaron; Raymond, Victoria M.; Kandathil, Asha; Caoili, Elaine M.; Jolly, Shruti; Miller, Barbra S.; Giordano, Thomas J.

    2014-01-01

    Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, often with an unfavorable prognosis. Here we summarize the knowledge about diagnosis, epidemiology, pathophysiology, and therapy of ACC. Over recent years, multidisciplinary clinics have formed and the first international treatment trials have been conducted. This review focuses on evidence gained from recent basic science and clinical research and provides perspectives from the experience of a large multidisciplinary clinic dedicated to the care of patients with ACC. PMID:24423978

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

    PubMed Central

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

    2012-01-01

    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 H2O2 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

  20. Oral bacteria in pancreatic cancer: mutagenesis of the p53 tumour suppressor gene.

    PubMed

    Öğrendik, Mesut

    2015-01-01

    Carcinoma of exocrine pancreas is the fourth leading cause of cancer deaths, worldwide. The prevalence of this disease is very high in patients with chronic pancreatitis. Orodigestive cancers are frequently seen in patients with periodontitis. These findings suggest that this type of cancer may have some bacterial origins. This study hypothesizes that the peptidyl arginine deaminase (PAD) enzymes found in oral bacteria may be responsible for the p53 point mutations that occur in patients with pancreatic cancer. Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Treponema denticola possess the PAD enzyme, and p53 arginine mutations have been detected in patients with pancreatic cancer. Moreover, the Pro allele p53Arg72-Pro is a risk factor for the development of this cancer. Anti-P. gingivalis antibody titers have been found to be higher in patients with pancreatic cancer as compared to healthy controls. The hypothesis in question can be tested if the DNA of P. gingivalis or the antibodies against P. gingivalis can be detected in patients with the p53 arginine mutation.If this hypothesis is true, it could reveal the real cause of pancreatic cancer, which is a fatal disease. Further studies are necessary in order to confirm this hypothesis.

  1. PKC delta and tissue transglutaminase are novel inhibitors of autophagy in pancreatic cancer cells.

    PubMed

    Ozpolat, Bulent; Akar, Ugur; Mehta, Kapil; Lopez-Berestein, Gabriel

    2007-01-01

    Apoptosis (type I) and autophagy (type II) are both highly regulated forms of programmed cell death and play crucial roles in physiological processes such as the development, homeostasis and selective, moderate to massive elimination of cells, if needed. Accumulating evidence suggests that cancer cells, including pancreatic cancer cells, in general tend to have reduced autophagy relative to their normal counterparts and premalignant lesions, supporting the contention that defective autophagy provides resistance to metabolic stress such as hypoxia, acidity and chemotherapeutics, promotes tumor cell survival and plays a role in the process of tumorigenesis. However, the mechanisms underlying the reduced capability of undergoing autophagy in pancreatic cancer remain elusive. In a recent study, we demonstrated a novel mechanism for regulation of autophagy in pancreatic ductal carcinoma cells. We found that protein kinase C-delta (PKC delta) constitutively suppresses autophagy through induction of tissue transglutaminase (TG2). Inhibition of PKC delta/TG2 signaling resulted in significant autophagic cell death that was mediated by Beclin 1. Elevated expression of TG2 in pancreatic cancer cells has been implicated in the development of drug resistance, metastatic phenotype and poor patient prognosis. In conclusion, our data suggest a novel role of PKC delta/TG2 in regulation of autophagy, and that TG2 may serve as an excellent therapeutic target in pancreatic cancer cells.

  2. [Cystic dystrophy of aberrant pancreatic tissue in the duodenal wall. Diagnostic and therapeutic problems].

    PubMed

    Visset, J; Jais, F; Le Bodic, M F; Letessier, E; Hamy, A; Courant, O; Paineau, J

    1992-01-01

    The authors report the case of a 28-year-old man with a cystic dystrophy of aberrant pancreatic tissue (C.D.A.P.T.) presenting with a history of major abdominal pain. First diagnosis was chronic pancreatitis because of clinical presentation, alcoholic intoxication, and the results of medical imaging techniques. A vagotomy associated with a gastroenterostomy was performed. Several years later the abdominal pain relapsed and failed to be cure by means of medical treatment. A duodenopancreatectomy was performed. Histology demonstrated the diagnosis of C.D.A.P.T. C.D.A.P.T. is a benign disease of the pancreas, limited to its cephalic portion, without demonstrated pathogenesis. C.D.A.P.T. can be either isolated or associated with a chronic pancreatitis. Clinical diagnosis can be particularly difficult as indicated by a literature review. Abdominal pain is the main symptom. Clinical presentation is rarely related to a complication (stenosis). Endoscopy, sonogram, and CAT scan are three techniques of diagnosis value, but intraluminal-sonography is more efficient. Tumor excision is not recommendable. Treatment of C.D.A.P.T. by duodeno-pancreatectomy (D.P.) is often indicated because of concurrent chronic pancreatitis or suspected pancreatic carcinoma. In case of clinical diagnosis of C.D.A.P.T., fenestration of the cysts under endoscopic control is the only local treatment that can avoid D.P.

