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Sample records for pancreatic adenosquamous carcinoma

  1. Unstable cellular differentiation in adenosquamous cell carcinoma

    SciTech Connect

    Steele, V.E.; Netteshelm, P.

    1981-07-01

    For the determination of whether two or more stem lines with fixed or stable differentiation are present in a growing mixed adenosquamous cell carcinoma, two different mixed tumors, derived from transformed F344 rat tracheal epithelium, were dissociated and ten single cells were isolated from each tumor. All clones were then inoculated into animals for the assessment of in vivo differentiation. Of the ten single cell clones isolated from the first tumor, seven clones produced mixed adenosquamous carcinomas and three produced adenocarcinomas in which no squamous cell component was found. From the second tumor, eight clones produced mixed tumors and two produced squamous cell carcinomas in which no adenocarcinoma component was found. These studies strongly suggest that the mixture of differentiated cell types in adenosquamous cell carcinomas is not the result of a mixture of stem cells with one fixed phenotype within the tumor, but rather is the result of an instability of differentiation; the neoplastic cells can express both types of differentiation.

  2. Molecular profiling of lung adenosquamous carcinoma: hybrid or genuine type?

    PubMed Central

    Vassella, Erik; Langsch, Stephanie; Dettmer, Matthias S.; Schlup, Cornelia; Neuenschwander, Maja; Frattini, Milo; Gugger, Mathias; Schäfer, Stephan C.

    2015-01-01

    Lung adenosquamous carcinoma is a particular subtype of non-small cell lung carcinoma that is defined by the coexistence of adenocarcinoma and squamous cell carcinoma components. The aim of this study was to assess the mutational profile in each component of 16 adenosquamous carcinoma samples from a Caucasian population by a combination of next generation sequencing using the cancer hotspot panel as well as the colon and lung cancer panel and FISH. Identified mutations were confirmed by Sanger sequencing of DNA from cancer cells of each component collected by Laser Capture microdissection. Mutations typical for adenocarcinoma as well as squamous cell carcinoma were identified. Driver mutations were predominantly in the trunk suggesting a monoclonal origin of adenosquamous carcinoma. Most remarkably, EGFR mutations and mutations in the PI3K signaling pathway, which accounted for 30% and 25% of tumors respectively, were more prevalent while KRAS mutations were less prevalent than expected for a Caucasian population. Surprisingly, expression of classifier miR-205 was intermediate between that of classical adenocarcinoma and squamous cell carcinoma suggesting that adenosquamous carcinoma is a transitional stage between these tumor types. The high prevalence of therapy-relevant targets opens new options of therapeutic intervention for adenosquamous carcinoma patients. PMID:26068980

  3. Adenosquamous carcinoma of the pancreas, a rare tumor entity: a case report

    PubMed Central

    2009-01-01

    Introduction Adenosquamous carcinoma of the pancreas is a rare variant of exocrine pancreatic tumor. This type of tumor is extremely rare as only few similar cases have been described in the literature. Case presentation We present a case of a 72 years old male patient who was admitted to the hospital complaining of epigastric pain and jaundice. Pancreatic carcinoma of the head was diagnosed and a pylorus preserving pancreaticoduodenectomy was performed. Conclusion This type of cancer is a very aggressive tumor followed by a dismisal prognosis. Multimodality therapy seems to be a reasonable approach but more studies are needed, to propose the most effective treatment. PMID:20062646

  4. Clear cell adenosquamous carcinoma of the cervix: a case report with discussion of the differential diagnosis.

    PubMed

    Garg, Megha Mittal; Arora, Vinod K

    2012-05-01

    Clear cell adenosquamous carcinoma is an extremely rare and recently described variant of adenosquamous carcinoma of the cervix. It has a unique histologic appearance and has been shown to be associated with human papillomavirus-18. Its significance lies in the fact that it is associated with an aggressive clinical course and has to be differentiated microscopically from clear cell carcinoma and glassy cell carcinoma. PMID:22498949

  5. Good syndrome with thymic adenosquamous carcinoma--report of a case.

    PubMed

    Ishibashi, Hironori; Akamatsu, Hideki; Kojima, Katsuo; Usui, Hiroshi; Akashi, Takumi; Sunamori, Makoto

    2007-02-01

    A 68-year-old man with recurrent bilateral severe pneumonia and invasive thymic carcinoma was admitted to our hospital. An extended thymo-thymectomy with lymph nodes dissection was performed for an irregular shaped anterior mediastinum mass. The tumor was mainly composed of type C, adenosquamous carcinoma, and found to have a small area of types B2 and B3 thymoma. History and laboratory findings were compatible with the diagnosis of Good syndrome. Although there are some reports of thymic carcinoma arising from thymoma, this is the first report of co-existence of adenosquamous carcinomas and thymoma with Good syndrome as far as reviewed articles. Thymic carcinoma with severe infection should be examined carefully for co-existence of thymoma, and co-existence of thymoma and thymic carcinoma suggests a close histogenetic relationship between the 2 tumors. PMID:17392673

  6. Primary gastric adenosquamous carcinoma in a Caucasian woman: a case report

    PubMed Central

    2010-01-01

    Introduction Most gastric tumors are adenocarcinomas. Primary gastric adenosquamous carcinoma is a rare malignancy, mostly associated with Asian populations. It constitutes less than one percent of all gastric carcinomas and its clinical presentation is the same as adenocarcinoma. It occurs more frequently in the proximal stomach, usually presents with muscular layer invasion and tends to be found in advanced stages at diagnosis, with a worse prognosis than adenocarcinoma. Case presentation We report the case of an 84-year-old Caucasian woman with an adenosquamous carcinoma extending to her serosa with lymphatic and venous invasion (T3N1M1). Nodal and hepatic metastasis presented with both cellular types, with dominance of the squamous component. Conclusions Adenosquamous gastric cancer is a rare diagnosis in western populations. We present the case of a woman with a very aggressive adenosquamous carcinoma with a preponderance of squamous cell component in the metastasis. Several origins have been proposed for this kind of carcinoma; either evolution from adenocarcinoma de-differentiation or stem cell origin might be possible. The hypothesis that a particular histological type of gastric cancer may arise from stem cells might be a field of research in oncological disease of the stomach. PMID:21034475

  7. Squamous cell and adenosquamous carcinomas of the gallbladder: clinicopathological analysis of 34 cases identified in 606 carcinomas.

    PubMed

    Roa, Juan C; Tapia, Oscar; Cakir, Asli; Basturk, Olca; Dursun, Nevra; Akdemir, Deniz; Saka, Burcu; Losada, Hector; Bagci, Pelin; Adsay, N Volkan

    2011-08-01

    The information in the literature on squamous cell and adenosquamous carcinomas of the gallbladder is highly limited. In this study, 606 resected invasive gallbladder carcinoma cases were analyzed. Squamous differentiation was identified in 41 cases (7%). Those without any identifiable glandular-type invasive component were classified as pure squamous cell carcinomas (8 cases) and those with the squamous component constituting 25-99% of the tumors were classified as adenosquamous carcinomas (26 cases) and included into the analysis. The remaining 7 that had <25% squamous component were classified as adenocarcinoma with focal squamous change and excluded. The clinicopathological characteristics of adenosquamous carcinoma/squamous cell carcinomas were documented and contrasted with that of ordinary gallbladder adenocarcinomas. The average patient age was 65 years (range 26-81); female/male ratio, 3.8. In only 13%, there was a preoperative clinical suspicion of malignancy. Grossly, 58% presented as thickening and hardening of the wall and 6% were polypoid. In 12%, mucosa adjacent to the tumor revealed squamous metaplasia. All pure squamous cell carcinomas had prominent keratinization. Giant cells and tumor-infiltrating eosinophils were observed in 29 and 51% of the squamous cell carcinomas/adenosquamous carcinomas versus 10% (P=0.02) and 6% (P=0.001) in gallbladder adenocarcinomas, respectively. All but three cases had 'advanced' (pT2 and above) carcinomas. Follow-up was available in 31 patients: 25 died of disease (median=5 months, range 0-20), and 6 were alive (median=64 months, range 5-112.5). The survival of patients with squamous cell carcinomas/adenosquamous carcinomas was significantly worse than that of gallbladder adenocarcinomas (P=0.003), and this adverse prognosis persisted when compared with stage-matched advanced gallbladder adenocarcinoma cases (median=11.4 months, P=0.01). In conclusion, squamous differentiation was noted in 7% of gallbladder carcinomas. The incidence of adenosquamous carcinoma (defined as 25-99% of the tumor being squamous) was 4%, and that of pure squamous cell carcinoma (without any documented invasive glandular component) was 1%. Pure squamous cell carcinomas often showed prominent keratinization. The overall prognosis of adenosquamous carcinoma/squamous cell carcinoma appears to be even worse than that of ordinary adenocarcinomas. Most patients died within a few months; however, those few who were alive beyond 2 years in this cohort experienced long-term survival. PMID:21532545

  8. [A case of pulmonary adenosquamous cell carcinoma with thin-wall cavities].

    PubMed

    Kobashi, Yoshihiro; Mouri, Keiji; Fukuda, Minoru; Yoshida, Kouichiro; Miyashita, Naoyuki; Niki, Yoshihito; Nakata, Masao; Mikio, Oka

    2005-01-01

    A 68-year-old man was admitted to our hospital because of continuous cough of three months duration and for investigation of a thin-wall cavitary lesion (> 3 cm) in the right upper lung field. Thin-wall cavity (40 x 35 mm) with notch and spiculation was observed in the right S2 on chest CT. A histological diagnosis of pulmonary adenocarcinoma was obtained by bronchoscopic examination, and he was transferred to the Department of Thoracic Surgery where a right upper lobectomy was performed. Subsequently, cavity formation (45 x 40 x 35 mm) was disclosed in the right S2. Most of the surrounding cavity consisted of the components of a well differentiated squamous cell carcinoma with keratinization and slightly different components of a poorly differentiated adenocarcinoma with mucous production. The final diagnosis was pulmonary adenosquamous cell carcinoma and the postoperative histological classification was T2N2M0 (Stage 3A) because of metastasis to the lymph nodes (#4 and #11). A communicating bronchus was histologically identified and we presumed that the thin-wall cavity developed by a check valve mechanism. Although squamous cell carcinoma has been reported to be the histological type, tending to form thin-wall cavities among patients with lung cancer reported to be squamous cell carcinoma, recently an increasing number of such cavities have been reported among patients with pulmonary adenocarcinoma. Herein, we have reported a rare case of histological diagnosis of pulmonary adenosquamous cell carcinoma with cavity formation. PMID:15704455

  9. Intraluminal superior vena cava metastasis from adenosquamous carcinoma of the duodenum: A case report

    PubMed Central

    TAKAYOSHI, KOTOE; ARIYAMA, HIROSHI; TAMURA, SHINGO; YODA, SHUNSUKE; ARITA, TAKESHI; YAMAGUCHI, TOSHIHIRO; OZONO, KEIGO; YAMAMOTO, HIDETAKA; INADOMI, KYOKO; KUMAGAI, HOZUMI; TANAKA, MAMORU; OKUMURA, YUTA; SAGARA, KOSUKE; NIO, KENTA; NAKANO, MICHITAKA; ARITA, SHUJI; KUSABA, HITOSHI; ODASHIRO, KEITA; ODA, YOSHINAO; AKASHI, KOICHI; BABA, EISHI

    2016-01-01

    In 2013, a 76-year-old male with a cardiac pacemaker was diagnosed with adenosquamous carcinoma of the duodenum. Subsequently, a pancreatoduodenectomy and lymph node dissection were performed, and 12 cycles of adjuvant chemotherapy (modified FOLFOX6 regimen), which consisted of fluorouracil, leucovorin and oxaliplatin, were administered via a central venous catheter. At 5 months after the completion of adjuvant chemotherapy, the patient experienced the sudden onset of severe pain at the back right of the ear, edema of the right side of the face and right jugular vein dilatation. Computed tomography (CT) revealed filling defects in the superior vena cava (SVC) and right brachiocephalic vein, indicating catheter-induced venous thrombosis. Although the catheter was removed and anti-coagulation therapy, aspiration of the thrombosis and ballooning dilatation were performed immediately, the patient's symptoms were not ameliorated. Notably, histological examination following thrombus aspiration revealed metastatic cancer cells, and fluorodeoxyglucose-positron emission tomography/CT identified metabolically active nodules in the SVC at locations consistent with the initial duodenal tumors detected by CT and in the first thoracic vertebrae. The tumor thrombus rapidly increased in size and resulted in worsening dyspnea. Subsequently, radiotherapy was performed, followed by chemotherapy, which relieved the systemic symptoms and suppressed the tumor growth. Adenosquamous carcinoma of the duodenum is extremely rare, and to the best of our knowledge, intraluminal SVC metastasis as a result of adenosquamous carcinoma of the duodenum has not been reported previously. The placement of a cardiac pacemaker, central venous catheter and tumor cells possessing high metastatic potential are hypothesized to have contributed to this rare case of metastasis. PMID:26870254

  10. [A case of adenosquamous carcinoma of the sigmoid colon with inferior mesenteric vein thrombosis].

    PubMed

    Otsuka, Ryota; Maruyama, Takashi; Tanaka, Hajime; Matsuzaki, Hiroshi; Natsume, Toshiyuki; Miyazaki, Akinari; Sato, Yayoi; Sazuka, Tetsutaro; Yamamoto, Yuji; Yoshioka, Takafumi; Kanada, Yoko; Yanagihara, Akitoshi; Yokoyama, Masaya; Kobayashi, Hiroshi; Shimizu, Shinichiro

    2014-11-01

    A 63-year-old man who had been admitted to another institute with sepsis and renal failure was referred to our hospital after computed tomography (CT) findings showed thickening of the walls in the sigmoid colon and a defect in contrast enhancement in the portal and inferior mesenteric veins. Emergency sigmoid colon resection with D2 lymphadenectomy was performed after detection of perforation due to sigmoid colon cancer. The histopathological diagnosis was adenosquamous carcinoma, pSS, int, INF b, ly1, v0, pN2, pStage IIIband inferior mesenteric vein thrombosis. He was discharged on day 12, and we administered anticoagulant warfarin therapy. PMID:25731288

  11. Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma

    PubMed Central

    2009-01-01

    Background Adenosquamous carcinoma of the uterine cervix is an infrequent but aggressive subtype of cervical cancer. A better understanding of its biological behaviour is warranted to define more accurate prognosis and therapeutic targets. Currently, the blockage of receptor tyrosine kinase (RTKs) activity is an efficient therapeutic strategy for many different cancers. The objective of this study was to investigate EGFR, PDGFRA and VEGFR2 RTKs overexpression and activating gene mutations in a cohort of 30 adenosquamous carcinomas of the uterine cervix. Methods EGFR, PDGFRA and VEGFR2 immunohistochemistry was performed in all samples, followed by DNA isolation from the gross macroscopically dissection of the neoplastic area. Screening for EGFR (exons 18–21) and PDGFRA (exons 12, 14 and 18) mutations was done by PCR – single-strand conformational polymorphism (PCR-SSCP). Results Despite the presence of EGFR immunohistochemical positive reactions in 43% (13/30) of the samples, no EGFR activating mutations in the hotspot region (exons 18–21) were identified. A silent base substitution (CAG>CAA) in EGFR exon 20 at codon 787 (Q787Q) was found in 17 cases (56%). All PDGFRA immunohistochemical reactions were positive and consistently observed in the stromal component, staining fibroblasts and endothelial cells, as well as in the cytoplasm of malignant cells. No activating PDGFRA mutations were found, yet, several silent mutations were observed, such as a base substitution in exon 12 (CCA>CCG) at codon 567 (P567P) in 9 cases and in exon 18 (GTC>GTT) at codon 824 (V824V) in 4 cases. We also observed the presence of base substitutions in intron 14 (IVS14+3G>A and IVS14+49G>A) in two different cases, and in intron 18 (IVS18-50insA) in 4 cases. VEGFR2 positivity was observed in 22 of 30 cases (73.3%), and was significantly associated with lack of metastasis (p = 0.038). Conclusion This is the most extensive analysis of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinomas. Despite the absence of EGFR and PDGFRA activating mutations, the presence of overexpression of these three important therapeutic targets in a subset of cases may be important in predicting the sensitivity of adenosquamous carcinoma to specific anti-RTKs drugs. PMID:19563658

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

    PubMed Central

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

    2014-01-01

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

  13. [An autopsy case of carcinomatous sensory neuropathy associated with gastric adenosquamous carcinoma].

    PubMed

    Yamamoto, K; Ohnishi, A; Noda, S; Umezaki, H; Yamamoto, T

    1989-04-01

    A 61-year-old man was admitted on May 1986 with complaints of hypesthesia and pain in the both legs, and of progressive difficulty in walking. Physical examination was unremarkable. On neurological examination, deep tendon reflexes were decreased in all extremities without pathological reflexes. Vibration sense was decreased severely at the medial malleolus and moderately at the anterior superior iliac spine. Joint sensation of the toes was moderately decreased. Light touch, temperature discrimination, and pinprick sensation were slightly decreased on fingers bilaterally and distal to the middle part of both legs. Muscle strength was normal. His gait was unsteady and Romberg's sign was positive. Finger to nose test and heel to knee test were mildly disturbed bilaterally. The sural nerve action potential was not elicited on electrical stimulation. Laboratory studies for malignancy showed gastric cancer. Only July 4, he underwent subtotal gastrectomy. Histologically it showed adenosquamous carcinoma. Postoperatively gait disturbance and pain in both legs improved slightly. Peak latencies of P2 of SEP following right and left posterior tibial nerve stimulation were 47. 9 msec and 48.8 msec on February 14, and 44.5 msec and 43.9 msec on October 6, 1986, respectively, and their postoperative shortening was evident. He died of multiple liver and lung metastasis of the gastric cancer in November 28, 1986. At autopsy, tumor metastasis were noted in liver, lung and perigastroduodenal and retroperitoneal lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2612103

  14. Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review.

    PubMed

    Borazanci, Erkut; Millis, Sherri Z; Korn, Ron; Han, Haiyong; Whatcott, Clifford J; Gatalica, Zoran; Barrett, Michael T; Cridebring, Derek; Von Hoff, Daniel D

    2015-09-15

    Adenosquamous carcinoma of the pancreas (ASCP) is a rare entity. Like adenocarcinoma of the pancreas, overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP. Molecular characterization revealed overexpression in MRP1 (80%), MGMT (79%), TOP2A (75), RRM1 (42%), TOPO1 (42%), PTEN (45%), CMET (40%), and C-KIT (10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered for treatments of this rare type of exocrine pancreas cancer. Molecular profiling may be appropriate to provide maximum information regarding the patient's tumor. Further work should be pursued to better characterize this disease. PMID:26380056

  15. Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review

    PubMed Central

    Borazanci, Erkut; Millis, Sherri Z; Korn, Ron; Han, Haiyong; Whatcott, Clifford J; Gatalica, Zoran; Barrett, Michael T; Cridebring, Derek; Von Hoff, Daniel D

    2015-01-01

    Adenosquamous carcinoma of the pancreas (ASCP) is a rare entity. Like adenocarcinoma of the pancreas, overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP. Molecular characterization revealed overexpression in MRP1 (80%), MGMT (79%), TOP2A (75), RRM1 (42%), TOPO1 (42%), PTEN (45%), CMET (40%), and C-KIT (10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered for treatments of this rare type of exocrine pancreas cancer. Molecular profiling may be appropriate to provide maximum information regarding the patients tumor. Further work should be pursued to better characterize this disease. PMID:26380056

  16. Surgical specimen histology revealed inadequacy of conventional transbronchial needle aspiration sample in the diagnosis of adenosquamous lung carcinoma

    PubMed Central

    Chen, Jing; Cao, Yan; Yang, Jiong; Luo, Guang-Wei

    2015-01-01

    Objective We retrospectively reviewed the accuracy of conventional transbronchial needle aspiration (cTBNA) in the subtyping of lesions located in or around central airways by comparing the histological diagnosis based on TBNA and surgical specimens. Materials and methods cTBNA was conducted in consecutive patients with lesions located in or around the central airways (trachea, left and right primary bronchi, hilar and mediastinal masses or lymph nodes) between October 2012 and May 2014 in Wuhan No. 1 Hospital. The aspirated specimens in all patients were performed cytological and/or histopathological examination. Of these patients, some were subjected to surgical resection and histopathological examination was performed by the Department of Pathology. In the patients with gross specimens, the final diagnosis was established based on histopathological results from these specimens. Results In 63 patients diagnosed with cTBNA for the lesions located in or around the central airways, 23 patients with a diagnosis of lung cancer or atypical hyperplasia underwent surgery. The final diagnosis based on histopathology of surgery specimen was lung cancer in 22 patients [3 small cell lung cancer (SCLC), 9 squamous cell carcinoma (SCC), 5 adenocarcinoma (ADC), 4 adenosquamous carcinoma (ADS) and 1 neuroendocrine carcinoma], and inflammatory pseudotumor in 1 patient. The overall diagnostic yield of cTBNA for lung cancer was 95.7% (22/23), but the accuracy for histological typing of lung cancer is only 63.6% (14/22), for adenosquamous lung carcinoma was only 25% (1/4). Conclusions cTBNA is a safe and effective procedure that can be used for the diagnosis of central lung cancer. However, the accuracy of TBNA for the histological classification of lung cancer is relatively low, especially for adenosquamous lung carcinoma. PMID:25973234

  17. 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; Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan ; Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh; Lee, Steve P.; Hong, Ji-Hong; Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan

    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.

  18. 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.

  19. Correlation of HMGB1 expression to progression and poor prognosis of adenocarcinoma and squamous cell/adenosquamous carcinoma of gallbladder

    PubMed Central

    Shi, Zilu; Huang, Qian; Chen, Jian; Yu, Pengcheng; Wang, Xiaosong; Qiu, Hong; Chen, Yijie; Dong, Yangyang

    2015-01-01

    HMGB1 (High mobility group box 1) expressions in adenocarcinoma (AC) and squamous cell/adenosquamous (SC/ASC) carcinoma of gallbladder, as well as its prognostic significance, have not yet been evaluated. We investigated HMGB1 expression in 80 cases of AC gallbladder cancer and 52 cases of SC/ASC gallbladder cancer. Survival information was concomitantly collected. The association of HMGB1 expression with clinicopathological characteristics and the possible prognostic role of HMGB1 for two aforementioned subtypes of gallbladder cancers were also analyzed. siRNA technique was utilized to explore the role of HMGB1 in proliferation and invasion of gallbladder cancer cells in vitro. HMGB1 overexpression is present in AC and SC/ASC gallbladder cancers. HMGB1 expression significantly associates with growth and metastasis of AC and SC/ASC gallbladder cancers. In vitro cell experiments based on siRNA demonstrated that HMGB1 downregulation inhibits proliferation and invasion of gallbladder cancer cells. Kaplan-Meier analysis revealed that HMGB1 expression is negatively associated with overall survival time of patients with AC or SC/ASC gallbladder cancer. Cox multivariate analysis confirmed that HMGB1 is an independent risk factor for survival of patients with AC or SC/ASC gallbladder cancer. HMGB1 overexpression closely correlates with progression and poor prognosis of AC and SC/ASC gallbladder cancers. PMID:26692945

  20. Current management of pancreatic carcinoma.

    PubMed Central

    Lillemoe, K D

    1995-01-01

    OBJECTIVE: The author seeks to provide an update on the current management of pancreatic carcinoma, including diagnosis and staging, surgical resection and adjuvant therapy for curative intent, and palliation. SUMMARY BACKGROUND DATA: During the 1960s and 1970s, the operative mortality and long-term survival after pancreaticoduodenectomy for pancreatic carcinoma was so poor that some authors advocated abandoning the procedure. Several recent series have reported a marked improvement in perioperative results with 5-year survival in excess of 20%. Significant advances also have been made in areas of preoperative evaluation and palliation for advanced disease. CONCLUSION: Although carcinoma of the pancreas remains a disease with a poor prognosis, advances in the last decade have led to improvements in the overall management of this disease. Resection for curative intent currently should be accomplished with minimal perioperative mortality. Surgical palliation also may provide the optimal management of selected patients. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 7. PMID:7531966

  1. Screening for major driver oncogene alterations in adenosquamous lung carcinoma using PCR coupled with next-generation and Sanger sequencing methods.

    PubMed

    Shi, Xiaohua; Wu, Huanwen; Lu, Junliang; Duan, Huanli; Liu, Xuguang; Liang, Zhiyong

    2016-01-01

    We investigated the frequency of major driver oncogenes in lung adenosquamous cell carcinoma (ASC) cases. Frequency of EGFR, K-Ras, B-Raf, PIK3CA, DDR2, ALK, and PDGFRA gene mutations was examined in 56 patients using next-generation sequencing, polymerase chain reaction, and Sanger sequencing. Macrodissection or microdissection was performed in 37 cases to separate the adenomatous and squamous components of ASC. The overall mutation rate was 64.29%, including 55.36%, 7.14%, and 1.79% for EGFR, K-Ras, and B-Raf mutations, respectively. PIK3CA mutation was detected in three cases; all involved coexisting EGFR mutations. Of the 37 cases, 34 were convergent in two components, while three showed EGFR mutations in the glandular components and three showed PIK3CA mutations in the squamous components. With respect to EGFR mutations, the number of young female patients, nonsmokers, and those with positive pleural invasion was higher in the mutation-positive group than that in the mutation-negative. K-Ras mutation was significantly associated with smoking. Overall survival in the different EGFR mutation groups differed significantly. The frequency and clinicopathological characteristics of EGFR- and K-Ras-mutated adenosquamous lung carcinoma were similar to that noted in Asian adenocarcinomas patients. The high convergence mutation rate in both adenomatous and squamous components suggests monoclonality in ASC. PMID:26923333

  2. Screening for major driver oncogene alterations in adenosquamous lung carcinoma using PCR coupled with next-generation and Sanger sequencing methods

    PubMed Central

    Shi, Xiaohua; Wu, Huanwen; Lu, Junliang; Duan, Huanli; Liu, Xuguang; Liang, Zhiyong

    2016-01-01

    We investigated the frequency of major driver oncogenes in lung adenosquamous cell carcinoma (ASC) cases. Frequency of EGFR, K-Ras, B-Raf, PIK3CA, DDR2, ALK, and PDGFRA gene mutations was examined in 56 patients using next-generation sequencing, polymerase chain reaction, and Sanger sequencing. Macrodissection or microdissection was performed in 37 cases to separate the adenomatous and squamous components of ASC. The overall mutation rate was 64.29%, including 55.36%, 7.14%, and 1.79% for EGFR, K-Ras, and B-Raf mutations, respectively. PIK3CA mutation was detected in three cases; all involved coexisting EGFR mutations. Of the 37 cases, 34 were convergent in two components, while three showed EGFR mutations in the glandular components and three showed PIK3CA mutations in the squamous components. With respect to EGFR mutations, the number of young female patients, nonsmokers, and those with positive pleural invasion was higher in the mutation-positive group than that in the mutation-negative. K-Ras mutation was significantly associated with smoking. Overall survival in the different EGFR mutation groups differed significantly. The frequency and clinicopathological characteristics of EGFR- and K-Ras-mutated adenosquamous lung carcinoma were similar to that noted in Asian adenocarcinomas patients. The high convergence mutation rate in both adenomatous and squamous components suggests monoclonality in ASC. PMID:26923333

  3. 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.

  4. Epithelial-Mesenchymal Transition in Pancreatic Carcinoma

    PubMed Central

    Maier, Harald J.; Wirth, Thomas; Beug, Hartmut

    2010-01-01

    Pancreatic carcinoma is the fourth-leading cause of cancer death and is characterized by early invasion and metastasis. The developmental program of epithelial-mesenchymal transition (EMT) is of potential importance for this rapid tumor progression. During EMT, tumor cells lose their epithelial characteristics and gain properties of mesenchymal cells, such as enhanced motility and invasive features. This review will discuss recent findings pertinent to EMT in pancreatic carcinoma. Evidence for and molecular characteristics of EMT in pancreatic carcinoma will be outlined, as well as the connection of EMT to related topics, e.g., cancer stem cells and drug resistance. PMID:24281218

  5. 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.

  6. Nectin-2 and DDX3 are biomarkers for metastasis and poor prognosis of squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder.

    PubMed

    Miao, Xiongying; Yang, Zhu-Lin; Xiong, Li; Zou, Qiong; Yuan, Yuan; Li, Jinghe; Liang, Lufeng; Chen, Meigui; Chen, Senlin

    2013-01-01

    The clinicopathological and biological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of gallbladder have not been well documented because it is a rare subtype of gallbladder cancer. In this study, the protein expression of Nectin-2 and DDX3 in 46 SC/ASCs and 80 adenocarcinomas was measured using immunohistochemistry. We demonstrated that positive Nectin-2 and DDX3 expression was significantly associated with large tumor size, high TNM stage, and lymph node metastasis of SC/ASC and AC. Positive Nectin-2 and DDX3 expression was significantly associated with invasion and surgical curability of AC. Univariate Kaplan-Meier analysis showed that positive Nectin-2 and DDX3 expression, degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis, and surgical curability were significantly associated with post-operative survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive Nectin-2 and DDX3 expression, degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis, and no surgical curability are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive Nectin-2 and DDx3 expression is closely correlated with clinical, pathological, and biological behaviors as well as poor-prognosis of gallbladder cancer. PMID:23330003

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

    PubMed Central

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

    2013-01-01

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

  8. Characterization of gamma-glutamyltranspeptidase from human exocrine pancreatic carcinomas.

    PubMed

    Yamaguchi, N; Sugimoto, M; Kawai, K

    1985-06-30

    Two different types of gamma-glutamyltranspeptidase (gamma-GTP) have been found in normal human pancreas following bromelain treatment. On the other hand, three human pancreatic ductal cell carcinomas have only a single type of gamma-GTP upon analysis with polyacrylamide gel electrophoresis, anion-exchange column chromatography and isoelectric focusing. Carcinoma gamma-GTPs were almost identical to one of the two types of normal pancreatic gamma-GTPs. The gamma-GTP from pancreatic carcinomas bound to anion-exchange column and was eluted at the same NaCl fractions as normal pancreatic gamma-GTP. The properties of pancreatic carcinoma-gamma-GTP, as assessed by binding to concanavalin A and lentil lectin affinity columns, were also similar to one of the two enzymes of normal pancreas. No apparent difference in isoelectric points was found between the carcinoma gamma-GTPs and one of the two normal pancreatic gamma-GTPs. PMID:2863014

  9. Bacteriolytic therapy of experimental pancreatic carcinoma

    PubMed Central

    Maletzki, Claudia; Gock, Michael; Klier, Ulrike; Klar, Ernst; Linnebacher, Michael

    2010-01-01

    AIM: To investigate the effectiveness of Clostridium novyi (C. novyi)-NT spores for the treatment of established subcutaneous pancreatic tumor in the syngeneic, immunocompetent Panc02/C57Bl/6 model. METHODS: C. novyi-NT spores were applied intravenously to animals carrying established pancreatic tumors of three different sizes. Systemic immune responses in peripheral blood and spleen were examined by flow cytometry. Supplementary, cytotoxic activity of lymphocytes against syngeneic tumor targets was analyzed. RESULTS: Application of spores identified, that (1) small tumors (< 150 mm3) were completely unaffected (n = 10); (2) very large tumors (> 450 mm3) responded with substantial necrosis followed by shrinkage and significant lethality most likely due to tumor lysis syndrome (n = 6); and (3) an optimal treatment window exists for tumors of approximately 250 mm3 (n = 21). In this latter group, all tumor-bearing animals had complete tumor regression and remained free of tumor recurrence. In subsequent tumor rechallenge experiments a significant delay in tumor growth compared to the initial tumor cell inoculation was observed (tumor volume at day 28: 197.8 87.3 mm3 vs 500.1 50.9 mm3, P < 0.05). These effects were accompanied by systemic activation of immune response mechanisms predominantly mediated by the innate arm of the immune system. CONCLUSION: The observed complete tumor regression is encouraging and shows that immunotherapy with C. novyi-NT is an interesting strategy for the treatment of pancreatic carcinomas of defined sizes. PMID:20653063

  10. A Case of Esophageal Squamous Cell Carcinoma with Pancreatic Metastasis

    PubMed Central

    Park, Choulki; Kim, Youn Hwa; Hwang, Eun Jung; Na, Ki Yong; Kim, Kyung-Yup; Park, Jae Hyun; Chang, Young Woon

    2013-01-01

    Solitary pancreatic metastasis of esophageal cancer is extremely rare. We report the case of a 58-year-old male admitted with esophageal cancer. Additional asymptomatic solitary hepatic and pancreatic masses were observed in the staging work-up for esophageal cancer. The hepatic mass was confirmed as a primary hepatocellular carcinoma with an ultrasound-guided needle biopsy. An esophagectomy with a distal pancreatectomy and radiofrequency ablation for hepatocellular carcinoma were performed. Histologically, the pancreatic mass was confirmed to be a metastasis from the esophageal cancer. The patient has been followed up with chemotherapy. PMID:23614134

  11. Pancreatic carcinoma accompanied by pseudocyst: report of two cases.

    PubMed

    Kimura, W; Sata, N; Nakayama, H; Muto, T; Matsuhashi, N; Sugano, K; Atomi, Y

    1994-12-01

    Two cases of pancreatic cancer accompanied by pseudocyst are reported. Case 1 was a 60-year-old man who was admitted to our hospital complaining of left lower abdominal discomfort. A cystic lesion, about 3 cm in diameter, was found in the pancreatic tail by ultrasonography (US) and computed tomography (CT). No signs of chronic pancreatitis were found. At operation, an elastic, hard, white tumor, about 1 cm in diameter, was felt adjacent to the cystic lesion on the duodenal side. Histologically, this tumor was a duct cell carcinoma with an adjacent pseudocyst upstream of the pancreas. Case 2 was a 57-year-old man who complained of back pain and loss of body weight. US and CT examination revealed a cystic lesion, 11 x 7 cm in size, in the tail of the pancreas. Histological examination of the resected specimen revealed both a duct cell carcinoma, 3 cm in size, in the body of the pancreas and a pseudocyst, 9 cm in size. Pseudocysts accompanying carcinoma are thought to develop from obstruction of the pancreatic duct by the carcinoma, followed by intraductal high pressure and disruption of ductules upstream of the pancreas. Thus, we should pay careful attention to pseudocyst of the pancreas, especially when signs of diffuse chronic inflammation cannot be found, to help identify duct cell carcinoma in the early stage. Further detailed examinations of the cyst fluid or pancreatic juice, such as cytology, tumor marker determinations, or establishment of K-ras codon 12 mutation, are needed. PMID:7874278

  12. Ectopic mediastinal parathyroid carcinoma presenting as acute pancreatitis.

    PubMed

    Tseng, Chih-Wei; Lin, Shan-Zu; Sun, Chih-Hao; Chen, Chun-Chia; Yang, An-Hang; Chang, Full-Young; Lin, Han-Chieh; Lee, Shou-Dong

    2013-02-01

    Parathyroid carcinoma is a rare cause of hyperparathyroidism, accounting for fewer than 1% of cases. The incidence of acute pancreatitis in patients with hyperparathyroidism was reported to be only 1.5%. We report a very rare case of ectopic mediastinal parathyroid carcinoma presenting as acute pancreatitis. A 72-year-old man presented with acute pancreatitis and hypercalcemia. During the work-up for hypercalcemia, a mediastinal parathyroid tumor was identified by (99m)Tc-sestamibi scintigraphy and magnetic resonance imaging. The tumor was completely removed via a lower cervical collar incision. The histopathology revealed parathyroid carcinoma. There was no tumor recurrence or abdominal symptoms at 3-year follow-up. PMID:23351422

  13. [Stress and pancreatic carcinoma--?-adrenergic signaling and tumor biology].

    PubMed

    Hefner, J; Csef, H; Kunzmann, V

    2014-02-01

    In several carcinomas, ?-adrenergic signaling has been found to regulate relevant processes of cancer biology. Until recently, pancreatic cancer has not been in the focus of respective research. But in view of the incidence and poor prognosis of pancreatic cancer, new insights in biology and therapeutic strategies are of prime importance. Nowadays, several reports describe influences of the catecholaminergic system on pancreatic cancer in vitro and in vivo. Effects were shown on proliferation and apoptosis of carcinoma cells as well as on interactions with tumor-microenvironment and dissemination and metastasis formation. In contrast to other entities, evidence even suggests links between ?-adrenergic signaling and initiation of the disease. The following report summarizes the most relevant results demonstrating implications for further research and possible interventions. PMID:24496896

  14. CA 19-9 assay in differential diagnosis of pancreatic carcinoma from inflammatory pancreatic diseases.

    PubMed

    Piantino, P; Andriulli, A; Gindro, T; Pecchio, F; Masoero, G; Cavallini, G; Naccarato, R; Dobrilla, G

    1986-06-01

    Levels of a new carbohydrate antigen CA 19-9, which is a monosialoganglioside identified by a monoclonal antibody raised against colorectal carcinoma cells, were compared to carcinoembryonic antigen and tissue polypeptide antigen assays in 250 sera from patients with different pancreatic diseases including acute pancreatitis, chronic pancreatitis, and pancreatic cancer. All three tumoral markers were elevated at the onset of an acute pancreatic attack in a few patients. All but five patients with chronic pancreatitis displayed normal levels with each of the three markers; in two of these five cases an extraintestinal cancer was later discovered. CA 19-9 displayed higher sensitivity and predictive value of a negative result than the other two markers. The best operational characteristic of CA 19-9 was its high predictive value for a positive test which suggests a "ruling in" usage of it for pancreatic cancer diagnosis. CA 19-9 assay was of extreme value in disclosing both localized and metastatic pancreatic cancer while the other two markers were more often positive in the latter case. Of 71 cancer patients with positive markers, only four would have escaped a right diagnosis by assaying CA 19-9 alone. PMID:3458359

  15. Magnetic resonance imaging of pancreatic metastases from renal cell carcinoma.

    PubMed

    Sikka, Amrita; Adam, Sharon Z; Wood, Cecil; Hoff, Frederick; Harmath, Carla B; Miller, Frank H

    2015-01-01

    Pancreatic metastases are rare but are thought to be most commonly from renal cell carcinoma (RCC). These metastases can present many years after the initial tumor is resected, and accordingly, these patients require prolonged imaging follow-up. Although the computed tomographic findings of these metastases have been extensively reviewed in the literature, little has been written about the magnetic resonance imaging appearance of these metastases. Pancreatic metastases from RCC are typically T1 hypointense and T2 hyperintense. After intravenous administration of gadolinium, they are typically hypervascular and less commonly hypovascular. Chemical shift and diffusion-weighted imaging can aid in the diagnosis of these metastases. PMID:26324216

  16. Surgery for periampullary and pancreatic carcinoma: a Liverpool experience.

    PubMed Central

    Kingsnorth, A. N.