  3. Comparison of subtypes of penile squamous cell carcinoma from high and low incidence geographical regions.

    PubMed

    Chaux, Alcides; Lezcano, Cecilia; Cubilla, Antonio L; Tamboli, Pheroze; Ro, Jae; Ayala, Alberto

    2010-08-01

    There is a worldwide geographical variation in the incidence of penile squamous cell carcinoma (PSCC); some subtypes are HPV-related (warty, basaloid) while others (keratinizing variants) are not. The aims of this study were to compare the distribution of different histological subtypes of PSCC from regions of low (Paraguay, 144 cases) and high (USA, 157 cases) incidence and to identify and compare tumors with and without warty and/or basaloid morphology. The distribution of subtypes in the Paraguayan and the American series was: usual, 49.3 and 46.5%; verrucous, 8.3 and 7.6%; papillary NOS, 7.6 and 5.7%; warty, 6.9 and 8.3%; basaloid, 4.2 and 7.0%; sarcomatoid, 0.7 and 0.6%; adenosquamous, 3.5 and 0.6%; and mixed, 19.4 and 23.6%, respectively. The distribution of mixed PSCC was: warty-basaloid, 50.0 and 59.5%; usual-verrucous, 21.4 and 21.6%; usual-warty, 14.3 and 8.1%; usual-basaloid, 7.1 and 0.0%; usual-papillary, 3.6 and 5.4%; and others, 3.6 and 5.4%, respectively. In conclusion, we found no geographical difference in the incidence of histological subtypes (p = 0.6501), mixed PSCC (p = 0.5937) or HPV-related tumors (p = 0.2505). Geographical variation may be the result of staging variation at clinical presentation or of pathological diagnosis. The identification of similar histological subtypes in both series validates this classification approach for penile cancer. The tendency for typical SCC to mix with verrucous and papillary carcinomas and of the basaloid to preferentially mix with benign condyloma and condylomatous (warty) carcinomas would support the hypothesis of the existence of an etiologically different dual population of penile tumors.

  4. [A Case of Unresectable Advanced Rectal Cancer with a Pancreatic Tumor That Was Successfully Treated with FOLFIRINOX].

    PubMed

    Yabe, Nobushige; Murai, Shinji; Ozawa, Hiroki; Yokose, Takahiro; Oto, Ippei; Yoshikawa, Takahisa; Kitasato, Kenjiro; Shimizu, Hirotomo; Kojima, Kenji; Hasegawa, Hirotoshi; Kitagawa, Yuko

    2016-11-01

    A 72-year-old man was admitted to our hospital department in September 2014 because of a positive fecal occult blood test.Colonoscopy showed a type 2 tumor in half of the AV 15 cm rectosigmoid colon.Histology of the biopsy indicated a moderately differentiated adenocarcinoma, and the RAS gene test found wild type.On CT examination, there were multiple liver lung metastases and a 30mm diameter tumor with pancreatic duct extension to the pancreatic body.A PET-CT examination had a high SUVmax at the same site.Because of the location of the tumor EUS-FNA was not used.However, the possibility of pancreatic body cancer could not be denied after the CT examination.Treatment by radical resection was impossible because of the spread of the cancer so we selected chemotherapy.Undeniable pancreatic metastasis of rectal cancer, pancreatic cancer was used as a prognostic factor as double cancer of rectal cancer and pancreatic cancer, from that UGT1A1 test side effects appearance was a low-risk decision, was selected FOLFIRINOX in the treatment regimen.After 25 cycles, the pancreatic body tumor and liver metastases and also the primary tumor were reduced, the multiple lung metastases disappeared, and disease control was good.Side effects were diarrhea on the day of administration of irinotecan, but this was controllable by administering oral loperamide when starting the infusion.Grade 3 or more peripheral neuropathy has not developed, and this regimen is continuing.Pancreatic cancer is a solid cancer with a poor prognosis; if you do not reach the tissue diagnosis of metastatic pancreatic cancer, was a case in which no choice but to select a regimen to carcinoma of the prognostic.

  5. Disconnected pancreatic duct syndrome: complete pancreas transection secondary to acute pancreatitis.

    PubMed

    Gámez-del-Castillo, Juan Manuel; Garcés-Albir, Marina; Fernández-Moreno, María Carmen; Morera-Ocón, Francisco Javier; Villagrasa, Rosana; Sabater-Ortí, Luis

    2016-03-01

    Disconnected pancreatic duct syndrome is a serious complication of acute pancreatitis which is defined by a complete discontinuity of the pancreatic duct, such that a viable side of the pancreas remains isolated from the gastrointestinal tract. This pancreatic disruption is infrequently observed in the clinical practice and its diagnostic and therapeutic management are controversial. We present an extreme case of disconnected pancreatic duct syndrome with complete duct disruption and pancreatic transection following acute pancreatitis, as well as the diagnostic and therapeutic processes carried out.

  6. Overexpression of GalNAc-transferase GalNAc-T3 Promotes Pancreatic Cancer Cell Growth

    PubMed Central

    Taniuchi, Keisuke; Cerny, Ronald L.; Tanouchi, Aki; Kohno, Kimitoshi; Kotani, Norihiro; Honke, Koichi; Saibara, Toshiji; Hollingsworth, Michael A.

    2011-01-01

    O-linked glycans of secreted and membrane bound proteins play an important role in the pathogenesis of pancreatic cancer by modulating immune responses, inflammation, and tumorigenesis. A critical aspect of O-glycosylation, the position at which proteins are glycosylated with N-acetyl-galactosamine on serine and threonine residues, is regulated by the substrate specificity of UDP-GalNAc: polypeptide N-acetylgalactosaminyl-transferases (GalNAc-Ts). Thus, GalNAc-Ts regulate the first committed step in O-glycosylated protein biosynthesis, determine sites of O-glycosylation on proteins, and are important for understanding normal and carcinoma-associated O-glycosylation. We have found that one of these enzymes, GalNAc-T3, is overexpressed in human pancreatic cancer tissues, and suppression of GalNAc-T3 significantly attenuates growth of pancreatic cancer cells in vitro and in vivo. In addition, suppression of GalNAc-T3 induces apoptosis of pancreatic cancer cells. Our results indicate that GalNAc-T3 is likely to be involved in pancreatic carcinogenesis. Modification of cellular glycosylation occurs in nearly all types of cancer as a result of alterations in the expression levels of glycosyltransferases. We report guanine nucleotide binding protein, alpha transducing activity polypeptide 1 (GNAT1) as a possible substrate protein of GalNAc-T3. GalNAc-T3 is associated with O-glycosylation of GNAT1, and affects the subcellular distribution of GNAT1. Knocking down endogenous GNAT1 significantly suppresses the growth/survival of PDAC cells. Our results imply that GalNAc-T3 contributes to the function of O-glycosylated proteins and thereby affects the growth and survival of pancreatic cancer cells. Thus, substrate proteins of GalNAc-T3 should serve as important therapeutic targets for pancreatic cancers. PMID:21625220

  7. Overexpression of GalNAc-transferase GalNAc-T3 promotes pancreatic cancer cell growth.

    PubMed

    Taniuchi, K; Cerny, R L; Tanouchi, A; Kohno, K; Kotani, N; Honke, K; Saibara, T; Hollingsworth, M A

    2011-12-08

    O-linked glycans of secreted and membrane-bound proteins have an important role in the pathogenesis of pancreatic cancer by modulating immune responses, inflammation and tumorigenesis. A critical aspect of O-glycosylation, the position at which proteins are glycosylated with N-acetyl-galactosamine on serine and threonine residues, is regulated by the substrate specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferases (GalNAc-Ts). Thus, GalNAc-Ts regulate the first committed step in O-glycosylated protein biosynthesis, determine sites of O-glycosylation on proteins and are important for understanding normal and carcinoma-associated O-glycosylation. We have found that one of these enzymes, GalNAc-T3, is overexpressed in human pancreatic cancer tissues and suppression of GalNAc-T3 significantly attenuates the growth of pancreatic cancer cells in vitro and in vivo. In addition, suppression of GalNAc-T3 induces apoptosis of pancreatic cancer cells. Our results indicate that GalNAc-T3 is likely involved in pancreatic carcinogenesis. Modification of cellular glycosylation occurs in nearly all types of cancer as a result of alterations in the expression levels of glycosyltransferases. We report guanine the nucleotide-binding protein, α-transducing activity polypeptide-1 (GNAT1) as a possible substrate protein of GalNAc-T3. GalNAc-T3 is associated with O-glycosylation of GNAT1 and affects the subcellular distribution of GNAT1. Knocking down endogenous GNAT1 significantly suppresses the growth/survival of PDAC cells. Our results imply that GalNAc-T3 contributes to the function of O-glycosylated proteins and thereby affects the growth and survival of pancreatic cancer cells. Thus, substrate proteins of GalNAc-T3 should serve as important therapeutic targets for pancreatic cancers.

  8. Targeting EGFR in bilio-pancreatic and liver carcinoma.

    PubMed

    Fratto, Maria Elisabetta; Santini, Daniele; Vincenzi, Bruno; Silvestris, Nicola; Azzariti, Amalia; Tommasi, Stefania; Zoccoli, Alice; Galluzzo, Sara; Maiello, Evaristo; Colucci, Giuseppe; Tonini, Giuseppe

    2011-01-01

    The key role of epidermal growth factor receptor(EGFR) in tumorigenesis has been demonstrated in several cancer types, so recent clinical trials have investigated their activity/efficacy in different settings. Two different types of EGFR-targeted agents were developed: monoclonal antibodies such as cetuximab and panitumumab, and tyrosine kinase inhibitors, such as gefitinib and erlotinib. In this review, we summarize the preclinical rational of potential activity and the most important clinical trials evaluated anti-EGFR targeted agents in non-colorectal digestive cancer, both in monotherapy and in combination with other chemotherapeutic or targeted agents. Patient selection by use of biologic markers will identify which patients are more likely to respond, contributing to the successful use of these agents.