    1997-01-01

    The development of a single-surgeon specialist referral practice for pancreatic surgery which evolved over an 8 year period is described. Source of referral, protocol for patient management, and operative strategy are outlined. Preoperative endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy, and stent placement where possible (85% of cases), high-resolution contrast-enhanced CT and standard pylorus-preserving pancreaticoduodenectomy with a unique reconstructive technique were employed. In 105 patients receiving curative resection for pancreatic or periampullary tumours, the overall operative mortality was 4.8% and overall morbidity 26%. Actuarial 5-year survival rates were 11% for pancreatic carcinoma and 34% for ampullary carcinoma. Resectability rate was 81% without the use of time-consuming and expensive imaging techniques for staging such as laparoscopy, intraoperative ultrasound or laparoscopic ultrasound. No specific regimen of perioperative chemoirradiation was utilised over the study period. To achieve comparable results it is recommended that patients should be referred to regional specialist surgeons in whose hands mortality and morbidity is low, costs reduced and training of pancreatic surgeons can be undertaken. PMID:9244068

  17. Contrast-Enhanced Ultrasonography of Pancreatic Carcinoma: Correlation with Pathologic Findings.

    PubMed

    Wang, Yanjie; Yan, Kun; Fan, Zhihui; Sun, Li; Wu, Wei; Yang, Wei

    2016-04-01

    We concluded that contrast-enhanced ultrasound (CEUS) has clinical value in identifying the pathologic changes of pancreatic carcinomas. Forty-three patients diagnosed with pancreatic carcinoma through surgery were retrospectively investigated. CEUS examinations were performed on all patients before surgery. Enhancement patterns on CEUS were observed. Time-intensity curves of CEUS were generated for the regions of interest in the pancreas, and quantitative parameters were obtained. Resected cancer specimens were stained with hematoxylin and eosin for histologic analysis, and the microvascular density (MVD) of the specimens was determined by CD34 immunohistochemical staining. Enhancement patterns of CEUS were compared with histopathologic findings in pancreatic carcinomas. Correlations between time-intensity curve parameters and microvascular density were analyzed. Twenty cases manifested centripetal enhancement, and 23 cases, global enhancement. The amount of tumor necrosis or mucus in the centripetally enhanced pancreatic carcinomas was greater than that in the globally enhanced pancreatic carcinomas (p = 0.027). Thirty-eight of 43 (88.4%) pancreatic carcinomas manifested hypo-enhancement with a maximum intensity (IMAX) <90%. Contrast arrival time in pancreatic carcinoma was longer than that in adjacent pancreatic tissue (p < 0.05). IMAX was positively correlated with microvascular density (r = 0.577, p < 0.05). We concluded that CEUS manifestations could reflect the histologic changes of pancreatic carcinomas and CEUS can be used to evaluate blood perfusion of tumors, as IMAX is positively correlated with microvascular density. PMID:26806440

  18. Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma

    PubMed Central

    Hagmann, Wolfgang; Faissner, Ralf; Schnolzer, Martina; Lohr, Matthias; Jesnowski, Ralf

    2011-01-01

    Pancreatic cancer ranks among the tumors most resistant to chemotherapy. Such chemoresistance of tumors can be mediated by various cellular mechanisms including dysregulated apoptosis or ineffective drug concentration at the intracellular target sites. In this review, we highlight recent advances in experimental chemotherapy underlining the role of cellular transporters in drug resistance. Such contribution to the chemoresistant phenotype of tumor cells or tissues can be conferred both by uptake and export transporters, as demonstrated by in vivo and in vitro data. Our studies used human pancreatic carcinoma cells, cells stably transfected with human transporter cDNAs, or cells in which a specific transporter was knocked down by RNA interference. We have previously shown that 5-fluorouracil treatment affects the expression profile of relevant cellular transporters including multidrug resistance proteins (MRPs), and that MRP5 (ABCC5) influences chemoresistance of these tumor cells. Similarly, cell treatment with the nucleoside drug gemcitabine or a combination of chemotherapeutic drugs can variably influence the expression pattern and relative amount of uptake and export transporters in pancreatic carcinoma cells or select for pre-existing subpopulations. In addition, cytotoxicity studies with MRP5-overexpressing or MRP5-silenced cells demonstrate a contribution of MRP5 also to gemcitabine resistance. These data may lead to improved strategies of future chemotherapy regimens using gemcitabine and/or 5-fluorouracil. PMID:24212609

  19. Lymphocytic mural folliculitis and pancreatic carcinoma in a cat.

    PubMed

    Lobetti, Remo

    2015-06-01

    A 9-year-old castrated domestic shorthair cat was presented with a 6 week history of progressive non-pruritic alopecia, polyphagia and weight loss. A diagnosis of lymphocytic mural folliculitis was made and the cat was treated with a combination of prednisolone and ciclosporin; this produced an improvement in the alopecia but no resolution. Sixteen months after the initial assessment and diagnosis, the cat was re-evaluated for intermittent vomiting and weight loss with normal appetite. On examination the dermatopathy was still evident and a mass involving the duodenum and pancreas was present, which was diagnosed as a pancreatic carcinoma. From this case it would appear that lymphocytic mural folliculitis might be an early dermatological manifestation of pancreatic neoplasia. PMID:25406176

  20. Chemotherapy for advanced poorly differentiated pancreatic neuroendocrine carcinoma.

    PubMed

    Ikeda, Masafumi; Okuyama, Hiroyuki; Takahashi, Hideaki; Ohno, Izumi; Shimizu, Satoshi; Mitsunaga, Shuichi; Kondo, Shunsuke; Morizane, Chigusa; Ueno, Hideki; Okusaka, Takuji

    2015-08-01

    Pancreatic neuroendocrine carcinoma (P-NEC) resembles small cell lung carcinoma in its biologic and clinical features, such as rapid growth and relatively high sensitivity to platinum-based chemotherapy. And, etoposide plus cisplatin (EP) or irinotecan plus cisplatin (IP), recommended by guidelines for the treatment of small cell lung carcinoma, has also been widely used for the treatment of unresectable NEC. Both regimens have been demonstrated to show favorable efficacy and have been acknowledged as de facto standard regimens for unresectable NEC, although it remains unclear which of the two regimens might yield more favorable outcomes. Therefore, a phase III trial of EP vs. IP has been planned for unresectable gastrointestinal, hepatobiliary or pancreatic NEC by the Japan Clinical Oncology Group. For patients with unresectable NEC who are refractory or intolerant to these regimens, no standard regimens have been established. Everolimus, an mTOR inhibitor, is likely to be effective in such patients, as there have been sporadic reports of the usefulness of everolimus in the treatment of P-NEC. A multicenter phase II trial is underway to elucidate the efficacy and safety of everolimus in patients with P-NEC who are refractory or intolerant to EP or IP. PMID:25755102

  1. Pancreatic metastasis resulting from thymic neuroendocrine carcinoma: A case report

    PubMed Central

    DU, YANG; WANG, YING; TANG, JIE; GE, JUN; QIN, QING; JIANG, LI; LIU, XIAOKE; ZHU, XIANGLAN; WANG, YONGSHENG

    2016-01-01

    Thymic neuroendocrine carcinoma (NEC) is a rare type of cancer. Unlike other thymic epithelial tumors and carcinoids originating in other locations, thymic NEC possesses a more aggressive biological behavior, including invasion to proximal structures, local recurrence and distant hematogenous metastasis. Distant metastasis is often observed in the bones, lungs, spleen, liver and adrenal glands. However, pancreatic metastasis resulting from thymic NEC is extremely uncommon, and only a few cases of patients with this disease have been reported. The current study presents the case of a patient with pancreatic metastasis resulting from thymic NEC. The patient was admitted to hospital with an anterior mediastinal neoplasm, which was identified using chest enhanced computed tomography. The patient underwent a monobloc excision of the tumor with resection of involved structures. Subsequently, a pathological diagnosis of atypical thymic carcinoid was provided, according to the morphological characteristics observed and the expression of neuroendocrine markers, as identified by immunohistochemistry. Following surgery, the patient received adjuvant chemotherapy and radiotherapy. However, ~2 years after surgery, metastasis at the pancreatic head was identified. The patient underwent a total pancreatectomy and splenectomy, and did not receive any post-operative therapies; however, the patient succumbed to the disease 9 months following surgery. Overall, the results from the present study demonstrate the clinical features of thymic NEC, which may aid with the diagnosis of this rare disease in other patients. PMID:26998098

  2. Macrophage Polarization in Pancreatic Carcinoma: Role of Heparanase Enzyme

    PubMed Central

    Hermano, Esther; Meirovitz, Amichay; Meir, Karen; Nussbaum, Gabriel; Appelbaum, Limor; Peretz, Tamar

    2014-01-01

    Background Tumor microenvironment, and particularly tumor-associated macrophages (TAMs), represent a key contributing factor in pancreatic ductal adenocarcinoma (PDAC) pathogenesis. Here we report that heparanase (predominant enzyme degrading heparan sulfate, the main polysaccharide found at the cell surface and extracellular matrix) directs tumor-promoting behavior of TAM in PDAC. Methods A mouse model of heparanase-overexpressing pancreatic carcinoma (n = 5 mice/group), tumor-associated macrophages ex vivo, primary wild-type and heparanase-null macrophages, and histological specimens from PDAC patients (n = 16), were analyzed, applying immunostaining, enzyme-linked immunosorbent assay, real-time reverse transcriptionpolymerase chain reaction, cell proliferation, and heparanase activity assays. All statistical tests are two-sided. Results We found that overexpression of heparanase is associated with increased TAM infiltration in both experimental (P = .002) and human (P = .01) PDAC. Moreover, macrophages derived from heparanase-rich tumors (which grew faster in mouse hosts), display pronounced procancerous phenotype, evidenced by overexpression of MSR-2, IL-10, CCL2, VEGF, and increased production of IL-6, an important player in PDAC pathogenesis. Furthermore, in vitro heparanase enzymerendered macrophages (stimulated by necrotic cells which are often present in PDAC tissue) procancerous, as exemplified by their enhanced production of key cytokines implicated in PDAC (including IL-6), as well as by their ability to induce STAT3 signaling and to augment pancreatic carcinoma cell proliferation. In agreement, we observed activation of STAT3 in experimental and clinical specimens of heparanase-overexpressing PDAC. Conclusions Our findings underscore a novel function of heparanase in molecular decision-making that guides cancer-promoting action of TAM and imply that heparanase expression status may become highly relevant in defining a target patient subgroup that is likely to benefit the most from treatment modalities targeting TAM/IL-6/STAT3. PMID:25326645

  3. Expression of PTEN and KAI1 tumor suppressor genes in pancreatic carcinoma and its association with different pathological factors

    PubMed Central

    HUANG, WEIDONG; YANG, JIE; REN, JUN; TANG, JIANJUN

    2016-01-01

    Pancreatic carcinoma is a common cancer type with a poor prognosis. The aim of the present study was to examine the expression of tumor suppressor genes phosphatase and tensin homolog deleted in chromosome 10 (PTEN) and KAI1 in pancreatic carcinoma and its association with clinical pathological factors. A total of 50 hospitalized cases of pancreatic cancer including 28 males and 22 females aged 31–82 years were included in the present study. Ten cases of normal pancreatic tissue were obtained from cadavers and served as the controls. The pancreatic specimens were embedded in paraffin blocks and slides were prepared for immunohistochemical analysis to determine the expression of PTEN and KAI1 in normal pancreatic tissue and pancreatic carcinoma samples. The positive expression rate of PTEN in the normal pancreatic tissue was higher than that in pancreatic carcinoma (P<0.05), while the positive expression rate of KAI1 in the normal pancreatic tissue was lower than that in pancreatic carcinoma (P<0.05). Pathological factors such as clinical stage of disease, histological grade and the presence or absence of lymphatic metastasis significantly affected the expression of PTEN and KAI1 (P<0.05). In conclusion, the positive expression of PTEN and KAI1 in pancreatic carcinoma is closely associated with the development of pancreatic carcinoma. PMID:26870247

  4. 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.

  5. Role of heparanase in radiation-enhanced invasiveness of pancreatic carcinoma

    PubMed Central

    Meirovitz, Amichay; Hermano, Esther; Lerner, Immanuel; Zcharia, Eyal; Pisano, Claudio; Peretz, Tamar; Elkin, Michael

    2011-01-01

    Pancreatic cancer is characterized by very low survival rates because of high intrinsic resistance to conventional therapies. Ionizing radiation (IR)-enhanced tumor invasiveness is emerging as one mechanism responsible for the limited benefit of radiotherapy in pancreatic cancer. In this study, we establish the role of heparanase - the only known mammalian endoglycosidase that cleaves heparan sulfate - in modulating the response of pancreatic cancer to radiotherapy. We found that clinically relevant doses of IR augment the invasive capability of pancreatic carcinoma cells in vitro and in vivo by upregulating heparanase. Changes in the levels of the transcription factor Egr-1 occurred in pancreatic cancer cells following radiation, underlying the stimulatory effect of IR on heparanase expression. Importantly, the specific heparanase inhibitor SST0001 abolished IR-enhanced invasiveness of pancreatic carcinoma cells in vitro, while combined treatment with SST0001 and IR, but not IR alone, attenuated the spread of orthotopic pancreatic tumors in vivo. Taken together, our results suggest that combining radiotherapy with heparanase inhibition is an effective strategy to prevent tumor resistance and dissemination, observed in many IR-treated pancreatic cancer patients. Further, the molecular mechanism underlying heparanase upregulation in pancreatic cancer that we identified in response to IR may help identify patients in which radiotherapeutic intervention may confer increased risk of metastatic spread, where anti-heparanase therapy may be particularly beneficial. PMID:21447736

  6. Image-Guided Intensity-Modulated Radiotherapy for Pancreatic Carcinoma

    PubMed Central

    Fuss, Martin; Wong, Adrian; Fuller, Clifton D.; Salter, Bill J.; Fuss, Cristina; Thomas, Charles R.

    2007-01-01

    Purpose To present the techniques and preliminary outcomes of ultrasound-based image-guided intensity-modulated radiotherapy (IG-IMRT) for pancreatic cancer. Materials and Methods Retrospective analysis of 41 patients treated between November 2000 and March 2005 with IG-IMRT to mean total doses of 55 Gy (range, 4564 Gy). We analyzed the clinical feasibility of IG-IMRT, dosimetric parameters, and outcomes, including acute gastrointestinal toxicity (RTOG grading). Survival was assessed for adenocarcinoma (n = 35) and other histologies. Results Mean daily image-guidance corrective shifts were 4.8 4.3 mm, 7.5 7.2 mm, and 4.6 5.9 mm along the x-, y-, and z-axes, respectively (mean 3D correction vector, 11.7 8.4 mm). Acute upper gastrointestinal toxicity was grade 01 in 22 patients (53.7%), grade 2 in 16 patients (39%), and grade 3 in 3 patients (7.3%). Lower gastrointestinal toxicity was grade 01 in 32 patients (78%), grade 2 in 7 patients (17.1%), and grade 4 in 2 patients (4.9%). Treatment was stopped early in 4 patients following administration of 30 to 54 Gy. Median survival for adenocarcinoma histology was 10.3 months (18.6 months in patients alive at analysis; n = 8) with actuarial 1- and 2-year survivals of 38% and 25%, respectively. Conclusion Daily image-guidance during delivery of IMRT for pancreatic carcinoma is clinically feasible. The data presented support the conclusion that safety margin reduction and moderate dose escalation afforded by implementation of these new radiotherapy technologies yields preliminary outcomes at least comparable with published survival data. PMID:19262697

  7. Triple approach strategy for patients with locally advanced pancreatic carcinoma

    PubMed Central

    Giardino, Alessandro; Girelli, Roberto; Frigerio, Isabella; Regi, Paolo; Cantore, Maurizio; Alessandra, Auriemma; Lusenti, Annita; Salvia, Roberto; Bassi, Claudio; Pederzoli, Paolo

    2013-01-01

    Background Radiofrequency ablation (RFA) is a relatively new technique, applied to metastatic solid tumours which, in recent studies, has been shown to be feasible and safe on locally advanced pancreatic carcinoma (LAPC). RFA can be combined with radio-chemotherapy (RCT) and intra-arterial plus systemic chemotherapy (IASC). The aim of this study was to investigate the impact on the prognosis of a multimodal approach to LAPC and define the best timing of RFA. Methods This is a retrospective observational study of patients who have consecutively undergone RFA associated with multiple adjuvant approaches. Results Between February 2007 and December 2011, 168 consecutive patients were treated by RFA, of which 107 were eligible for at least 18 months of follow-up. Forty-seven patients (group 1) underwent RFA as an up-front treatment and 60 patients as second treatment (group 2) depending on clinician choice. The median overall survival (OS) of the whole series was 25.6 months: 14.7 months in the group 1 and 25.6 months in the group 2 (P = 0.004). Those patients who received the multimodal treatment (RFA, RCT and IASC-triple approach strategy) had an OS of 34.0 months. Conclusions The multimodal approach seems to be feasible and associated with an improved longer survival rate. PMID:23458679

  8. Perspectives of TGF-? inhibition in pancreatic and hepatocellular carcinomas

    PubMed Central

    Tijeras-Raballand, Annemila; de Mestier, Louis; Cros, Jrome; 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-? (TGF-?) as a common key-signalling mediator, involved in epithelial-to-mesenchymal transition, invasion, and stroma-tumour dialogue. Recently, novel drugs blocking the TGF-? pathway have entered clinical evaluation demonstrating activity in patients with advanced PDAC and HCC. TGF-? 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-? 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-? as a target for therapeutic intervention in PDAC and HCC, and explore perspectives to optimize TGF-? inhibition therapy PMID:24393789

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

    PubMed Central

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

    2011-01-01

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

  10. Transformation of Nonfunctioning Pancreatic Neuroendocrine Carcinoma Cells into Insulin Producing Cells after Treatment with Sunitinib

    PubMed Central

    Ohn, Jung Hun; Kim, Yeong Gi; Lee, Se-Hoon

    2013-01-01

    We report a rare case of severe hypoglycemia after sunitinib treatment for pancreatic neuroendocrine carcinoma. We describe the initial clinical presentation, laboratory results, pathologic findings, and managment in a patient with a nonfunctioning pancreatic neuroendocrine carcinoma with liver metastases who developed life threatening hypoglycemia after 2 months of sunitinib therapy. A 46-year-old woman presented to the emergency department with loss of consciousness from hypoglycemia. Serum C-peptide and insulin levels at fasting state revealed that the hypoglycemia resulted from endogenous hyperinsulinemia. She had been diagnosed with nonfunctioning pancreatic neuroendocrine carcinoma based on a biopsy of metastatic cervical lymph node and was being treated with sunitinib, a small molecule tyrosine kinase inhibitor. Immunohistochemical stain of the metastatic liver mass demonstrated that the initially nonfunctioning neuroendocrine carcinoma cells had changed into insulin-producing cells after sunitinib therapy. Transarterial chemoembolization of the liver masses and systemic chemotherapy with streptozotocin/adriamycin relieved the hypoglycemia. A nonfunctioning pancreatic neuroendocrine carcinoma was transformed into an insulin-producing tumor after treatment with sunitinib, causing endogenous hyperinsulinemia and severe hypoglycemia. PMID:24396670

  11. Omental acinar cell carcinoma of pancreatic origin in a child: a clinicopathological rarity.

    PubMed

    Sharma, Shilpa; Agarwal, Shipra; Nagendla, Murali Krishna; Gupta, Devendra K

    2016-03-01

    A 6-year-old boy presented with a large subhepatic mass associated with pain abdomen. Exploration revealed a tumor in lesser omentum, completely separate from the normal pancreas that was excised completely. Histopathology suggested acinar cell carcinoma of pancreatic origin in an ectopic location. The child is well at 5months follow-up. PMID:26694824

  12. Pathology and Surgical Treatment of High-Grade Pancreatic Neuroendocrine Carcinoma: an Evolving Landscape.

    PubMed

    Haugvik, Sven-Petter; Kaemmerer, Daniel; Gaujoux, Sebastien; Labori, Knut Jørgen; Verbeke, Caroline Sophie; Gladhaug, Ivar Prydz

    2016-05-01

    Pancreatic neuroendocrine neoplasms (PNENs) are rare, accounting for less than 5 % of all pancreatic tumors. High-grade pancreatic neuroendocrine carcinomas (hgPNECs) represent about 5 % of all PNENs. They show highly aggressive behavior with dismal prognosis. Throughout the last two decades, there has been a notable progress in basic and clinical research of PNENs and a therapeutic trend towards both more aggressive and minimally invasive surgery. Despite these advances, hgPNECs as a distinct clinical entity remains largely unexplored among surgeons. This review of current development in pathology reporting and surgical treatment of hgPNECs aims at increasing the awareness of an evolving field in pancreatic surgery. PMID:26984415

  13. [Successful endoscopic transpapillary pancreaticobiliary drainage for omental panniculitis by hepatocellular carcinoma complicated by biliary fistula and pancreatic fistula].

    PubMed

    Shindo, Yuji; Miyatani, Hiroyuki; Uehara, Takeshi; Ikeya, Takashi; Yamanaka, Kenichi; Ikeda, Masatoshi; Tokai, Kouichi; Ushimaru, Shinya; Matsumoto, Satohiro; Asano, Takeharu; Takamatsu, Toru; Fukunishi, Masanori; Iwaki, Takaaki; Sagihara, Yoshinori; Asabe, Shinichi; Yoshida, Yukio

    2012-07-01

    A 78-year-old man with hepatocellular carcinoma treated by chemoembolization and percutaneous ethanol injection was admitted to our hospital because of acute abdomen. The CT scan showed biliary fistula caused by hepatocellular carcinoma protruding from S3. Endoscopic retrograde cholangiopancreatography showed disruption of an intrahepatic duct and the main pancreatic duct, and contrast agent leaked into the peritoneal cavity from each duct. Omental panniculitis with biliary fistula and pancreatic fistula was diagnosed. The symptoms improved by endoscopic nasobiliary drainage and endoscopic pancreatic stenting. On the 13th day after admission, we added endoscopic nasopancreatic drainage because his abdominal pain had been exacerbated by pancreatic juice leakage. Omental panniculitis by hepatocellular carcinoma complicated by biliary fistula and pancreatic fistula is extremely rare. Endoscopic transpapillary pancreaticobiliary drainage was effective for omental panniculitis in this case. PMID:22790630

  14. Distinct Claudin Expression Profiles of Hepatocellular Carcinoma and Metastatic Colorectal and Pancreatic Carcinomas

    PubMed Central

    Holczbauer, Ágnes; Gyöngyösi, Benedek; Lotz, Gábor; Szijártó, Attila; Kupcsulik, Péter; Schaff, Zsuzsa

    2013-01-01

    Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 colorectal adenocarcinomas (CRLMs) and 15 pancreatic adenocarcinomas (PLMs) were studied together with paired surrounding non-tumorous liver samples and 5 normal liver samples. Strong claudin-3 and -7 immunohistochemical positivities were detected in CRLM samples, each with significantly stronger staining when compared with HCC and PLM groups. Claudin-1 protein was found highly expressed in CRLM, in contrast to lower expression in PLM and HCC. CRLMs and PLMs also were strongly positive for claudin-4, while being virtually undetectable in HCC. Claudin-2 showed strong positivity in non-tumorous liver tissue, whereas significantly weaker positivity was observed in all tumors. Differences in mRNA expression were mostly similar to those found by immunohistochemistry. In conclusion, HCC and both CRLM and PLM display distinct claudin expression profiles, which might provide better understanding of the pathobiology of these lesions and might be used for differential diagnosis. PMID:23385421

  15. 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.

  16. Percutaneous ethanol ablation of hepatocellular carcinoma: Periprocedural onset alcohol toxicity and pancreatitis following conventional percutaneous ethanol ablation treatment

    PubMed Central

    Burton, Kirsteen Rennie; O’Dwyer, Helena; Scudamore, Charles

    2009-01-01

    A novel case of acute pancreatitis in a patient treated with percutaneous ethanol injection (PEI) ablation for hepatocellular carcinoma is described. The most commonly reported adverse effects of PEI are hepatic or peritoneal hemorrhage, hepatic insufficiency or infarction. There are no previous reports of fatal acute pancreatitis as a result of conventional PEI. PMID:19668800

  17. 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

  18. Clinical value of serum CA19-9 levels in evaluating resectability of pancreatic carcinoma

    PubMed Central

    Zhang, Shun; Wang, Yi-Ming; Sun, Chuan-Dong; Lu, Yun; Wu, Li-Qun

    2008-01-01

    AIM: To evaluate the clinical value of serum CA19-9 levels in predicting the respectability of pancreatic carcinoma according to receiver operating characteristic (ROC) curve analysis. METHODS: Serum CA19-9 levels were measured in 104 patients with pancreatic cancer which were possible to be resected according to the imaging. ROC curve was plotted for the CA19-9 levels. The point closest to the upper left-hand corner of the graph were chosen as the cut-off point. The sensitivity, specificity, positive and negative predictive values of CA19-9 at this cut-off point were calculated. RESULTS: Resectable pancreatic cancer was detected in 58 (55.77%) patients and unresectable pancreatic cancer was detected in 46 (44.23%) patients. The area under the ROC curve was 0.918 and 95% CI was 0.843-0.992. The CA19-9 level was 353.15 U/mL, and the sensitivity and specificity of CA19-9 at this cut-off point were 93.1% and 78.3%, respectively. The positive and negative predictive value was 84.38% and 90%, respectively. CONCLUSION: Preoperative serum CA19-9 level is a useful marker for further evaluating the resectability of pancreatic cancer. Obviously increased serum levels of CA19-9 (> 353.15 U/mL) can be regarded as an ancillary parameter for unresectable pancreatic cancer. PMID:18595144

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

    ClinicalTrials.gov

    2016-01-13

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

  20. Prolonged Survival in a Patient with a Pancreatic Acinar Cell Carcinoma

    PubMed Central

    Ploquin, Anne; Baldini, Capucine; Vuagnat, Perrine; Makhloufi, Samira; Desauw, Christophe; Hebbar, Mohamed

    2015-01-01

    Pancreatic acinar cell carcinoma (ACC) is a rare entity. Herein we present the case of a 50-year-old male patient with an unlimited mass on the pancreatic corpus and tail with peripancreatic effusion and multiple metastases in the liver and spleen. A liver biopsy showed a pancreatic ACC. The patient received 9 cycles of gemcitabine plus oxaliplatin (GEMOX regimen), which had to be stopped because of a persistent grade 2 neuropathy. A CT scan showed complete response after 14 years. At the age of 61 years, a localized prostatic cancer was diagnosed, treated by prostatectomy. The patient carried a BRCA2 mutation. None of the precedent case reports describe a chemosensibility to the GEMOX regimen. In spite of the lack of study in these patients, chemotherapy with oxaliplatin seems to be the most effective. Long survival can be expected. PMID:26600777

  1. Prolonged Survival in a Patient with a Pancreatic Acinar Cell Carcinoma.

    PubMed

    Ploquin, Anne; Baldini, Capucine; Vuagnat, Perrine; Makhloufi, Samira; Desauw, Christophe; Hebbar, Mohamed

    2015-01-01

    Pancreatic acinar cell carcinoma (ACC) is a rare entity. Herein we present the case of a 50-year-old male patient with an unlimited mass on the pancreatic corpus and tail with peripancreatic effusion and multiple metastases in the liver and spleen. A liver biopsy showed a pancreatic ACC. The patient received 9 cycles of gemcitabine plus oxaliplatin (GEMOX regimen), which had to be stopped because of a persistent grade 2 neuropathy. A CT scan showed complete response after 14 years. At the age of 61 years, a localized prostatic cancer was diagnosed, treated by prostatectomy. The patient carried a BRCA2 mutation. None of the precedent case reports describe a chemosensibility to the GEMOX regimen. In spite of the lack of study in these patients, chemotherapy with oxaliplatin seems to be the most effective. Long survival can be expected. PMID:26600777

  2. Acute oxalate nephropathy due to pancreatic atrophy in newly diagnosed pancreatic carcinoma.

    PubMed

    Moinuddin, Irfan; Bala, Asif; Ali, Butool; Khan, Husna; Bracamonte, Erika; Sussman, Amy

    2016-02-01

    Acute oxalate nephropathy can occur due to primary hyperoxaluria and secondary hyperoxaluria. The primary hyperoxalurias are a group of autosomal recessive disorders of endogenous oxalate overproduction. Secondary hyperoxaluria may occur as a result of excess dietary intake, poisoning with oxalate precursors (ethylene glycol), or enteric hyperoxaluria. The differential diagnosis of enteric hyperoxaluria includes inflammatory bowel disease, short bowel syndrome, bariatric surgery (with jejunoileal bypass or Roux-en-Y gastric bypass), celiac disease, partial colectomy, and chronic pancreatitis. The common etiology in all these processes is fat malabsorption, steatorrhea, saponification of calcium, and absorption of free oxalate. Hyperoxaluria causes increased urinary oxalate excretion, urolithiasis (promoted by hypovolemia, decreased urinary pH caused by metabolic acidosis, and decreased citrate and magnesium concentrations in urine), tubulointerstitial oxalate deposits, and tubulointerstitial nephritis. We report a rare case of acute oxalate nephropathy due to pancreatic atrophy and exocrine insufficiency caused by newly diagnosed pancreatic cancer. PMID:26614399

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

    PubMed Central

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

    2007-01-01

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

  4. 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.

  5. [The value of poly-C-specific serum ribonuclease and CEA in the diagnosis of pancreatic carcinoma (author's transl)].

    PubMed

    Hlbling, N; Funovics, J; Euler, J; Karner, J; Zch, G; Sauermann, G

    1981-11-01

    The possible role of poly(C)RNase serum activity and CEA serum level for early detection and differentiation of pancreatic carcinoma and its specificity and valuability were critically analyzed: Serum RNase (median, min-max) with polycytidin as substrate was determined in 13 "normal" patients (14.6 E/ml, 4.3--29.8 E/ml), 16 patients with pancreatic cancer (T3 or metastases) (17.6 E/ml, 6--49-9 E/ml), 15 patients with chronic pancreatitis (9.5 E/ml, 4.9--26.5 E/ml), 7 patients with acute pancreatitis (14.2 E/ml, 5.5--67.3 ng/ml), and 13 patients with other types of malignomas (15 E/ml, 4.3--42.5 E/ml). Serum CEA level was evaluated in 18 "normal" patients (1.15 ng/ml, 0--4.3 ng/ml), 12 patients with pancreatic carcinoma (T3 or metastases) (6.5 mg/ml, 2--456.5 ng/ml), 13 patients with chronic pancreatitis (2.3 ng/ml, 0--8.5 ng/ml), 8 patients with acute pancreatitis (2.7 ng/ml, 0.1--4.6 ng/ml) and 5 patients without operative verification of suspected pancreatic carcinoma (0.9 ng/ml, 0--1.7 ng/ml). The serum RNase activity in pancreatic cancer patients did not show any significant increase in comparison to the other groups, and these patients could not be distinguished from those with the other diseases when excluding other factors influencing serum RNase level such as: Renal insufficiency, nutrition, age, sex. Their CEA level was significantly higher in comparison to the other groups (p less than 0.05). Using 2.5 ng/ml as the limit, the sensitivity was found to be 80% (10/12 of pancreatic carcinomas positive) and the specificity being 70.5% (31/44 of other groups without malignant diseases negative). The presented study and data in the literature show that poly (C) RNase measurement is not useful in early detection of pancreatic carcinoma, but the CEA test could be helpful in the differential diagnosis of pancreatic diseases due to its specificity (70.5%) and seems to be valuable in detection of residual and in monitoring for recurrent pancreatic carcinoma in view of its sensitivity and correlation with the stage of cancer. PMID:7311390

  6. An extremely rare case of pancreatic metastasis of esophageal squamous cell carcinoma.

    PubMed

    Okamoto, Hiroshi; Hara, Yasuyuki; Chin, Masahiro; Hagiwara, Motohisa; Onodera, Yuji; Horii, Shinichiro; Shirahata, Yasuhiro; Kamei, Takashi; Hashizume, Eiji; Ohuchi, Noriaki

    2014-01-14

    We report a rare case of a 68-year-old male with metachronous pancreatic metastasis that was resected 2 years after salvage esophagectomy for local recurrence of esophageal squamous cell carcinoma (ESCC). Two years and 8 mo ago, he had undergone definitive chemoradiotherapy for the lower thoracic ESCC and achieved a complete response. Chemoradiotherapy used the protocol of the Japan Clinical Oncology Group trial 9906. Approximately 8 mo later, he developed a local recurrence of the ESCC and underwent thoracoscopic salvage esophagectomy followed by reconstruction with a conduit colon graft via a subcutaneous route. Recently, a tumor of the pancreatic body was found on routine follow-up computed tomography (CT). The tumor diameter was 15 mm on CT, and the maximum standardized uptake value of the lesion was 5.49 at 18F-2-fluoro-2-deoxy-D-glucose positron-emission tomography, strongly suggesting pancreatic cancer. In addition, all tumor markers were within the reference intervals. Therefore, distal pancreatectomy was performed with the resultant histological diagnosis being confirmed as pancreatic metastasis of the ESCC. He was treated with adjuvant chemotherapy, and there has been no evidence of recurrence 9 mo after the surgery. Resection of pancreatic metastasis offers a good prognosis and should be considered for solitary ESCC metastasis. PMID:24574730

  7. An extremely rare case of pancreatic metastasis of esophageal squamous cell carcinoma

    PubMed Central

    Okamoto, Hiroshi; Hara, Yasuyuki; Chin, Masahiro; Hagiwara, Motohisa; Onodera, Yuji; Horii, Shinichiro; Shirahata, Yasuhiro; Kamei, Takashi; Hashizume, Eiji; Ohuchi, Noriaki

    2014-01-01

    We report a rare case of a 68-year-old male with metachronous pancreatic metastasis that was resected 2 years after salvage esophagectomy for local recurrence of esophageal squamous cell carcinoma (ESCC). Two years and 8 mo ago, he had undergone definitive chemoradiotherapy for the lower thoracic ESCC and achieved a complete response. Chemoradiotherapy used the protocol of the Japan Clinical Oncology Group trial 9906. Approximately 8 mo later, he developed a local recurrence of the ESCC and underwent thoracoscopic salvage esophagectomy followed by reconstruction with a conduit colon graft via a subcutaneous route. Recently, a tumor of the pancreatic body was found on routine follow-up computed tomography (CT). The tumor diameter was 15 mm on CT, and the maximum standardized uptake value of the lesion was 5.49 at 18F-2-fluoro-2-deoxy-D-glucose positron-emission tomography, strongly suggesting pancreatic cancer. In addition, all tumor markers were within the reference intervals. Therefore, distal pancreatectomy was performed with the resultant histological diagnosis being confirmed as pancreatic metastasis of the ESCC. He was treated with adjuvant chemotherapy, and there has been no evidence of recurrence 9 mo after the surgery. Resection of pancreatic metastasis offers a good prognosis and should be considered for solitary ESCC metastasis. PMID:24574730

  8. 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.

  9. Paclitaxel and concurrent radiation for locally advanced pancreatic carcinoma.

    PubMed

    Safran, H; Cioffi, W; Iannitti, D; Mega, A; Akerman, P

    1998-11-01

    An effective local-regional therapy is needed for adenocarcinomas of the pancreas. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton NJ) may enhance the effect of radiation therapy. Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent radiation (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer (NSCLC). This suggested that paclitaxel/RT was a rationale treatment approach for other malignancies which frequently harbor p53 mutations such as upper gastrointestinal malignancies. We have completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancers. The maximum tolerated dose (MTD) of paclitaxel was 50 mg/m2/week for 6 weeks with abdominal radiation. The dose limiting toxicities were abdominal pain within the radiation field, nausea and anorexia. Twenty-five patients with locally advanced pancreatic cancer have now completed treatment at the phase II dose level of paclitaxel 50 mg/m2/week with 50 Gy concurrent RT. Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions in 2 patients, asymptomatic grade 4 neutropenia in 3 patients, and non-neutropenic biliary sepsis in 1 patient. Of the first 22 assessable patients treated at the phase II study, 8 obtained a partial response (PR) for a preliminary response rate of 36%. These findings demonstrate that paclitaxel/RT is well tolerated with substantial activity for locally advanced pancreatic cancer. PMID:9792903

  10. Zerumbone, a Southeast Asian Ginger Sesquiterpene, Induced Apoptosis of Pancreatic Carcinoma Cells through p53 Signaling Pathway.

    PubMed

    Zhang, Songyan; Liu, Qiaojing; Liu, Yanju; Qiao, Hong; Liu, Yu

    2012-01-01

    Pancreatic carcinoma is one common cancer with gradually increasing incidence during the past several decades. However, currently the candidate drugs to suppress pancreatic cancer remain lacking. This research was carried out to investigate if zerumbone, a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith, will produce the anticancer effects on pancreatic carcinoma cell lines. The results showed that zerumbone concentration, and time, dependently produced inhibitory actions on cell viability of PANC-1 cells. In addition, Hoechst 33342, AO/EB, TUNEL staining, and caspase-3 activity assay further showed that zerumbone induced apoptosis of PANC-1 cells. The expression of p53 protein was markedly upregulated, and the p21 level was also obviously elevated in zerumbone-treated PANC-1 cells. Moreover, ROS production was increased by about 149% in PANC-1 cells treated by zerumbone 30 μM. Zerumbone also produced the same antitumor activity in pancreatic carcinoma cell lines SW1990 and AsPC-1. In summary, we found that zerumbone was able to induce apoptosis of pancreatic carcinoma cell lines, indicating to be a promising treatment for pancreatic cancer. PMID:22454691

  11. Pancreatic panniculitis.

    PubMed

    Garca-Romero, Diana; Vanaclocha, Francisco

    2008-10-01

    Pancreatic panniculitis is an uncommon complication of pancreatic disease, most frequently pancreatitis and pancreatic carcinoma. The pathogenesis of the process remains unknown, but possibly the release of pancreatic enzymes may induce permeability of the microcirculation and cause fat necrosis. Clinically, pancreatic panniculitis presents with tender, ill-defined, red-brown nodules in the lower extremities that may ulcerate and drain an oily substance and usually precedes pancreatic disease. The histopathologic picture consists of a mostly lobular panniculitis without vasculitis, with the presence of the typical ghost cells that correspond to necrotic and calcified adipocytes. Treatment should be directed at the underlying pancreatic disease. PMID:18793978

  12. 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.

  13. 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.