  9. Lipolysis of Visceral Adipocyte Triglyceride by Pancreatic Lipases Converts Mild Acute Pancreatitis to Severe Pancreatitis Independent of Necrosis and Inflammation

    PubMed Central

    Patel, Krutika; Trivedi, Ram N.; Durgampudi, Chandra; Noel, Pawan; Cline, Rachel A.; DeLany, James P.; Navina, Sarah; Singh, Vijay P.

    2016-01-01

    Visceral fat necrosis has been associated with severe acute pancreatitis (SAP) for over 100 years; however, its pathogenesis and role in SAP outcomes are poorly understood. Based on recent work suggesting that pancreatic fat lipolysis plays an important role in SAP, we evaluated the role of pancreatic lipases in SAP-associated visceral fat necrosis, the inflammatory response, local injury, and outcomes of acute pancreatitis (AP). For this, cerulein pancreatitis was induced in lean and obese mice, alone or with the lipase inhibitor orlistat and parameters of AP induction (serum amylase and lipase), fat necrosis, pancreatic necrosis, and multisystem organ failure, and inflammatory response were assessed. Pancreatic lipases were measured in fat necrosis and were overexpressed in 3T3-L1 cells. We noted obesity to convert mild cerulein AP to SAP with greater cytokines, unsaturated fatty acids (UFAs), and multisystem organ failure, and 100% mortality without affecting AP induction or pancreatic necrosis. Increased pancreatic lipase amounts and activity were noted in the extensive visceral fat necrosis of dying obese mice. Lipase inhibition reduced fat necrosis, UFAs, organ failure, and mortality but not the parameters of AP induction. Pancreatic lipase expression increased lipolysis in 3T3-L1 cells. We conclude that UFAs generated via lipolysis of visceral fat by pancreatic lipases convert mild AP to SAP independent of pancreatic necrosis and the inflammatory response. PMID:25579844

  10. Acute and chronic pancreatitis: surgical management.

    PubMed

    Dzakovic, Alexander; Superina, Riccardo

    2012-08-01

    Pancreatitis is becoming increasingly prevalent in children, posing new challenges to pediatric health care providers. Although some general adult treatment paradigms are applicable in the pediatric population, diagnostic workup and surgical management of acute and chronic pancreatitis have to be tailored to anatomic and pathophysiological entities peculiar to children. Nonbiliary causes of acute pancreatitis in children are generally managed nonoperatively with hydration, close biochemical and clinical observation, and early initiation of enteral feeds. Surgical intervention including cholecystectomy or endoscopic retrograde cholangiopancreatography is often required in acute biliary pancreatitis, whereas infected pancreatic necrosis remains a rare absolute indication for pancreatic debridement and drainage via open, laparoscopic, or interventional radiologic procedure. Chronic pancreatitis is characterized by painful irreversible changes of the parenchyma and ducts, which may result in or be caused by inadequate ductal drainage. A variety of surgical procedures providing drainage, denervation, resection, or a combination thereof are well established to relieve pain and preserve pancreatic function.

  11. Ampullary carcinoma developing after androgenic steroid therapy for aplastic anemia: Report of a case.

    PubMed

    Fujino, Y; Ku, Y; Suzuki, Y; Ajiki, T; Hasegawa, Y; Kuroda, Y

    2001-04-01

    Sex steroids influence the development and course of human genital carcinomas including breast, testis, prostata, and ovarian cancers. (1) Other carcinomas such as hepatoma, cholangioma, and pancreatic cancer have also been reported to be related to sex hormones. (2-4) The existence of sex hormone receptors has been demonstrated immunohistochemically in specimens of these diseases. We recently encountered a patient in whom an ampullary carcinoma developed 39 months after the start of androgenic steroid therapy for aplastic anemia. Immunohistochemic analysis of resected tumor specimens of the patient suggested a possible hormonal effect on the tumor oncology.

  12. Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-07-01

    Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Bladder Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Transitional Cell Carcinoma of the Bladder; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  13. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  14. Blunt pancreatic trauma: A persistent diagnostic conundrum?

    PubMed Central

    Kumar, Atin; Panda, Ananya; Gamanagatti, Shivanand

    2016-01-01

    Blunt pancreatic trauma is an uncommon injury but has high morbidity and mortality. In modern era of trauma care, pancreatic trauma remains a persistent challenge to radiologists and surgeons alike. Early detection of pancreatic trauma is essential to prevent subsequent complications. However early pancreatic injury is often subtle on computed tomography (CT) and can be missed unless specifically looked for. Signs of pancreatic injury on CT include laceration, transection, bulky pancreas, heterogeneous enhancement, peripancreatic fluid and signs of pancreatitis. Pan-creatic ductal injury is a vital decision-making parameter as ductal injury is an indication for laparotomy. While lacerations involving more than half of pancreatic parenchyma are suggestive of ductal injury on CT, ductal injuries can be directly assessed on magnetic resonance imaging (MRI) or encoscopic retrograde cholangio-pancreatography. Pancreatic trauma also shows temporal evolution with increase in extent of injury with time. Hence early CT scans may underestimate the extent of injures and sequential imaging with CT or MRI is important in pancreatic trauma. Sequential imaging is also needed for successful non-operative management of pancreatic injury. Accurate early detection on initial CT and adopting a multimodality and sequential imaging strategy can improve outcome in pancreatic trauma. PMID:26981225

  15. Recurrent pancreatitis in ornithine transcarbamylase deficiency.

    PubMed

    Prada, Carlos E; Kaul, Ajay; Hopkin, Robert J; Page, Kimberley I; Nathan, Jaimie D; Bartholomew, Dennis W; Cohen, Mitchell B; Heubi, James E; Leslie, Nancy D; Burrow, T Andrew

    2012-08-01

    Ornithine transcarbamylase (OTC) deficiency is a urea cycle defect with varying frequency and severity of episodes of hyperammonemia. We report three patients with OTC deficiency with recurrent pancreatitis. The pathogenesis of acute pancreatitis in this patient population requires further elucidation. Pancreatitis significantly affected dietary/metabolic management and increased frequency of hospitalizations.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Management of acute pancreatitis (AP) – Polish Pancreatic Club recommendations

    PubMed Central

    Rosołowski, Mariusz; Lipiński, Michał; Dobosz, Marek; Durlik, Marek; Głuszek, Stanisław; Kuśnierz, Katarzyna; Lampe, Paweł; Małecka-Panas, Ewa; Nowakowska-Duława, Ewa; Nowak-Niezgoda, Magdalena; Radomańska, Barbara; Talar-Wojnarowska, Renata; Wereszczyńska-Siemiątkowska, Urszula

    2016-01-01

    The presented recommendations concern the current management of acute pancreatitis. The recommendations relate to the diagnostics and treatment of early and late phases of acute pancreatitis and complications of the disease taking into consideration surgical and endoscopic methods. All the recommendations were subjected to voting by the members of the Working Group of the Polish Pancreatic Club, who evaluated them every single time on a five-point scale, where A means full acceptance, B means acceptance with a certain reservation, C means acceptance with a serious reservation, D means rejection with a certain reservation and E means full rejection. The results of the vote, together with commentary, are provided for each recommendation. PMID:27350832

  19. The Pancreatic Islet Regulome Browser

    PubMed Central

    Mularoni, Loris; Ramos-Rodríguez, Mireia; Pasquali, Lorenzo

    2017-01-01

    The pancreatic islet is a highly specialized tissue embedded in the exocrine pancreas whose primary function is that of controlling glucose homeostasis. Thus, understanding the transcriptional control of islet-cell may help to puzzle out the pathogenesis of glucose metabolism disorders. Integrative computational analyses of transcriptomic and epigenomic data allows predicting genomic coordinates of putative regulatory elements across the genome and, decipher tissue-specific functions of the non-coding genome. We herein present the Islet Regulome Browser, a tool that allows fast access and exploration of pancreatic islet epigenomic and transcriptomic data produced by different labs worldwide. The Islet Regulome Browser is now accessible on the internet or may be installed locally. It allows uploading custom tracks as well as providing interactive access to a wealth of information including Genome-Wide Association Studies (GWAS) variants, different classes of regulatory elements, together with enhancer clusters, stretch-enhancers and transcription factor binding sites in pancreatic progenitors and adult human pancreatic islets. Integration and visualization of such data may allow a deeper understanding of the regulatory networks driving tissue-specific transcription and guide the identification of regulatory variants. We believe that such tool will facilitate the access to pancreatic islet public genomic datasets providing a major boost to functional genomics studies in glucose metabolism related traits including diabetes. PMID:28261261

  20. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer.

    PubMed

    Du, Juan; Cieslak, John A; Welsh, Jessemae L; Sibenaller, Zita A; Allen, Bryan G; Wagner, Brett A; Kalen, Amanda L; Doskey, Claire M; Strother, Robert K; Button, Anna M; Mott, Sarah L; Smith, Brian; Tsai, Susan; Mezhir, James; Goswami, Prabhat C; Spitz, Douglas R; Buettner, Garry R; Cullen, Joseph J

    2015-08-15

    The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer.

  1. PCMdb: Pancreatic Cancer Methylation Database

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

    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.

  2. Cystic Lesions in Autoimmune Pancreatitis.

    PubMed

    Gompertz, Macarena; Morales, Claudia; Aldana, Hernán; Castillo, Jaime; Berger, Zoltán

    2015-01-01

    Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases.

  3. Coordinate expression of cytokeratins 7 and 20 in feline and canine carcinomas.

    PubMed

    Espinosa de los Monteros, A; Fernández, A; Millán, M Y; Rodríguez, F; Herráez, P; Martín de las Mulas, J