  14. Pancreatic ampullary carcinoma with neck metastases: a case report

    PubMed Central

    2009-01-01

    Background An 18-year-old Turkish woman was referred with a 6-week history of rapidly enlarging cervical mass at the left side. Case report She was diagnosed of ampullary carcinoma for which pancreatoduodenectomy was performed 14 months ago. In our patient with a history of malignancy, a rapidly enlarging neck mass was considered a metastasis to the neck. Tumor resection was performed. Histopathological examination revealed the metastasis of the precedent ampullary adenocarcinoma. Conclusion Surgery does not improve survival for advanced metastatic ampullary cancer however, it can be mandatory in specific conditions as our patient. PMID:19946517

  15. Pancreatic undifferentiated rhabdoid carcinoma: KRAS alterations and SMARCB1 expression status define two subtypes.

    PubMed

    Agaimy, Abbas; Haller, Florian; Frohnauer, Judith; Schaefer, Inga-Marie; Strbel, Philipp; Hartmann, Arndt; Stoehr, Robert; Klppel, Gnter

    2015-02-01

    Pancreatic undifferentiated carcinoma is a heterogeneous group of neoplasms, including pleomorphic giant cell, sarcomatoid, round cell, and rhabdoid carcinomas, the molecular profiles of which have so far been insufficiently characterized. We studied 14 undifferentiated carcinomas with prominent rhabdoid cells, occurring as advanced tumors in seven females and seven males aged 44-96 years (mean: 65 years). Histologically, 10 tumors qualified as pleomorphic giant cell and 4 as monomorphic anaplastic carcinomas. A glandular component, either in the primary or in the metastases, was seen in 5 out of 14 tumors (4 out of 10 pleomorphic giant cell and 1 out of 4 monomorphic anaplastic subtypes, respectively). Osteoclast-like giant cells were absent. Immunohistochemistry revealed coexpression of cytokeratin and vimentin, and loss of membranous ?-catenin and E-cadherin staining in the majority of cases. Nuclear SMARCB1 (INI1) expression was lost in 4 out of 14 cases (28%), representing all 4 tumors of the monomorphic anaplastic subtype. FISH and mutation testing of KRAS revealed KRAS amplification in 5 out of 13 (38%) and exon 2 mutations in 6 out of 11 (54%) successfully analyzed cases. A strong correlation was found between KRAS alterations (mutation and/or copy number changes) and intact SMARCB1 expression (7 out of 8; 87%). On the other hand, loss of SMARCB1 expression correlated with the absence of KRAS alterations (3 out of 5 cases; 60%). The results suggest that rhabdoid phenotype in pancreatic undifferentiated rhabdoid carcinomas has a heterogeneous genetic background. SMARCB1 loss is restricted to the anaplastic monomorphic subtype and correlates with the absence of KRAS alterations, whereas the pleomorphic giant cell subtype is characterized by KRAS alterations and intact SMARCB1 expression. Recognition and appropriate subtyping of these rare variants might become necessary for future therapeutic strategies. PMID:25103069

  16. Potential plasticity of T regulatory cells in pancreatic carcinoma in relation to disease progression and outcome.

    PubMed

    Vizio, Barbara; Novarino, Anna; Giacobino, Alice; Cristiano, Carmen; Prati, Adriana; Ciuffreda, Libero; Montrucchio, Giuseppe; Bellone, Graziella

    2012-07-01

    CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) are understood to maintain peripheral tolerance to self-antigens and inhibit antitumor immune responses. However, compelling evidence suggests that, Tregs provide no anti-inflammatory protection in the tumor microenvironment, but rather contribute to a T helper 17 (Th17)-driven pro-carcinogenic process. Using three-color flow cytometry, we evaluated the percentage of circulating CD4(+)CD25(+)FoxP3(+) Tregs in the peripheral blood of pancreatic carcinoma patients prior to and after chemotherapy [gemcitabine (GEM) alone, or GEM+oxaliplatin (GEMOX) or bevacizumab+capecitabine+radiotherapy (BEV+CAPE+RT)]. Correlations were sought between Treg counts and plasma levels of cytokines relevant to controlling the Treg/Th17 balance, i.e., interleukin (IL)-23, IL-17A, IL-6 and transforming growth factor ? 1 (TGF-?1), as measured by ELISA and the clinical features of pancreatic cancer. Treg, IL-6 and TGF-?1 levels were higher in locally advanced and metastatic pancreatic carcinoma patients compared to controls. No parameter was correlated with disease stage except IL-6. IL-17A and TGF-?1 were significantly associated with increased risk of poor prognosis. IL-17A was positively correlated with IL-23. Treg and IL-6 levels decreased following GEM monochemotherapy, IL-17A levels decreased after GEMOX, and IL-6 levels were reduced subsequent to BEV+CAPE+RT treatment. IL-23, IL-17A and TGF-?1 levels were significantly lower in patients responding to chemotherapy (partial remission/stable disease) than in nonresponders to chemotherapy (progressive disease). These results suggest an impact of the Treg/Th17-balance in pancreatic carcinoma, highlighting the significance of TGF-?1 and IL-17A as potential prognostic and predictive indicators. Immunological changes induced by mono and/or combined chemotherapy indicate specific windows of opportunity for introducing integrative interventions on a new target in pancreatic cancer, i.e. IL-17A, possibly improving survival in this highly lethal disease. PMID:23060925

  17. CD44 in normal human pancreas and pancreatic carcinoma cell lines.

    PubMed

    Ringel, J; Jesnowski, R; Schmidt, C; Ringel, J; Köhler, H J; Rychly, J; Batra, S K; Löhr, M

    2001-01-01

    CD44 is an integral cell-surface glycoprotein. Overexpression of the CD44 standard (CD44st) and its variants (CD44v) has been implicated in transformation and progression of many cancer types. Here, we investigated expression of CD44st, CD44v3-7, CD44v7/8, and v10 in five human pancreatic tumor cell lines and normal human pancreatic duct cells transfected with the SV40 large T antigen. CD44st and its variant proteins were quantified using immunocytochemistry and flow cytometry. CD44v7 was expressed at low levels, whereas CD44st, CD44v3, CD44 v4, CD44v, and CD44v6 were expressed at moderate levels in all pancreatic tumor cell lines. In contrast, CD44v7/8 and CD44v10 were expressed at very low levels in two out of the five pancreatic tumor cell lines. Overall, staining of CD44st and CD44 variants was significantly weaker compared to another surface molecule, ICAM-1, reported to be overexpressed in pancreatic cancer cells. Furthermore, the SV40 large T transfected duct cells showed only a weak staining for CD44st, CD44v5, and CD44v6. To determine a possible mechanism for the regulation of surface expression of CD44st, v5 and v6, we incubated Panc-1 cells with bFGF, TGF-beta1, EGF, TNFalpha, and IFNgamma. Only IFNgamma affected the CD44 expression by down-regulation of CD44v6. The constitutive expression of CD44 variants seems to be associated with the malignant state of invasive carcinoma. PMID:11135324

  18. Upregulated matrix metalloproteinase-2 and downregulated tissue factor pathway inhibitor-2 are risk factors for lymph node metastasis and perineural invasion in pancreatic carcinoma

    PubMed Central

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

    2015-01-01

    Background Dysregulated expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 is closely associated with tumorigenesis and tumor progression. The aim of this work was to determine the predictive values of MMP-2 and TFPI-2 in identifying lymph node metastasis (LNM) and perineural invasion (PNI) in pancreatic carcinoma. Methods Formalin-fixed and paraffin-embedded tissue samples containing pancreatic carcinoma tissues and their corresponding para-carcinoma tissues were obtained from 122 patients with pancreatic carcinoma. The expression levels of MMP-2 and TFPI-2 were evaluated by immunohistochemistry. The roles of MMP-2 and TFPI-2 in predicting LNM and PNI in pancreatic carcinoma were analyzed. Results The level of MMP-2 expression was markedly increased in pancreatic carcinoma tissues (76.9%) compared with para-carcinoma tissues (29.2%; P<0.05). In contrast, there was obviously decreased TFPI-2 expression level in pancreatic carcinoma tissues (29.2%) compared with para-carcinoma tissues (77.7%; P<0.001). Additionally, MMP-2 expression was significantly positively correlated with LNM (r=0.468, P<0.01) and PNI (r=0.637, P<0.01). In contrast, TFPI-2 expression was strongly negatively correlated with LNM (r=?0.396, P<0.001) and PNI (r=?0.460, P<0.001). Logistic regression analysis showed that high MMP-2 expression and low TFPI-2 expression acted as independent predictors for LNM and PNI in pancreatic carcinoma. Conclusion Taken together, our findings suggest that upregulated MMP-2 and downregulated TFPI-2 serve as useful predictors for a high risk of LNM and PNI. Obtaining information on the expression of MMP-2 and TFPI-2 before surgery may predict the occurrence of LNM and PNI, thereby permitting reasonable and effective surgical treatment for patients with pancreatic carcinoma. PMID:26504399

  19. Strategy for reversing resistance to a single anticancer agent in human prostate and pancreatic carcinomas.

    PubMed

    Lebedeva, Irina V; Washington, Ilyas; Sarkar, Devanand; Clark, Jennifer A; Fine, Robert L; Dent, Paul; Curiel, David T; Turro, Nicholas J; Fisher, Paul B

    2007-02-27

    Effective therapies for most solid cancers, especially those that have progressed to metastasis, remain elusive because of inherent and acquired resistance of tumor cells to conventional treatments. Additionally, the effective therapeutic window for many protocols can be very narrow, frequently resulting in toxicity. The present study explores an anticancer strategy that effectively eliminates resistant cancer cells without exerting deleterious effects on normal cells. This approach employs melanoma differentiation-induced gene-7/interleukin-24 (mda-7/IL-24), a cancer-specific, apoptosis-inducing cytokine, in combination with nontoxic doses of a chemical compound from the endoperoxide class that decomposes in water generating singlet oxygen. This combinatorial regimen specifically induced in vitro apoptosis in prostate carcinoma cells, with innate resistance to chemotherapy or engineered resistance to mda-7/IL-24, as well as pancreatic carcinoma cells inherently resistant to any treatment modality, including mda-7/IL-24. Apoptosis induction correlated with increased cellular reactive oxygen species production and was prevented by general antioxidants, such as N-acetyl-l-cysteine or Tiron. Induction of apoptosis in combination-treated cancer cells correlated with a reduction in the antiapoptotic protein BCL-x(L). In contrast, both normal prostate and pancreatic epithelial cells were unaffected by the single or combination treatment. These provocative findings suggest that this combinatorial strategy might provide a platform for developing effective treatments for therapy-resistant cancers. PMID:17360670

  20. 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.

  1. Cell motility and spreading promoted by CEACAM6 through cyclinD1/CDK4 in human pancreatic carcinoma.

    PubMed

    Yan, Lu; Wang, Yuan; Wang, Zhi-Zhi; Rong, Yan-Ting; Chen, Lin-Lin; Li, Qian; Liu, Ting; Chen, Yong-Heng; Li, Yan-Dong; Huang, Zhao-Hong; Peng, Jie

    2016-01-01

    Carcinoembryonic antigen-related cell adhesion molecule6 (CEACAM6) belongs to the human carcino-embryonic antigen (CEA) family. Numerous lines of studies have indicated that altered expression of CEACAM6 may have a role in carcinogenesis and development. However, few studies have defined functional roles and mechanisms of action. In the present study, the relationship between clinical and pathological parameters was also analyzed. The relative CEACAM6 protein expression of pancreatic carcinoma was significantly higher than that in non-cancerous tissue. Different clinical stages and lymph node metastasis between groups were significantly different (P<0.05). We used siRNA and forced-expression in multiple cell lines to define the role of CEACAM6 in the regulation of proliferation of pancreatic carcinoma invitro and invivo. Knockdown of endogenous CEACAM6 decreased proliferation of BxPC-3 and SW1990 cells. These changes significantly reduced cyclinD1 and CDK4 protein levels. Conversely, overexpression of CEACAM6 in MIA PaCa-2 cells stimulated proliferation and increased cyclinD1 and CDK4 protein levels. Our results confirm that CEACAM6 promoted cell proliferation, and these changes were mediated by cyclinD1/CDK4. These observations contribute to our understanding of the important roles of CEACAM6 in pancreatic carcinoma development and progression and could be a promising molecular target for the development of new diagnostic and therapeutic strategies of pancreatic carcinoma. PMID:26497080

  2. An unusual neoplasm of the pancreas: Pancreatic metastasis of a Merkel cell carcinoma. Case report and review of the literature.

    PubMed

    De Cock, E; Remery, M; De Vuyst, M; Lecluyse, K

    2015-01-01

    Isolated pancreatic metastases are rare. The differential diagnosis of pancreatic neoplasms can be difficult, especially it can be troublesome to obtain tissue diagnosis. However, pancreatic lesions in patients with a history of a malignancy must be considered to be metastases. We present a case of a patient with a history of a Merkel cell carcinoma (MCC) in the neck. Twelve months after this diagnosis a follow-up CT shows a large isolated tumor in the head of the pancreas. Histological and immunohistochemical studies of specimen obtained through ultrasound-guided transabdominal biopsy, show similar characteristics as the primary MCC. To our knowledge twelve cases of a pancreatic metastasis of a MCC have been reported in English literature. A review of the literature was performed. PMID:26448416

  3. Clinical significance of serum p53 antigen in patients with pancreatic carcinomas.

    PubMed Central

    Suwa, H; Ohshio, G; Okada, N; Wang, Z; Fukumoto, M; Imamura, T; Imamura, M

    1997-01-01

    BACKGROUND: Alterations in the p53 gene are often found in pancreatic cancer, and accumulation of the p53 protein has been noted in tumour cells. AIMS: To investigate whether serum p53 protein concentrations could be used as markers for p53 gene mutations in neoplasms of the pancreas. METHODS: Serum p53 protein concentrations were determined by an enzyme linked immunosorbent assay (ELISA) in 104 cases of pancreatic adenocarcinoma, and 61 matched formalin fixed tissue sections were also stained by an anti-p53 DO-7 monoclonal antibody. RESULTS: The mean serum concentration of p53 protein in the adenocarcinoma patients was 0.27 (SEM 0.02) ng/ml, and was significantly higher than in 35 healthy blood donors (0.15 (0.02) ng/ml, SD = 0.11) or in 15 cases of chronic pancreatitis (0.15 (0.02) ng/ml). Adopting an arbitrary cut off value for the serum p53 protein concentration of 0.37 ng/ml, which corresponded to a value 2 SD above the mean value from the healthy blood donors, positive serum p53 protein concentrations were found in 23 out of 104 (22.1%) patients with adenocarcinomas examined, 16 out of 47 (34.0%) patients with carcinomas with distant metastases, but only seven of 57 patients (12.3%) with carcinomas without metastases (p < 0.05). In 11 patients with pancreatic adenocarcinomas, the mean serum p53 protein concentration after tumour resection was 0.21 (0.05) ng/ml, and had decreased compared with the preoperative concentrations (0.25 (0.05) ng/ml) (P < 0.05). There were no significant associations between the serum concentrations of p53 protein and serum concentrations of markers such as CA19-9 or CEA; however, serum concentrations of p53 protein demonstrated a potential role as an additional tumour marker. Immunohistochemical studies disclosed that the p53 protein was expressed in 28 out of 61 pancreatic adenocarcinomas (45.9%). Serum p53 protein concentrations in the positively immunostained cases were significantly higher than in the negatively immunostained cases (0.35 (0.05) ng/ml v 0.15 (0.01) ng/ml; p < 0.005). Furthermore, positive immunostaining for p53 protein was found in eight out of 10 (80%) serum positive p53 protein cases with adenocarcinomas. CONCLUSION: An increase in serum p53 protein concentrations appears during the progression of pancreatic adenocarcinoma and correlates with the accumulation of p53 protein as a result of a mutation of the p53 gene. An analysis of p53 antigen concentrations can detect p53 gene alterations, which could be useful for the selection of treatment regimens. Images PMID:9203945

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

    ClinicalTrials.gov

    2016-01-27

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

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

    PubMed

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

    2015-01-01

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

  6. Recombinant adenovirus-p53 (Gendicine) sensitizes a pancreatic carcinoma cell line to radiation

    PubMed Central

    Li, Jinluan; Pan, Jianji; Zhu, Xianggao; Su, Ying; Bao, Lingling; Qiu, Sufang; Zou, Changyan; Tham, Ivan W.K.

    2013-01-01

    Objective In this study, we examine the effects of recombinant adenovirus-p53 (rAd-p53) on the pancreatic carcinoma cell line SW1990. Specifically, we determine if expression of rAd-p53 sensitizes these cells to radiation. Methods Following transfection of SW1990 cells with rAd-p53, we measured expression of P53, P21 and Bax by immunocytochemistry. Both transfected and control cell lines were irradiated with a range of doses, and the survival fractions (SF) were calculated. Dose survival curves were constructed and modeled for comparison. Results Transfection of SW1990 cells with rAd-p53 resulted in increased expression of P53, P21 and Bax in a time-dependent manner. At 96 h after transfection, 89.92% of cells expressed P53, 56.8% expressed P21, and 76.50% expressed Bax. The SF following radiation was lower in the rAd-p53 transfected cells compared to the control cells, suggesting that rAd-p53 sensitizes SW1990 cells to radiation (D0 for the experimental and control groups was 2.199 and 2.462, respectively). Conclusions Use of the adenoviral vector is an effective means of transfecting SW1990 cells with wild-type P53, and this sensitizes the cell line to irradiation. This work suggests that combining rAd-p53 with radiation therapy in pancreatic cancer may be therapeutically beneficial. PMID:24385699

  7. Mesopancreas: A boundless structure, namely the rationale for dissection of the paraaortic area in pancreaticoduodenectomy for pancreatic head carcinoma

    PubMed Central

    Peparini, Nadia

    2015-01-01

    This review highlights the rationale for dissection of the 16a2 and 16b1 paraaortic area during pancreaticoduodenectomy (PD) for carcinoma of the head of the pancreas. Recent advances in surgical anatomy of the mesopancreas indicate that the retropancreatic area is not a single entity with well defined boundaries but an anatomical site of embryological fusion of peritoneal layers, and that continuity exists between the neuro lymphovascular adipose tissues of the retropancreatic and paraaortic areas. Recent advances in surgical pathology and oncology indicate that, in pancreatic head carcinoma, the mesopancreatic resection margin is the primary site for R1 resection, and that epithelial-mesenchymal transition-related processes involved in tumor progression may impact on the prevalence of R1 resection or local recurrence rates after R0 surgery. These concepts imply that mesopancreas resection during PD for pancreatic head carcinoma should be extended to the paraaortic area in order to maximize retropancreatic clearance and minimize the likelihood of an R1 resection or the persistence of residual tumor cells after R0 resection. In PD for pancreatic head carcinoma, the rationale for dissection of the paraaortic area is to control the spread of the tumor cells along the mesopancreatic resection margin, rather than to control or stage the nodal spread. Although mesopancreatic resection cannot be considered complete or en bloc, it should be extended as far as possible or be maximal, including dissection of 16a2 and 16b1 paraaortic areas. PMID:25780282

  8. 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. PMID:25989715

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

    ClinicalTrials.gov

    2015-02-19

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

  10. Metachronous biliary carcinoma with intraductal pancreatic adenocarcinoma 13?years after curative resection of hilar bile duct cancer

    PubMed Central

    Maekawa, Hisatsugu; Fujikawa, Takahisa; Tanaka, Akira

    2014-01-01

    We report a case of a 68-year-old woman with metachronous bile duct cancer and a pancreatic adenocarcinoma. She had undergone extended left hepatic lobectomy for hilar bile duct carcinoma. However, when she was admitted to our hospital 13?years later for an annual follow-up, abdominal CT revealed a mass in the dilated remnant of her lower bile duct. This was diagnosed as a second primary tumour, a pancreaticoduodenectomy was performed and 15?months after the second operation, she remains recurrence-free. Nineteen cases of patients with metachronous bile duct carcinomas were identified in the literature and have been reviewed. PMID:24596413

  11. 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.

  12. The ATP-Competitive mTOR Inhibitor INK128 enhances in vitro and in vivo radiosensitivity of pancreatic carcinoma cells

    PubMed Central

    Hayman, Thomas J.; Wahba, Amy; Rath, Barbara H.; Bae, Heekyong; Kramp, Tamalee; Shankavaram, Uma T.; Camphausen, Kevin; Tofilon, Philip J.

    2013-01-01

    Purpose Radiotherapy remains a primary treatment modality for pancreatic carcinoma, a tumor characterized by aberrant mTOR activity. Given mTOR's regulatory role in gene translation, in this study we defined the effects of the clinically relevant, ATP-competitive mTOR inhibitor, INK128 on the radiosensitivity of pancreatic carcinoma cell lines. Experimental Design Clonogenic survival was used to determine the effects of INK128 on in vitro radiosensitivity on 3 pancreatic carcinoma cell lines and a normal fibroblast cell line with mTOR activity defined using immunoblots. DNA double strand breaks were evaluated according to ?H2AX foci. The influence of INK128 on radiation-induced gene translation was determined by microarray analysis of polysome-bound mRNA. Leg tumor xenografts grown from pancreatic carcinoma cells were evaluated for mTOR activity, eIF4F cap complex formation and tumor growth delay. Results INK128, while inhibiting mTOR activity in each of the cell lines, enhanced the in vitro radiosensitivity of the pancreatic carcinoma cells, but had no effect on normal fibroblasts. The dispersal of radiation-induced ?H2AX foci was inhibited in pancreatic carcinoma cells by INK128 as were radiation-induced changes in gene translation. Treatment of mice with INK128 resulted in an inhibition of mTOR activity as well as cap-complex formation in tumor xenografts. Whereas INK128 alone had no effect of tumor growth rate, it enhanced the tumor growth delay induced by single and fractionated doses of radiation. Conclusion These results indicate that mTOR inhibition induced by INK128 enhances the radiosensitivity of pancreatic carcinoma cells and suggest that this effect involves the inhibition of DNA repair. PMID:24198241

  13. Chromic-P32 phosphate treatment of implanted pancreatic carcinoma: Mechanism involved

    PubMed Central

    Liu, Lu; Feng, Guo-Sheng; Gao, Hong; Tong, Guan-Sheng; Wang, Yu; Gao, Wen; Huang, Ying; Li, Cheng

    2005-01-01

    AIM: To study the effects of chromic-P32 phosphate (32P colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism. METHODS: Ninety-eight tumor bearing nude mice were killed at different time points after the injection of 32P colloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32P colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Bax-related gene expression were observed too. RESULTS: The half-life of effective medication is 13 d after injection of 32P colloids to the tumor stroma, in 1-6 groups, the tumor cell necrosis rates were 20%, 45%, 65%, 70%, 95% and 4%, respectively (F = 4.14-105.36, P<0.01). MVD were 38.54.0, 28.02.9, 17.02.9, 8.81.5, 5.72.3 and 65.05.2 (t = 11.9-26.1, P<0.01), respectively. Under TEM fairly differentiated Pc-3 cells were found. Thirty days after medication, tumors were shrunk and dried with scabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM in animals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiation-induced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. CONCLUSION: 32P colloids intra-tumor injection having prominent anticancer effectiveness may reveal the ability of promoting cell differentiation. The low dose 32P colloids may induce human pancreatic carcinoma Pc-3 implanted tumor cell apoptosis; Apo2.7, caspase-3, Bcl-2 and Bax protein participated in regulating the process of irradiation induced cell apoptosis. PMID:15810075

  14. Pancreatic panniculitis.

    PubMed

    Rongioletti, F; Caputo, V

    2013-08-01

    Pancreatic panniculitis (PP) is a rare variant of panniculitis characterized by subcutaneous fat necrosis, that affects 0.3-3% of patients across a range of different pancreatic disorders. It presents with painful, tender, erythematous to violaceous nodules that may undergo spontaneous ulceration and discharge of an oily brown, viscous material, resulting from liquefactive necrosis of adipocytes. These lesions usually involve the lower extremities, although may also spread over the buttocks, trunk, arms and scalp. In addition to the skin, fat necrosis may involve periarticular, abdominal and intramedullary adipose tissue. In 40% of cases, skin manifestations can precede by 1 to 7 months the abdominal symptoms of pancreatic disease, which include mostly acute and chronic pancreatitis, pancreatic carcinoma, more frequently of acinar cell type, and pancreatic abnormalities. Histopathologically, PP shows characteristic features of mostly lobular panniculitis with marked necrosis of adipocytes. The necrotic adipocytes with finely granular and basophilic material in the cytoplasm due to calcium deposits are known as "ghost adipocytes". The treatment of pancreatic panniculitis is directed to the underlying pancreatic disease. The prognosis is poor in cases associated with pancreatic carcinoma. When there is widespread and persistent disease, frequent relapses, or ulceration, the possibility of an occult carcinoma of the pancreas should be always considered. While describing three patients seen at the Dermatology Section of the University of Genova from 1990 to 2012, we highlight that, in addition to the rarity of the disease, the precise diagnosis requires adequate samples consisting in large-scalpel incisional biopsies of fully developed lesions. PMID:23900163

  15. Apoptosis of human pancreatic carcinoma cell-1 cells induced by Yin Chen Hao Decoction

    PubMed Central

    Zhou, Hai-Bo; Chen, Jing-Ming; Shao, Li-Ming; Chen, Zhi-Gang

    2015-01-01

    AIM: To evaluate human pancreatic carcinoma cell line (PANC-1) cells apoptosis and Bcl-2 and Bax expression induced by Yin Chen Hao Decoction (YCHD). METHODS: The cell growth inhibitory rate was determined by MTT assay. Apoptosis of PANC-1 cells before and after treatment with YCHD was determined by TUNEL staining. Expression of the apoptosis-associated genes, Bcl-2 and Bax, was detected by immunohistochemical staining and reverse transcription -PCR. RESULTS: YCHD inhibited the growth of PANC-1 cells. Following treatment with YCHD for 24-96 h, the apoptotic rate of PANC-1 cells increased with time. In addition, the positive rate of Bcl-2 protein expression decreased in a time-dependent manner, whereas the positive rate of Bax protein expression increased in a time-dependent manner. Following treatment of with YCHD for 24-96h, expression of BAX mRNA increased gradually and BCL-2 mRNA reduced gradually with time. CONCLUSION: YCHD induces apoptosis of PANC-1 cells mediated in part via up-regulation of BAX and down-regulation of BCL-2. PMID:26217086

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

    PubMed

    Kaur, Manjinder; Deep, Gagan; Jain, Anil K; Raina, Komal; Agarwal, Chapla; Wempe, Michael F; Agarwal, Rajesh

    2013-07-01

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

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

    PubMed Central

    Agarwal, Rajesh

    2013-01-01

    Prognosis of pancreatic cancer is extremely poor, suggesting critical needs for additional drugs to improve disease outcome. In this study, we examined efficacy and associated mechanism of a novel agent bitter melon juice (BMJ) against pancreatic carcinoma cells both in culture and nude mice. BMJ anticancer efficacy was analyzed in human pancreatic carcinoma BxPC-3, MiaPaCa-2, AsPC-1 and Capan-2 cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide, cell death enzyme-linked immunosorbent assay and annexin/propidium iodide assays. BMJ effect on apoptosis regulators was assessed by immunoblotting. In vivo BMJ efficacy was evaluated against MiaPaCa-2 tumors in nude mice, and xenograft was analyzed for biomarkers by immunohistochemistry (IHC). Results showed that BMJ (25% v/v) decreases cell viability in all four pancreatic carcinoma cell lines by inducing strong apoptotic death. At molecular level, BMJ caused caspases activation, altered expression of Bcl-2 family members and cytochrome-c release into the cytosol. Additionally, BMJ decreased survivin and X-linked inhibitor of apoptosis protein but increased p21, CHOP and phosphorylated mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2 and p38) levels. Importantly, BMJ activated adenosine monophosphate-activated protein kinase (AMPK), a biomarker for cellular energy status, and an AMPK inhibitor (Compound C) reversed BMJ-induced caspase-3 activation suggesting activated AMPK involvement in BMJ-induced apoptosis. In vivo, oral administration of lyophilized BMJ (5mg in 100 l water/day/mouse) for 6 weeks inhibited MiaPaCa-2 tumor xenograft growth by 60% (P < 0.01) without noticeable toxicity in nude mice. IHC analyses of MiaPaCa-2 xenografts showed that BMJ also inhibits proliferation, induces apoptosis and activates AMPK in vivo. Overall, BMJ exerts strong anticancer efficacy against human pancreatic carcinoma cells, both in vitro and in vivo, suggesting its clinical usefulness. PMID:23475945

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

    PubMed Central

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

    2013-01-01

    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. PMID:24092664

  19. 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.

  20. Dynamic telecytopathology of on site rapid cytology diagnoses for pancreatic carcinoma

    PubMed Central

    Kim, Burton; Chhieng, David C; Crowe, David R; Jhala, Darshana; Jhala, Nirag; Winokur, Thomas; Eloubeidi, Mohamad A; Eltoum, Isam E

    2006-01-01

    Background Diagnosis of pancreatic lesions can be accurately performed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) with onsite cytopathologists to assess specimen adequacy and to determine a preliminary diagnosis. Considerable time is needed to perform on-site assessments. This takes away work time of cytopathologists and prohibits them from serving remote locations. It is therefore logical to ask if real-time telecytopathology could be used to assess specimen adequacy and if telecytopathology diagnosis has the same level of agreement to the final diagnosis as that of onsite evaluation. In this study, we compare agreement between cytodiagnoses rendered using telecytopathology with onsite and final interpretations. Method 40 Diff-Quik-stained EUS-FNA were re-evaluated retrospectively (patient ages 3162, 19:21 male:female, 15 non-malignant lesions, 25 malignant lesions as classified by final diagnosis). Each previously assessed by a cytopathologist and finally reviewed by the same or different cytopathologist. Blinded to the final diagnosis, a resident pathologist re-screened all slides for each case, selected a slide and marked the diagnostic cells most representative of the lesion. Blinded to the diagnosis, one cytopathologist assessed the marked cells through a real time remotely operated telecytopathology system (MedMicroscopy). Diagnosis and time spent were recorded. Kappa statistic was used to compare agreements between telecytopathology vs. original onsite vs. final diagnoses. Results Time spent for prescreening ranged from 1 to 5 minutes (mean 2.6 +/- 1.3 minutes) and time spent for telecytopathology diagnosis ranged from 220 minutes (mean 7.5 +/- 4.5 minutes). Kappa statistics, K, was as follows: telecytopathology versus onsite diagnosis K, 95% CI = 0.65, 0.410.88, for telecytopathology versus final K, 95% CI = 0.61, 0.370.85 and for onsite diagnosis versus final K, 95% CI = 0.79, 0.610.98. There is no significant difference in agreement between onsite and telecytopathology diagnoses. Kappa values for telecytopathology were less than onsite evaluation when compared to the final diagnosis; however, the difference was not statistically significant. Conclusion This retrospective study demonstrates the potential use of telecytopathology as a valid substitute for onsite evaluation of pancreatic carcinoma by EUS-FNA. PMID:17156485

  1. Subcutaneous fat necrosis/panniculitis and polyarthritis associated with acinar cell carcinoma of the pancreas: a rare presentation of pancreatitis, panniculitis and polyarthritis syndrome.

    PubMed

    Borowicz, Jessica; Morrison, Megan; Hogan, Daniel; Miller, Richard

    2010-09-01

    An 82-year-old man presented with a two-week history of three painful, inflamed nodules on his lower extremities with symmetric arthritis of multiple joints. He was under the care of hospice for end-stage acinar cell carcinoma of the pancreas. His serum amylase and lipase levels were markedly elevated. An incisional biopsy revealed lobular inflammation of subcutaneous fat, focal fat necrosis with saponification/ghost cells and scattered foreign-body type giant cells consistent with pancreatic fat necrosis/pancreatic panniculitis. This is hypothesized to be initiated by autodigestion of subcutaneous fat secondary to systemic spillage of excess digestive pancreatic enzymes. Enzymes such as amylase, lipase and trypsin are increased in the bloodstream and can affect remote tissues, such as the subcutaneous fat and articular surfaces of joints. This report, along with the patient's clinical findings, was consistent with PPP syndrome: pancreatic disease, polyarthritis and panniculitis. Although the pancreatic disease of PPP syndrome usually includes pancreatitis, this case represents a report of polyarthritis and panniculitis occurring in the presence of pancreatic carcinoma. PMID:20865849

  2. Inframesocolic Superior Mesenteric Artery First Approach as an Introductory Procedure of Radical Antegrade Modular Pancreatosplenectomy for Carcinoma of the Pancreatic Body and Tail.

    PubMed

    Aosasa, Suefumi; Nishikawa, Makoto; Hoshikawa, Mayumi; Noro, Takuji; Yamamoto, Junji

    2016-02-01

    Superior mesenteric artery (SMA)-first approaches are operative tactics used to determine tumor resectability early during pancreatoduodenectomy. With locally advanced carcinoma of the pancreatic body and tail, early determination of SMA involvement also helps establish whether curative resection is feasible. During either radical antegrade modular pancreatosplenectomy (RAMPS) or classic left-to-right distal pancreatectomy, dissection of the SMA is performed after transection of the pancreas or wide detachment of the distal pancreas and spleen. Herein, we describe an inframesocolic SMA-first approach as an introductory procedure when treating carcinoma of the pancreatic body and tail. This first approach procedure provides a reliable and safe introduction to RAMPS. PMID:26601979

  3. Targeting of cancer stem cell marker EpCAM by bispecific antibody EpCAMxCD3 inhibits pancreatic carcinoma

    PubMed Central

    Salnikov, Alexei V; Groth, Ariane; Apel, Anja; Kallifatidis, Georgios; Beckermann, Benjamin M; Khamidjanov, Akmal; Ryschich, Eduard; Büchler, Markus W; Herr, Ingrid; Moldenhauer, Gerhard

    2009-01-01

    Patients with pancreatic cancer have a poor survival rate, and new therapeutic strategies are needed. Epithelial cell adhesion molecule (EpCAM), suggested as a marker for cancer stem cells, is over-expressed on most pancreatic tumour cells but not on normal cells and may be an ideal therapeutic target. We evaluated the anti-tumour efficiency of bispecific EpCAMxCD3 antibody linking tumour cells and T lymphocytes. In NOD SCID mice, EpCAMxCD3 had a long serum half-life (t1/2∼ 7 days). EpCAMxCD3 significantly retarded growth of BxPC-3 pancreatic carcinoma xenografts. For mimicking a pancreatic cancer microenvironment in vitro, we used a three-dimensional tumour reconstruct system, in which lymphocytes were co-cultured with tumour cells and fibroblasts in a collagen matrix. In this in vivo–like system, EpCAMxCD3 potently stimulated production of the effector cytokines IFN-γ and TNF-α by extracorporally pre-activated lymphocytes. Moreover, compared with a bivalent anti-CD3 antibody, EpCAMxCD3 more efficiently activated the production of TNF-α and IFN-γ by non-stimulated peripheral blood mononuclear cells. Most excitingly, we demonstrate for the first time that EpCAMxCD3 induces prolonged contacts between lymphocytes and tumour cells, which may be the main reason for the observed anti-tumour effects. As an important prerequisite for future use in patients, EpCAMxCD3 did not alter lymphocyte migration as measured by time-lapse video microscopy. Our data may open a way to improve the immune response and treatment outcome in patients with pancreatic cancer. PMID:20196789

  4. Hepatocyte growth factor activator inhibitor type 1 suppresses metastatic pulmonary colonization of pancreatic carcinoma cells.