    1999-05-01

    Forty-seven feline and 60 canine epithelial tumors were studied to test the coordinate expression of cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) using commercially available monoclonal antibodies and an avidin-biotin immunoperoxidase staining technique. Previously, the distribution of both cytokeratins was examined in normal tissues from 4 cats and 4 dogs. The pattern of distribution of CK 7 in normal tissues was similar, with minor differences, to that described in humans, whereas the reactivity pattern of CK 20 in cats and dogs was wider than that in humans. The subset of tumors strongly expressing CK 7 and CK 20 included pancreatic adenocarcinomas (100%), transitional cell carcinomas (75%), and endometrial carcinomas (67%) in the cat. None of the canine tumors had this immunophenotype. Feline (50%) and canine (56%) mammary gland carcinomas and canine cholangiocarcinomas (67%) were the only tumors presenting the CK 7 +/CK 20- immunophenotype, whereas the CK 7-/CK 20+ immunophenotype included thyroid carcinomas (100%), intestinal adenocarcinomas (60%), bronchioloalveolar carcinomas (50%), and renal carcinomas (50%) in the cat and intestinal adenocarcinomas (56%), gastric adenocarcinomas (50%), and ovarian carcinomas (50%) in the dog. The CK 7-/CK 20- immunophenotype included the rest of the analyzed tumors. The immunohistochemical evaluation of coordinate expression of both CK 7 and CK 20 in feline and canine carcinomas using monoclonal antibodies provides important information that can help to discriminate among carcinomas from different primary sites and could be particularly helpful in the determination of the primary site of origin of carcinomas presenting as metastatic disease.

  4. Carcinoma gallbladder.

    PubMed

    Biswas, P K

    2010-07-01

    Carcinoma gallbladder (CaGb) is a rare disease. The aetiology of CaGb is yet not known. However the risk of CaGb is increased in anomalous pancreaticobiliary duct junction (APBDJ), gall stones, xanthogranulomatus cholecystitis, calcified or porcelain gallbladder, cholelithiasis with typhoid carriers, gallbladder adenoma, red meat consumption and tobacco uses. There are protective effects of vegetables on CaGb. Most of the cases present with advanced disease. In early carcinoma of a gallbladder sign and symptoms mimic benign disease. The diagnosis is established by ultrasonography, computerized tomography and guided fine needle aspiration cytology (FNAC). Biochemical tests are of very little value in making a diagnosis. The treatment depends on the clinical stage at presentation. Surgery offers the best chance of cure. In stage T1a, laparoscopic or open cholecystectomy alone is curative, and in T1b, cholecystectomy with hepatoduodenal lymph node dissection without combined resection of an adjacent organ is required. Segment S4a+5 hepatectomy combined with extrahepatic bile duct resection (BDR) and D2 lymph node dissection is a highly recommended operation for the treatment of T2 and T3 CaGb. The dye injection method is useful in determining the appropriate extent of hepatic resection for advanced CaGb. Resurgery is required only in those cases where tumour has invaded the serosa and/ or adjacent structures when diagnosed postoperatively. Biliary bypass is required for palliation. Prognosis depends on early diagnosis and appropriate surgical excision.

  5. Fluid resuscitation in acute pancreatitis

    PubMed Central

    Aggarwal, Aakash; Manrai, Manish; Kochhar, Rakesh

    2014-01-01

    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

  6. Ascariasis of the pancreatic duct.

    PubMed

    Klimovskij, Michail; Dulskas, Audrius; Kraulyte, Zita; Mikalauskas, Saulius

    2015-09-15

    Ascariasis is a common helminthic disease worldwide, although Lithuania and other European countries are not considered endemic areas. The presence of the Ascaris worm in the biliary tree causes choledocholithiasis-like symptoms. We report a case of pancreatic duct ascariasis causing such symptoms. A 73-year-old Lithuanian woman underwent endoscopic retrograde cholangiopancreatography (ERCP) suspecting choledocholithiasis. Contrast injection into the common bile duct demonstrated a slightly dilated biliary tree without any filling defects, and the tail of an Ascaris worm protruding from the opening of the papilla Vater. The worm was captured by a snare but escaped deep into the duct. After a small wirsungotomy the worm was retrieved from the pancreatic duct. The patient received a 150 mg dose of levamisole orally repeated 7 days later and was discharged after complete resolution of symptoms. This first reported sporadic case of pancreatic duct ascariasis in Lithuania was successfully treated with ERCP and Levamisole.

  7. Endoscopic Palliation of Pancreatic Cancer

    PubMed Central

    Coté, Gregory A.; Sherman, Stuart

    2012-01-01

    Endoscopy has an increasingly important role in the palliation of patients with pancreatic ductal adenocarcinoma. Endoscopic biliary drainage is still requested in the majority of patients who present with obstructive jaundice, and the increased use of self-expandable metallic stents has reduced the incidence of premature stent occlusion. First-line use of metallic stents is expected to be utilized more frequently as neoadjuvant protocols are improved. The efficacy of endoscopy for palliating gastroduodenal obstruction has advanced with the development of through-the-scope, self-expandable gastroduodenal stents. There have been advances in pain management, with endoscopic ultrasound-guided celiac plexus neurolysis reducing opiate requirements and pain for patients with unresectable malignancy. Future applications of endoscopy in pancreatic cancer may include fine needle injection of chemotherapeutic and other agents into the lesion itself. This review will summarize the evidence of endoscopy in the management of patients with pancreatic cancer. PMID:23187846

  8. Percutaneous ablation of pancreatic cancer

    PubMed Central

    D’Onofrio, Mirko; Ciaravino, Valentina; De Robertis, Riccardo; Barbi, Emilio; Salvia, Roberto; Girelli, Roberto; Paiella, Salvatore; Gasparini, Camilla; Cardobi, Nicolò; Bassi, Claudio