    PubMed

    Fukushima, Tsuyoshi; Kawaguchi, Makiko; Yamasaki, Masatoshi; Tanaka, Hiroyuki; Yorita, Kenji; Kataoka, Hiroaki

    2011-02-01

    Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a transmembrane protease inhibitor that regulates the activities of membrane-bound and extracellular serine proteases. HAI-1 has two Kunitz-type inhibitor domains with the N-terminal Kunitz domain (KD1) responsible for inhibiting known target proteases. Previously, we reported that knockdown of HAI-1 in the human pancreatic carcinoma cell line SUIT-2 resulted in epithelial to mesenchymal transition. To evaluate the role of HAI-1 in metastasis, we examined the metastatic capability of SUIT-2 cells that did or did not stably express HAI-1 short-hairpin RNA in an experimental pulmonary metastasis assay using nude mice. The extent of pulmonary metastasis was verified by histological examination and direct measurement of human cytokeratin 19 mRNA levels. One week after injecting SUIT-2 cells into mouse tail veins, apparent metastatic colonization was observed in 36% (4/11) of mice injected with HAI-1-knockdown SUIT-2, whereas none (0/11) of the control mice were positive for metastasis. After 2 weeks the metastasis positive ratios were 80% (4/5) and 40% (2/5), and after 4 weeks the ratios were 82% (9/11) and 45% (5/11) for HAI-1-knockdown and control SUIT-2 cells, respectively. Thus, loss of HAI-1 promoted pulmonary metastasis. Co-injection of recombinant KD1 abolished metastasis produced by HAI-1-knockdown SUIT-2 cells after 1 week. Moreover, recombinant KD1 restored E-cadherin levels in HAI-1 knockdown SUIT-2 cells and reduced their invasiveness in vitro. These data indicate that HAI-1 regulates pulmonary metastasis of SUIT-2, and KD1 may have therapeutic application for inhibiting metastatic cancer cell spreading. PMID:21166957

  5. Clinical value of serum tumor markers CA19-9, CA125 and CA72-4 in the diagnosis of pancreatic carcinoma.

    PubMed

    Wang, Zi; Tian, Ya-Ping

    2014-03-01

    CA125 and CA72-4 are members of a family of high-molecular weight glycosylated proteins and are commonly considered as biomarkers in the diagnosis of ovarian and gastric cancer, respectively. However, recent studies have revealed that these two markers may be of clinical value in the diagnosis of pancreatic cancer. As the availability of data regarding CA72-4 and CA125 in the diagnosis of pancreatic cancer is limited, the aim of this study was to investigate the clinical value of serum tumor markers CA19-9, CA125 and CA72-4 in the diagnosis of pancreatic carcinoma according to logistic regression analysis and receiver operating characteristic (ROC) curves and to investigate the correlation of these markers with tumor TNM stage and location. An immunoradiometric assay was used to measure pre-operative serum CA19-9, CA125 and CA72-4 levels in 75 patients with pancreatic carcinoma and 70 patients with benign pancreatic diseases. The concentrations of serum CA19-9, CA125 and CA72-4 in patients with pancreatic carcinoma were found to be significantly higher (P<0.05) compared with those with benign pancreatic diseases. The combined detection of two serum markers (CA19-9 + CA72-4) yielded a ROC value of 0.895 that was significantly higher compared to others (P<0.05) in distinguishing pancreatic cancer from benign pancreatic diseases. At optimal cut-off, the sensitivity and specificity of combined detection (CA19-9 + CA72-4) were 70.6 and 92.8%, respectively. The concentrations of CA125 and CA19-9 in patients with pancreatic adenocarcinoma were found to be significantly higher (P<0.05) compared with those of pancreatic neuroendocrine carcinoma. In conclusion, the combined detection of CA19-9 and CA72-4) may significantly improve the diagnostic specificity and the serum concentrations of CA125 and CA19-9 are correlated with tumor histological type. PMID:24649344

  6. Acute cholangitis due to pancreatic metastasis from squamous cell lung carcinoma: a case report and review of literature

    PubMed Central

    2009-01-01

    Introduction The pancreas is a well-documented but relatively uncommon site of non-small-cell cancer metastases. However, at the time of diagnosis the disease is usually locoregionally advanced, therefore therapeutic management is mostly palliative and symptomatic. Case Presentation We report the case of a 77-year-old Caucasian male patient who presented initially with a clinical picture of acute cholangitis approximately 2 years after a left lower lobectomy for a low-grade squamous lung carcinoma. CT scan imaging of the abdomen and chest revealed an abnormal growth of the pancreatic head and distention of both the intra- and extra-hepatic billiary tree, whereas osteolytic abnormalities were observed of the 5th left rib, consistent with secondary deposits. Initially an endoscopic retrograde cholangio-pancreatography (ERCP) and sphincterectomy was performed and a plastic stent was placed in the common bile duct to decompress the biliary tree. Cytological examination of the aspirate collected by FNA of the pancreatic lession under EUS guidance revealed cells consistent with a low grade squamous lung carcinoma. Two months later an open cholecystectomy along with a gastrojejunostomy was performed to relieve the patient's gastric outlet obstruction symptoms. Following remission of the patient's attack of acute cholangitis and excessive vomiting he was released from the hospital and instructed to initiate chemotherapy with vinorelbine. The patient succumbed to disseminated disease almost 5 months later. Conclusion Symptomatic metastatic lesions of the pancreas from squamous cell carcinoma of the lung are infrequent. Typically, the patients remain asymptomatic until their disease reaches a fairly advanced stage and therapeutic options are limited to palliative measures. A high index of suspicion is the only way of early detection and potentially effective treatment for this rare localization of metastatic squamous lung carcinoma. PMID:20062690

  7. Increased matrix metalloproteinase-2 expression and reduced tissue factor pathway inhibitor-2 expression correlate with angiogenesis and early postoperative recurrence of pancreatic carcinoma

    PubMed Central

    Zhai, Lu-Lu; Wu, Yang; Huang, Da-Wei; Tang, Zhi-Gang

    2015-01-01

    Matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 are known to influence tumor angiogenesis and progression. This work aimed to describe the levels of MMP-2 and TFPI-2 expression associated with tumor angiogenesis and early postoperative recurrence in patients with pancreatic carcinoma. Expression of MMP-2 and TFPI-2 in carcinoma tissues and paracarcinomatous tissues was assayed by immunostaining. Expression of vascular endothelial growth factor (VEGF) and CD34 in tumor tissues was also assayed by immunostaining. The correlations of MMP-2 and TFPI-2 with VEGF, microvessel density (MVD), and early postoperative recurrence were analyzed. The results showed that MMP-2 expression was significantly increased (P < 0.05) and TFPI-2 expression was significantly decreased (P < 0.001) in carcinoma tissues compared with paracarcinomatous tissues. MMP-2 expression was positively correlated with VEGF (r = 0.594, P < 0.001) and MVD (r = 0.432, P < 0.001) in carcinoma tissues. TFPI-2 expression was negatively correlated with VEGF (r = -0.654, P < 0.001) and MVD (r = -0.360, P < 0.001) in carcinoma tissues. Multivariate logistic regression analysis showed that up-regulated MMP-2 and down-regulated TFPI-2 were independent predictors of early postoperative recurrence of pancreatic carcinoma. Receiver operating characteristic curve analysis showed that the combination of MMP-2 and TFPI-2 was a reliable predictive model of early recurrence. We conclude that increased MMP-2 expression and reduced TFPI-2 expression are closely linked to angiogenesis and early postoperative recurrence of pancreatic carcinoma. Immunohistochemical assay of MMP-2 and TFPI-2 may be useful for predicting early relapse of pancreatic carcinoma after surgery. PMID:26807187

  8. 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

    2016-03-31

    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

  9. Autoimmune pancreatitis mimicking carcinoma of the head of the pancreas: a case report

    PubMed Central

    2012-01-01

    Introduction We report on a case of autoimmune pancreatitis presenting as pancreatic head cancer, which is extremely rare in Iran. Currently, on the PubMed database, no such cases exist. Case presentation A 70-year-old Iranian man presented with recurrent abdominal pain, jaundice and elevated bilirubin and alkaline phosphatase levels. An abdominal computed tomography scan revealed a heterogeneous presence in the pancreatic head as well as dilated intra- and extrahepatic bile ducts. A common bile duct stent had been inserted. Our patient was subsequently diagnosed with pancreatic head cancer. Due to his continued recurrent abdominal pain, our patient returned to the hospital. His levels of bilirubin, alkaline phosphatase and tumor markers were all normal but his immunoglobulin G4 and antinuclear antibodies were extremely high. A biopsy of the pancreatic head heterogeneity by endoscopic ultrasonography was performed. Pathologic samples showed fibrosis associated with lymphoplasmacytic infiltration and no evidence of malignancy. A diagnosis of autoimmune pancreatitis was confirmed, the bile duct stent removed, and an appropriate treatment plan was undertaken. Conclusion Autoimmune pancreatitis should be considered in suspected cases of pancreatic cancer. In these instances, a biopsy of the pancreas will help to differentiate between the two and prevent complications due to disease progression as well as unnecessary surgery. PMID:22236871

  10. ACTH-secreting pancreatic neuroendocrine carcinoma with ovarian and pelvic metastases causing Cushings syndrome: a case report

    PubMed Central

    Yao, Wen-Qing; Wu, Xia; Li, Gan-Di; Wu, Wei-Lu; Wang, Wei-Ya

    2015-01-01

    Adrenocorticotropin hormone (ACTH)-secreting pancreatic neuroendocrine carcinoma (NEC) with ovarian and pelvic metastases causing Cushings syndrome is very rare and might be misdiagnosed. We describe a case of ACTH-secreting pancreatic poorly differentiated NEC developing bilateral ovarian and pelvic metastases. A 27-year-old woman presented with thirst, polydipsia, fatigue and poorly controlled hyperglycemia. Laboratory and imaging investigations revealed hypokalemia, hyperglycaemia, ACTH-dependent hypercortisolemia and a 12-cm mass at the junction of body and tail of the pancreas with ovarian and pelvic nodules. The patient underwent partial pancreatectomy and splenectomy, uterectomy, bilateral oophorectomy, and excision of peritoneal nodules. Tumors in pancreas, ovaries and pelvis were diagnosed as poor-differentiated NEC. After 19-month chemotherapy, she developed pelvic metastasis. The tumor in our case is a large, poorly differentiated NEC secreting ACTH and causing CS, with ovarian metastases. To our knowledge, this new additional case of ACTH-secreting pancreatic NEC with ovarian metastases would add to the better understanding of this tumor. PMID:26823901

  11. DNT cell inhibits the growth of pancreatic carcinoma via abnormal expressions of NKG2D and MICA invivo.

    PubMed

    Xu, Hong; Zhu, Xing-Xing; Chen, Jiong

    2016-01-01

    This research aimed to investigate the effects of natural killer group 2 member D (NKG2D) and its ligands major histocompatibility complex class I chain-related molecules A(MICA) in DNT cell killing pancreatic carcinoma. Antibodies adsorption was used to separate DNT cell from human peripheral blood. Human pancreatic tumor models were established via implanting BXPC-3cells into nude mice. Then randomly divided mice into blank group, gemcitabine group and DNT group. Mice weights and mice tumor volumes were measured every 5 days. 50 days later mice were euthanized at cervical dislocation method. Tumor weights were measured. Relative tumor volume and tumor inhibition rate were calculated. Western blot and qPCR were used to detect the expressions of NKG2D and MICA in the transplanted tumors of the three groups. DNT cell significantly increased over time. The blank group tumor volume and weight were significantly larger than the other groups (p<0.001, p<0.001), but there were no significantly difference between DNT group and gemcitabine group (p>0.05). Gemcitabine and DNT cell tumor inhibition rate were 40.4% and 35.5%. Western blot and qPCR showed that MICA mRNA and protein levels in blank group were significantly higher than DNT group (p=0.001, p=0.003). NKG2D mRNA and protein levels in blank group were significantly lower than DNT cells group (p<0.001, p=0.001). In conclusion DNT cell can significantly inhibit the growth of pancreatic carcinoma invivo, and the mechanism may be involved in abnormal expressions of MICA and NKG2D. PMID:26616050

  12. Epidermal growth factor-like domain 7 promotes cell invasion and angiogenesis in pancreatic carcinoma.

    PubMed

    Shen, Xiaochun; Han, Ye; Xue, Xiaofeng; Li, Wei; Guo, Xiaobo; Li, Pu; Wang, Yunliang; Li, Dechun; Zhou, Jin; Zhi, Qiaoming

    2016-02-01

    Epidermal growth factor-like domain 7 (EGFL7), also known as vascular endothelial stain, was firstly identified as a modulator of smooth muscle cell migration. Though the expression of EGFL7 was reported to be up-regulated during tumorigenesis, the clinical and biological functions of EGFL7 in pancreatic carcinoma (PC) were still not fully elucidated. In this study, we found that the serum EGFL7 level in PC tissues was statistically higher than that in normal subjects (p<0.001), and its level in non-resectable patients was also higher than that in resectable ones (p=0.013). Among these resectable PC patients, the postoperative EGFL7 expression was significantly down-regulated when tumors were resected (p=0.018). Using the immunohistochemistry method, our results demonstrated that the positive expression of EGFL7 was significantly associated with the TNM stage (p=0.024), lymph node metastasis (p=0.003) and local invasion (p=0.022), and the EGFL7 expression closely correlated to the micro-vessel density (MVD) in PC tissues by Spearman analysis (r=0.941, p=0.000). In vitro, EGFL7 was silenced by the small interference RNA in PC cells, and our data indicated that down-regulation of EGFL7 did not influence the cycle progression, proliferation, colony formation and apoptosis of PC cells (p>0.05), whereas inhibition of EGFL7 expression could decrease PaCa-2 cell invasion (p<0.05). More interestingly, by tubular formation, Chick embryo chorioallantoic membrane (CAM) and ELISA assays, our results revealed that silencing EGFL7 expression represented a strong inhibiting effect on tubular formation of micro-vessels through down-regulating the protein levels of VEGF and Ang-2 (p<0.05). Our results raised the possibility of using EGFL7as a potential prognostic biomarker and therapy target of PC, and down-regulation of EGFL7 might be considered to be a potentially important molecular treatment strategy for patients with PC. PMID:26796281

  13. 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 pancreatic cancer, CTAI with systemic chemotherapy appeared to be effective and may prolong their survival. The development of a reservoir port system allowing for the homogeneous distribution of anticancer drugs is necessary to improve the prognosis of patients with advanced pancreatic cancer.

  14. 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.

  15. [Incretin-based antidiabetic treatment and diseases of the pancreas (pancreatitis, pancreas carcinoma)].

    PubMed

    Jermendy, György

    2016-04-01

    In the last couple of years incretin-based antidiabetic drugs became increasingly popular and widely used for treating patients with type 2 diabetes. Immediately after launching, case reports and small case series were published on the potential side effects of the new drugs, with special attention to pancreatic disorders such as acute pancreatitis or pancreatic cancer. As clinical observations accumulated, these side-effects were noted with nearly all drugs of this class. Although these side-effects proved to be rare, an intensive debate evolved in the literature. Opinion of diabetes specialists and representatives of pharmaceutical industry as well as position statements of different international scientific boards and health authorities were published. In addition, results of randomized clinical trials with incretin-based therapy and meta-analyses became available. Importantly, in everyday clinical practice, the label of the given drug should be followed. With regards to incretins, physicians should be cautious if pancreatitis in the patients' past medical history is documented. Early differential diagnosis of any abdominal pain during treatment of incretin-based therapy should be made and the drug should be discontinued if pancreatitis is verified. Continuous post-marketing surveillance and side-effect analysis are still justified with incretin-based antidiabetic treatment in patients with type 2 diabetes. Orv. Hetil., 2016, 157(14), 523-528. PMID:27017851

  16. Inhibition of mutant Kras(G12D)-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. PMID:26683769

  17. 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.

  18. Pancreatic tuberculosis.

    PubMed

    Sharma, Vishal; Rana, Surinder S; Kumar, Amit; Bhasin, Deepak K

    2016-02-01

    Pancreatic tuberculosis is very rare, but recently, there has been a spurt in the number of reports on pancreatic involvement by tuberculosis. It closely mimics pancreatic cancer, and before the advent of better imaging modalities it was often detected as a histological surprise in patients resected for a presumed pancreatic malignancy. The usual presentation involves abdominal pain, loss of appetite and weight, jaundice which can be associated with cholestasis, fever and night sweats, palpable abdominal lump, and peripheral lymphadenopathy. Computed tomography (CT) of the abdomen is an important tool for evaluation of patients with pancreatic tuberculosis. This CT imaging yields valuable information about the size and nature of tubercular lesions along with the presence of ascites and lymphadenopathy. However, there are no distinctive features on CT that distinguish it from pancreatic carcinoma. Endoscopic ultrasound provides high resolution images of the pancreatic lesions as well as an opportunity to sample these lesions for cytological confirmation. The presence of granulomas is the most common finding on histological/cytological examination with the presence of acid fast bacilli being observed only in minority of patients. As there are no randomized or comparative studies on treatment of pancreatic tuberculosis it is usually treated like other forms of tuberculosis. Excellent cure rates are reported with standard anti tubercular therapy given for 6-12?months. PMID:26414325

  19. Pancreatic metastasis of papillary thyroid carcinoma: a case report with review of the literature.

    PubMed

    Li, Xiao-Ou; Li, Zheng-Peng; Wang, Ping; Li, Cheng-Lin; Wu, Ji-Hua; Zhang, Jian-Zhong; Cui, Yan

    2014-01-01

    In this article we give a case report on a PTC patient with pancreatic metastasis. In this case, the patient was admitted to our hospital for recurrence of PTC and occupying pancreatic lesions. We considered that the pancreatic neoplasm may be pancreatic metastasis of PTC but there is no previous experience about therapeutic approaches to this type of metastases. After some discussion the distant metastasis within the pancreas was successfully removed by a laparotomy and postoperative histology confirmed the diagnosis. After that surgery, the patient recovered well and then received total thyroidectomy and cervical lymph node dissection for recurrent thyroid cancer. After recovery he was discharged from hospital without further treatment. Eventually, he died of acute myocardial infarction in January 2010. To conclude, it is widely believed that the surgical operation should be chosen more positively in the management of those patients without multiple organ metastases. Thus on one hand it can serve to make a definite diagnosis, and on the other hand it can help the body get rid of the bulk of the tumor burden to prolong survival time of the patients. PMID:24551310

  20. An ISCOM vaccine combined with a TLR9 agonist breaks immune evasion mediated by regulatory T cells in an orthotopic model of pancreatic carcinoma.

    PubMed

    Jacobs, Collin; Duewell, Peter; Heckelsmiller, Klaus; Wei, Jiwu; Bauernfeind, Franz; Ellermeier, Jonathan; Kisser, Ulrich; Bauer, Christian A; Dauer, Marc; Eigler, Andreas; Maraskovsky, Eugene; Endres, Stefan; Schnurr, Max

    2011-02-15

    Vaccines based on immune stimulatory complexes (ISCOM) induce T-cell responses against tumor antigen (Ag). However, immune responses are impaired in pancreatic cancer patients. We investigated the efficacy of an ISCOM vaccine in a murine pancreatic carcinoma model. Panc02 cells expressing OVA as a model Ag were induced subcutaneously or orthotopically in the pancreas of C57BL/6 mice. Treatment consisted of an OVA containing ISCOM vaccine, either used alone or in combination with the TLR9 agonist CpG. The ISCOM vaccine effectively induced Ag-specific CTL capable of killing tumor cells. However, in mice with established tumors CTL induction by the vaccine was inefficient and did not affect tumor growth. Lack of efficacy correlated with increased numbers of Treg. Depletion of Treg with anti-CD25 mAb restored CTL induction and prolonged survival. Adding low-dose CpG to the ISCOM vaccine reduced Treg numbers, enhanced CTL responses and induced regression of pancreatic tumors in a CD8(+) T cell-dependent manner. Mice cured from the primary tumor mounted a memory T-cell response against wild-type Panc02 tumors, indicative of epitope spreading. Combining ISCOM vaccines with TLR agonists is a promising strategy for breaking tumor immune evasion and deserves further evaluation for the treatment of pancreatic carcinoma. PMID:20473889

  1. Distal bile duct carcinomas and pancreatic ductal adenocarcinomas: postulating a common tumor entity.

    PubMed

    Schmuck, Rosa B; de Carvalho-Fischer, Cynthia V; Neumann, Christopher; Pratschke, Johann; Bahra, Marcus

    2016-01-01

    The set definition of distal cholangiocarcinomas and adenocarcinomas of the pancreatic head is challenged by their close anatomical relation, similar growth pattern, and corresponding therapeutic outcome. They show a mutual development during embryologic organ formation and share phenotypic characteristics. This review will highlight the similarities with regard to the common origin of their primary organs, histopathological similarities, and modern clinical management. Thus, we propose to subsume those entities under a common superfamily. PMID:26645826

  2. A combinatory use of adenoviruses expressing melanoma differentiation-associated gene-7 and replication-competent adenoviruses produces synergistic effects on pancreatic carcinoma cells.

    PubMed

    Ma, Guangyu; Zhong, Boya; Okamoto, Shinya; Jiang, Yuanyuan; Kawamura, Kiyoko; Liu, Hongdan; Li, Quanhai; Shingyoji, Masato; Sekine, Ikuo; Tada, Yuji; Tatsumi, Koichiro; Shimada, Hideaki; Hiroshima, Kenzo; Tagawa, Masatoshi

    2015-09-01

    Type 5 adenoviruses expressing mda-7 gene (Ad-mda-7) induced cell death in various kinds of human tumors, but pancreatic carcinoma cells were relatively resistant to Ad-mda-7-mediated cytotoxicity. We then examined whether infection of Ad-mda-7 together with replication-competent Ad produced combinatory cytotoxic effects. We prepared replication-competent Ad, defective of the E1B55kDa gene or activated by a transcriptional regulatory region of the midkine or the survivin gene of which the expression was up-regulated in human tumors. Type 5 Ad bearing the exogenous regulatory region were further modified by replacing the fiber-knob region with that of type 35 Ad. Pancreatic carcinoma cells were infected with replication-incompetent Ad-mda-7 and the replication-competent Ad. Combinatory effects were examined with the CalcuSyn software and cell cycle analyses. Ad-mda-7 and the replication-competent Ad achieved cytotoxicity to pancreatic carcinoma. A combinatory use of Ad-mda-7 and either Ad defective of the E1B55kDa gene or Ad activated by the regulatory region produced synergistic cytotoxic effects. Cell cycle analyses demonstrated that the combination increased sub-G1 populations. These data collectively suggest that expression of MDA-7 augments cytotoxicity of replication-competent Ad and achieves adjuvant effects on Ad-mediated cell death. PMID:25990458

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

    PubMed Central

    Brull, Laura; Vandamme, Marc; Ris, Delphine; Martel, Eric; Robert, Eric; Lerondel, Stphanie; Trichet, Valrie; 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. PMID:23300736

  4. 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. PMID:23300736

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

    TOXLINE Toxicology Bibliographic Information

    Brullé L; Vandamme M; Riès D; Martel E; Robert E; Lerondel S; Trichet V; Richard S; Pouvesle JM; Le Pape A

    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.

  6. 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

  7. VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma

    PubMed Central

    Beckermann, B M; Kallifatidis, G; Groth, A; Frommhold, D; Apel, A; Mattern, J; Salnikov, A V; Moldenhauer, G; Wagner, W; Diehlmann, A; Saffrich, R; Schubert, M; Ho, A D; Giese, N; Bchler, M W; Friess, H; Bchler, P; Herr, I

    2008-01-01

    Little is known about the factors that enable the mobilisation of human mesenchymal stem cells (MSC) from the bone marrow into the blood stream and their recruitment to and retention in the tumour. We found specific migration of MSC towards growth factors present in pancreatic tumours, such as PDGF, EGF, VEGF and specific inhibitors Glivec, Erbitux and Avastin interfered with migration. Within a few hours, MSC migrated into spheroids consisting of pancreatic cancer cells, fibroblasts and endothelial cells as measured by time-lapse microscopy. Supernatant from subconfluent MSC increased sprouting of HUVEC due to VEGF production by MSC itself as demonstrated by RT-PCR and ELISA. Only few MSCs were differentiated into endothelial cells in vitro, whereas in vivo differentiation was not observed. Lentiviral GFP-marked MSCs, injected in nude mice xenografted with orthotopic pancreatic tumours, preferentially migrated into the tumours as observed by FACS analysis of green fluorescent cells. By immunofluorescence and intravital microscopic studies, we found the interaction of MSC with the endothelium of blood vessels. Mesenchymal stem cells supported tumour angiogenesis in vivo, that is CD31+ vessel density was increased after the transfer of MSC compared with siVEGF-MSC. Our data demonstrate the migration of MSC toward tumour vessels and suggest a supportive role in angiogenesis. PMID:18665180

  8. Retinoic acid receptor alpha mediates growth inhibition by retinoids in rat pancreatic carcinoma DSL-6A/C1 cells.

    PubMed Central

    Brembeck, F. H.; Kaiser, A.; Detjen, K.; Hotz, H.; Foitzik, T.; Buhr, H. J.; Riecken, E. O.; Rosewicz, S.

    1998-01-01

    During carcinogenesis, pancreatic acinar cells can dedifferentiate into ductal adenocarcinoma of the pancreas. DSL-6A/C1 cells represent an in vitro model of this carcinogenic sequence. This study was designed to examine the effects of retinoids on cell growth in DSL-6A/C1 cells and to characterize further the molecular mechanisms underlying the antiproliferative actions of retinoids. Treatment of DSL-6A/C1 cells with retinoids results in a time- and dose-dependent inhibition of cell growth, paralleled by a retinoid-mediated transactivation of a pTK::betaRAREx2-luciferase reporter construct transiently transfected into DSL-6A/C1 cells. Retinoid receptor expression was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) using subtype-specific primers and demonstrated expression of retinoic acid receptor alpha (RAR-alpha), RAR-beta and retinoid X receptor alpha (RXR-alpha). Using a panel of receptor subtype-specific agonists, the RAR-alpha specific agonist Ro 40-6055 was the most potent retinoid in terms of growth inhibition. Furthermore, all-trans-retinoic acid-mediated growth inhibition and transactivation was completely blocked by the RAR-alpha-specific antagonist Ro 41-5253. In summary, the RAR-alpha subtype predominantly mediates the antiproliferative effects of retinoids in DSL-6A/C1 cells. Furthermore, this cell system provides a feasible tool to study the molecular mechanisms underlying the growth inhibitory effects of retinoids in ductal pancreatic carcinoma cells derived from a primary acinar cell phenotype. Images Figure 1 Figure 5 PMID:9823968

  9. 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)

  10. Suppression of matrix metalloproteinase-2 via RNA interference inhibits pancreatic carcinoma cell invasiveness and adhesion

    PubMed Central

    Zhi, Ying-Hui; Song, Mao-Min; Wang, Pi-Lin; Zhang, Tie; Yin, Zi-Yi

    2009-01-01

    AIM: To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line, BxPC-3. METHODS: RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line, BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1, pGPU6-2, pGPU6-3 and pGPU6-4, and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers. RESULTS: The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect, followed by pGPU6-2 and pGPU6-3 groups. Invasiveness and adhesion were more significantly reduced in pGPU6-1, pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However, no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups. CONCLUSION: RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line, BxPC-3, leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor. PMID:19266599

  11. Characterisation of immune responses in pancreatic carcinoma patients after mutant p21 ras peptide vaccination.

    PubMed Central

    Gjertsen, M. K.; Saeterdal, I.; Thorsby, E.; Gaudernack, G.

    1996-01-01

    This is a study of immune responses generated by mutant ras peptide vaccination of patients with pancreatic adenocarcinoma. Responding T cells from one patient were cloned and two CD4+ T-lymphocyte clones (TLC) specific for the 12 Val peptide and restricted by HLA-DR6 or DQ2 were obtained. These class II molecules have not previously been found to bind or present mutant ras peptides to T cells. The DR6-restricted TLC showed marked cytotoxicity against autologous target cells pulsed with the 12 Val peptide. Target cells pulsed with the control peptide were not killed. Responding T cells from another patient showed cross-reactivity towards the homologous ras peptides. Investigation by limiting dilution analysis (LDA) revealed different T-cell precursor frequencies for the immunising, mutant ras peptide (1:28000), compared with the normal ras peptide (1:110000). PMID:8956801

  12. 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. PMID:26517093

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

    PubMed Central

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

    2015-01-01

    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. PMID:26517093

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

    ClinicalTrials.gov

    2015-12-07

    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

  15. 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.

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

    PubMed Central

    Glenn, Sean T.; Jones, Craig A.; Sexton, Sandra; LeVea, Charles M.; Caraker, Susan M.; Hajduczok, George; Gross, Kenneth W.

    2014-01-01

    Efforts to model human pancreatic neuroendocrine tumors (PanNET) in animals have been moderately successful, with minimal evidence for glucagonomas or metastatic spread. The renin gene while classically associated with expression in the kidney is also expressed in many other extra-renal tissues including the pancreas. To induce tumorigenesis within renin 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 lymph nodes and 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 a unique opportunity to dissect the timeline of disease, examining mechanisms of the metastatic process, as well as recovering primary and metastatic cells for identifying co-operating mutations that are necessary for progression of disease. PMID:24292676

  17. Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010

    PubMed Central

    Sharma, Chakshu; Eltawil, Karim M; Renfrew, Paul D; Walsh, Mark J; Molinari, Michele

    2011-01-01

    Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic. PMID:21412497

  18. 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.

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

    PubMed

    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

    2016-03-01

    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

  20. Taxotere resistance in SUIT Taxotere resistance in pancreatic carcinoma cell line SUIT 2 and its sublines

    PubMed Central

    Liu, Bin; Staren, Edgar; Iwamura, Takeshi; Appert, Hubert; Howard, John

    2001-01-01

    AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC). METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and its sublines (S-007, S-013, S-020, S-028 and TXT selected SUIT-2 cell line, S2/TXT) to TXT. Mdr1 (P-gp), multidrug resistance associated protein (MRP), lung resistance protein (LRP) and ?-tubulin isotype gene expressions were detected by RT-PCR. The functionality of P-gp and MRP was tested using their specific blocker verapamil (Ver) and indomethacin (IMC), respectively. The transporter activity of P-gp was also confirmed by Rhodamine 123 accumulation assay. RESULTS: S-020 and S2/TXT were found to be significantly resistant to TXT (19 and 9.5-fold to their parental cell line SUIT-2, respectively). RT-PCR demonstrated strong expression of Mdr1 in these two cell lines, but weaker expression or no expression in other cells lines. MRP and LRP expressions were found in most of these cell lines. The TXT-resistance in S2-020 and S2/TXT could be reversed almost completely by Ver, but not by IMC. Flow cytometry showed that Ver increased the accumulation of Rhodamine-123 in these two cell lines. Compared with S-020 and SUIT-2, the levels of ?-tubulin isotype II, III expressio ns in S-2/TXT were increased remarkably. CONCLUSION: The both intrinsic and acquired TXT-related drug resistance in these PAC cell lines is mainly mediated by P-gp, but had no relationship to MRP and LRP express ions. The increases of ?-tubulin isotype II, III might be collateral changes that occur when the SUIT-2 cells are treated with TXT. PMID:11854916

  1. Hereditary pancreatitis for the endoscopist

    PubMed Central

    Patel, Milan R.; Eppolito, Amanda L.

    2013-01-01

    Hereditary pancreatitis shares a majority of clinical and morphologic features with chronic alcoholic pancreatitis, but may present at an earlier age. The term hereditary pancreatitis has primarily been associated with mutations in the serine protease 1 gene (PRSS1) which encodes for cationic trypsinogen. PRSS1 mutations account for approximately 6881% of hereditary pancreatitis. Mutations in other genes, primarily serine protease inhibitor Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) are also associated with hereditary pancreatitis. While chronic alcoholic pancreatitis may develop in the fourth or fifth decades, patients with hereditary pancreatitis may develop symptoms in the first or second decades of life. Hereditary pancreatitis is diagnosed either by detecting a causative gene mutation or by the presence of chronic pancreatitis in two first-degree or three second-degree relatives, in two or more generations, without precipitating factors and with a negative workup for known causes. Patients with hereditary pancreatitis may have recurrent acute pancreatitis and may develop pancreatic exocrine and endocrine insufficiency. Hereditary pancreatitis may involve premature trypsinogen activation or decreased control of trypsin. Recurrent inflammation can lead to acute pancreatitis and subsequently to chronic pancreatitis with parenchymal calcification. There is a markedly increased risk of pancreatic carcinoma compared with the general population. Patients are often referred for evaluation of pancreatitis, biliary or pancreatic ductal dilatation, jaundice, biliary obstruction, pancreatic duct stone or stricture, pancreatic pseudocysts, and for evaluation for malignancy. Medical treatment includes pancreatic enzyme supplementation, nutritional supplementation, diabetes management, and palliation of pain. Patients should avoid tobacco use and alcohol exposure. Hereditary pancreatitis is reviewed and recommendations for genetic testing are discussed. PMID:23503650

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-10-01

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

  4. A prospective, randomized trial of pancreatectomy combined with isolated hepatic perfusion via a dual route or conventional postoperative adjuvant therapy in patients with advanced pancreatic head carcinoma

    PubMed Central

    He, Xiaojun; Kong, Yalin; Wen, Dongqing; Liu, Chengli; Xiao, Mei; Zhao, Gang; Zhen, Yuying; Zhang, Hongyi

    2015-01-01

    Prognosis of locally advanced pancreatic head carcinoma after Whipple remains poor. This study is to investigate the efficacy and safety of regional lymphadenectomy and chemotherapy of isolated hypoxic perfusion (IHP) via dual-route, and to analyze the effect for survival period. Consecutive patients subjected to our department from January 1, 2006 to December 31 2011 for locally advanced pancreatic head carcinoma were prospectively divided into two groups according to therapeutic modality, and clinical and follow-up data was recorded. In study group, operation duration and postoperative stay time were shorter, blood loss and blood transfusion were less, and incidence of complications was lower. The mean and median survival time was 17.4 ± 0.76 months and 18.0 months in study group, longer than control group of 14.1 ± 0.85 months and 17.6 months. Regional lymphadenectomy can be performed with low mortality and morbidity, and combined postoperative IHP via dual-route can improve survival time. PMID:26131274

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

    PubMed Central

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

    2015-01-01

    Purpose To test the following hypotheses in a murine model of pancreatic cancer: (a) Vaccination with antigen-loaded iron-labeled dendritic cells reduces T2-weighted signal intensity at magnetic resonance (MR) imaging within peripheral draining lymph nodes (LNlymph nodes) and (b) such signal intensity reductions are associated with tumor size changes after dendritic cell vaccination. Materials and Methods The institutional animal care and use committee approved this study. Panc02 cells were implanted into the flanks of 27 C57BL/6 mice bilaterally. After tumors reached 10 mm, cell viability was evaluated, and iron-labeled dendritic cell vaccines were injected into the left hind footpad. The mice were randomly separated into the following three groups (n = 9 in each): Group 1 was injected with 1 million iron-labeled dendritic cells; group 2, with 2 million cells; and control mice, with 200 mL of phosphate-buffered saline. T1- and T2-weighted MR imaging of labeled dendritic cell migration to draining LNlymph nodes was performed before cell injection and 6 and 24 hours after injection. The signal-to-noise ratio (SNRsignal-to-noise ratio) of the draining LNlymph nodes was measured. One-way analysis of variance (ANOVAanalysis of variance) was used to compare Prussian blue–positive dendritic cell measurements in LNlymph nodes. Repeated-measures ANOVAanalysis of variance was used to compare in vivo T2-weighted SNRsignal-to-noise ratio LNlymph node measurements between groups over the observation time points. Results Trypan blue assays showed no significant difference in mean viability indexes (unlabeled vs labeled dendritic cells, 4.32% ± 0.69 [standard deviation] vs 4.83% ± 0.76; P = .385). Thirty-five days after injection, the mean left and right flank tumor sizes, respectively, were 112.7 mm2 ± 16.4 and 109 mm2 ± 24.3 for the 1-million dendritic cell group, 92.2 mm2 ± 9.9 and 90.4 mm2 ± 12.8 for the 2-million dendritic cell group, and 193.7 mm2 ± 20.9 and 189.4 mm2 ± 17.8 for the control group (P = .0001 for control group vs 1-million cell group; P = .00007 for control group vs 2-million cell group). There was a correlation between postinjection T2-weighted SNRsignal-to-noise ratio decreases in the left popliteal LNlymph node 24 hours after injection and size changes at follow-up for tumors in both flanks (R = 0.81 and R = 0.76 for left and right tumors, respectively). Conclusion MR imaging approaches can be used for quantitative measurement of accumulated iron-labeled dendritic cell–based vaccines in draining LNlymph nodes. The amount of dendritic cell–based vaccine in draining LNlymph nodes correlates well with observed protective effects. © RSNA, 2014 Online supplemental material is available for this article. PMID:25222066

  6. Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor.

    PubMed

    Kamohara, Hidenobu; Takahashi, Masashi; Ishiko, Takatoshi; Ogawa, Michio; Baba, Hideo

    2007-09-01

    Pancreatic carcinoma is one of the most lethal of the gastrointestinal malignant tumors. Chronic inflammation leads to cancer development and progression. Interleukin-8 (CXCL-8) is a CXC chemokine, which plays an important role in neutrophil chemotaxis and activation. We previously reported that CXCL-8 was produced by a variety of human carcinoma cells and tissues, and that CXCL-8 promoted proliferation in pancreatic carcinoma cells (SUIT-2). In the present study, we analyzed whether various cytokines affect cell proliferation by CXCL-8 expression in pancreas carcinoma cells. All examined pancreatic carcinoma cells expressed CXCL-8 and TNFRII mRNA constitutively in RPMI-1640 medium without FBS. TNF-alpha, LIF, IL-1beta, IL-6, IL-8, or IFN-beta enhanced the expression of CXCL-8 mRNA, but IL-10 did not in Hs-700T cells. Actinomycin D suppressed and cycloheximide augmented CXCL-8 mRNA which was induced by TNF-alpha or not. The half-life of CXCL-8 mRNA was 36.5 min by TNF-alpha and 35.2 min by no stimulation. In our previous study, LIF promoted cell growth in Hs-700T cells. LIF induced CXCL-8 mRNA in a dose- and time-dependent manner. Addition of recombinant CXCL-8 did not induce cell growth of Hs-700T. Anti-CXCL-8 IgG significantly suppressed cell growth. CXCL-8 would act as an autocrine growth factor in Hs-700T cells, which expressed CXCL-8 mRNA highly without stimulation. Curcumin (diferuloylmethane), NF-kappaB inhibitor, suppressed cell proliferation in Hs-700T cells. These results suggest that CXCL-8 plays a pivotal role in progression of pancreatic cancer, and its expression is influenced by inflammatory cytokines in pancreatic tumor microenvironment. PMID:17671691

  7. Fibrocalculous pancreatic diabetes.

    PubMed

    Goundan, Poorani; Junqueira, Ana; Kelleher-Yassen, Donna; Steenkamp, Devin

    2016-03-01

    The aim of this paper is to review the relevant literature related to the epidemiology, pathophysiology, natural history, clinical features and treatment of fibrocalculous pancreatic diabetes (FCPD). We review the English-language literature on this topic published between 1956 and 2014. FCPD is a form of diabetes usually associated with chronic calcific pancreatitis. It has been predominantly, though not exclusively, described in lean, young adults living in tropical developing countries. Historically linked to malnutrition, the etiology of this phenotype has not been clearly elucidated, nor has there been a clear consensus on specific diagnostic criteria or clinical features. Affected individuals usually present with a long-standing history of abdominal pain, which may begin as early as childhood. Progressive pancreatic endocrine and exocrine dysfunction, consistent with chronic pancreatitis is expected. Common causes of chronic pancreatitis, such as alcohol abuse, are usually absent. Typical radiographic and pathological features include coarse pancreatic calcifications, main pancreatic duct dilation, pancreatic fibrosis and atrophy. Progressive microvascular complications are common, but diabetic ketoacidosis is remarkably unusual. Pancreatic carcinoma is an infrequently described long term complication. FCPD is an uncommon diabetes phenotype characterized by early onset non-alcoholic chronic pancreatitis with hyperglycemia, insulin deficiency and a striking resistance to ketosis. PMID:26472503

  8. Pancreatic Arteriovenous Malformation

    PubMed Central

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

    2014-01-01

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

  9. CT and MRI Findings of Autoimmune Polymorph Bifocal Pancreatitis Mimicking Pancreatic Adenocarcinoma

    PubMed Central

    Blker, Hendrik; Bahra, Marcus; Denecke, Timm; Grieser, Christian

    2015-01-01

    Autoimmune pancreatitis is a rare type of chronic pancreatitis. It is supposed to be a pancreatic manifestation of an immune-complex modulated systemic disorder. In contrast, pancreatic adenocarcinoma is the most frequent malignant neoplasm of the pancreas. Within the rare type of focal autoimmune pancreatitis, only few presentations with multifocal pancreatic lesions have been described. Herein we report a case of a 58-year-old patient with autoimmune pancreatitis presenting with bifocal manifestations of the pancreatic head and tail, mimicking pancreatic adenocarcinoma clinically, on computed tomography and magnetic resonance imaging. Typical imaging findings of autoimmune pancreatitis are compared with typical findings in pancreatic carcinoma. The diagnostic dilemma of differentiating between both entities is discussed. A review of the present literature regarding multifocal presence of autoimmune pancreatitis is performed. PMID:26425636

  10. Carcinoma of the endometrium.

    PubMed

    Cavanagh, D; Marsden, D E; Ruffolo, E H

    1984-01-01

    Endometrial cancer is the cause of considerable morbidity among women, but the disease has been underrated and its management more casual than its virulence warrants. Endometrial carcinoma is the most frequently diagnosed invasive neoplasm of the female genital tract in the US, and is third in incidence after breast and colonic cancer. The white population of the US has the highest age standardized incidence of endometrial cancer in the world, India and Japan have the lowest, and the European countries occupy intermediate positions. Between 75% and 80% of women diagnosed with endometrial cancer are postmenopausal, and the mean age at diagnosis is about 60 years. In many cases endometrial hyperplasia is misdiagnosed as frank malignancy. The predisposing factors for endometrial cancer seem to be obesity, hypertension, diabetes mellitus or an abnormal glucose tolerance curve, and prolonged or unopposed estrogen stimulation. Raised estrogen levels may occur in the following situations: 1) women with functioning ovarian tumors that produce estrogen; 2) women with polycystic ovarian disease; 3) women with ovarian dysgensis (Turner's syndrome) managed with estrogen replacement therapy; 4) women taking high estrogen sequential oral contraceptives (OCs); and 5) women undergoing estrogen replacement therapy. There is an increased risk of endometrial carcinoma associated with nulliparity. Carcinoma of the endometrium occurs in a variety of subtypes, the most frequent being adenocarcinoma, followed by adenocanthoma, adenosquamous carcinoma, clear cell carcinoma, papillary adenocarcinoma, and secretory carcinoma. Overall 5-year survival rates are 72% for adenocarcinoma, 68% for adenocanthoma, and 26% for adenosquamous carcinoma. The true extent of endometrial cancer can be ascertained only after exploratory laparotomy and then various therapies may be used according to the stage of the disease. PMID:6371616

  11. Undifferentiated carcinoma of the head of pancreas with osteoclast-like giant cells presenting as a symptomatic cystic mass, following acute pancreatitis: Case report and review of the literature

    PubMed Central

    Georgiou, Georgios ?.; Balasi, Ephimia; Siozopoulou, Vasiliki; Tsili, Athina; Fatouros, Michalis; Glantzounis, Georgios

    2015-01-01

    Introduction Undifferentiated head of pancreas carcinoma with osteoclast-like giant cells (UC-OGC) is a rare neoplasm, with less than a hundred cases reported. We present such a case, in which the UC-OGC presented atypically as a cystic lesion following acute pancreatitis and led to late diagnosis. Presentation of case A 75-year-old female patient, who had suffered acute pancreatitis three years ago, was referred with a diagnosis of osteoclast-like giant cell (OGC) tumor of the head of pancreas. She had suffered acute pancreatitis three years ago. Two years ago she developed abdominal pain, steatorrhea and weight loss. Abdominal computed tomography imaging showed a cystic mass in the head of the pancreas (maximum diameter 4cm). The initial diagnosis was pancreatic pseudocyst; however as the mass gradually increased in size and the patient continued to be symptomatic, a CT-guided biopsy was performed. Histological examination revealed an OGC pancreatic tumor. In laparotomy a large (9cm) encapsulated heterogeneous mass was found with partial involvement of the common hepatic artery. Pancreaticoduodenectomy was performed and the involved part of the common hepatic artery was replaced with a homologous graft from the major saphenous vein. Post-operative course was uneventful. Histology revealed an undifferentiated pancreatic adenocarcinoma with OGCs. She survived 10 months after the operation. Discussion Pancreatic undifferentiated carcinomas with OGCs are very rare neoplasms and can present with an atypical clinical picture. Conclusions A symptomatic cystic lesion of the pancreas, which is growing in size, should be investigated promptly in order to exclude the presence of malignancy. PMID:26745313

  12. Non-radiological investigation of pancreatic disease.

    PubMed

    Brown, C M; Valori, R M

    Pancreatic exocrine insufficiency is investigated by long established techniques: either by duodenal intubation studies, or by indirect functional methods. Serum markers and specific gastrointestinal hormones are available for the diagnosis of pancreatic inflammation, carcinoma, and rare pancreatic endocrine tumours. The clinical utility of these diagnostic tests is discussed in this article. PMID:8535594

  13. Antroquinonol, a natural ubiquinone derivative, induces a cross talk between apoptosis, autophagy and senescence in human pancreatic carcinoma cells.

    PubMed

    Yu, Chia-Chun; Chiang, Po-Cheng; Lu, Pin-Hsuan; Kuo, Mao-Tien; Wen, Wu-Che; Chen, Peini; Guh, Jih-Hwa

    2012-08-01

    Pancreatic cancer is a malignant neoplasm of the pancreas. A mutation and constitutive activation of K-ras occurs in more than 90% of pancreatic adenocarcinomas. A successful approach for the treatment of pancreatic cancers is urgent. Antroquinonol, a ubiquinone derivative isolated from a camphor tree mushroom, Antrodia camphorata, induced a concentration-dependent inhibition of cell proliferation in pancreatic cancer PANC-1 and AsPC-1 cells. Flow cytometric analysis of DNA content by propidium iodide staining showed that antroquinonol induced G1 arrest of the cell cycle and a subsequent apoptosis. Antroquinonol inhibited Akt phosphorylation at Ser(473), the phosphorylation site critical for Akt kinase activity, and blocked the mammalian target of rapamycin (mTOR) phosphorylation at Ser(2448), a site dependent on mTOR activity. Several signals responsible for mTOR/p70S6K/4E-BP1 signaling cascades have also been examined to validate the pathway. Moreover, antroquinonol induced the down-regulation of several cell cycle regulators and mitochondrial antiapoptotic proteins. In contrast, the expressions of K-ras and its phosphorylation were significantly increased. The coimmunoprecipitation assay showed that the association of K-ras and Bcl-xL was dramatically augmented, which was indicative of apoptotic cell death. Antroquinonol also induced the cross talk between apoptosis, autophagic cell death and accelerated senescence, which was, at least partly, explained by the up-regulation of p21(Waf1/Cip1) and K-ras. In summary, the data suggest that antroquinonol induces anticancer activity in human pancreatic cancers through an inhibitory effect on PI3-kinase/Akt/mTOR pathways that in turn down-regulates cell cycle regulators. The translational inhibition causes G1 arrest of the cell cycle and an ultimate mitochondria-dependent apoptosis. Moreover, autophagic cell death and accelerated senescence also explain antroquinonol-mediated anticancer effect. PMID:21840189

  14. 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

  15. Acute pancreatitis secondary to ifosfamide.

    PubMed

    Gerson, R; Serrano, A; Villalobos, A; Sternbach, G L; Varon, J

    1997-01-01

    Acute pancreatitis in cancer patients can be secondary to the malignant process itself. It is also a rare complication of antineoplastic agent administration. Ifosfamide is an effective drug in the treatment of several tumors and has known neurologic, renal, and hematologic toxicities. There is only one recent report in the literature of pancreatitis associated with ifosfamide. We report a case of a 65-year-old woman with small cell bronchogenic carcinoma without pancreatic metastases who developed acute pancreatitis after ifosfamide administration. PMID:9348053

  16. Clinicopathologic Characteristics of 29 Invasive Carcinomas Arising in 178 Pancreatic Mucinous Cystic Neoplasms With Ovarian-type Stroma

    PubMed Central

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

    2015-01-01

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

  17. 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.

  18. Small Cell and Large Cell Neuroendocrine Carcinomas of the Pancreas Are Genetically Similar and Distinct from Well-differentiated Pancreatic Neuroendocrine Tumors

    PubMed Central

    Yachida, Shinichi; Vakiani, Efsevia; White, Catherine M.; Zhong, Yi; Saunders, Tyler; Morgan, Richard; de Wilde, Roeland F.; Maitra, Anirban; Hicks, Jessica; DeMarzo, Angelo M.; Shi, Chanjuan; Sharma, Rajni; Laheru, Daniel; Edil, Barish H.; Wolfgang, Christopher L.; Schulick, Richard D.; Hruban, Ralph H.; Tang, Laura H.; Klimstra, David S.; Iacobuzio-Donahue, Christine A.

    2011-01-01

    Poorly differentiated neuroendocrine carcinomas (NEC) of the pancreas are rare malignant neoplasms with a poor prognosis. The aim of this study was to determine the clinicopathologic and genetic features of poorly differentiated NECs and compare them to other types of pancreatic neoplasms. We investigated alterations of KRAS, CDKN2A/p16, TP53, SMAD4/DPC4, DAXX, ATRX, PTEN, Bcl2 and RB1 by immunohistochemistry and/or targeted exomic sequencing in surgically resected specimens of nine small cell NEC, 10 large cell NECs and 11 well-differentiated neuroendocrine tumors (PanNETs) of the pancreas. Abnormal immunolabeling patterns of p53 and Rb were frequent (p53, 18 of 19, 95%; Rb, 14 of 19, 74%) in both small cell and large cell NEC, whereas Smad4/Dpc4, DAXX and ATRX labeling were intact in virtually all of these same carcinomas. Abnormal immunolabeling of p53 and Rb proteins correlated with intragenic mutations in the TP53 and RB1 genes. By contrast, DAXX and ATRX was lost in 45% of PanNETs whereas p53 and Rb immunolabeling was intact in these same cases. Overexpression of Bcl-2 protein was observed in all nine small cell NECs (100%) and in five of 10 (50%) large cell NECs compared to only two of 11 (18%) PanNETs. Bcl-2 overexpression was significantly correlated with higher mitotic rate and Ki-67 labeling index in neoplasms in which it was present. Small cell NECs are genetically similar to large cell NECs, and these genetic changes are distinct from those reported in PanNETs. The finding of Bcl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients. PMID:22251937

  19. Tumor cell expression of MMP3 as a prognostic factor for poor survival in pancreatic, pulmonary, and mammary carcinoma

    PubMed Central

    Mehner, Christine; Miller, Erin; Nassar, Aziza; Bamlet, William R.; Radisky, Evette S.; Radisky, Derek C.

    2015-01-01

    Breast, lung, and pancreatic cancers collectively represent one third of all diagnosed tumors and are responsible for almost 40% of overall cancer mortality. Despite improvements in current treatments, efforts to develop more specific therapeutic options are warranted. Here we identify matrix metalloproteinase 3 (MMP3) as a potential target within all three of these tumor types. MMP3 has previously been shown to induce expression of Rac1b, a tumorigenic splice isoform of Rac1. In this study we find that MMP3 and Rac1b proteins are both strongly expressed by the tumor cells of all three tumor types and that expression of MMP3 protein is prognostic of poor survival in pancreatic cancer patients. We also find that MMP3 gene expression can serve as a prognostic marker for patient survival in breast and lung cancer. These results suggest an oncogenic MMP3-Rac1b signaling axis as a driver of tumor progression in three common poor prognosis tumor types, further suggesting that new therapies to target these pathways could have substantial therapeutic benefit. PMID:26807201

  20. 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

  1. 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 ...

  2. Synergism between a novel amphibian oocyte ribonuclease and lovastatin in inducing cytostatic and cytotoxic effects in human lung and pancreatic carcinoma cell lines.

    PubMed Central

    Mikulski, S. M.; Viera, A.; Darzynkiewicz, Z.; Shogen, K.

    1992-01-01

    A novel anti-tumour amphibian oocyte RNase, ONCONASER (ONC), previously known as P-30 Protein, is in the clinical trials. The effect of ONC alone and in combination with lovastatin (LVT), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of mevalonate (MVA) and cholesterol synthesis pathway, in three human tumour cell lines ASPC-1 pancreatic, A-549 lung, and HT-520 lung carcinomas, has been presently studied. A synergism between ONC and LVT in inducing the cytostatic and cytotoxic effects was observed. The cytostatic effect, seen during the early phase of the treatment with this combination of drugs was manifested as prolongation of the cell cycle duration, especially of the G1 phase; cell death was apparent after 72 h of treatment. The synergistic effect of ONC and LVT was also evident in the clonogenicity assays. Both LVT lactone and its in vitro activated beta-hydroxy acid form, alone and in respective combinations with ONC, exerted similar degree of growth suppression. The effects of both forms of LVT (used alone or in combination with ONC) were reversed by MVA, which suggests that HMG-CoA reductase inhibition is a primary mechanism of LVT action. The data indicate that the LVT lactone can be activated intracellularly by tumour cells studied, and that the combination of ONC with LVT can produce significantly enhanced anti-tumour activities. PMID:1503903

  3. 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 potentially a novel target for gene therapy. PMID:26572251

  4. Isolation and characterization of a human colon carcinoma-secreted enzyme with pancreatic ribonuclease-like activity.

    PubMed

    Shapiro, R; Fett, J W; Strydom, D J; Vallee, B L

    1986-11-18

    A ribonuclease was isolated from serum-free supernatants of the human colon adenocarcinoma cell line HT-29. It was purified by cation-exchange and C18 reversed-phase high-performance liquid chromatography. The protein is basic, has a molecular weight of approximately 16,000, and has an amino acid composition that is significantly different from that of human pancreatic ribonuclease. The amino terminus is blocked, and the carboxyl-terminal residue is glycine. The catalytic properties of this ribonuclease resemble those of the pancreatic ribonucleases in numerous respects. Thus, it exhibits a pH optimum of approximately 6 for dinucleotide cleavage and employs a two-step mechanism in which transphosphorylation to a cyclic 2',3'-phosphate is followed by slower hydrolysis to produce a 3'-phosphate. It does not cleave NpN' substrates in which adenosine or guanosine is at the N position and prefers purines at the N' position. Like bovine ribonuclease A, the HT-29-derived ribonuclease is inactivated by reductive methylation or by treatment with iodoacetate at pH 5.5 and is strongly inhibited by the human placental ribonuclease inhibitor. However, in contrast, the tumor enzyme does not cleave CpN bonds at an appreciable rate and prefers poly(uridylic acid) as substrate 1000-fold over poly(cytidylic acid). It also hydrolyzes cytidine cyclic 2',3'-phosphate at least 100 times more slowly than uridine cyclic 2',3'-phosphate and is inhibited much less strongly by cytidine 2'-monophosphate than by uridine 2'-monophosphate. Other ribonucleases known to prefer poly(uridylic acid) were isolated both from human serum and from liver and were compared with the tumor enzyme. The physical, functional, and chromatographic properties of the serum ribonuclease are essentially identical with those of the tumor enzyme. The liver enzymes, however, differ markedly from the HT-29 ribonuclease. The potential utility of the tumor ribonuclease in the diagnosis of cancer is considered. PMID:3467790

  5. Pancreatic Metastases from Tumors in the Urogenital Tract

    PubMed Central

    Strobel, Oliver; Bchler, Markus W.

    2015-01-01

    Background Isolated pancreatic metastases or pancreatic metastases with limited extrapancreatic disease are uncommon and account for only 2-4% of resected malignant pancreatic lesions in surgical series. However, clear-cell renal cell carcinoma is the predominant primary tumor and accounts for more than 60% of cases with isolated pancreatic metastases. Pancreatectomy is the treatment of choice for most patients with isolated pancreatic metastases from renal cell cancer. Summary This review provides an overview of clinical presentation and diagnosis as well as surgical management, including patient selection for surgery and surgical technique for pancreatic metastases of renal cell carcinoma. Key Message Although there is no high-level evidence that surgical resection of pancreatic metastases improves survival, the survival results of several observational series and of systematic reviews are promising and support pancreatic resection as part of a multimodal treatment. The reported median survival and 5-year survival rates after pancreatic resection range from 6 to 10 years and from 55 to 75%, respectively. Pancreatic resection is effective for local control. However, extrapancreatic progression frequently occurs. With the introduction of novel systemic therapy options such as tyrosine kinase inhibitors, the prognosis of metastatic renal cell carcinoma has improved, and this will affect the role of pancreatic resection for metastases. Practical Implications Pancreatic resection for isolated renal cell carcinoma is safe and effective, may confer a survival benefit and should, therefore, be considered in patients for whom no contraindication for surgery exists. PMID:26673854

  6. Acute Pancreatitis and Pregnancy

    MedlinePLUS

    ... NPF Centers Animated Pancreas Patient About the Pancreas Pancreatic Cancer Chronic Pancreatitis Acute Pancreatitis Children/Pediatric Other Pancreas ... Common Disorders of the Pancreas Genetics & The Pancreas Pancreatic Cancer Pancreatic Cancer Risks and Symptoms Diagnosis of Pancreatic ...

  7. Pancreatic involvement in small cell lung cancer

    PubMed Central

    Gonlugur, Ugur; Mirici, Arzu; Karaayvaz, Muammer

    2014-01-01

    Background Few data are available concerning incidence, clinical picture, and prognosis for pancreatic metastases of small cell lung carcinoma. In this paper we review the related literature available in English language. Conclusions Although pancreatic metastases are generally asymptomatic, they can rarely produce clinical symptoms or functional abnormalities. The widespread use of multi-detector computerised tomography (CT) in contemporary medical practice has led to an increased detection of pancreatic metastases in oncology patients. Tissue diagnosis is imperative because radiological techniques alone are incapable of differentiating them from primary pancreatic tumours. Pancreatic metastases occur in the relative end stage of small cell lung cancer. The main complications of these lesions, although rare, are acute pancreatitis and obstructive jaundice. Early chemotherapy can provide a survival benefit even in patients with mild acute pancreatitis or extrahepatic biliary obstruction. PMID:24587774

  8. Hereditary pancreatitis.

    PubMed

    Charnley, Richard M

    2003-01-01

    Hereditary pancreatitis is an autosomal dominant condition, which results in recurrent attacks of acute pancreatitis, progressing to chronic pancreatitis often at a young age. The majority of patients with hereditary pancreatitis express one of two mutations (R122H or N29I) in the cationic trypsinogen gene (PRSS1 gene). It has been hypothesised that one of these mutations, the R122H mutation causes pancreatitis by altering a trypsin recognition site so preventing deactivation of trypsin within the pancreas and prolonging its action, resulting in autodigestion. Families with these two mutations have been identified in many countries and there are also other rarer mutations, which have also been linked to hereditary pancreatitis. Patients with hereditary pancreatitis present in the same way as those with sporadic pancreatitis but at an earlier age. It is common for patients to remain undiagnosed for many years, particularly if they present with non-specific symptoms. Hereditary pancreatitis should always be considered in patients who present with recurrent pancreatitis with a family history of pancreatic disease. If patients with the 2 common mutations are compared, those with the R122H mutation are more likely to present at a younger age and are more likely to require surgical intervention than those with N29I. Hereditary pancreatitis carries a 40 % lifetime risk of pancreatic cancer with those patients aged between 50 to 70 being most at risk in whom screening tests may become important. PMID:12508340

  9. Postburn pancreatitis.

    PubMed Central

    Ryan, C M; Sheridan, R L; Schoenfeld, D A; Warshaw, A L; Tompkins, R G

    1995-01-01

    OBJECTIVE: The authors examined the prevalence and complications of pancreatitis in severely burned patients. Factors predictive for the development of pancreatitis after burns are considered. SUMMARY BACKGROUND DATA: Pancreatitis has been documented at necropsy after burns; however, it is not clinically recognized as a common complication of burn injury. Recent improvements in survival rates could yield previously unrecognized complications, such as pancreatitis, particularly in those patients who previously would have not survived. The hypothesis is that pancreatitis is a frequent complication after major burn injury and causes significant morbidity for patients with large burns. METHODS: This retrospective review of adult patients with large burns examines postburn pancreatitis using stepwise logistic regression analysis. RESULTS: Forty-nine of 121 (40%) patients developed hyperamylasemia or hyperlipasemia well after the admission period (23 +/- 3 days), and all enzyme abnormalities were temporally associated with emerging infections. Most of these patients (40/49, 82%) had symptoms of pancreatitis. Three patients (6%) had pancreatic pseudocysts or abscesses. Inhalation injury (p = 0.0001), associated trauma (p = 0.0311), and escharotomy (p = 0.0415) were risk factors for pancreatitis. Using Fischer's exact test, patients with pancreatitis had increased mortality and length of stay. Patients with high enzyme elevations and > or = 50% body surface area burned were at severe risk of pancreatic pseudocyst or abscess development (43%; 90% confidence interval of 23-77%). CONCLUSIONS: Pancreatitis is a frequent complication after large burn injuries. Patients at high risk for pancreatitis complications should receive surveillance examinations during their acute hospitalization. PMID:7543741

  10. Hereditary pancreatitis

    PubMed Central

    Charnley, Richard M

    2003-01-01

    Hereditary pancreatitis is an autosomal dominant condition, which results in recurrent attacks of acute pancreatitis, progressing to chronic pancreatitis often at a young age. The majority of patients with hereditary pancreatitis express one of two mutations (R122H or N29I) in the cationic trypsinogen gene (PRSS1 gene). It has been hypothesised that one of these mutations, the R122H mutation causes pancreatitis by altering a trypsin recognition site so preventing deactivation of trypsin within the pancreas and prolonging its action, resulting in autodigestion. Families with these two mutations have been identified in many countries and there are also other rarer mutations, which have also been linked to hereditary pancreatitis. Patients with hereditary pancreatitis present in the same way as those with sporadic pancreatitis but at an earlier age. It is common for patients to remain undiagnosed for many years, particularly if they present with non-specific symptoms. Hereditary pancreatitis should always be considered in patients who present with recurrent pancreatitis with a family history of pancreatic disease. If patients with the 2 common mutations are compared, those with the R122H mutation are more likely to present at a younger age and are more likely to require surgical intervention than those with N29I. Hereditary pancreatitis carries a 40% lifetime risk of pancreatic cancer with those patients aged between 50 to 70 being most at risk in whom screening tests may become important. PMID:12508340

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

    PubMed

    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

  12. 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.

  13. 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. PMID:15084979

  14. Imaging preoperatively for pancreatic adenocarcinoma

    PubMed Central

    Pietryga, Jason Alan

    2015-01-01

    Pancreatic cancer is a highly lethal malignancy which is increasing in incidence and mortality. The fourth leading cause of cancer death in the U.S., pancreatic cancer is projected to become the second leading cause of cancer death by 2020. Patients with pancreatic cancer have an abysmal 5-year survival of 6%, and 90% of these patients eventually die from the disease. This is in large part due to the commonly advanced stage of disease at the time of diagnosis. Currently, the only potentially curative therapy for pancreatic carcinoma is complete surgical resection. Patients who undergo incomplete resection with residual disease have similar survival rates to those patients with metastatic disease and should be spared this relatively morbid surgery. Thus, the key to impacting prognosis is the detection of smaller and earlier stage lesions, and the key to optimal management is accurately determining which patients have potentially resectable surgery and which patients would not benefit from surgery. Cross-sectional imaging plays an essential role in both the diagnosis and appropriate staging of pancreatic carcinoma. The diagnosis and staging of pancreatic adenocarcinoma is performed with cross-sectional imaging. Multi-detector computed tomography (MDCT) is the most commonly used, best-validated imaging modality for the diagnosis and staging of pancreatic cancer. Modern contrast-enhanced magnetic resonance imaging (MRI) has been demonstrated to be equivalent to MDCT in detection and staging of pancreatic cancer. Endoscopic ultrasound (EUS) is very sensitive for detecting pancreatic masses; however, due to limitations in adequate overall abdominal staging, it is generally used in addition to or after MDCT. Transabdominal ultrasound and positron emission tomography/computed tomography (PET/CT) have limited roles in the diagnosis and staging of pancreatic cancer. Preoperative imaging is used to characterize patients as having resectable disease, borderline resectable disease, locally advanced disease (unresectable) and metastatic disease (unresectable). As the definitions of borderline resectable and unresectable may vary from institution to institution and within institutions, it is essential to accurately assess and describe the factors relevant to staging including: local extent of tumor, vascular involvement, lymph node involvement and distant metastatic disease. To facilitate this, standardized reporting templates for pancreatic ductal adenocarcinoma have been created and published. Structured reporting for pancreatic cancer has been reported to provide superior evaluation of pancreatic cancer, facilitate surgical planning, and increase surgeons confidence about tumor resectability. PMID:26261722

  15. Chronic pancreatitis

    PubMed Central

    DiMagno, Matthew J.; DiMagno, Eugene P.

    2015-01-01

    Purpose of review We review selected important clinical observations reported in 2012. Recent findings Celiac disease is a risk factor for pancreatitis. Patients with recurrent acute pancreatitis likely have chronic pancreatitis, do not benefit from pancreatic sphincterotomy, and may not benefit from biliary sphincterotomy. Analysis of endoscopic ultrasonography (EUS) images with an artificial neural network (ANN) program may improve chronic pancreatitis diagnosis compared with clinical interpretation of images. In a multicenter, randomized controlled trial of chronic pancreatitis patients, 90 000 USP U of pancreatin with meals decreased fat malabsorption compared with placebo. Detection of visceral pain in chronic pancreatitis predicts pain relief from various treatments, but nonvisceral pain due to altered central pain processing may respond to agents such as pregabalin. Predictors of surgical pain relief include onset of symptoms less than 3 years and preoperatively no opioid use and less than five endoscopic procedures. Total pancreatectomy for presumed painful chronic pancreatitis remains controversial. Summary Celiacs are at risk for pancreatitis. The diagnosis of chronic pancreatitis may be enhanced by ANN analysis of EUS imaging. Treatment of fat malabsorption requires 90 000 USP U of lipase with meals. Relief of pain from organ directed treatment of chronic pancreatitis may depend upon timing of interventions and whether pain is visceral or nonvisceral. PMID:23852141

  16. Pancreatic Cancer

    PubMed Central

    Maitra, Anirban; Hruban, Ralph H.

    2009-01-01

    The past two decades have witnessed an explosion in our understanding of pancreatic cancer, and it is now clear that pancreatic cancer is a disease of inherited (germ-line) and somatic gene mutations. The genes mutated in pancreatic cancer include KRAS2, p16/CDKN2A, TP53, and SMAD4/DPC4, and these are accompanied by a substantial compendium of genomic and transcriptomic alterations that facilitate cell cycle deregulation, cell survival, invasion, and metastases. Pancreatic cancers do not arise de novo, and three distinct precursor lesions have been identified. Experimental models of pancreatic cancer have been developed in genetically engineered mice, which recapitulate the multistep progression of the cognate human disease. Although the putative cell of origin for pancreatic cancer remains elusive, minor populations of cells with stem-like properties have been identified that appear responsible for tumor initiation, metastases, and resistance of pancreatic cancer to conventional therapies. PMID:18039136

  17. Pancreatic Ductal Adenocarcinoma

    Cancer.gov

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

  18. [Surgery for pancreatic cancer].

    PubMed

    Welsch, T; Bchler, M W; Schmidt, J

    2008-12-01

    Ductal pancreatic carcinomas are currently the fourth most common fatal cancer disease with a survival rate of less than 5 % when all stages are considered. Other malignant pancreatic tumours have markedly better prognoses. Even after complete resection and adjuvant chemotherapy, the 5-year survival rate amounts to merely 20 - 25%. Besides a high resistance to chemotherapy and early lympho- and haematogenic metastases, the reason for this is often tumour extension beyond the medial and dorsal resection margins. In standardised pathological examinations cancer cells can be detected in the resection margins in about 75 % of the cases, which reflect the aggressive and infiltrative tumour growth and probably explains the high rate of local recurrence. Standard operations for curative tumour resection are the pylorus-preserving pancreatoduodenectomy (PPPD) and the left pancreatic resection with splenectomy in cases of pancreas tail tumours. In high-volume centres the mortality can be reduced to under 3 % and the long-term survival improved with an increase of the resection rate. Considering surgical complications, pancreatic fistulas with a prevalence of up to 10 % play a decisive role. The technique of the pancreatic anastomosis as well as closure of the pancreatic tail thus represents major surgical challenges. In view of the high recurrence rate of pancreatic carcinomas, extended surgical procedures have been examined in numerous studies. Although infiltration of the portal vein is not a contraindication for curative resection with vascular reconstruction which gives comparable survival rates, a radical, extended lymphadenectomy does not seem reasonable on the basis the available data. In selected, individual cases, patients may benefit from neoadjuvant radiochemotherapy to down-stage an unresectable tumour with subsequent tumour resection, a metastasis resection, or a resection of a local recurrence. An R0 resection and tumour-free lymph nodes (N0 stage) are the two factors that can provide the best prognosis for the patient with a median survival of 2 years and a good quality of life. Pancreas surgery is being increasingly oriented to the evidence-based data from randomised, controlled studies. In order to achieve a further and urgently needed improvement in treatment results, one should consider, if possible, all suitable patients for enrolment in current clinical studies on neoadjuvant, surgical, or adjuvant therapy. PMID:19053009

  19. 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. PMID:20037846

  20. Pancreatic Cystic Neoplasms

    PubMed Central

    Limaiem, Faten; Khalfallah, Tahar; Farhat, Leila Ben; Bouraoui, Sadia; Lahmar, Ahlem; Mzabi, Sabeh

    2014-01-01

    Background: Cystic neoplasms of the pancreas are rare and constitute approximately 0.5% of all pancreatic neoplasms. Aims: The study was to describe clinicopathological features of pancreatic cystic tumors. Patients and Methods: In our retrospective study, we reviewed 10 cases of pancreatic cystic neoplasms that were diagnosed at the pathology department of Mongi Slim hospital over a 14-year period (2000-2013). We adopted the latest World Health Organization (WHO) classification (2010) in grouping all tumors. Results: There were one male and nine female patients (sex ratio M/F = 1:9) aged between 21 and 68 years (mean = 37.5 years). The most common clinical presentation was epigastric and abdominal pain (n = 6) followed by vomiting (n = 3). Abdominal computed tomography (CT) scan disclosed a cystic lesion of the pancreas ranging in size between 2 and 10 cm (mean = 6.75 cm). All patients underwent surgical treatment. Histopathological examination of the surgical specimen established the diagnosis of solid pseudopapillary neoplasm (n = 2), serous cystic neoplasm (n = 2), mucinous cystadenoma (n = 4), mucinous cystadenocarcinoma (n = 1), and intraductal papillary mucinous neoplasm with invasive carcinoma (n = 1). Conclusion: Better understanding of pancreatic cystic neoplasms is essential for clinicians to make accurate diagnosis and to provide the best management for patients. PMID:25210676

  1. Replication-competent adenoviruses with the type 35-derived fiber-knob region achieve reactive oxygen species-dependent cytotoxicity and produce greater toxicity than those with the type 5-derived region in pancreatic carcinoma.

    PubMed

    Yamauchi, Suguru; Kawamura, Kiyoko; Okamoto, Shinya; Morinaga, Takao; Jiang, Yuanyuan; Shingyoji, Masato; Sekine, Ikuo; Kubo, Shuji; Tada, Yuji; Tatsumi, Koichiro; Shimada, Hideaki; Hiroshima, Kenzo; Tagawa, Masatoshi

    2015-12-01

    Pancreatic carcinoma is relatively resistant to chemotherapy and cell death induced by replication of adenoviruses (Ad) can be one of the therapeutic options. Transduction efficacy of conventional type 5 Ad (Ad5) is however low and the cytotoxic mechanism by replication-competent Ad was not well understood. We constructed replication-competent Ad5 of which the E1A promoter region was replaced with a transcriptional regulatory region of the midkine, the survivin or the cyclooxygenase-2 gene, all of which were expressed at a high level in human tumors. We also prepared replication-competent Ad5 that were activated with the same region but had the type 35 Ad-derived fiber-knob region (AdF35) to convert the major cellular receptor for Ad infection from the coxsackie adenovirus receptor to CD46 molecules. Replication-competent AdF35 that were activated with the exogenous region produced cytotoxic effects on human pancreatic carcinoma cells greater than the corresponding Ad5 bearing with the same regulatory region. Cells infected with the AdF35 showed cytopathic effects and increased sub-G1 fractions. Caspase-9, less significantly caspase-8 and poly (ADP-ribose) polymerase, but not caspase-3 was cleaved and expression of molecules involved in autophagy and caspase-independent cell death pathways remained unchanged. Nevertheless, H2A histone family member X molecules were phosphorylated, and N-acetyl-L-cystein, an inhibitor for reactive oxygen species, suppressed the AdF35-mediated cytotoxicity. These data indicated a novel mechanism of Ad-mediated cell death and suggest a possible clinical application of the fiber-knob modified Ad. PMID:26373551

  2. Detection of point mutation in K-ras oncogene at codon 12 in pancreatic diseases

    PubMed Central

    Ren, Yue-Xin; Xu, Guo-Ming; Li, Zhao-Shen; Song, Yu-Gang

    2004-01-01

    AIM: To investigate frequency and clinical significance of K-ras mutations in pancreatic diseases and to identify its diagnostic values in pancreatic carcinoma. METHODS: 117 ductal lesions were identified in the available sections from pancreatic resection specimens of pancreatic ductal adenocarcinoma, comprising 24 pancreatic ductal adenocarcinoma, 19 peritumoral ductal atypical hyperplasia, 58 peritumoral ductal hyperplasia and 19 normal duct at the tumor free resection margin. 24 ductal lesions were got from 24 chronic pancreatitis. DNA was extracted. Codon 12 K-ras mutations were examined using the two-step polymerase chain reaction (PCR) combined with restriction enzyme digestion, followed by nonradioisotopic single-strand conformation polymorphism (SSCP) analysis and by means of automated DNA sequencing. RESULTS: K-ras mutation rate of the pancreatic carcinoma was 79%(19/24) which was significantly higher than that in the chronic pancreatitis 33%(8/24) (P < 0.01). It was also found that K-ras mutation rate was progressively increased from normal duct at the tumor free resection margin, peritumoral ductal hyperplasia, peritumoral ductal atypical hyperplasia to pancreatic ductal adenocarcinoma. The mutation pattern of K-ras 12 codon of chronic pancreatitis was GGT?GAT, GGT and CGT, which is identical to that in pancreatic carcinoma. CONCLUSION: K-ras mutation may play a role in the malignant transformation of pancreatic ductal cell. K-ras mutation was not specific enough to diagnose pancreatic carcinoma. PMID:15040037

  3. Expression of laminin in pancreatic neoplasms and in chronic pancreatitis.

    PubMed

    Haglund, C; Roberts, P J; Nordling, S; Ekblom, P

    1984-09-01

    The distribution of laminin, a basement membrane glycoprotein, was studied by immunohistological techniques in 10 samples of normal pancreatic tissue, in 15 samples of chronic pancreatitis, and in 33 pancreatic neoplasms. Sections of formalin-fixed, paraffin-embedded specimens were pretreated with pepsin and immunostained for laminin. As judged by the expression of laminin, normal pancreatic glands were surrounded by a continuous, intact basement membrane. In chronic pancreatitis the basement membrane was also mainly continuous, but focally weaker and thinner than around normal glands. In pancreatic adenocarcinomas laminin was irregularly distributed and in large areas totally absent. In anaplastic carcinomas no extracellular laminin was seen, but two cases showed some intracellular laminin in a punctate pattern. The findings suggest that these cancers have defects in the deposition of a basement membrane or that it is degraded. Our data suggest that the integrity of the basement membrane correlates with the degree of malignancy in ductal adenocarcinomas, but this is not the case for mucinous cystic neoplasms or for islet cell tumors. In these neoplasms a nearly intact basement membrane was seen both in malignant tumors and in their benign counterparts. PMID:6089598

  4. Pancreatic cancer

    MedlinePLUS

    ... a diet high in fat and low in fruits and vegetables Have diabetes Have long-term exposure to certain chemicals Have long-term inflammation of the pancreas ( chronic pancreatitis ) Smoke Pancreatic cancer is slightly more common in women than in ...

  5. 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 ?-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

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

    PubMed Central

    Abd El Maksoud, Walid

    2014-01-01

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

  7. 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

  8. Chronic Pancreatitis in Children

    MedlinePLUS

    ... NPF Centers Animated Pancreas Patient About the Pancreas Pancreatic Cancer Chronic Pancreatitis Acute Pancreatitis Children/Pediatric Other Pancreas ... will be at an increased risk of developing pancreatic cancer compared to the general population. The degree of ...

  9. ERCP-Guided Percutaneous Fine-Needle Pancreatic Biopsy

    PubMed Central

    Freeny, Patrick C.; Kidd, Reiley; Ball, Terrence J.

    1980-01-01

    In patients with a radiologic diagnosis of unresectable pancreatic carcinoma, exploratory laparotomy for tissue diagnosis is no longer required. Histologic confirmation of the diagnosis may be obtained safely and accurately with percutaneous fine-needle aspiration biopsy. Endoscopic retrograde cholangiopancreatography (ERCP) precisely localized the biopsy site for cytologic diagnosis of adenocarcinoma in 13 of 14 patients (93 percent) with pancreatic carcinoma. ImagesFigure 1Figure 2.Figure 3.Figure 4. PMID:7385832

  10. Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy

    PubMed Central

    Yekebas, Emre F; Bogoevski, Dean; Bubenheim, Michael; Link, Bjrn-Christian; Kaifi, Jussuf T; Wachowiak, Robin; Mann, Oliver; Kutup, Asad; Cataldegirmen, Guellue; Wolfram, Lars; Erbersdobler, Andreas; Klein, Christoph; Pantel, Klaus; Izbicki, Jakob R

    2006-01-01

    AIM: To study the prognostic value of adjuvant chemo-therapy in patients with pancreatic, ductal adenocar-cinoma. METHODS: Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays. Forty-three (41%) of the 106 patients were staged as pT1/2, 63 (59%) as pT3/4, 51 (48%) as pN0, and 55 (52%) as pN1. The study population included 59 (56%) patients exhibiting G1/2, and 47 (44%) patients with G3 tumors. Patients received no adjuvant chemo- or radiation therapy and were followed up for a median of 12 (range: 3.5 to 139) mo. RESULTS: Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as tumor free by conventional histopathology in 73 (69%) out of the 106 patients. Twenty-nine (57%) of 51 patients staged histopathologically as pN0 had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free (relative risk 2.92, P = 0.005) and overall (relative risk 2.49, P = 0.009) survival. CONCLUSION: The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports may help to improve risk stratification of patients with pancreatic cancer. PMID:17072983

  11. Epicatechin-rich cocoa polyphenol inhibits Kras-activated pancreatic ductal carcinoma cell growth in vitro and in a mouse model.

    PubMed

    Siddique, Hifzur Rahman; Liao, D Joshua; Mishra, Shrawan Kumar; Schuster, Todd; Wang, Lei; Matter, Brock; Campbell, Paul M; Villalta, Peter; Nanda, Sanjeev; Deng, Yibin; Saleem, Mohammad

    2012-10-01

    Activated Kras gene coupled with activation of Akt and nuclear factor-kappa B (NF-?B) triggers the development of pancreatic intraepithelial neoplasia, the precursor lesion for pancreatic ductal adenocarcinoma (PDAC) in humans. Therefore, intervention at premalignant stage of disease is considered as an ideal strategy to delay the tumor development. Pancreatic malignant tumor cell lines are widely used; however, there are not relevant cell-based models representing premalignant stages of PDAC to test intervention agents. By employing a novel Kras-driven cell-based model representing premalignant and malignant stages of PDAC, we investigated the efficacy of ACTICOA-grade cocoa polyphenol (CP) as a potent chemopreventive agent under in vitro and in vivo conditions. It is noteworthy that several human intervention/clinical trials have successfully established the pharmacological benefits of cocoa-based foods. The liquid chromatography (LC)-mass spectrometry (MS)/MS data confirmed epicatechin as the major polyphenol of CP. Normal, nontumorigenic and tumorigenic pancreatic ductal epithelial (PDE) cells (exhibiting varying Kras activity) were treated with CP and epicatechin. CP and epicatechin treatments induced no effect on normal PDE cells, however, caused a decrease in the (i) proliferation, (ii) guanosine triphosphate (GTP)-bound Ras protein, (iii) Akt phosphorylation and (iv) NF-?B transcriptional activity of premalignant and malignant Kras-activated PDE cells. Further, oral administration of CP (25 mg/kg) inhibited the growth of Kras-PDE cell-originated tumors in a xenograft mouse model. LC-MS/MS analysis of the blood showed epicatechin to be bioavailable to mice after CP consumption. We suggest that (i) Kras-driven cell-based model is an excellent model for testing intervention agents and (ii) CP is a promising chemopreventive agent for inhibiting PDAC development. PMID:22190076

  12. Pancreatic Enzymes

    MedlinePLUS

    ... This fluid contains pancreatic enzymes to help with digestion and bicarbonate to neutralize stomach acid as it ... the formation of toxic substances due to incomplete digestion of proteins. Increased risk for intestinal infections. Amylase ...

  13. Pancreatitis - discharge

    MedlinePLUS

    ... ask you to take extra capsules, called pancreatic enzymes. These will help your body absorb fats in ... tell you how many. When you take these enzymes, you may also need to take another medicine ...

  14. Clinicopathologic characteristics of 29 invasive carcinomas arising in 178 pancreatic mucinous cystic neoplasms with ovarian-type stroma: implications for management and prognosis.