    2016-01-01

    Pancreatic ductal adenocarcinoma is a highly aggressive tumor with an overall 5-year survival rate of less than 5%. Prognosis and treatment depend on whether the tumor is resectable or not, which mostly depends on how quickly the diagnosis is made. Chemotherapy and radiotherapy can be both used in cases of non-resectable pancreatic cancer. In cases of pancreatic neoplasm that is locally advanced, non-resectable, but non-metastatic, it is possible to apply percutaneous treatments that are able to induce tumor cytoreduction. The aim of this article will be to describe the multiple currently available treatment techniques (radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation), their results, and their possible complications, with the aid of a literature review. PMID:27956791

  9. Percutaneous ablation of pancreatic cancer.

    PubMed

    D'Onofrio, Mirko; Ciaravino, Valentina; De Robertis, Riccardo; Barbi, Emilio; Salvia, Roberto; Girelli, Roberto; Paiella, Salvatore; Gasparini, Camilla; Cardobi, Nicolò; Bassi, Claudio

    2016-11-28

    Pancreatic ductal adenocarcinoma is a highly aggressive tumor with an overall 5-year survival rate of less than 5%. Prognosis and treatment depend on whether the tumor is resectable or not, which mostly depends on how quickly the diagnosis is made. Chemotherapy and radiotherapy can be both used in cases of non-resectable pancreatic cancer. In cases of pancreatic neoplasm that is locally advanced, non-resectable, but non-metastatic, it is possible to apply percutaneous treatments that are able to induce tumor cytoreduction. The aim of this article will be to describe the multiple currently available treatment techniques (radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation), their results, and their possible complications, with the aid of a literature review.

  10. Emphysematous pancreatitis predisposed by Olanzapine

    PubMed Central

    Samanta, Sukhen; Samanta, Sujay; Banik, Krishanu; Baronia, Arvind Kumar

    2014-01-01

    A 32-year-old male presented to our intensive care unit with severe abdominal pain and was diagnosed as acute pancreatitis after 2 months of olanzapine therapy for bipolar disorder. His serum lipase was 900 u/L, serum triglyceride 560 mg/dL, and blood sugar, fasting and postprandial were 230 and 478 mg/dL, respectively on admission. Contrast enhanced computed tomography (CECT) of abdomen was suggestive of acute pancreatitis. Repeat CECT showed gas inside pancreas and collection in peripancreatic area and patient underwent percutaneous drainage and antibiotics irrigation through the drain into pancreas. We describe the rare case of emphysematous pancreatitis due to development of diabetes, hypertriglyceridemia and immunosuppression predisposed by short duration olanzapine therapy. PMID:25024479

  11. Hydrocarbon exposure, pancreatitis, and bile acids.

    PubMed Central

    Hotz, P; Pilliod, J; Bourgeois, R; Boillat, M A

    1990-01-01

    The data on hydrocarbon induced pancreatitis are conflicting. This question was therefore studied in a non-selected population exposed to hydrocarbons and in "formerly" exposed workers. Neither the past clinical history nor the pancreatic tests provided any evidence for a causal relation between exposure and pancreatitis. No signs of hydrocarbon induced liver damage were seen either. As a healthy worker effect cannot be totally excluded, however, a case-control study in a group of patients suffering from non-alcohol induced pancreatitis could give useful indications for finally excluding the possibility of pancreatitis being induced by hydrocarbons. PMID:2271391

  12. Tumor-to-tumor metastasis: report of two cases of renal cell carcinoma metastasizing to microcystic serous cystadenoma of the pancreas.

    PubMed

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

    2015-02-01

    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.

  13. Notch Signaling in Pancreatic Development

    PubMed Central

    Li, Xu-Yan; Zhai, Wen-Jun; Teng, Chun-Bo

    2015-01-01

    The Notch signaling pathway plays a significant role in embryonic cell fate determination and adult tissue homeostasis. Various studies have demonstrated the deep involvement of Notch signaling in the development of the pancreas and the lateral inhibition of Notch signaling in pancreatic progenitor differentiation and maintenance. The targeted inactivation of the Notch pathway components promotes premature differentiation of the endocrine pancreas. However, there is still the contrary opinion that Notch signaling specifies the endocrine lineage. Here, we review the current knowledge of the Notch signaling pathway in pancreatic development and its crosstalk with the Wingless and INT-1 (Wnt) and fibroblast growth factor (FGF) pathways. PMID:26729103

  14. Drug metabolism and pancreatic cancer.

    PubMed

    Flores, John Paul E; Diasio, Robert B; Saif, Muhammad Wasif

    2017-01-01

    Pancreatic cancer remains a fatal disease in the majority of patients. The era of personalized medicine is upon us: customizing therapy according to each patient's individual cancer. Potentially, therapy can be targeted at individuals who would most likely have a favorable response, making it more efficacious and cost effective. This is particularly relevant for pancreatic cancer, which currently portends a very poor prognosis. However, there is much to be done in this field, and more studies are needed to bring this concept to reality.

  15. Adjuvant therapy in pancreatic cancer.

    PubMed

    Jones, Owain Peris; Melling, James Daniel; Ghaneh, Paula

    2014-10-28

    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.