    TOXLINE Toxicology Bibliographic Information

    Jang KT; Park SM; Basturk O; Bagci P; Bandyopadhyay S; Stelow EB; Walters DM; Choi DW; Choi SH; Heo JS; Sarmiento JM; Reid MD; Adsay V

    2015-02-01

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

  15. Pancreatic resection combined with intraoperative radiation therapy for pancreatic cancer.

    PubMed Central

    Farrell, T J; Barbot, D J; Rosato, F E

    1997-01-01

    OBJECTIVE: The objective of the study was to analyze a single center's experience in the treatment of pancreatic carcinoma with a combination of pancreatic resection and intraoperative radiation therapy (IORT). SUMMARY BACKGROUND DATA: Pancreatic cancer is the most lethal form of gastrointestinal malignancy. Historically, it carries a 20% 1-year survival and a 5-year survival of 3% to 5%. Since 1987, patients at Thomas Jefferson University Hospital have been offered IORT in an attempt to improve their survival. METHODS: The authors reviewed all patients treated at Thomas Jefferson University Hospital with pancreatic adenocarcinoma from 1987 to 1994. From this population, 14 patients were identified who received IORT in conjunction with curative surgery. Duration of hospital stay, perioperative complications, duration of postoperative ileus, and survival were assessed by retrospective review. RESULTS: Of the 14 patients, 6 were male and 8 were female. Patient median age was 61. Six patients had stage I disease, 2 had stage II, 6 had stage III. Two patients had total pancreatectomy, 2 had distal pancreatectomy, and the remaining had pancreaticoduodenectomy (Whipple resection). Median survival was 16 months with a 15.5% 5-year survival. Postoperative complications, duration of hospital stay, and duration of postoperative ileus were not adversely affected by the addition of IORT when compared to in-house control subjects. CONCLUSIONS: Intraoperative radiation therapy is a useful adjunct to surgical resection as treatment of pancreatic cancer. The authors' data suggested it can prolong median survival and long-term survival without adding significant morbidity. PMID:9242339

  16. 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

  17. Clinical Impact of the KL-6 Concentration of Pancreatic Juice for Diagnosing Pancreatic Masses

    PubMed Central

    Matsumoto, Kazuya; Takeda, Yohei; Harada, Kenichi; Onoyama, Takumi; Kawata, Soichiro; Horie, Yasushi; Sakamoto, Teruhisa; Ueki, Masaru; Miura, Norimasa; Murawaki, Yoshikazu

    2015-01-01

    Background and Aim. Pancreatic juice cytology (PJC) is considered optimal for differentially diagnosing pancreatic masses, but the accuracy of PJC ranges from 46.7% to 93.0%. The aim of this study was to evaluate the clinical impact of measuring the KL-6 concentration of pancreatic juice for diagnosing pancreatic masses. Methods. PJC and the KL-6 concentration measurements of pancreatic juice were performed for 70 consecutive patients with pancreatic masses (39 malignancies and 31 benign). Results. The average KL-6 concentration of pancreatic juice was significantly higher for pancreatic ductal adenocarcinomas (PDACs) (167.7 396.1?U/mL) and intraductal papillary mucinous carcinomas (IPMCs) (86.9 21.1?U/mL) than for pancreatic inflammatory lesions (17.5 15.7?U/mL, P = 0.034) and intraductal papillary mucinous neoplasms (14.4 2.0?U/mL, P = 0.026), respectively. When the cut-off level of the KL-6 concentration of pancreatic juice was 16?U/mL, the sensitivity, specificity, and accuracy of the KL-6 concentration of pancreatic juice alone were 79.5%, 64.5%, and 72.9%, respectively. Adding the KL-6 concentration of pancreatic juice to PJC when making a diagnosis caused the values of sensitivity and accuracy of PJC to increase by 15.3% (P = 0.025) and 8.5% (P = 0.048), respectively. Conclusions. The KL-6 concentration of pancreatic juice may be as useful as PJC for diagnosing PDACs. PMID:26451373

  18. 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.

  19. [New molecular targets in pancreatic cancer].

    PubMed

    Torrisani, Jrme; Bournet, Barbara; Cordelier, Pierre; Buscail, Louis

    2008-05-01

    The understanding of the biology of pancreatic carcinoma has greatly benefited from studies of genetic alterations and molecular expression in experimental models as well as in pre-cancerous and cancerous tissues by mean of molecular amplification and large scale transcriptome analysis. P16, TP53, DPC4/Smad4 tumor suppressor pathways are genetically inactivated in the majority of pancreatic carcinomas, whereas oncogenic k-ras is activated. The activating mutation of the K-ras oncogene on codon 12 seems to occur early in pancreatic carcinogenesis and detecting its mutation in tumor samples could have a clinical relevance in term of positive (improvement of current histological diagnosis) and differential diagnosis (versus chronic pancreatitis) of pancreatic cancer. At a late stage of tumor development, an increase of telomerase activity, an over expression of growth factors and/or their receptors (EGF, nerve growth factor, gastrin, bombesin), of proangiogenic factors (VEGF, FGF, PDGF), of invasiveness factors (metalloproteinases, E-cadherin, beta integrin, urokinase and tissue plasminogen activator) occur. All these molecular events contribute to the progression and to the metastatic potential of this carcinoma. New markers and targets are currently studied among microRNA and epigenetics events such as methylation and acetylation. Among all these molecular markers, some are now tested for their potential clinical interest in term of diagnosis or therapeutic target. PMID:18541514

  20. Therapeutic designed poly (lactic-co-glycolic acid) cylindrical oseltamivir phosphate-loaded implants impede tumor neovascularization, growth and metastasis in mouse model of human pancreatic carcinoma

    PubMed Central

    Hrynyk, Michael; Ellis, Jordon P; Haxho, Fiona; Allison, Stephanie; Steele, Joseph AM; Abdulkhalek, Samar; Neufeld, Ronald J; Szewczuk, Myron R

    2015-01-01

    Poly (lactic-co-glycolic acid) (PLGA) copolymers have been extensively used in cancer research. PLGA can be chemically engineered for conjugation or encapsulation of drugs in a particle formulation. We reported that oseltamivir phosphate (OP) treatment of human pancreatic tumor-bearing mice disrupted the tumor vasculature with daily injections. Here, the controlled release of OP from a biodegradable PLGA cylinder (PLGA-OP) implanted at tumor site was investigated for its role in limiting tumor neovascularization, growth, and metastasis. PLGA-OP cylinders over 30 days in vitro indicated 20%–25% release profiles within 48 hours followed by a continuous metronomic low dose release of 30%–50% OP for an additional 16 days. All OP was released by day 30. Surgically implanted PLGA-OP containing 20 mg OP and blank PLGA cylinders at the tumor site of heterotopic xenografts of human pancreatic PANC1 tumors in RAGxCγ double mutant mice impeded tumor neovascularization, growth rate, and spread to the liver and lungs compared with the untreated cohort. Xenograft tumors from PLGA and PLGA-OP-treated cohorts expressed significant higher levels of human E-cadherin with concomitant reduced N-cadherin and host CD31+ endothelial cells compared with the untreated cohort. These results clearly indicate that OP delivered from PLGA cylinders surgically implanted at the site of the solid tumor show promise as an effective treatment therapy for cancer. PMID:26309402

  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. A new indication for pancreas transplantation: high grade pancreatic dysplasia.

    PubMed

    Charpentier, Kevin P; Brentnall, Teresa A; Bronner, Mary P; Byrd, David; Marsh, Christopher

    2004-02-01

    A 42-yr-old male presented with a family history of pancreatic carcinoma inherited an autosomal dominant pattern. The development of endocrine and exocrine pancreatic insufficiency served as early markers for neoplastic transformation. Screening endoscopic ultrasound and ERCP showed abnormalities suggestive of pancreatic dysplasia. Total pancreatectomy was performed and pathology confirmed carcinoma in situ, also known as high-grade pancreatic ductal dysplasia or Pan IN-3. The patient's post-operative course was complicated by life threatening, brittle diabetes. Pancreas transplantation was successfully performed. One year following transplantation, the patient has excellent pancreas graft function. He remains insulin free and has no signs of malignancy. Total pancreatectomy followed by pancreas transplantation is a viable therapeutic option for patients in the dysplastic but still pre-malignant phase of familial pancreatic adenocarcinoma who develop hypoglycemic unawareness following total pancreatectomy. PMID:15108779

  3. Ectopic spleen and liver hemangioma mimicking metastatic pancreatic neuroendocrine tumor

    PubMed Central

    Engler, Christine C.; Lemke, Johannes; Kornmann, Marko; Barth, Thomas F.; Schmidt, Stefan A.; Henne-Bruns, Doris

    2015-01-01

    Pancreatic tumors comprise benign lesion and malignant lesion, most importantly pancreatic adenocarcinoma, acinar cell carcinoma, neuroendocrine carcinoma or metastasis. Surgical resection provides the only chance for cure for malignant pancreatic tumors. In some cases, surgical resection is performed because a malignant lesion is suspected, however, histopathological examinations eventually reveal a benign lesion. Here, we report the case of a 49-year-old woman, who was initially diagnosed with a neuroendocrine tumor of the pancreas with metastasis to the liver. The patient underwent distal pancreatectomy and atypical liver resection. Surprisingly, however, histopathological examination revealed an intrapancreatic accessory spleen (IPAS) of the pancreatic tail as well as liver hemangioma. This unique case report highlights the impact of extensive preoperative examinations to differentiate benign and malignant pancreatic lesions and, possibly, prevent patients from unnecessary surgery. PMID:26670205

  4. Autoimmune pancreatitis

    PubMed Central

    Ketwaroo, Gyanprakash A.; Sheth, Sunil

    2013-01-01

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

  5. Diagnosis of pancreatic adenocarcinoma by polymerase chain reaction from pancreatic secretions.

    PubMed Central

    Trmper, L. H.; Brger, B.; von Bonin, F.; Hintze, A.; von Blohn, G.; Pfreundschuh, M.; Daus, H.

    1994-01-01

    As mutations at codon 12 of the Ki-ras oncogene have been shown to occur in 90% of pancreatic adenocarcinomas, a novel strategy for the detection of these mutations in pancreatic secretions obtained at routine endoscopies was developed. Ki-ras DNA was amplified and screened for the presence of mutations at codon 12 with a combination of different rapid, non-radioactive molecular biology techniques. Examination of DNA from cell lines and paraffin-embedded tumour samples was used to establish and test the strategy employed. Pancreatic secretions from 27 patients were examined for the presence of Ki-ras mutations. Mutations at codon 12 were detected in 16/16 secretions from patients with histologically confirmed carcinoma and from one patient with carcinoma of the bile duct. In six patients a mutation identical to the one found in the pancreatic secretions was also demonstrated in paraffin-embedded fine-needle biopsy or surgical samples. Of the remaining ten patients (who had pancreatitis or cholelithiasis) mutations were not found in nine. Ki-ras codon 12 mutation was identified in one of these patients however, and mucous cell hyperplasia of pancreatic ducts was found upon histological examination. These findings establish Ki-ras polymerase chain reaction from pancreatic secretions as a valuable new diagnostic procedure for the demonstration of malignant cells, possibly at an early stage of the disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8054276

  6. Pancreatic Ductal Adenocarcinoma Associated with Autoimmune Pancreatitis

    PubMed Central

    Pezzilli, Raffaele; Vecchiarelli, Silvia; Di Marco, Maria Cristina; Serra, Carla; Santini, Donatella; Calculli, Lucia; Fabbri, Dario; Rojas Mena, Betzab; Imbrogno, Andrea

    2011-01-01

    Autoimmune pancreatitis (AIP), in contrast to other benign chronic pancreatic diseases, can be cured with immunosuppressant drugs, thus the differentiation of AIP from pancreatic cancer is of particular interest in clinical practice. There is the possibility that some patients with AIP may develop pancreatic cancer, and this possibility contributes to increasing our difficulties in differentiating AIP from pancreatic cancer. We herein report the case of a 70-year-old man in whom pancreatic adenocarcinoma and AIP were detected simultaneously. We must carefully monitor AIP patients for the simultaneous presence of pancreatic cancer, even when a diagnosis of AIP is confirmed. PMID:21769291

  7. A two-cohort phase 1 study of weekly oxaliplatin and gemcitabine, then oxaliplatin, gemcitabine and erlotinib during radiotherapy for unresectable pancreatic carcinoma

    PubMed Central

    Raftery, Laura; Tepper, Joel E; Goldberg, Richard M.; Blackstock, A. William; Aklilu, Mebea; Bernard, Stephen A.; Ivanova, Anastasia; Davies, Janine M.; ONeil, Bert H.

    2012-01-01

    Objectives Gemcitabine is a potent radiosensitizer. When combined with standard radiotherapy (XRT) the gemcitabine dose must be reduced to about 10% of its conventional dose. Oxaliplatin and erlotinib also have radiosensitizing properties. In vitro, oxaliplatin and gemcitabine have demonstrated synergy. We aimed to determine the maximum tolerated dose of oxaliplatin and gemcitabine with concurrent XRT, then oxaliplatin, gemcitaibine and erlotinib with XRT in the treatment of locally advanced and low volume metastatic pancreatic or biliary cancer. Methods A modified 3 + 3 dose escalation design was employed testing 4 dose levels of oxaliplatin and gemcitabine given once weekly for a maximum of 6 weeks with daily XRT in fractions of 1.8 Gy to a total dose of 50.4 Gy. Dose limiting toxicity (DLT) was defined as any grade 4 toxicity or grade 3 toxicity resulting in treatment delay greater than one week. Additionally, dose reduction in two of three patients in a given cohort was counted as a DLT in dose escalation-deescalation rule in the modified 3 + 3 design. Results Eighteen patients were enrolled, all with pancreatic cancer. Grade 4 transaminitis in a patient in cohort 3 resulted in cohort expansion. Cohort 4, the highest planned dose cohort, had no DLTs. The recommended phase II dose (RPTD) is oxaliplatin 50 mg/m2/wk with gemcitabine 200 mg/m2/wk and 50.4 Gy XRT The most prevalent grade 3 toxicities were nausea (22%), elevated transaminases (17%), leucopenia (17%) and hyperglycemia (17%). Median progression free survival was 7.1 months (95% CI, 4.611.1 months) and median overall survival was 10.8 months (95% CI, 7.116.7 months). The addition of erlotinib was poorly tolerated at the first planned dose level, but full study of the combination was hindered by early closure of the study. Conclusions Weekly oxaliplatin 50 mg/m2/wk combined with gemcitabine 200 mg/m2/wk and XRT for pancreatic cancer has acceptable toxicity and interesting activity. PMID:22547007

  8. Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

    PubMed

    Inal, A; Kos, F T; Algin, E; Yildiz, R; Dikiltas, M; Unek, I T; Colak, D; Elkiran, E T; Helvaci, K; Geredeli, C; Dane, F; Balakan, O; Kaplan, M A; Durnali, A G; Harputoglu, H; Goksel, G; Ozdemir, N; Buyukberber, S; Gumus, M; Kucukoner, M; Ozkan, M; Uncu, D; Benekli, M; Isikdogan, A

    2012-01-01

    The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm. PMID:22329849

  9. [Pancreatitis in intestinal diseases].

    PubMed

    Gubergrits, N B; Lukashevich, G M; Golubova, O A; Fomenko, P G

    2010-01-01

    In article review of the literature and own data about pathogenesis of pancreatitis and secondary pancreatic insufficiency in various diseases of small and large intestines is presented. The special attention is given to pancreatic insufficiency in celiac disease and in inflammatory bowel disease. The main directions of pancreatitis and exocrine pancreatic insufficiency therapy are grounded. PMID:21268323

  10. Glypican-3 expression in gastrointestinal and pancreatic epithelial neoplasms.

    PubMed

    Mounajjed, Taofic; Zhang, Lizhi; Wu, Tsung-Teh

    2013-04-01

    Glypican-3 (GPC3) is a plasma membrane-bound proteoglycan that can be overexpressed in certain malignancies but has been particularly linked to hepatocellular carcinoma (HCC). GPC3 is currently used as an immunohistochemical marker for HCC, but its expression in epithelial neoplasms of the gastrointestinal (GI) tract and pancreas, a common source of liver metastasis, has not been studied in detail. In this study, we examined GPC3 immunoreactivity in 98 neoplasms of the GI tract including 30 adenocarcinomas (ADCA), 29 squamous cell carcinomas (esophageal and anal), and 39 neuroendocrine carcinomas, and 60 neoplasms of the pancreas including 22 ADCA, 26 pancreatic neuroendocrine neoplasms, and 12 pancreatic acinar cell carcinomas. Two control groups of 32 HCCs and 16 intrahepatic cholangiocarcinomas were also stained with GPC3. Although most (7/12, 58.5%) acinar cell carcinomas were GPC3 positive, pancreatic ADCA and neuroendocrine neoplasms were GPC3 negative. In addition, 27.5%, (8/29) of squamous cell carcinomas, 20% (6/30) of ADCA, and 2.5% (1/39) of neuroendocrine carcinomas of the GI tract were immunoreactive for GPC3. HCC was positive for GPC3 in 75% (24/32) of cases but cholangiocarcinoma was negative. While significant correlation between GPC3 positivity and poor differentiation was observed in HCC only, GPC3 expression did not correlate with tumor size. In conclusion, 14% of GI tract and pancreatic carcinomas/neoplasms (particularly pancreatic acinar cell carcinoma) can express GPC3 by immunohistochemistry. As these tumors commonly metastasize to the liver, this offers a potential pitfall in differentiating between HCC and metastatic carcinoma when evaluating tumors involving the liver. PMID:23079207

  11. Pancreatic Cancer Stage 3

    MedlinePLUS

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

  12. Pancreatic Cancer Stage 4

    MedlinePLUS

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

  13. Whole Exome Sequencing of Pancreatic Neoplasms with Acinar Differentiation

    PubMed Central

    Jiao, Yuchen; Yonescu, Raluca; Offerhaus, G Johan A; Klimstra, David S; Maitra, Anirban; Eshleman, James R; Herman, James G; Poh, Weijie; Pelosof, Lorraine; Wolfgang, Christopher L.; Vogelstein, Bert; Kinzler, Kenneth W; Hruban, Ralph H; Papadopoulos, Nickolas; Wood, Laura D

    2014-01-01

    Pancreatic carcinomas with acinar differentiation, including acinar cell carcinoma, pancreatoblastoma, and carcinomas with mixed differentiation, are distinct pancreatic neoplasms with poor prognosis. Although recent whole exome sequencing analyses have defined the somatic mutations that characterize the other major neoplasms of the pancreas, the molecular alterations underlying pancreatic carcinomas with acinar differentiation remain largely unknown. In the current study, we sequenced the exomes of 23 surgically resected pancreatic carcinomas with acinar differentiation. These analyses revealed a relatively large number of genetic alterations at both the individual base pair and chromosomal levels. There was an average of 119 somatic mutations per carcinoma. When three outliers were excluded, there was an average of 64 somatic mutations per tumor (range 12–189). The mean fractional allelic loss (FAL) was 0.27 (range 0–0.89) and heterogeneity at the chromosome level was confirmed in selected cases using fluorescent in situ hybridization (FISH). No gene was mutated in >30% of the cancers. Genes altered in other neoplasms of the pancreas were occasionally targeted in carcinomas with acinar differentiation; SMAD4 was mutated in six tumors (26%), TP53 in three (13%), GNAS in two (9%), RNF43 in one (4%) and MEN1 in one tumor (4%). Somatic mutations were identified in genes in which constitutional alterations are associated with familial pancreatic ductal adenocarcinoma, such as ATM, BRCA2, and PALB2 (one tumor each), as well as in genes altered in extra-pancreatic neoplasms, such as JAK1 in four tumors (17%) BRAF in three (13%), RB1 in three (13%), APC in two (9%), PTEN in two (9%), ARID1A in two (9%), MLL3 in two (9%), and BAP1 in one (4%). Perhaps most importantly, we found that more than a third of these carcinomas have potentially targetable genetic alterations including mutations in BRCA2, PALB2, ATM, BAP1, BRAF and JAK1. PMID:24293293

  14. 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

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

    PubMed

    Mohammed, Altaf; Janakiram, Naveena B; 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

    2015-06-20

    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

  16. 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.

  17. Apoptosis: Targets in Pancreatic Cancer

    PubMed Central

    Westphal, Sabine; Kalthoff, Holger

    2003-01-01

    Pancreatic adenocarcinoma is characterized by poor prognosis, because of late diagnosis and lack of response to chemo- and/or radiation therapies. Resistance to apoptosis mainly causes this insensitivity to conventional therapies. Apoptosis or programmed cell death is a central regulator of tissue homeostasis. Certain genetic disturbances of apoptotic signaling pathways have been found in carcinomas leading to tumor development and progression. In the past few years, the knowledge about the complex pathways of apoptosis has strongly increased and new therapeutic approaches based on this knowledge are being developed. This review will focus on the role of apoptotic proteins contributing to pancreatic cancer development and progression and will demonstrate possible targets to influence this deadly disease. PMID:12605713

  18. Pancreatic cancer

    PubMed Central

    Abate-Daga, Daniel; Rosenberg, Steven A; Morgan, Richard A

    2014-01-01

    Pancreatic cancer remains largely an incurable disease necessitating the development of novel therapeutic approaches. Adoptive immunotherapy using chimeric antigen receptor (CAR)-transduced T cells represents an alternative treatment with curative potential. We present an overview of the engineering of novel CARs targeting prostate stem cell antigen (PSCA), implications for the development of immunotherapies, and potential strategies to circumvent on-target/off-tumor toxicities. PMID:25083334

  19. Corticosteroid co-treatment induces resistance to chemotherapy in surgical resections, xenografts and established cell lines of pancreatic cancer

    PubMed Central

    Zhang, Chengwen; Kolb, Armin; Bchler, Peter; Cato, Andrew CB; Mattern, Jrgen; Rittgen, Werner; Edler, Lutz; Debatin, Klaus-Michael; Bchler, Markus W; Friess, Helmut; Herr, Ingrid

    2006-01-01

    Background Chemotherapy for pancreatic carcinoma often has severe side effects that limit its efficacy. The glucocorticoid (GC) dexamethasone (DEX) is frequently used as co-treatment to prevent side effects of chemotherapy such as nausea, for palliative purposes and to treat allergic reactions. While the potent pro-apoptotic properties and the supportive effects of GCs to tumour therapy in lymphoid cells are well studied, the impact of GCs to cytotoxic treatment of pancreatic carcinoma is unknown. Methods A prospective study of DEX-mediated resistance was performed using a pancreatic carcinoma xenografted to nude mice, 20 surgical resections and 10 established pancreatic carcinoma cell lines. Anti-apoptotic signaling in response to DEX was examined by Western blot analysis. Results In vitro, DEX inhibited drug-induced apoptosis and promoted the growth in all of 10 examined malignant cells. Ex vivo, DEX used in physiological concentrations significantly prevented the cytotoxic effect of gemcitabine and cisplatin in 18 of 20 freshly isolated cell lines from resected pancreatic tumours. No correlation with age, gender, histology, TNM and induction of therapy resistance by DEX co-treatment could be detected. In vivo, DEX totally prevented cytotoxicity of chemotherapy to pancreatic carcinoma cells xenografted to nude mice. Mechanistically, DEX upregulated pro-survival factors and anti-apoptotic genes in established pancreatic carcinoma cells. Conclusion These data show that DEX induces therapy resistance in pancreatic carcinoma cells and raise the question whether GC-mediated protection of tumour cells from cancer therapy may be dangerous for patients. PMID:16539710

  20. [Pancreatic insulinomas].

    PubMed

    Miani, S; Boneschi, M; Erba, M; Eusebio, D; Giordanengo, F

    1993-12-01

    Neuroendocrine pancreatic tumors are neoplasms derived from APUD cells, characterized by hyperincretion of several peptides of hormonal activity. The incidence of these tumor is low. They are usually classified according to the predominant secreted peptide: gastrinoma, insulinoma, VIPoma, glucagonoma. Insulinoma is the most frequent endocrine pancreatic tumor, characterized by a peculiar clinical picture due to insulin action. This neoplasm is prevalently benign (90%), and may cause symptoms due to hypo-glycemia such as epilepsy, asthenia, deep coma, dizziness, hunger and epigastric pain. Surgery still constitutes the principal therapy for insulinoma treatment, but an accurate tumor identification is necessary. Selective arteriography of the pancreas and new diagnostic investigations as intraoperative US, selective sampling of pancreatic veins with insulin Quick-RIA, aid the diagnosis and more precise localization of the tumor. When surgical therapy is not practicable, for diffuse metastases, octreotide has an inhibitory effect upon hormone release, and may be combined with chemotherapy for controlling clinical symptoms. We review the clinical records of 2 patients from our Institute, who had hyper-insulinism due to benign insulinomas of the tail of the pancreas. Surgical treatment was performed with enucleation of the neoplasms. PMID:8177452

  1. Current understanding of precursors to pancreatic cancer.

    PubMed

    Takaori, Kyoichi

    2007-01-01

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

  2. Chronic Pancreatitis and Pancreatic Cancer

    PubMed Central

    Kong, Xiangyu; Sun, Tao; Kong, Fanyang; Du, Yiqi; Li, Zhaoshen

    2014-01-01

    Background Pancreatic cancer (PC) is one of the most lethal diseases with an incidence rate almost equal to the rate of mortality. Chronic pancreatitis (CP) is a common chronic inflammatory disease of unknown etiology that affects the pancreas. Epidemiological studies have identified CP to be a major risk factor for PC. Summary A greater understanding of the molecular mechanisms linking CP and PC has identified several common pathways that provide targets for future interventions. This article reviews those components in the CP-PC connection, including the role of macrophages, the maintenance of genome stability, cytokines, and other nodal factors such as nuclear factor kappa B, COX-2 and reactive oxygen species. Key Message The molecular mechanisms that underlie CP and PC provide novel targets for future therapies for PC. Practical Implications The stromal-desmoplastic reaction plays an important role in initiating and sustaining chronic inflammation and tumor progression. Recently, two targeted anti-tumor agents, erlotinib and nab-paclitaxel, have shown promising therapeutic efficacy. Notably, both these agents target components (EGFR and SPARC) within the inflammatory stroma surrounding malignant cells, underscoring the importance of inflammation in pancreatic carcinogenesis. Identifying the common pathways linking CP and PC may help uncover additional novel targets for future therapies. PMID:26674754

  3. Histomolecular profiling of pleomorphic, spindle cell, and giant cell carcinoma of the lung for targeted therapies.

    PubMed

    Forest, Fabien; Yvorel, Violaine; Karpathiou, Georgia; Stachowicz, Marie-Laure; Vergnon, Jean-Michel; Fournel, Pierre; Tiffet, Olivier; Trombert, Batrice; Poc'h, Michel

    2016-03-01

    In pleomorphic, spindle cell, and giant cell carcinoma (PSCGC) of the lung, we wondered if an integrated diagnosis including morphological and immunohistochemical features could be related to molecular status. We performed immunohistochemistry on 35 PSCGCs against TTF1, napsin A, p40, ALK, ROS1, and c-MET. Mutational status regarding EGFR, KRAS, BRAF, HER2, and PIK3CA genes was established. Of 18 PSCGCs with adenocarcinomatous or "undifferentiated" carcinoma differentiation, 8 were mutated for EGFR (n = 1), KRAS (n = 2), BRAF (n = 1), HER2 (n = 3), and PIK3CA (n = 1). No PSCGC (0/4) with only squamous cell or adenosquamous (0/2) differentiation was mutated. c-MET overexpression was only seen in PSCGC with adenocarcinomatous or undifferentiated component (n = 5) without squamous cell component. ROS1 and ALK were negative. The presence of a "targetable mutation" was correlated to the presence of morphological or immunohistochemical adenocarcinomatous differentiation (P = .0137). Integrated diagnosis of an adenocarcinomatous component in PSCGC could be associated with the presence of targetable gene mutation. Because only PSCGC with adenocarcinomatous or undifferentiated carcinoma harbors mutations, whereas PSCGC with only squamous or adenosquamous differentiation does not in our study, this might represent a prescreening for patients with PSCGC to be tested for molecular targets. Our results emphasize that careful morphological examination and the use of immunohistochemistry might be useful for the selection of PSCGC tested for a mutational target. PMID:26826416

  4. Severe Acute Pancreatitis and Necrotizing Pancreatitis.

    PubMed

    Maheshwari, Rahul; Subramanian, Ram M

    2016-04-01

    Acute pancreatitis results in nearly 250,000 admissions annually. Acute pancreatitis varies widely in its clinical presentation. Pancreatic necrosis accounts for substantial additional morbidity, with mortality rates remaining as high as 10% to 20% despite advances in critical care. The extent of necrosis correlates well with the incidence of infected necrosis, multiorgan failure, need for pancreatic debridement, and morbidity and mortality. Having established the diagnosis of pancreatic necrosis, goals of appropriately aggressive resuscitation should be established and adhered to in a multidisciplinary approach involving both medical and surgical critical care. PMID:27016168

  5. Is alcoholic pancreatitis associated with enteroviral infection?

    PubMed Central

    Khan, Jahangir; Nordback, Isto; Seppnen, Hanna; Lappalainen-Lehto, Riitta; Jrvinen, Satu; Oikarinen, Sami; Tauriainen, Sisko; Rty, Sari; Hyty, Heikki; Sand, Juhani

    2013-01-01

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

  6. 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. PMID:25548717

  7. [Advance in the biology of pancreatic of cancer].

    PubMed

    Buscail, Louis; Bournet, Barbara; Dufresne, Marlne; Torrisani, Jrme; Cordelier, Pierre

    2015-06-01

    The understanding of the biology of pancreatic carcinoma has greatly benefited from studies of genetic/epigenetic alterations and molecular expression in experimental models as well as precancerous and cancerous tissues by mean of molecular amplification and large-scale transcriptoma analysis. P16, TP53, DPC4/Smad4 tumor suppressor pathways are genetically inactivated in the majority of pancreatic carcinomas, whereas oncogenic k-ras is activated. The activating point mutation of the KRAS oncogene on codon 12 is the major event and occurs early in pancreatic carcinogenesis. At a late stage of tumor development, an increase of telomerase activity, an over expression of growth factors and/or their receptors (EGF, Nerve Growth Factor, gastrin), of pro-angiogenic factors (VEGF, FGF, PDGF), of invasiveness factors (metalloproteinases, tissue plasminogen activators) occurs. The microenvironment plays also a key role in the invasive and metastatic process of pancreatic carcinoma with a strong relationship between cancerous cells and pancreatic stellate cells as well as extracellular matrix. This microenvironment strongly participates to the tumor fibrosis, hypoxia and hypovascularization inducing an inaccessibility of drugs. Nowadays, the targeting of microenvironment takes a special place in the new therapeutic strategies of pancreatic cancer in combination with chemotherapy. PMID:26118878

  8. [Nutritional repercussions and management of chronic pancreatitis].

    PubMed

    Botella Romero, F; Alfaro Martínez, J J

    2008-05-01

    The pancreas is a retroperitoneal organ that releases water, bicarbonate and digestive enzymes by the main pancreatic duct (MPD) into the duodenum. Chronic pancreatitis (CP) is typically caused, in adults, by chronic alcohol abuse and, less frequently hypertriglyceridemia, primary hyperparathyroidism or cystic fibrosis. Exocrine dysfunction results in malabsorption of fat and subsequent steatorrhea. Damage to pancreatic endocrine function is a late finding in CP and results in hyperglycaemia or overt diabetes mellitus. Care of patients with CP principally involves management of pain. A significant change in the pain pattern or the sudden onset of persistent symptoms suggests the need to rule out other potential etiologies, including peptic ulcer disease, biliary obstruction, pseudocysts, pancreatic carcinoma, and pancreatic duct stricture or stones, then is important to establish a secure diagnosis. Management of pain should then proceed in a judicious stepwise approach avoiding opioids dependence. Patients should be advised to stop alcohol intake. Fat malabsorption and other complications may also arise. Management of steatorrhea should begin with small meals and restriction in fat intake. Pancreatic enzyme supplements can relieve symptoms and reduce malabsorption in patients who do not respond to dietary restriction. Enzymes at high doses should be used with meals. Treatment with acid suppression to reduce inactivation of the enzymes from gastric acid are recommended. Supplementation with medium chain triglycerides and fat soluble vitamin replacement may be required. Management of other complications (such as pseudocysts, bile duct or duodenal obstruction, pancreatic ascites, splenic vein thrombosis and pseudoaneurysms) often requires aggressive approach with the patient kept on total parenteral nutrition to minimize pancreatic stimulation. PMID:18714412

  9. Peroxisome Proliferator-Activated Receptor Gamma and Regulations by the Ubiquitin-Proteasome System in Pancreatic Cancer

    PubMed Central

    Stravodimou, Athina; Mazzoccoli, Gianluigi; Voutsadakis, Ioannis A.

    2012-01-01

    Pancreatic cancer is one of the most lethal forms of human cancer. Although progress in oncology has improved outcomes in many forms of cancer, little progress has been made in pancreatic carcinoma and the prognosis of this malignancy remains grim. Several molecular abnormalities often present in pancreatic cancer have been defined and include mutations in K-ras, p53, p16, and DPC4 genes. Nuclear receptor Peroxisome Proliferator-Activated Receptor gamma (PPAR?) has a role in many carcinomas and has been found to be overexpressed in pancreatic cancer. It plays generally a tumor suppressor role antagonizing proteins promoting carcinogenesis such as NF-?B and TGF?. Regulation of pathways involved in pancreatic carcinogenesis is effectuated by the Ubiquitin Proteasome System (UPS). This paper will examine PPAR? in pancreatic cancer, the regulation of this nuclear receptor by the UPS, and their relationship to other pathways important in pancreatic carcinogenesis. PMID:23049538

  10. Acute Pancreatitis Accelerates Initiation and Progression to Pancreatic Cancer in Mice Expressing Oncogenic Kras in the Nestin Cell Lineage

    PubMed Central

    Carrire, Catherine; Young, Alison L.; Gunn, Jason R.; Longnecker, Daniel S.; Korc, Murray

    2011-01-01

    Targeting of oncogenic Kras to the pancreatic Nestin-expressing embryonic progenitor cells and subsequently to the adult acinar compartment and Nestin-expressing cells is sufficient for the development of low grade pancreatic intraepithelial neoplasia (PanIN) between 2 and 4 months. The mice die around 6 month-old of unrelated causes, and it is therefore not possible to assess whether the lesions will progress to carcinoma. We now report that two brief episodes of caerulein-induced acute pancreatitis in 2 month-old mice causes rapid PanIN progression and pancreatic ductal adenocarcinoma (PDAC) development by 4 months of age. These events occur with similar frequency as observed in animals where the oncogene is targeted during embryogenesis to all pancreatic cell types. Thus, these data show that oncogenic Kras-driven PanIN originating in a non-ductal compartment can rapidly progress to PDAC when subjected to a brief inflammatory insult. PMID:22140463

  11. Biotherapeutic approaches to pancreatic cancer.

    PubMed

    Rosenberg, Lawrence; Lipsett, Mark

    2003-04-01

    The incidence of adenocarcinoma of the pancreas has risen steadily over the past four decades. Since pancreatic cancer is usually diagnosed at an advanced stage and because of the lack of effective therapies, the prognosis of such patients is extremely poor. Despite advances in our understanding of the molecular biology of pancreatic cancer, the systemic treatment of this disease remains unsatisfactory. Conventional chemotherapy has not produced dramatic improvements in response rates or patient survival. New treatment strategies are clearly needed. This paper will review emerging therapies for pancreatic carcinoma. A deeper understanding of the molecular biology of cell growth and proliferation, as well as of neoplastic cell transformation, has led to advances in several areas, including the use of hormones and antihormones as adjuvant therapy; inhibition of tumour growth and metastasis by inhibitors of matrix metalloproteases and angiogenesis, and by small molecules, such as retinoids, which interfere with progression through the cell cycle; immunotherapy with monoclonal antibodies; disruption of intracellular signal transduction with farnesyltransferase inhibitors; and, finally, gene therapy with specifically designed vaccines. PMID:12662145

  12. Galectin-9: An anticancer molecule for gallbladder carcinoma.

    PubMed

    Tadokoro, Tomoko; Morishita, Asahiro; Fujihara, Shintaro; Iwama, Hisakazu; Niki, Toshiro; Fujita, Koji; Akashi, Emiko; Mimura, Shima; Oura, Kyoko; Sakamoto, Teppei; Nomura, Takako; Tani, Joji; Miyoshi, Hisaaki; Yoneyama, Hirohito; Himoto, Takashi; Hirashima, Mitsuomi; Masaki, Tsutomu

    2016-03-01

    Gallbladder cancer (GBC) is the most common and aggressive type of biliary tract cancer. There are various histological types of GBC, and the vast majority of GBC cases are adenocarcinomas. Squamous and adenosquamous carcinomas are rare GBC subtypes that are traditionally considered to be more aggressive and to be associated with a poorer prognosis than adenocarcinoma. Galectin-9 (Gal-9), a tandem-repeat-type galectin, has been reported to induce apoptosis-mediated elimination of various cancers, including hepatocellular carcinoma, cholangiocarcinoma, and hematologic malignancies. Therefore, we investigated the antitumor effects of Gal-9 on GBC invitro and invivo. In our invitro experiments, Gal-9 suppressed cell proliferation in various GBC cell lines but not in the OCUG-1 cell line, which represents a poorly differentiated type of adenosquamous carcinoma. Gal-9 induced the apoptosis of Gal-9-sensitive GBC cells by increasing the levels of caspase-cleaved keratin 18 and phosphorylated p53. However, Gal-9 did not affect the expression of various cell cycle-related proteins. In addition, Gal-9 suppressed tumor growth by implanted human GBC cells in a xenograft model. Furthermore, Gal-9 induced the phosphorylation of the Ephrin type-B receptor, and the microRNA (miRNA) expression profile was markedly altered by Gal-9. Based on these results, various miRNAs might contribute to the suppression of tumor growth. Our data reveal that Gal-9 suppresses the growth of GBC, possibly by inducing apoptosis and altering miRNA expression. Thus, Gal-9 might serve as a therapeutic agent for the treatment of GBC. PMID:26797414

  13. [Acute pancreatitis].

    PubMed

    Ruiz Chvez, R

    1991-01-01

    This article review newer concepts of diagnosis and therapy for patients with acute pancreatitis. Although the pathogenesis are incompletely understood, much progress has recently been made in treatment of symptoms and medical support of the critically ill patients. The most common associate factors include: biliary tract disease (lithiasis), alcohol abuse, trauma and hyperlipoproteinemia. Most patients have abdominal pain, nausea and vomiting, fever, abdominal tenderness and hypovolemia of varying degrees. Renal clearance of amilase is increased, the ratio of renal clearance to that of creatinine is very important in patients with hypovolemia or an underlying renal disease. The definition of risk factors, with regard to morbility or mortality. Those patients at great risk require critical care treatment in an ICU and meticulous pulmonary, cardiac, hematological and metabolic monitoring and treatment of any the abdominal complications. PMID:1820183

  14. Expression of maspin in pancreatic neoplasms: application of maspin immunohistochemistry to the differential diagnosis.

    PubMed

    Oh, Young Lyun; Song, Sang-Yong; Ahn, Geunghwan

    2002-03-01

    Maspin is a unique member of the serpin family, which inhibits tumor invasion and metastasis of the human breast and prostate cancers. Immunohistochemical evaluation of the maspin expression in pancreatic neoplasms has never been performed. The authors examined the expression of maspin in various pancreatic neoplasms to investigate its usefulness as an adjunct diagnostic marker. Formalin-fixed, paraffin-embedded tissue sections from 107 pancreatic neoplasms were immunostained with anti-maspin antibody using an EnVision+ System. Maspin was expressed in all ductal adenocarcinomas, of which 78.9% (30/38) were high expressors and 21.1% (8/38) were low expressors. All 13 intraductal papillary mucinous tumors and 11 of the 13 mucinous cystic tumors reacted to maspin with stronger expressions in carcinomatous lesions. In contrast, acinar cell carcinoma, pancreatic endocrine tumors, solid-pseudopapillary tumors, and serous cystadenomas demonstrated no maspin expression. In addition, nonneoplastic pancreatic parenchyma and chronic pancreatitis lacked expression. The current study suggests that maspin may be of importance in the pathobiology of pancreatic neoplasms with epithelial origin, especially pancreatic tumors that are composed of mucin-producing cells. It may be useful in separating ductal adenocarcinoma from acinar cell carcinoma, pancreatic endocrine tumor, solid-pseudopapillary tumor, and chronic pancreatitis, especially in needle biopsy specimens. PMID:11893038

  15. Quantitative assessment of telomerase activity and human telomerase reverse transcriptase messenger RNA levels in pancreatic juice samples for the diagnosis of pancreatic cancer.

    PubMed

    Ohuchida, Kenoki; Mizumoto, Kazuhiro; Ogura, Yasuhiro; Ishikawa, Nami; Nagai, Eishi; Yamaguchi, Koji; Tanaka, Masao

    2005-03-15

    Measurement of telomerase activity is a promising diagnostic tool for pancreatic cancer. Detection of mRNA for human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is also a diagnostic candidate. In the present study, we developed a telomeric repeat amplification protocol assay with real-time PCR and a protocol for quantification of hTERT mRNA with real-time PCR. To evaluate the feasibility of these methods for diagnosis of pancreatic cancer, we measured telomerase activity and hTERT expression in pancreatic cancer cell lines, pancreatic tissues, and pancreatic juice samples from patients with different pancreatic diseases. There were significant correlations between telomerase activity and hTERT expression in cell lines, tissues, and juice samples. The levels of telomerase activity and hTERT expression were significantly higher in tumoral tissues than in nontumoral tissues. In pancreatic juice specimens, some carcinoma samples showed remarkably high expression of hTERT. However, there were no significant differences in hTERT expression between patients with carcinoma and those with benign diseases, although significant differences in telomerase activity were observed. Our present results suggest that the combined assessment of hTERT and telomerase activities in pancreatic juice provides a potent diagnostic method for pancreatic cancer. PMID:15788678

  16. 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.

  17. Pancreatitis-imaging approach

    PubMed Central

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

    2014-01-01

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

  18. Pancreatic Cancer Action Network

    MedlinePLUS

    ... for pancreatic cancer. Learn more LEARN MORE OUR CORPORATE CHAMPIONS Corporate Champions stand beside us as we ... are tax-deductible to the extent permitted by law. The Pancreatic Cancer Action Networks tax identification number ...

  19. Pancreatic Cancer: Surgery

    MedlinePLUS

    ... patients with pancreatic NETs. In rare cases, a liver transplant might be used to treat pancreatic NETs that ... Bureau Health On The Net National Health Council © 2016 American Cancer Society, Inc. All rights reserved. The ...

  20. 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. PMID:25170207

  1. Mutational spectrum of intraepithelial neoplasia in pancreatic heterotopia.

    PubMed

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

    2016-02-01

    Heterotopic pancreatic parenchyma recapitulates the normal pancreas in extrapancreatic locations and, on rare occasions, can even give rise to pancreatic adenocarcinoma. The genetic signatures of pancreatic adenocarcinoma and its precursor lesions are well characterized. We explored the genetic alterations in precursor lesions (intraductal papillary mucinous neoplasms [IPMN], pancreatic intraepithelial neoplasia [PanIN]) in patients with pancreatic heterotopias but without concomitant pancreatic ductal adenocarcinomas. This allowed us to determine whether the stereotypical dysplasia--infiltrating carcinoma sequence also occurs in these extrapancreatic foci. Seven cases of heterotopic pancreas with ductal precursor lesions were identified. These included 2 IPMNs with focal high-grade dysplasia and 5 PanINs with low- to moderate-grade dysplasia (PanIN grades 1-2). Neoplastic epithelium was microdissected and genomic DNA was extracted. Sequencing of commonly mutated hotspots (KRAS, TP53, CDKN2A, SMAD4, BRAF, and GNAS) in pancreatic ductal adenocarcinoma and its precursor lesions was performed. Both IPMNs were found to have KRAS codon 12 mutations. The identification of KRAS mutations suggests a genetic pathway shared with IPMN of the pancreas. No mutations were identified in our heterotopic PanINs. One of the possible mechanisms for the development of dysplasia in these lesions is field effect. At the time of these resections, there was no clinical or pathologic evidence of a prior or concomitant pancreatic lesion. However, a clinically undetectable lesion is theoretically possible. Therefore, although a field effect cannot be excluded, there was no evidence for it in this study. PMID:26626780

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

    PubMed Central

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

    2012-01-01

    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. PMID:22736913

  3. Strategies for early detection of resectable pancreatic cancer

    PubMed Central

    Okano, Keiichi; Suzuki, Yasuyuki

    2014-01-01

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

  4. Middle Segment-Preserving Pancreatectomy for Recurrent Metastasis of Renal Cell Carcinoma after Pancreatoduodenectomy: A Case Report

    PubMed Central

    Takeshi, Aiyama; Mitsuhiro, Inagaki; Hiromitsu, Akabane; Naoyuki, Yanagida; Taiichiro, Shibaki; Hiroki, Shomura; Takeaki, Kudo; Tatsuya, Shonaka; Futoshi, Oikawa; Hiroharu, Sakurai; Shiro, Nakano

    2014-01-01

    Many cases of surgical resection of metastatic pancreatic tumors originating from renal cell carcinoma have been reported; however, cases of reresection of recurrent pancreatic metastasis of renal cell carcinoma in the remnant pancreas are rare. We performed a second resection for recurrent pancreatic metastasis of renal cell carcinoma six years after pancreatoduodenectomy with pancreaticogastrostomy reconstruction. By performing middle segment-preserving pancreatectomy, we were able to successfully spare the exocrine and endocrine pancreatic function compared to that observed after total pancreatectomy, with no signs of recurrence for two years after the surgery. PMID:25061531

  5. Pancreatitis after percutaneous ethanol injection into HCC: a minireview of the literature

    PubMed Central

    Zardi, Enrico M; Di Matteo, Francesco; Santini, Daniele; Uwechie, Valentina; Crucitti, Pierfilippo; Carassiti, Massimiliano; Picardi, Antonio; Perrella, Eleonora; Caricato, Marco; Tonini, Giuseppe; Coppola, Roberto; Afeltra, Antonella

    2008-01-01

    Deaths after percutaneous ethanol injection (PEI) into hepatocellular carcinoma (HCC) may occur within a few hours to a few days following the procedure because of hemoperitoneum and haemorrhage from oesophageal varices or hepatic insufficiency. Pancreatitis has been recently reported as a rare lethal complication of intra-arterial PEI, another modality for treating HCCs. In this minireview, we analyze the literature concerning the development of acute pancreatitis after PEI. Pathogenesis of pancreatitis from opioids and ethanol is also addressed. Treatment with opioids to reduce the patient's abdominal pain after PEI in combination with the PEI itself may lead to direct toxic effects, thus favouring the development of pancreatitis. PMID:18702805

  6. Biology of pancreatic cancer.

    PubMed Central

    Poston, G J; Gillespie, J; Guillou, P J

    1991-01-01

    Pancreatic cancer is the fifth leading cause of death from malignant disease in Western society. Apart from the fortunate few patients who present with a resectable small pancreatic adenocarcinoma, conventional treatment offers no hope of cure and has little palliative value. Over the past two decades major steps have been made in our understanding of the biology of pancreatic growth and neoplasia. This review sets out to explore these advances, firstly in the regulation of normal pancreatic growth, and secondly the mechanism which may be involved in malignant change of the exocrine pancreas. From an understanding of this new biology, new treatment strategies may be possible for patients with pancreatic cancer. PMID:1855689

  7. 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

  8. Diabetes and Pancreatic Cancer

    PubMed Central

    Li, Donghui

    2011-01-01

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

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

    PubMed

    Garg, Shivani; Mulki, Ramzi; Sher, Daniel

    2016-01-01

    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. PMID:26957034

  10. [Effusions rich in amylase without pancreatitis. 14 cases].

    PubMed

    Saugier, B; Emonot, A; Plauchu, M; Galy, P

    1976-12-01

    This study involved 14 cases or pleural effusions or ascites rich in amylase and unrelated to chronic pancreatitis, a pseudo-cyst of the pancreas or acute pancreatitis. A pleural effusion rich in amylase may be secondary to a pancreatic neoplasm but this possibility seems rare. Amylase-containing effusions related to a nonpancreatic neoplasm are more common. The lesion is in general an advanced pleuro-pulmonary carcinoma, frequently an adenocarcinoma. The amylase activity of neoplastic effusion fluid is significantly increased but although levels similar to those of certain pancreatic effusions may be seen, very high figures would appear to be rare. Finally, two cases of amylase-rich pleural effusions were related to a pleuro-digestive fistula and one left-sided effusion was secondary to abdominal trauma. PMID:995607

  11. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    PubMed Central

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

    2015-01-01

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

  12. 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.

  13. 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

  14. Genetics Home Reference: Hereditary pancreatitis

    MedlinePLUS

    ... characterized by recurrent episodes of inflammation of the pancreas (pancreatitis). The pancreas produces enzymes that help digest food, and it ... leads to chronic pancreatitis, which occurs when the pancreas is persistently inflamed. Chronic pancreatitis usually develops by ...

  15. Pancreatic Cancer Stage 2A

    MedlinePLUS

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

  16. Pancreatic Cancer Stage 2B

    MedlinePLUS

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

  17. Autophagy and pancreatitis

    PubMed Central

    Gukovsky, Ilya

    2012-01-01

    Acute pancreatitis is an inflammatory disease of the exocrine pancreas that carries considerable morbidity and mortality; its pathophysiology remains poorly understood. Recent findings from experimental models and genetically altered mice summarized in this review reveal that autophagy, the principal cellular degradative pathway, is impaired in pancreatitis and that one cause of autophagy impairment is defective function of lysosomes. We propose that the lysosomal/autophagic dysfunction is a key initiating event in pancreatitis and a converging point of multiple deranged pathways. There is strong evidence supporting this hypothesis. Investigation of autophagy in pancreatitis has just started, and many questions about the upstream mechanisms mediating the lysosomal/autophagic dysfunction and the downstream links to pancreatitis pathologies need to be explored. Answers to these questions should provide insight into novel molecular targets and therapeutic strategies for treatment of pancreatitis. PMID:22961802

  18. Graft pancreatitis: literature review.

    PubMed

    Labruzzo, Cinzia; El Tayar, Adil R; Hakim, Nadey S

    2006-01-01

    Graft pancreatitis is an inflammatory disease leading to autodigestion of the gland. The failure of the pancreatic graft can be attributed to immunological or nonimmunological causes. It consists of a premature activation of pancreatic proenzymes. When complications such as bleeding or leaks have already occurred, surgical correction should be considered. The aim of this review is to draw the attention of surgeons to the complications that can easily be avoided. PMID:16774182

  19. 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. PMID:26310818

  20. 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.

  1. An evaluation of echography in the diagnosis of pancreatic disease.

    PubMed Central

    Fontana, G; Bolondi, L; Conti, M; Plicchi, G; Gullo, L; Caletti, G C; Labo, G

    1976-01-01

    In the present study an attempt to evaluate the efficacy of echography as a diagnostic tool has been made. A total of 52 patients (chronic pancreatitis (42); pancreatic cysts (three); and carcinoma of the pancreas (seven)) were studied and the results compared with those from other diagnostic techniques. In 65.7% of chronic pancreatitis patients, and in all cases of carcinoma of the pancreas, echography provided evidence of pancreatic abnormality but in no case could an unambiguous diagnosis of the disease be made. However, in all cases of pancreatic cyst, echography gave precise and unequivocal diagnostic information. There was good agreement between the echographic picture and surgical findings. Cholangiography and duodenography indicated duodenal and choledochal compression in a high proportion of cases in which echography revealed enlargement of the head of the pancreas. It is concluded that echography is a simple, safe, and valuable addition to the techniques available for studying the pancreas. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:1269992

  2. 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. PMID:26481685

  3. Minireview on laparoscopic hepatobiliary and pancreatic surgery

    PubMed Central

    Tan-Tam, Clara; Chung, Stephen W

    2014-01-01

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

  4. Hereditary pancreatitis in England and Wales.

    PubMed Central

    Sibert, J R

    1978-01-01

    Information from 72 patients from 7 families in England and Wales confirms that hereditary pancreatitis is inherited as an autosomal dominant conditions with limited penetrance. The degree of penetrance is approximately 80%. These patients have had recurrent attacks of abdominal pain starting from childhood or young adult life. The mean age of onset in the 7 families studied was 13.6 years. There were two peaks, with maximum numbers at 5 years and 17 years. The second peak was thought to represent genetically susceptible individuals having pain brought on by alcohol rather than representing evidence of genetic heterogeneity. Five of the 7 families had members with both childhood and adult ages of onset. Only 4 patients out of 72 had life-threatening disease and in the majority of cases the attacks of pain were of nuisance value only. Hereditary pancreatitis was implicated in only 1 patient's death and this was not definite. Patients appear to get better after a period of symptoms usually as they approach middle age, or after a severe attack. In older patients alcohol, emotional upsets, and fatty food appear to precipitate attacks. Pancreatic insufficiency (5.5%), diabetes mellitus (12.5%), pseudocysts (5.5%), and haemorrhagic pleural effusion are uncommon complications. Portal vein thrombosis occurred definitely in 2 patients and was suspected in 3 others. Carcinoma of the pancreas was not found in any of 72 patients studied in detail; however, 2 members from a family not visited personally had chronic pancreatitis and malabsorption going on to carcinoma. They may have suffered from a different disease. Genetic linkage information was too slight for many definite conclusions. However, there was no suggestion of linkage with any of the markers tested. PMID:671483

  5. Hereditary chronic pancreatitis

    PubMed Central

    Rosendahl, Jonas; Bdeker, Hans; Mssner, Joachim; Teich, Niels

    2007-01-01

    Hereditary chronic pancreatitis (HCP) is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary) as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer. PMID:17204147

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

    PubMed Central

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

    2013-01-01

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

  7. Acute and Chronic Pancreatitis.

    PubMed

    Berenson; Wyllie

    1995-10-01

    Pancreatitis, once thought to be almost exclusively a disease of adults, is increasingly being found as the cause of abdominal pain in adolescents. The authors review the pathophysiology, diagnosis, managment, and complications of acute and chronic pancreatitis, noting that a high index of suspicion is needed to properly diagnose and provide optimal care to these patients. PMID:10358323

  8. Pancreatic Cancer Interest Group

    Cancer.gov

    Mission Statement Pancreatic cancer is the most deadliest of all cancers and there is no effective treatment. There are a number of investigators at NCI, both in the basic and clinical disciplines, who are working on pancreatic cancer and who would like t

  9. Imatinib-induced pancreatitis

    PubMed Central

    Varma, Mahesh R.; Mathew, Shibi; Krishnadas, Devadas; Vinayakumar, K.R.

    2010-01-01

    Drug-induced pancreatitis is a rare but serious complication of many drugs, some of which have been well documented. Here we present a case of a middle-aged man with chronic myeloid leukemia who developed acute pancreatitis after being initiated on imatinib mesylate. The case history, the pharmacodynamics, uses, and adverse effects of imatinib mesylate are discussed in detail. PMID:20606838

  10. Pancreatic Islet Cell Transplantation

    PubMed Central

    Warnock, Garth L.; Rajotte, Ray V.

    1992-01-01

    Transplantation of insulin-producing tissue offers a physiologic approach to restoration of glycemic control. Whereas transplantation of vascularized pancreatic grafts has recently achieved encouraging results, pancreatic islet cell transplantation holds the promise of low morbidity and reduced requirements for agressive immunosuppression for recipients. Islet cell transplantation was recently demonstrated to induce euglycemia with insulin independence. Imagesp1656-a PMID:21221366

  11. Is Pancreatic Cancer Hereditary?

    MedlinePLUS

    ... The genetics of hereditary pancreatic cancer is a focus of research at Johns Hopkins. It has been estimated that ten percent of pancreatic cancers are hereditary. Many of these occur as part of rare medical syndromes. These include: Familial breast cancer gene(BRCA2) ...

  12. K-ras gene mutation in the diagnosis of ultrasound guided fine-needle biopsy of pancreatic masses

    PubMed Central

    Zheng, Min; Liu, Lian-Xin; Zhu, An-Long; Qi, Shu-Yi; Jiang, Hong-Chi; Xiao, Zhu-Ying

    2003-01-01

    AIM: To investigate the utility of K-ras mutation analysis of ultrasound guided fine-needle aspirate biopsy of pancreatic masses. METHODS: Sixty-six ultrasound guided fine-needle biopsies were evaluated by cytology, histology and K-ras mutation. The mutation at codon 12 of the K-ras oncogene was detected by artificial restriction fragment length polymorphisms using BstN I approach. RESULTS: The presence of malignant cells was reported in 40 of 54 pancreatic carcinomas and K-ras mutations were detected in 45 of the 54 FNABs of pancreatic carcinomas. The sensitivity of cytology and K-ras mutation were 74% and 83%, respectively. The speciality of cytology and K-ras mutation were both 100%. The sensitivity and speciality of K-ras mutation combined with cytology were 83% and 100%, respectively. CONCLUSION: High diagnostic accuracy with acceptable discomfort of FNAB make it useful in diagnosis of pancreatic carcinoma. Ultrasound guided fine-needle biopsy is a safe and feasible method for diagnosing pancreatic cancer. Pancreatic carcinoma has the highest K-ras mutation rate among all solid tumors. The mutation rate of K-ras is about 80%-100%. The usage of mutation of codon 12 of K-ras oncogene combined with cytology is a good alternative for evaluation of pancreatic masses. PMID:12508380

  13. Evolution and dynamics of pancreatic cancer progression

    PubMed Central

    Yachida, S; Iacobuzio-Donahue, CA

    2013-01-01

    Efficient metastasis is believed as the result of multiple genetic, epigenetic and/or post-translational events in the lifetime of a carcinoma. At the genetic level, these events may be categorized into those that occur during carcinogenesis, and those that occur during subclonal evolution. This review summarizes current knowledge of the genetics of pancreatic cancer from its initiation within a normal cell until the time that is has disseminated to distant organs, many features of which can be extrapolated to other solid tumor types. The implications of these findings to personalize genome analyses of an individual patients tumor are also discussed. PMID:23416985

  14. Primary pancreatic plasmacytoma.

    PubMed

    Deguchi, Yasunori; Nonaka, Atsushi; Takeuchi, Eiji; Funaki, Naomi; Kono, Yukihiro; Mizuta, Kazuhiko

    2004-06-01

    We report an extremely rare case of primary pancreatic plasmacytoma. A 56-year-old man had a 4-cm mass in the pancreatic tail and received distal pancreatectomy. This mass mainly consisted of plasma cells, but we failed to demonstrate their monoclonality in spite of the immunohistological staining. One and a half years later, this patient's right inguinal node swelled, and this node also showed a dense plasma cell infiltration. A very precise immunohistological staining was performed for this lymph node and the previous pancreatic mass, and both were diffusely positive for kappa light chain, IgG, and CD38. In the absence of myeloma elsewhere, we thus reached the correct diagnosis of primary pancreatic plasmacytoma, which later metastasized to lymph nodes. In the presence of the plasma cell proliferation in a pancreatic mass, plasmacytoma should be taken into consideration, and a more careful immunohistological staining is definitely necessary. PMID:15170142

  15. The HMGA1-COX-2 axis: A key molecular pathway and potential target in pancreatic adenocarcinoma

    PubMed Central

    Hillion, Joelle; Smail, Shamayra S.; Di Cello, Francescopaolo; Belton, Amy; Shah, Sandeep; Huso, Tait; Schuldenfrei, Andrew; Nelson, Dwella Moton; Cope, Leslie; Campbell, Nathaniel; Karikari, Collins; Aderinto, Abimbola; Maitra, Anirban; Huso, David L.; Resar, Linda M. S.

    2012-01-01

    Context Although pancreatic cancer is a common, highly lethal malignancy, the molecular events that enable precursor lesions to become invasive carcinoma remain unclear. We previously reported that the high-mobility group A1 (HMGA1) protein is overexpressed in >90% of primary pancreatic cancers, with absent or low levels in early precursor lesions. Methods Here, we investigate the role of HMGA1 in reprogramming pancreatic epithelium into invasive cancer cells. We assessed oncogenic properties induced by HMGA1 in non-transformed pancreatic epithelial cells expressing activated K-RAS. We also explored the HMGA1-cyclooxygenase (COX-2) pathway in human pancreatic cancer cells and the therapeutic effects of COX-2 inhibitors in xenograft tumorigenesis. Results HMGA1 cooperates with activated K-RAS to induce migration, invasion, and anchorage-independent cell growth in a cell line derived from normal human pancreatic epithelium. Moreover, HMGA1 and COX-2 expression are positively correlated in pancreatic cancer cell lines (r2=0.93; p<0.001). HMGA1 binds directly to the COX-2 promoter at an AT-rich region in vivo in three pancreatic cancer cell lines. In addition, HMGA1 induces COX-2 expression in pancreatic epithelial cells, while knock-down of HMGA1 results in repression of COX-2 in pancreatic cancer cells. Strikingly, we also discovered that Sulindac (a COX-1/COX-2 inhibitor) or Celecoxib (a more specific COX-2 inhibitor) block xenograft tumorigenesis from pancreatic cancer cells expressing high levels of HMGA1. Conclusions Our studies identify for the first time an important role for the HMGA1-COX-2 pathway in pancreatic cancer and suggest that targeting this pathway could be effective to treat, or even prevent, pancreatic cancer. PMID:22898640

  16. Non-neoplastic pancreatic lesions that may mimic malignancy.

    PubMed

    Okun, Sherry D; Lewin, David N

    2016-01-01

    The widespread use of abdominal ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) has resulted in an increased identification of asymptomatic pancreatic lesions. Preoperative diagnoses of pancreatic lesions can be difficult. Solid and cystic lesions and anatomic variants of normal can all mimic tumor clinically and radiologically. Newer imaging modalities have increased the likelihood of the accurate diagnosis of non-neoplastic pancreatic disease, however, despite the many advances; it still remains a challenge to differentiate rarer non-neoplastic entities and inflammatory masses from adenocarcinoma, preoperatively. Adding to the challenge is the fact that a variety of inflammatory, solid and cystic non-neoplastic lesions have significant clinical and radiological overlap with malignancies. About 5-10% of pancreatectomies performed with the primary clinical diagnosis of pancreatic carcinoma are later proved to be essentially non-neoplastic lesions. It is vital to include these non-neoplastic entities in the differential diagnosis while working up abnormal clinical and radiological pancreatic findings because it may drastically alter therapeutic options for the patients. The significance of recognizing these lesions preoperatively is to help to guide the clinical decision-making process and the avoidance of an unnecessary pancreatectomy. Examples of such entities include chronic pancreatitis, sarcoidosis, intrapancreatic accessory spleen (IPAS), lymphoid hyperplasia, lipomatous pseudohypertrophy (LPH), lymphangioma, lymphoepithelial cyst (LEC) and endometriosis. PMID:26602569

  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, ??T, NK, and IFN? (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. PMID:24389175

  18. Proliferation Index and Karyometric Features of Pancreatic Intraductal Proliferative Lesions

    PubMed Central

    Tomaszewska, Romana; Oko?, Krzysztof; Nowak, Krystyna; Stachura, Jerzy

    1999-01-01

    The increasing frequency and poor prognosis in pancreatic cancer prompt us to search for morphological lesions being a substrate for its development. Studies of autopsy and surgically resected material as well as recent molecular studies have proved that one of the possible pathways of pancreatic neoplasia is the intraepithelial proliferation dysplasia cancer sequence. In the present paper we studied the proliferative activity (Ki?67 index) in pancreatic intraepithelial proliferative lesions and its correlation with geometric features of cell nuclei as signs of increasing dysplasia. The studies were carried out in a group of 35 patients operated on for pancreatic cancer, chronic pancreatitis and other conditions not associated with the pancreas. We used immunohistochemical methods and basic morphometric parameters. The results of our studies indicate that the cell proliferative activity depends both on the type of epithelial proliferation and underlying pancreatic disease. The values of Ki?67 index are significantly different in low?grade proliferation (flat and papillary hyperplasia) and high?grade proliferation (atypical papillary hyperplasia and carcinoma in situ). A set of karyometric features correlates with Ki?67 index but there is no single feature which would have a diagnostic value. PMID:10866280

  19. Multimodality treatment of recurrent pancreatic cancer: Mith or reality?

    PubMed

    Sperti, Cosimo; Moletta, Lucia; Merigliano, Stefano

    2015-12-15

    Pancreatic adenocarcinoma is the fourth cause of cancer-related death in the United States. Surgery is the only potentially curative treatment, but most patients present at diagnosis with unresectable or metastatic disease. Moreover, even with an R0 resection, the majority of patients will die of disease recurrence. Most recurrences occur in the first 2-year after pancreatic resection, and are commonly located in the abdomen, even if distant metastases can occur. Recurrent pancreatic adenocarcinoma remains a significant therapeutic challenge, due to the limited role of surgery and radio-chemotherapy. Surgical management of recurrence is usually unreliable because tumor relapse typically presents as a technically unresectable, or as multifocal disease with an aggressive growth. Therefore, treatment of patients with recurrent pancreatic adenocarcinoma has historically been limited to palliative chemotherapy or supportive care. Only few data are available in the Literature about this issue, even if in recent years more studies have been published to determine whether treatment after recurrence have any effect on patients outcome. Recent therapeutic advances have demonstrated the potential to improve survival in selected patients who had undergone resection for pancreatic cancer. Multimodality management of recurrent pancreatic carcinoma may lead to better survival and quality of life in a small but significant percentage of patients; however, more and larger studies are needed to clarify the role of the different therapeutic options and the optimal way to combine them. PMID:26689800

  20. Multimodality treatment of recurrent pancreatic cancer: Mith or reality?

    PubMed Central

    Sperti, Cosimo; Moletta, Lucia; Merigliano, Stefano

    2015-01-01

    Pancreatic adenocarcinoma is the fourth cause of cancer-related death in the United States. Surgery is the only potentially curative treatment, but most patients present at diagnosis with unresectable or metastatic disease. Moreover, even with an R0 resection, the majority of patients will die of disease recurrence. Most recurrences occur in the first 2-year after pancreatic resection, and are commonly located in the abdomen, even if distant metastases can occur. Recurrent pancreatic adenocarcinoma remains a significant therapeutic challenge, due to the limited role of surgery and radio-chemotherapy. Surgical management of recurrence is usually unreliable because tumor relapse typically presents as a technically unresectable, or as multifocal disease with an aggressive growth. Therefore, treatment of patients with recurrent pancreatic adenocarcinoma has historically been limited to palliative chemotherapy or supportive care. Only few data are available in the Literature about this issue, even if in recent years more studies have been published to determine whether treatment after recurrence have any effect on patients outcome. Recent therapeutic advances have demonstrated the potential to improve survival in selected patients who had undergone resection for pancreatic cancer. Multimodality management of recurrent pancreatic carcinoma may lead to better survival and quality of life in a small but significant percentage of patients; however, more and larger studies are needed to clarify the role of the different therapeutic options and the optimal way to combine them. PMID:26689800

  1. Significance of tumour cell HLA-G5/-G6 isoform expression in discrimination for adenocarcinoma from squamous cell carcinoma in lung cancer patients

    PubMed Central

    Yan, Wei-Hua; Liu, Di; Lu, Hai-Yan; Li, Ying-Ying; Zhang, Xia; Lin, Aifen

    2015-01-01

    Human leucocyte antigen (HLA)-G has seven isoforms, of which HLA-G1-G4 are membrane-bound and HLA-G5-G7 are soluble. Previous studies reinforced HLA-G expression was strongly related to poor prognosis in different types of cancers. Among these studies, the monoclonal antibody (mAb) 4H84 was used which detects all HLA-G isoform heavy chain; unfortunately, leaves the specific types of isoforms expressed in lesions undistinguished and its clinical significance needs to be clarified. To explore clinical significance of lesion soluble HLA-G (sHLA-G) in non-small-cell lung cancer (NSCLC), mAb 5A6G7 recognizing HLA-G5/-G6 molecules was used. Tumour cell sHLA-G expression in 131 primary NSCLC lesions (66 squamous cell carcinoma, 55 adenocarcinoma and 10 adenosquamous carcinoma) were analysed with immunohistochemistry. Data showed that sHLA-G expression was observed in 34.0% (45/131) of the NSCLC lesions, which was unrelated to patient age, sex, lymph nodal status, tumournodemetastasis stage and patient survival. However, tumour cell sHLA-G expression in lesions was predominately observed in adenocarcinoma lesions (73.0%, 40/55) which was significantly higher than that in squamous cell carcinoma (6.0%, 4/66) and adenosquamous carcinoma lesions (10.0%, 1/10, P<0.001). The area under the receiver operating characteristic curve for lesion sHLA-G was 0.833 (95% CI: 0.7540.912, P<0.001) for adenocarcinoma versus squamous cell carcinoma. Our findings for the first time showed that tumour cell sHLA-G was predominately expressed in lung adenocarcinoma, which could be a useful biomarker to discriminate adenocarcinoma from squamous cell carcinoma in NSCLC patients. PMID:25689063

  2. Expression and diagnostic value of HE4 in pancreatic adenocarcinoma.

    PubMed

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

    2015-01-01

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

  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. 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.

  5. [Emphysematous necrotizing pancreatitis].

    PubMed

    Ghidirim, Gh; Gagauz, I; Mi?in, Ig; Gu?u, E; Vozian, M

    2005-01-01

    The authors present an additional case of emphysematous necrotizing pancreatitis caused by Escherichia coli. Emphysematous necrotizing pancreatitis represents a rare and potentially life-threatening infection and is characterized by gas formation within or around the pancreas. A 26-year-old man presented with severe upper abdominal pain and vomiting, 7 hours from onset. Acute pancreatitis was initially diagnosed based on high amylase level, abdominal ultrasonography and primary CT scan. On the 7th day he developed fever, increasing abdominal pain and shortness of breath. On the second abdominal CT scan, the pancreatic bed was filled with gas. The diagnosis of emphysematous necrotizing pancreatitis was confirmed at laparotomy. The patient was treated successfully by extensive pancreatic necrosectomy, open packing and scheduled repeated debridements. Culture from the lesser sac, and retroperitoneal space, examined for aerobes and anaerobes, revealed growth of Escherichia coli. The authors analyze and discuss pathogenesis, diagnosis and treatment of emphysematous necrotizing pancreatitis. Based on the available data and this case, early surgical debridement and appropriate antibiotics appear to be the preferred treatment. PMID:16106939

  6. Autoimmune pancreatitis and cholangitis.

    PubMed

    Jani, Niraj; Buxbaum, James

    2015-11-01

    Autoimmune pancreatitis (AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4 (IgG4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreatic manifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings. PMID:26558153

  7. Autoimmune pancreatitis and cholangitis

    PubMed Central

    Jani, Niraj; Buxbaum, James

    2015-01-01

    Autoimmune pancreatitis (AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4 (IgG4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreatic manifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings. PMID:26558153

  8. Diagnosis of autoimmune pancreatitis

    PubMed Central

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

    2014-01-01

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

  9. 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

  10. CT contrast enhancement correlates with pathological grade and microvessel density of pancreatic cancer tissues.

    PubMed

    Wang, Shu-Hong; Sun, Yun-Feng; Liu, Yang; Zhou, Yang; Liu, Ying

    2015-01-01

    Pancreatic cancer typically carries a poor prognosis, and new methods of diagnosis and treatment are needed to improve outcomes for the disease. Non-invasive imaging techniques that accurately predict disease severity may aid in the treatment of pancreatic cancer patients. This study sought to investigate the correlation between computed tomography (CT) contrast enhancement and the histopathological grades and intratumoral angiogenesis in pancreatic carcinoma. The study included 54 patients with pancreatic carcinoma who underwent surgical resection in our hospital. All participants received a CT scan with contrast enhancement before surgery. Pathological specimens obtained during surgery were paraffin embedded for immunohistochemistry to assess microvessel density (MVD; CD31 staining) and angiogenesis activity [vascular endothelial growth factor (VEGF) staining]. Results were analyzed using t tests and Spearman correlation. CT enhancement of pancreatic tumors was negatively correlated with the pathological grade (rs=-0.784, P<0.05) and the MVD count in tumor hot spots (rs=-0.790, P<0.05). Additionally, the pathological grade positively correlated with MVD count (rs=0.516, P<0.05). However, there was no correlation between pathological grade and VEGF expression (rs=-0.195, P>0.05). Finally, MVD was higher in individuals positive for VEGF expression than in those negative for VEGF expression (P<0.05). Thus, the extent of CT enhancement is related to the MVD in tumor hot spots and the malignant degree of pancreatic carcinoma. This suggests CT can be used to reflect the disease severity and extent. PMID:26191248

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

    ClinicalTrials.gov

    2013-05-07

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

  12. Pancreatic tuberculosis with acquired immunodeficiency syndrome: A case report and systematic review

    PubMed Central

    Meesiri, Somchai

    2012-01-01

    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. PMID:22363146

  13. Familial Pancreatic Adenocarcinoma.

    PubMed

    Petersen, Gloria M

    2015-08-01

    Familial pancreatic cancer (FPC) kindreds have at least 2 first-degree relatives with pancreatic ductal adenocarcinoma. Studies of FPC have focused on the discovery of genetic cause and on the management of those at genetically high risk. Research reveals that a half dozen known hereditary syndromes or genes are associated with increased risk of developing pancreatic cancer, the most prominent of which are BRCA2 and CDKN2A. Genetic risk assessment and testing is already available. Owing to limited experience worldwide, guidance is often based on expert opinion, although all agree that research is needed to improve the shaping of options. PMID:26226902

  14. Pancreatic fistula and postoperative pancreatitis after pancreatoduodenectomy for pancreatic cancer

    PubMed Central

    Rudis, Jan

    2014-01-01

    The most serious complication after pancreatoduodenectomy (PD) is pancreatic fistula (PF) type C, either as a consequence or independently from postoperative pancreatitis (PP). Differentiating between these two types of complications is often very difficult, if not impossible. The most significant factor in early diagnosis of PP after PD is an abrupt change in clinical status. In our retrospective study we also observed significantly higher levels of serum concentrations of CRP and AMS comparing to PF without PP. Based on our findings, CT scan is not beneficial in the early diagnosis of PP. Meantime PF type C is indication to operative revision with mostly drainage procedure which is obviously not much technically demanding, there are no definite guidelines on how to proceed in PP. Therefore the surgeon’s experience determines not only whether PP will be diagnosed early enough and will be differentiated from PF without PP, but also whether a completion pancreatectomy will be performed in indicated cases. PMID:25392838

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

    ClinicalTrials.gov

    2016-03-14

    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

  16. Precursor Lesions of Pancreatic Cancer

    PubMed Central

    Higashi, Michiyo; Yamada, Norishige; Goto, Masamichi

    2008-01-01

    This review article describes morphological aspects, gene abnormalities, and mucin expression profiles in precursor lesions such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm (MCN) of the pancreas, as well as their relation to pancreatic ductal adenocarcinoma (PDAC). The gene abnormalities in precursors of PDAC are summarized as follows: (1) KRAS mutation and p16/CDKN2A inactivation are early events whose frequencies increase with the dysplasia grade in both PanIN and IPMN; (2) TP53 mutation and SMAD4/DPC4 inactivation are late events observed in PanIN3 or carcinomatous change of IPMN in both PanIN and IPMN, although the frequency of the TP53 mutation is lower in IPMN than in PDAC; and (3) also in MCN, KRAS mutation is an early event whose frequency increases with the dysplasia grade, whereas TP53 mutation and SMAD4/DPC4 inactivation are evident only in the carcinoma. The mucin expression profiles in precursors of PDAC are summarized as follows: (1) MUC1 expression increases with the PanIN grade, and is high in PDAC; (2) the expression pattern of MUC2 differs markedly between the major subtypes of IPMN with different malignancy potentials (i.e., IPMN-intestinal type with MUC2+ expression and IPMN-gastric type with MUC2- expression); (3) MUC2 is not expressed in any grade of PanINs, which is useful for differentiating PanIN from intestinal-type IPMN; (4) de novo expression of MUC4, which appears to increase with the dysplasia grade; and (5) high de novo expression of MUC5AC in all grades of PanINs, all types of IPMN, MCN, and PDAC. PMID:20485640

  17. Surgical Approaches to Chronic Pancreatitis

    PubMed Central

    Hartmann, Daniel; Friess, Helmut

    2015-01-01

    Chronic pancreatitis is a progressive inflammatory disease resulting in permanent structural damage of the pancreas. It is mainly characterized by recurring epigastric pain and pancreatic insufficiency. In addition, progression of the disease might lead to additional complications, such as pseudocyst formation or development of pancreatic cancer. The medical and surgical treatment of chronic pancreatitis has changed significantly in the past decades. With regard to surgical management, pancreatic head resection has been shown to be a mainstay in the treatment of severe chronic pancreatitis because the pancreatic head mass is known to trigger the chronic inflammatory process. Over the years, organ-preserving procedures, such as the duodenum-preserving pancreatic head resection and the pylorus-preserving Whipple, have become the surgical standard and have led to major improvements in pain relief, preservation of pancreatic function, and quality of life of patients. PMID:26681935

  18. [Experimental models of acute pancreatitis].

    PubMed

    Ceranowicz, Piotr; Cieszkowski, Jakub; Warzecha, Zygmunt; Dembi?ski, Artur

    2015-01-01

    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. PMID:25720613

  19. [Latest advances in chronic pancreatitis].