  16. Pancreatic adenocarcinoma pathology: changing “landscape”

    PubMed Central

    Brosens, Lodewijk A. A.; Hackeng, Wenzel M.; Offerhaus, G. Johan; Hruban, Ralph H.

    2015-01-01

    Pancreatic cancer is a devastating disease. At time of diagnosis the disease is usually advanced and only a minority of patients are eligible for surgical resection. The overall 5-year survival is 6%. However, survival of patients with early stage pancreatic cancer is significantly better. To improve the prognosis of patients with pancreatic cancer, it is essential to diagnose and treat pancreatic cancer in the earliest stage. Prevention of pancreatic cancer by treating noninvasive precursor lesions just before they invade tissues can potentially lead to even better outcomes. Pancreatic carcinogenesis results from a stepwise progression in which accumulating genetic alterations drive neoplastic progression in well-defined precursor lesions, ultimately giving rise to an invasive adenocarcinoma. A thorough understanding of the genetic changes that drive pancreatic carcinogenesis can lead to identification of biomarkers for early detection and targets for therapy. Recent next-generation sequencing (NGS) studies have shed new light on our understanding of the natural history of pancreatic cancer and the precursor lesions that give rise to these cancers. Importantly, there is a significant window of opportunity for early detection and treatment between the first genetic alteration in a cell in the pancreas and development of full-blown pancreatic cancer. The current views on the pathology and genetics of pancreatic carcinogenesis that evolved from studies of pancreatic cancer and its precursor lesions are discussed in this review. PMID:26261723

  17. Three cases of mediastinal pancreatic pseudocysts

    PubMed Central

    Fujihara, Yoshio; Maeda, Kazunori; Okamoto, Masaru; Yanagitani, Atsushi; Tanaka, Kiwamu; Nakamura, Kazuhiko; Ogawa, Toshihide

    2016-01-01

    A rare complication of acute or chronic pancreatitis is the formation of a mediastinal pancreatic pseudocyst (MPP), which is caused by tracking of pancreatic fluids through anatomical openings of the diaphragm into the mediastinum. Herein, we report the imaging characteristics of three cases of this condition. Our results revealed three features in common: (i) the connection between the mediastinum and the pancreatic cystic lesion; (ii) the presence of pleural effusions; and (iii) imaging findings consistent with chronic pancreatitis, such as pancreatic atrophy and calcifications and dilatation and/or stricture of main pancreatic duct (MPD). Serial diameter changes of the MPD and of the adjacent pseudocysts were necessary for the determination of the therapeutic strategy used in each case. PMID:27330827

  18. Ultrasonography in diagnosing chronic pancreatitis: New aspects

    PubMed Central

    Dimcevski, Georg; Erchinger, Friedemann G; Havre, Roald; Gilja, Odd Helge

    2013-01-01

    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

  19. Relationship between tea consumption and pancreatic cancer risk: a meta-analysis based on prospective cohort studies and case-control studies.

    PubMed

    Chen, Ke; Zhang, Qi; Peng, Min; Shen, Yanping; Wan, Peng; Xie, Guoming

    2014-09-01

    The aim of this study was to evaluate the relationship between regular tea consumption and the risk of pancreatic cancer by a meta-analysis. Two investigators independently performed a computer retrieve on the electronic databases of Embase, PubMed, and Ovidsp for prospective cohort studies and case-control studies on regular tea consumption and the risk of pancreatic cancer incidence. The keywords using for search were ('Pancreas' OR 'pancreatic') AND ('neoplasms' OR 'carcinoma' OR 'cancer') AND 'tea'. Risk ratios (RRs) and 95% confidence interval (CI) were used to determine the effect of tea consumption on pancreatic cancer. A total of 14 studies were included (8078 pancreatic cancer patients, with a total of 859 783 patients) in the present meta-analysis. The pooled results of effect size indicated that tea consumption has no significant relationship with risk of pancreatic cancer (RR=0.99, 95% CI: 0.89-1.11, P=0.922). However, the subgroup analysis of different countries showed a statistical decrease in pancreatic cancer risk by high consumption of tea in a Chinese population (RR=0.76, 95% CI: 0.59-0.98, P=0.036). Similar results were found in the elderly (>60 years old) (RR=0.76, 95% CI: 0.60-0.96, P=0.023). In conclusion, the present meta-analysis of 14 studies suggests that the correlation between tea consumption and the risk of pancreatic cancer in the general population is not significant, but an increase in tea consumption can reduce the risk of pancreatic cancer disease in Chinese populations and in individuals older than 60 years of age. It is necessary to formulate more rigorous designs of regional studies to further confirm the relationship between tea consumption and pancreatic cancer.

  20. Proteomic analysis of pancreatic endocrine tumor cell lines treated with the histone deacetylase inhibitor trichostatin A.

    PubMed

    Cecconi, Daniela; Donadelli, Massimo; Rinalducci, Sara; Zolla, Lello; Scupoli, Maria Teresa; Scarpa, Aldo; Palmieri, Marta; Righetti, Pier Giorgio

    2007-05-01

    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.