    PubMed

    Domnguez Muoz, 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. PMID:26520201

  20. 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

  1. Pancreatic cancer: a review of emerging therapies.

    PubMed

    Rosenberg, L

    2000-05-01

    The incidence of adenocarcinoma of the pancreas has risen steadily over the past 4 decades. Since pancreatic cancer is diagnosed at an advanced stage, and because of the lack of effective therapies, the prognosis of such patients is extremely poor. Despite advances in our understanding of the molecular biology of pancreatic cancer, the systemic treatment of this disease remains unsatisfactory. Conventional chemotherapy has not produced dramatic improvements in response rates or patient survival. New treatment strategies are clearly needed. This paper reviews emerging therapies for pancreatic carcinoma. A more profound understanding of the molecular biology of cell growth and proliferation, as well as of neoplastic cell transformation, has led to advances in several areas, including the use of somatostatin analogues and antiandrogens as adjuvant therapy; inhibition of tumour growth and metastasis by inhibitors of matrix metalloproteinases and angiogenesis, and by small molecules such as retinoids, which interfere with progression through the cell cycle; immunotherapy with monoclonal antibodies; disruption of intracellular signal transduction with farnesyltransferase inhibitors; and finally gene therapy with specifically designed vaccines. PMID:10852640

  2. Familial Pancreatic Cancer

    PubMed Central

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

    2010-01-01

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

  3. Management of necrotizing pancreatitis

    PubMed Central

    Slavin, John; Ghaneh, Paula; Sutton, Robert; Hartley, Mark; Rowlands, Peter; Garvey, Conall; Hughes, Mark; Neoptolemos, John

    2001-01-01

    Infection complicating pancreatic necrosis leads to persisting sepsis, multiple organ dysfunction syndrome and accounts for about half the deaths that occur following acute pancreatitis. Severe cases due to gallstones require urgent endoscopic sphincterotomy. Patients with pancreatic necrosis should be followed with serial contrast enhanced computed tomography (CE-CT) and if infection is suspected fine needle aspiration of the necrotic area for bacteriology (FNAB) should be undertaken. Treatment of sterile necrosis should initially be non-operative. In the presence of infection necrosectomy is indicated. Although traditionally this has been by open surgery, minimally invasive procedures are a promising new alternative. There are many unresolved issues in the management of pancreatic necrosis. These include, the use of antibiotic prophylaxis, the precise indications for and frequency of repeat CE-CT and FNAB, and the role of enteral feeding. PMID:11819813

  4. Hydration and Chronic Pancreatitis

    MedlinePLUS

    Fact Sheet - Hydration and Chronic Pancreatitis by Kathianne Sellers Proper hydration is important in the health of ... fluid needs are 8 cups per day. Kathianne Sellers, R.D., was a nutritionist at the Pancreas ...

  5. 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.

  6. Precursors to Pancreatic Cancer+

    PubMed Central

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

    2008-01-01

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

  7. Primary pancreatic pleomorphic leiomyosarcoma.

    PubMed

    Zhang, Q-Y; Shen, Q-Y; Yan, S; Zheng, S-S

    2011-01-01

    Primary pancreatic leiomyosarcoma is a rare mesenchymal tumour that is believed to arise from the walls of the pancreatic blood vessels or the pancreatic duct. A 56-year-old female was referred with epigastric pain and abdominal mass. Preoperative computed tomography showed a large soft tissue mass in the pancreatic body and tail. Fine needle aspiration biopsy indicated a spindle cell type tumour. The patient received distal pancreatectomy with no adjuvant treatment. Histology revealed a pleomorphic spindle cell neoplasm with an immunoprofile suggestive of smooth muscle origin. The absence of other lesions in the body was consistent with the diagnosis of primary pleomorphic leiomyosarcoma. The patient was well and tumour-free 14 months after surgery. Detailed immunohistochemical analyses are necessary in the diagnosis of this highly malignant tumour. Radical resection offers the only chance of long-term survival. PMID:21986161

  8. [Hereditary aspects of pancreatitis].

    PubMed

    Bak, Daniel; Sobczy?ska-Tomaszewska, Agnieszka; Bal, Jerzy

    2003-01-01

    Pancreatitis presents clinically as acute and chronic form. A common characteristic of these two forms is enzymatic autodigestion of pancreas in the course of the disease. It results from premature activation of pancreatic digestive enzymes and disturbance of subtle balance between proteolytic enzymes and their inhibitors. The way to understand the character of mechanisms leading to development of pancreatitis has been simplified by discovery of genetic factors, which are able to initiate pathological changes at tissue level. Mutations in the PRSS1 gene (first of all R122H and N29I mutations), which encodes for cationic trypsin, cause trypsin to be protected from autodegradation. These mutations also cause precursor of trypsin - trypsinogen, to be activated easier. On the other hand mutations in the SPINK1 gene have been identified. SPINK1 gene encodes for the most important protease inhibitor of the pancreatic fluid. The most frequent mutation, namely N34S, decrease SPINK1 protein in its activity. The link between the genotype and phenotype is not clear in every case. It is probable that pancreatitis will be recognized as poligenic with many genes engaged in the disease development. Pancreatic cancer is a frequent consequence of pancreatitis. It is a very invasive cancer with high mortality. In the course of pancreatic inflammation intensive cell proliferation takes place for regeneration of pancreas damage. It is the chance for amplification of pathological changes in DNA, which have arisen as a ROS's (Reactive Oxygen Species) and RNOS's (Reactive Nitrogen Oxide Species) action effect. ROS and RNOS are generated in the course of pancreas inflammation. PMID:13130170

  9. Locally advanced pancreatic cancer.

    PubMed

    Oikonomopoulos, Georgios M; Huber, Kathryn E; Syrigos, Konstantinos N; Saif, Muhammad Wasif

    2013-03-01

    Treatment of locally advanced pancreatic cancer is palliative, based on chemotherapy and according to response, chemoradiotherapy can be applied. The authors summarize three abstracts (#LBA146, #256 and #303) presented on the 2013 ASCO Gastrointestinal Cancers Symposium, which were focused on treatment of locally advanced pancreatic cancer. A discussion is presented about the different chemotherapy or chemoradiotherapy regimens, that move away from gemcitabine-based treatment, and the effort to find less toxic, but efficient therapeutic combinations. PMID:23474552

  10. Pancreatitis and atypical Kawasaki disease

    PubMed Central

    2010-01-01

    We report on pediatric patient with clinical and laboratory evidence of pancreatitis at onset of atypical Kawasaki disease (KD). In KD pancreatic inflammation was described previously, but clinical pancreatitis was rarely reported and its true incidence is unknown. In febrile pediatric patients suspected to have KD, but not fulfilling classical diagnostic criteria, signs of pancreatic inflammation may help in making correct diagnosis. Further analysis of cases with atypical KD developing pancreatitis may reveal if signs of pancreatic inflammation can be used as supportive diagnostic finding. PMID:20181201

  11. Pancreatitis and atypical Kawasaki disease.

    PubMed

    Prokic, Dragan; Ristic, Goran; Paunovic, Zoran; Pasic, Srdjan

    2010-01-01

    We report on pediatric patient with clinical and laboratory evidence of pancreatitis at onset of atypical Kawasaki disease (KD). In KD pancreatic inflammation was described previously, but clinical pancreatitis was rarely reported and its true incidence is unknown.In febrile pediatric patients suspected to have KD, but not fulfilling classical diagnostic criteria, signs of pancreatic inflammation may help in making correct diagnosis. Further analysis of cases with atypical KD developing pancreatitis may reveal if signs of pancreatic inflammation can be used as supportive diagnostic finding. PMID:20181201

  12. 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.

  13. Specific Antigen in Serum of Patients with Colon Carcinoma

    NASA Astrophysics Data System (ADS)

    Koprowski, Hilary; Herlyn, Meenhard; Steplewski, Zenon; Sears, Henry F.

    1981-04-01

    The binding of monoclonal antibody specific for colon carcinoma was inhibited by serum from patients with adenocarcinoma of the colon but not by serum from patients with other bowel diseases or from healthy volunteers. Of other malignancies studied, serum from two patients with gastric carcinoma and two patients with pancreatic carcinoma also inhibited the specific binding of monoclonal antibody. The levels of carcinoembryonic antigen in these serum samples were not correlated with their levels of binding inhibition. Such monoclonal antibodies may prove useful for the detection of colorectal carcinoma.

  14. [Diabetogenic tropical pancreatitis].

    PubMed

    Assan, R; Assan, D; Thiebaut, M F; Laloux, S; Clauser, E; Boukersi, A

    1988-01-01

    The tropical calcifying pancreatitis and/or fibrous pancreatitis are responsible for a number of cases of juvenile insulin-dependent diabetes in the Third World countries. World wide distributed in the tropical areas of Asia, Africa and South America, they can also be observed in Europe, in migrants from these countries. Intensive epidemiological and biochemical studies are currently developed in order to shed light on the many obscure points. Classification of the typical calcifying pancreatitis and the related syndromes is a matter of debate. The pathological basis is calcification of the pancreas and echography of the gland may become a cheap convenient relatively specific tool for epidemiology. The clinical syndrome consists of chronic painful pancreatic episodes since childhood, associated with pancreatic exocrine insufficiency, followed by the onset, during adolescence, of diabetes mellitus, which is most of the times insulin dependent. Patients' history is free of chronic alcoholism, but includes constantly chronic caloric and proteic malnutrition. Although insulin dependent this diabetes in not prone to ketosis, due presumably to carnitine deficiency and relative glucagon deficiency (or suppressibility). Insulin resistance is traditionally noted, the pathophysiology of which is unknown. The mechanism of calcification appearance is also undetermined. Either a deficiency in pancreatic stone protein, or the toxic effect of cyanogen glucosides present in cassava and other tropical foodstuffs, or the malnutrition-related deficiency in sulphur-containing aminoacids may be causal factors. No valid experimental model of the disease is available. PMID:3044866

  15. Management of necrotizing pancreatitis.

    PubMed Central

    Frey, C F

    1993-01-01

    A comprehensive management plan is presented for patients with severe acute pancreatitis. These patients may have pancreatic or peripancreatic necrosis or pancreatic fluid collections. Multiple organ failure often develops in patients with severe pancreatitis. We therefore recommend that all patients with acute pancreatitis be evaluated for pancreatic anatomy and function. If a patient is seriously ill, a computed tomographic (CT) scan with vascular enhancement should be done. Meanwhile, vigorous fluid replacement is necessary using Swan-Ganz monitoring. Patients with necrosis do not need surgical intervention unless the clinical course or CT scan-guided aspiration shows infection. The objective of an operation should be to remove all infected tissue and fluid. A preoperative CT scan with vascular enhancement should be used as a guide during the operation to ensure that all foci of infected necrosis or fluid are eliminated. We have found that open packing and irrigation with sodium oxychlorosene are helpful in patients with extensive necrosis or those who become infected early after the onset of symptoms. In all, 40% to 50% of patients treated by closed drainage will require reoperation because of incomplete debridement. Persistent sepsis is an indication for reoperation. Images PMID:8128676

  16. 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. PMID:26520702

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

    PubMed

    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

  18. 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

  19. Histogenesis of pancreatic carcinogenesis in the hamster: ultrastructural evidence

    SciTech Connect

    Flaks, B.

    1984-06-01

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

  20. [The epidemiology of pancreatic cancer].

    PubMed

    Lakatos, Gbor; Tulassay, Zsolt

    2010-10-31

    Pancreatic cancer is a relatively uncommon tumor, but even with early diagnosis, mortality rates are high, explaining why this form of cancer has now become a common cause of cancer mortality. There are no screening tests for early detection of pancreatic cancer. It is more common in men than women and is predominantly a disease of elderly people. There is wide variation in the incidence of pancreatic cancer around the world, suggesting that environmental factors are important in the pathogenesis. Smoking is the major known risk factor for pancreatic cancer, while dietary factors seem to be less important. Other possible risk factors include chronic pancreatitis, obesity and type 2 diabetes. Numerous inherited germ line mutations are associated with pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. Polymorphisms in genes that control detoxification of environmental carcinogens and metabolic pathways may alter the risk of pancreatic cancer. PMID:20961843

  1. Endoscopic treatment of chronic pancreatitis

    PubMed Central

    Heyries, Laurent; Sahel, Jose

    2007-01-01

    Treatment of chronic pancreatitis has been exclusively surgical for a long time. Recently, endoscopic therapy has become widely used as a primary therapeutic option. Initially performed for drainage of pancreatic cysts and pseudocysts, endoscopic treatments were adapted to biliary and pancreatic ducts stenosis. Pancreatic sphincterotomy which allows access to pancreatic ducts was firstly reported. Secondly, endoscopic methods of stenting, dilatation, and stones extraction of the bile ducts were applied to pancreatic ducts. Nevertheless, new improvements were necessary: failures of pancreatic stone extraction justified the development of extra-corporeal shock wave lithotripsy; dilatation of pancreatic stenosis was improved by forage with a new device; moreover endosonography allowed guidance for celiac block, gastro-cystostomy, duodeno-cystostomy and pancreatico-gastrostomy. Although endoscopic treatments are more and more frequently accepted, indications are still debated. PMID:18069750

  2. Pancreatic trauma: A concise review

    PubMed Central

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

    2013-01-01

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

  3. Magnetic resonance imaging in pancreatitis.

    PubMed

    Balci, Numan Cem; Bieneman, B Kirke; Bilgin, Mehmet; Akduman, Isin E; Fattahi, Rana; Burton, Frank R

    2009-02-01

    Pancreatitis can occur in acute and chronic forms. Magnetic resonance imaging (MRI) plays an important role in the early diagnosis of both conditions and complications that may arise from acute or chronic inflammation of the gland. Standard MRI techniques including T1-weighted and T2-weighted fat-suppressed imaging sequences together with contrast-enhanced imaging can both aid in the diagnosis of acute pancreatitis and demonstrate complications as pseudocysts, hemorrhage, and necrosis. Combined use of MRI and MR cholangiopancreatography can show both parenchymal findings that are associated with chronic pancreatitis including pancreatic size and signal and arterial enhancements, all of which are diminished in chronic pancreatitis. The degree of main pancreatic duct dilatation and/or the number of side branch ectasia determines the diagnosis of chronic pancreatitis and its severity. In this paper, we report the spectrum of imaging findings of acute and chronic pancreatitis on MRI and MR cholangiopancreatography. PMID:19687723

  4. 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

  5. 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. PMID:26527523

  6. 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

  7. Fibrocalculous pancreatic diabetes (FCPD).

    PubMed

    Unnikrishnan, Ranjit; Mohan, Viswanathan

    2015-02-01

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

  8. CD10/NEP in non-small cell lung carcinomas. Relationship to cellular proliferation.

    PubMed Central

    Ganju, R K; Sunday, M; Tsarwhas, D G; Card, A; Shipp, M A

    1994-01-01

    The cell surface metalloproteinase CD10/neutral endopeptidase 24.11 (NEP) hydrolyzes a variety of peptide substrates and reduces cellular responses to specific peptide hormones. Because CD10/NEP modulates peptide-mediated proliferation of small cell carcinomas of the lung (SCLC) and normal fetal bronchial epithelium, we evaluated the enzyme's expression in non-small cell lung carcinomas (NSCLC). Bronchoalveolar and large cell carcinoma cell lines had low levels of CD10/NEP expression whereas squamous, adenosquamous, and adenocarcinoma cell lines had higher and more variable levels of the cell surface enzyme. Regional variations in CD10/NEP immunostaining in primary NSCLC specimens prompted us to correlate CD10/NEP expression with cell growth. In primary carcinomas of the lung, clonal NSCLC cell lines and SV40-transformed fetal airway epithelium, subsets of cells expressed primarily CD10/NEP or the proliferating cell nuclear antigen (PCNA). Cultured airway epithelial cells had the lowest levels of CD10/NEP expression when the highest percentage of cells were actively dividing; in addition, these cells grew more rapidly when cell surface CD10/NEP was inhibited. NSCLC cell lines had receptors for a variety of mitogenic peptides known to be CD10/NEP substrates, underscoring the functional significance of growth-related variability in CD10/NEP expression. Images PMID:7962523

  9. 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-4R?, myeloid specific IL-4R?, 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

  10. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor

    PubMed Central

    Ceriolo, Paola; Fausti, Valentina; Cinotti, Elisa; Bonadio, Silvia; Raffaghello, Lizzia; Bianchi, Giovanna; Orcioni, Giulio Fraternali; Fiocca, Roberto; Rongioletti, Franco; Pistoia, Vito; Borgonovo, Giacomo

    2016-01-01

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokine-chemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10.

  11. Distribution of HPV Genotype in Invasive Cervical Carcinoma and Cervical Intraepithelial Neoplasia in Zhejiang Province, Southeast China: Establishing the Baseline for Surveillance.

    PubMed

    Xu, Xiao-Xian; Zhou, Jian-Song; Yuan, Shu-Hui; Yu, Hua; Lou, Han-Mei

    2015-09-01

    Human papillomavirus (HPV) are firmly established as the principal causative agent for cervical carcinoma. Current vaccines may provide some protection for women from cervical carcinoma linked to HPV genotype 16 and 18. This may be the best vaccine for Western women, but the geographical variation in HPV distributions may not make it the most appropriate vaccine for China or Asia. This study provided an observational, retrospective, hospital-based cross-sectional study on the distribution of HPV genotypes among 5410 women with invasive cervical cancer (ICC) or cervical intraepithelial neoplasia (CIN). Overall, the positive rates of the four HPV types included in current prophylactic vaccines were counted, the two high-risk types (HPV-16 and -18) covered by current vaccines represented 66.9% of women with squamous cancer, 55.0% with adenocarcinoma, 64.9% with adenosquamous carcinoma and 77.4% of other type ICC, as well as 59.5% of CIN III, 45.0% of CIN II and 38.1% of CIN I cases. As expected, two low-risk types (HPV-6 and -11) included in the quadrivalent vaccine did not show good coverage data. Particularly worth mentioning is the fact that the addition of HPV-52 and -58 to the vaccine cocktail would increase cancer protection in our population, potentially preventing up to beyond 16% of squamous/adenosquamous carcinoma and other type of cervical cancers, and 7.75% of adenocarcinomas. It might also potentially reduce the rate of CIN III by a further 28.6% and CIN II and I by a third. This study established the baseline for surveillance in Zhejiang Province, and provides data for further vaccine designs: a quadrivalent HPV vaccine covering HPV-16/-58/-18/-52, would be more welcome in our region in the forthcoming year compared to the currently available vaccine. PMID:26404339

  12. Distribution of HPV Genotype in Invasive Cervical Carcinoma and Cervical Intraepithelial Neoplasia in Zhejiang Province, Southeast China: Establishing the Baseline for Surveillance

    PubMed Central

    Xu, Xiao-Xian; Zhou, Jian-Song; Yuan, Shu-Hui; Yu, Hua; Lou, Han-Mei

    2015-01-01

    Human papillomavirus (HPV) are firmly established as the principal causative agent for cervical carcinoma. Current vaccines may provide some protection for women from cervical carcinoma linked to HPV genotype 16 and 18. This may be the best vaccine for Western women, but the geographical variation in HPV distributions may not make it the most appropriate vaccine for China or Asia. This study provided an observational, retrospective, hospital-based cross-sectional study on the distribution of HPV genotypes among 5410 women with invasive cervical cancer (ICC) or cervical intraepithelial neoplasia (CIN). Overall, the positive rates of the four HPV types included in current prophylactic vaccines were counted, the two high-risk types (HPV-16 and -18) covered by current vaccines represented 66.9% of women with squamous cancer, 55.0% with adenocarcinoma, 64.9% with adenosquamous carcinoma and 77.4% of other type ICC, as well as 59.5% of CIN III, 45.0% of CIN II and 38.1% of CIN I cases. As expected, two low-risk types (HPV-6 and -11) included in the quadrivalent vaccine did not show good coverage data. Particularly worth mentioning is the fact that the addition of HPV-52 and -58 to the vaccine cocktail would increase cancer protection in our population, potentially preventing up to beyond 16% of squamous/adenosquamous carcinoma and other type of cervical cancers, and 7.75% of adenocarcinomas. It might also potentially reduce the rate of CIN III by a further 28.6% and CIN II and I by a third. This study established the baseline for surveillance in Zhejiang Province, and provides data for further vaccine designs: a quadrivalent HPV vaccine covering HPV-16/-58/-18/-52, would be more welcome in our region in the forthcoming year compared to the currently available vaccine. PMID:26404339

  13. [Acute pancreatitis in children].

    PubMed

    Rottier, B L; Holl, R A; Draaisma, J M

    1998-02-21

    Acute pancreatitis is probably commoner in children than was previously thought. In children it is most commonly associated with trauma or viral infection. The presentation may be subtler than in adults, requiring a high index of suspicion in the clinician. In three children, two boys aged 4 and 10 and a girl of 15 years, acute pancreatitis was suspected because of the findings at ultrasonography and endoscopic retrograde cholangiopancreatography performed when the disease recurred (the boy aged 4), apathy and immobility without dehydration or other obvious causes (the boy aged 10), and severe abdominal pain in combination with vomiting (the girl). All three patients had severely increased (urinary) amylase levels. Most often, acute pancreatitis in children tends to be a self-limiting disease which responds well to conservative treatment. PMID:9562770

  14. Endotherapy in chronic pancreatitis

    PubMed Central

    Tandan, Manu; Reddy, D Nageshwar

    2013-01-01

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

  15. Nutrition and pancreatic cancer.

    TOXLINE Toxicology Bibliographic Information

    Pericleous M; Rossi RE; Mandair D; Whyand T; Caplin ME

    2014-01-01

    BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer death in men and women. Prognosis is poor with a 5-year survival rate of less than 5%. As there is no effective screening modality, the best way to reduce morbidity and mortality due to pancreatic cancer is by effective primary prevention.AIM: To evaluate the role of dietary components in pancreatic cancer.MATERIALS AND METHODS: Bibliographical searches were performed in PubMed using the terms "pancreatic cancer", together with "nutrition", "diet", "dietary factors", "lifestyle", "smoking", "alcohol" and "epidemiology".RESULTS: Fruits (particularly citrus) and vegetable consumption may be beneficial. The consumption of whole grains has been shown to reduce pancreatic cancer risk and fortification of whole grains with folate may confer further protection. Red meat, cooked at high temperatures, should be avoided, and replaced with poultry or fish. Total fat should be reduced. The use of curcumin and other flavonoids should be encouraged in the diet. There is no evidence for benefit from vitamin D supplementation. There may be benefit for dietary folate. Smoking and high Body Mass Index have both been inversely associated with pancreatic cancer risk.CONCLUSION: The lack of randomized trials and the presence of confounding factors including smoking status, physical activity, distance of habitat from the equator, obesity, and diabetes may often result in inconclusive results. There is evidence to encourage the use of whole grain in the staple diet and supplementation within the diet of folate, curcumin and other flavanoids. Carefully designed randomized trials are required to further elucidate these important matters.

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

    ClinicalTrials.gov

    2016-01-12

    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

  17. [An autopsy case of pancreatic cancer with carcinoid tumor of the appendix].

    PubMed

    Kawaura, Y; Ohike, E; Hirano, M; Iwa, T; Haratake, J

    1983-07-01

    A 78-year-old man with pancreatic carcinoma with carcinoid tumor of the appendix is reported. Upon autopsy, the tumor consisted of poorly differentiated adenocarcinoma with scirrhous-like spreading. In the appendix a carcinoid tumor, size measuring 2 mm X 1 mm, was seen; the carcinoid cells were argentaffin. PMID:6887529

  18. 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

  19. Pathogenic Microorganisms and Pancreatic Cancer

    PubMed Central

    Wang, Chunsaier; Li, Jingnan

    2015-01-01

    Background 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. Established risk factors for pancreatic cancer, including smoking, chronic pancreatitis, obesity and type 2 diabetes mellitus, collectively account for less than half of all pancreatic cancer cases. Accumulating reports have demonstrated that there is an association between pathogenic microorganisms and pancreatic cancer. Summary A substantial amount of preclinical and clinical evidence suggests that microbiota are likely to influence pancreatic carcinogenesis. This review summarizes the literature on studies examining infections that have been linked to pancreatic cancer. Key Message Helicobacter pylori infection may be a risk factor for pancreatic cancer; chronic hepatitis virus and oral microbiota may also play a role in pancreatic carcinogenesis. Practical Implications Considering the worldwide burden of the disease, the association between microbiota and pancreatic cancer in this review may provide new ideas to prevent and treat pancreatic cancer more efficiently. Further studies in this direction are urgently needed. PMID:26673459

  20. Solitary increased tibial uptake of 99mTc-diphosphonate unmasking pancreatic tumor-related medullary fat necrosis.

    PubMed

    Paycha, F; Russ, G; Bellivet, C; Vulpillat, M

    1989-01-01

    Pancreatic inflammation and tumors can induce various systemic lesions of steatonecrosis. We report here the case of a 73-year-old woman presenting a painful left leg. Roentgenograms and tomograms of the left tibia were normal. Radionuclide bone scan showed diffuse increased uptake in the whole tibia and a CT scan of the same region demonstrated an unusual pattern of bone tumor. Tibial biopsy revealed intra medullary steatonecrosis and led to the discovery of a pancreatic carcinoma. PMID:2806331

  1. Identification and Validation of Src and Phospho-Src Family Proteins in Circulating Mononuclear Cells as Novel Biomarkers for Pancreatic Cancer1

    PubMed Central

    Yokoi, Kenji; Hawke, David; Oborn, Carol J; Jang, Jin-Young; Nishioka, Yasuhiko; Fan, Dominic; Kim, Seung Wook; Kim, Sun-Jin

    2011-01-01

    There is an urgent need to develop novel markers of pancreatic cancer to facilitate early diagnosis. Pancreatic carcinoma is characterized by marked stroma formation with a high number of infiltrating tumor-associated macrophages (TAMs) that originate from circulating mononuclear cells (MNCs). We hypothesized that differential analysis of protein expression and phosphorylation in circulating MNCs from healthy nude mice and nude mice bearing orthotopic human pancreatic cancer would identify a surrogate marker of pancreatic cancer. These differences were analyzed by two-dimensional gel electrophoresis followed by Western blot analysis using antibody against phosphorylated tyrosine proteins (pY). Protein and phosphorylated protein spots of interest were identified by mass spectrometry and validated by Western blot analysis as candidate markers for pancreatic cancer. We found that the expression and phosphorylation of Src family proteins were significantly higher in circulating MNCs from mice bearing pancreatic cancer than in circulating MNCs from healthy mice. TAMs in mice with pancreatic tumors also had higher Src family protein expression and phosphorylation than resident macrophages in the pancreas of healthy mice. The expression and phosphorylation of Src family proteins were correlated with tumor weight; however, increased Src expression and phosphorylation also occurred in MNCs from mice with chronic pancreatitis. This is the first report to explore novel pancreatic tumor markers in circulating MNCs. Although the specificity of the marker for pancreatic cancer was low, it could be used to monitor the disease or to select high-risk patients with chronic pancreatitis. PMID:21461171

  2. Tonsil neuroendocrine carcinoma concurrent with hepatocellular carcinoma: A case report

    PubMed Central

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

    2014-01-01

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

  3. A Proteomic Comparison of Formalin-Fixed Paraffin-Embedded Pancreatic Tissue from Autoimmune Pancreatitis, Chronic Pancreatitis, and Pancreatic Cancer

    PubMed Central

    Paulo, Joao A; Kadiyala, Vivek; Brizard, Scott; Banks, Peter A; Steen, Hanno; Conwell, Darwin L

    2015-01-01

    Context Formalin-fixed paraffin-embedded (FFPE) tissue is a standard for specimen preservation, and as such FFPE tissue banks are an untapped resource of histologically-characterized specimens for retrospective biomarker investigation for pancreatic disease. Objectives We use liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to compare FFPE specimens from three different diseases of the exocrine pancreas. Design We investigated the proteomic profile of FFPE pancreatic tissue from 9 archived specimens that were histologically classified as: autoimmune pancreatitis (n=3), chronic pancreatitis (n=3), and pancreatic cancer (n=3), using LC-MS/MS. Setting This is a proteomic analysis experiment of FFPE pancreatic tissue in an academic center. Patients FFPE tissue specimens were provided by Dana-Farber/Harvard Cancer Center (Boston, MA, USA). Interventions FFPE tissue specimens were collected via routine surgical resection procedures. Main outcome measures We compared proteins identified from chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer FFPE pancreatic tissue. Results We identified 386 non-redundant proteins from 9 specimens. Following our filtering criteria, 73, 29, and 53 proteins were identified exclusively in autoimmune pancreatitis, chronic pancreatitis, and pancreatic cancer specimens, respectively. Conclusions We report that differentially-expressed proteins can be identified among FFPE tissues specimens originating from individuals with different histological diagnoses. These proteins merit further confirmation with a greater number of specimens and orthogonal validation, such as immunohistochemistry. The mass spectrometry-based methodology used herein has the potential to enhance diagnostic biomarker and therapeutic target discovery, further advancing pancreatic research. PMID:23846938

  4. Pancreatic vascular regulation in chronic pancreatitis in cats.

    PubMed

    Widdison, A L; Karanjia, N D; Reber, H A

    1995-01-01

    In experimental obstructive chronic pancreatitis the normal hyperaemic response to secretory stimulation is lost, suggesting abnormal vascular regulation. Vascular regulatory mechanisms were investigated by observing the effect of increments in portal pressure on pancreatic blood flow in normal cats and cats with chronic pancreatitis. Normal cats maintained pancreatic blood flow until portal pressure was > 15 mm Hg, after which it decreased. Total vascular resistance decreased until the portal pressure was 15 mm Hg and increased thereafter. These observations suggested that metabolic regulatory mechanisms prevailed while portal pressure was in the physiological range but myogenic mechanisms became dominant during portal hypertension. In chronic pancreatitis the basal pancreatic blood flow was reduced and was inversely proportional to portal pressure. Total vascular resistance increased as portal pressure increased. In chronic pancreatitis myogenic regulatory responses prevailed at all levels of portal pressure. In conclusion, intrinsic regulation of pancreatic blood flow was abnormal in cats with chronic pancreatitis. The loss of the predominance of metabolic regulation over the normal range of portal pressure may partly explain the reduction of pancreatic blood flow in response to secretory stimulation. PMID:7890217

  5. 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.

  6. Hepatobiliary and pancreatic ascariasis.

    PubMed

    Khuroo, M S

    2001-03-01

    Ascariasis is a helminthic infection of global distribution with more than 1.4 billion persons infected throughout the world. The majority of infections occur in the developing countries of Asia and Latin America. Of 4 million people infected in the United States, a large percentage are immigrants from developing countries. Ascaris-related clinical disease is restricted to subjects with heavy worm load, and an estimated 1.2 to 2 million such cases, with 20,000 deaths, occur in endemic areas per year. More often, recurring moderate infections cause stunting of linear growth, cause reduced cognitive function, and contribute to existing malnutrition in children in endemic areas. HPA is a frequent cause of biliary and pancreatic disease in endemic areas. It occurs in adult women and can cause biliary colic, acute cholecystitis, acute cholangitis, acute pancreatitis, and hepatic abscess. RPC causing hepatic duct calculi is possibly an aftermath of recurrent biliary invasion in such areas. Ultrasonography can detect worms in the biliary tract and pancreas and is a useful noninvasive technique for diagnosis and follow-up of such patients. ERCP can help diagnose biliary and pancreatic ascariasis, including ascaris in the duodenum. Also, ERCP can be used to extract worms from the biliary and pancreatic ducts when indicated. Pyrantel pamoate, mebendazole, albendazole and levamisole are effective drugs and can be used for mass therapy to control ascariasis in endemic areas. PMID:11293175

  7. [Hypertriglyceridemia-induced pancreatitis].

    PubMed

    Nagayama, Daiji; Shirai, Kohji

    2013-09-01

    In Japan, the frequency of acute pancreatitis is 27.7 per 100,000, which includes 1.4 % of hypertriglyceridemia-induced pancreatitis(HTGP). Severity and complication rates with HTGP have been reported as higher in comparison to acute pancreatitis from other etiologies. Havel has suggested that hydrolysis of excessive triglyceride-rich lipoproteins releases high concentrations of free fatty acid(FFA). The FFA micelles injure the vascular endothelium and acinar cells of the pancreas, producing a self-perpetuating ischemic and acidic environment with resultant toxicity. Lipoprotein lipase (LPL) abnormality has been reported to contribute to severe hypertriglyceridemia. However, patients without any LPL abnormality are often encountered clinically, suggesting that other factors may be involved in the development of severe hypertriglyceridemia. In 21 patients with HTGP, 9 patients(42.9 %) with apolipoprotein AV (ApoAV) Gly185-Cys polymorphism were observed, whereas 14.3 % with LPL gene variants. No patient had ApoCII deficiency. These results suggest that in addition to LPL gene variants, ApoAV variant may be numerously involved in HTGP. It is important for clinicians to routinely investigate pathogenesis of hypertriglyceridemia in case with pancreatitis because specific management may be needed. PMID:24205721

  8. Pancreatic Cancer Interest Group

    Cancer.gov

    Chairperson S. Perwez Hussain, Ph.D. Investigator Head, Pancreatic Cancer Unit Laboratory of Human Carcinogenesis CCR, National Cancer Institute Building 37, Room 3044B Bethesda, MD 20862 Phone: 301.402.3431 Steering Committee Laufey Amundadottir, Ph.D. I

  9. Diabetes and pancreatic cancer.

    PubMed

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

    2014-07-01

    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. PMID:25076332

  10. Nutrition in chronic pancreatitis

    PubMed Central

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

    2013-01-01

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

  11. Localized Autoimmune Pancreatitis

    PubMed Central

    Cao, Zhe; Tian, Rui; Zhang, Taiping; Zhao, Yupei

    2015-01-01

    Abstract Autoimmune pancreatitis (AIP) is a rare disease with clinical presentations that greatly mimic pancreatic cancer (PC). It is critical for clinicians to distinguish AIP from PC because their treatments and prognoses are entirely different. Typical images show characteristic features such as diffuse pancreatic swelling and strictures of the main pancreatic duct (MPD). However, AIP may present as a localized pancreatic mass, in which case it is very difficult to differentiate from PC. Here, we report a case of a 40-year-old man with computed tomography (CT) imaging studies confirming an area of low-density neoplasm in the uncinate process of the pancreas with dilation in the common biliary duct (CBD) and MPD. Increased uptake in the uncinate mass was observed by positron emission tomography (PET)/CT scan, which strongly suggested PC. Further laboratory analyses showed a marked elevation of serum IgG4. Because there was not enough evidence to rule out a diagnosis of malignancy, a histopathological biopsy became the criterion standard. An endoscopic ultrasound (EUS)-guided needle biopsy failed. As an alternative, a pancreaticoduodenectomy was conducted for the biopsy, and pathological analysis confirmed IgG4-related sclerotic chronic pancreatitis with moderate lymphoplasmacellular infiltration. We suggest that an accurate preoperative diagnosis for localized AIP with MPD and CBD obstructions mimicking PC is of great importance. Radiological imaging findings, particularly observations of diffused enlargement of the pancreas and delayed enhancement during the venous and portal phases, are essential for diagnosing AIP. Careful consideration should be given if serum IgG4 was taken as a special indicator for a differential diagnosis between AIP and PC. A history of IgG4-related diseases involving the biliary, lacrimal, salivary, retroperitoneal, renal, or pulmonary systems should also be highlighted. Thus, the pathology of extrapancreatic organs can be utilized as diagnostic evidence when the pathology for a pancreatic mass is not available, as in the case presented here. Furthermore, cautious use of hormone therapy is indicated for patients who cannot be ruled out as having PC. The results of future studies on localized AIP are eagerly awaited. PMID:26496272

  12. Temsirolimus in Treating Patients With Cervical Cancer That Is Recurrent, Locally Advanced, Metastatic, or Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2015-08-10

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  13. Influence of conjugated and conventional linoleic acid on tumor growth and lipid peroxidation in pancreatic adenocarcinoma in hamster.

    PubMed

    Kilian, M; Mautsch, I; Gregor, J I; Heinichen, D; Jacobi, C A; Schimke, I; Guski, H; Mller, J M; Wenger, F A

    2003-07-01

    Conventional linoleic acid (LA) is regarded as a promotor of carcinogenesis. However, the effect of its conjugated derivative on cancer is still unknown. Therefore we investigated the influence of conventional and conjugated LA on tumor growth and lipid peroxidation in a solid model of pancreatic adenocarcinoma in Syrian hamsters. 60 male hamsters were randomized in 4 groups (Gr.) (n=15). Gr. 1 and 2 received 0.5 ml 0.9% sodium chloride subcutaneously (s.c.) once a week while Gr. 3 and 4 were injected 10 mg N-nitrosobis-2-oxopropylamine (BOP)/kg body weight weekly for 12 weeks to induce pancreatic cancer. Gr. 1 and 3 received a diet containing conventional LA, Gr. 2 and 4 were fed a diet of conjugated LA. After 29 weeks all animals were sacrificed, pancreas was weighed and examined macroscopically and histologically. The level of lipid peroxidation and activities of glutathion peroxidase and superoxide dismutase were determined in tumor-free as well as in pancreatic carcinoma tissue. Different diets did not influence the incidence of pancreatic carcinoma, however, pancreas weight was increased by conjugated LA compared to conventional LA. Furthermore both diets decreased the activity of glutathion peroxidase and increased the level of lipid peroxidation in pancreatic intratumoral tissue. The content of conjugated LA in dietary did not influence pancreatic tumor growth in a solid model of pancreatic adenocarcinoma in Syrian hamsters. PMID:12878453

  14. Acute pancreatitis: Etiology and common pathogenesis

    PubMed Central

    Wang, Guo-Jun; Gao, Chun-Fang; Wei, Dong; Wang, Cun; Ding, Si-Qin

    2009-01-01

    Acute pancreatitis is an inflammatory disease of the pancreas. The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide. Many causes of acute pancreatitis have been discovered, but the pathogenetic theories are controversial. The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct. The majority of investigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux. Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed. However, little is known about the other acute pancreatitis. We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis. Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure, active trypsin reflux, and subsequent unregulated activation of trypsin within pancreatic acinar cells. Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation. Once the hypothesis is confirmed, traditional therapeutic strategies against acute pancreatitis may be improved. Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome. PMID:19322914

  15. Management of chronic pancreatitis.

    PubMed

    Giger, Urs; Stanga, Zeno; DeLegge, Mark H

    2004-02-01

    Chronic pancreatitis (CP) is an inflammatory disorder that results in permanent impairment of the glandular anatomy of the pancreas with or without functional abnormalities. The pathogenesis of CP is usually unclear, except in the case of alcohol-induced disease. The most common symptoms of CP are abdominal pain, diarrhea, and weight loss often requiring recurring hospitalization. Over time, pancreatic endocrine and exocrine dysfunction may develop as the disease progresses, and a variety of complications can occur. Among the possible complications are nutrient malabsorption and diabetes mellitus. The treatment of CP is difficult and challenging for every physician. Relieving pain is the first step in treating CP. This symptom needs to be controlled, often with narcotics, which can cause dependence. Diarrhea usually indicates the presence of steatorrhea, which is often treated with a high-calorie, high-protein, and low-fat diet to minimize symptoms of the underlying disease and to promote weight retention or gain. Pancreatic replacement therapy is used to combat maldigestion and malabsorption. Patients with diabetes may need insulin therapy for glycemic control. The use of parenteral nutrition for bowel rest is a standard approach in patients with symptomatic CP. The use of jejunal enteral feeding recently has been evaluated for efficacy in CP patients. The role of pancreatic endotherapy in the management of CP is evolving. Several reports have suggested that endoscopic therapy aimed at decompressing the obstructed pancreatic duct can be associated with pain relief in some patients. Surgery should be considered in patients who fail medical therapy. PMID:16215095

  16. Squamous Cell Carcinoma

    MedlinePLUS

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

  17. 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

  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

    2016-01-01

    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

  19. 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

  20. Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

    ClinicalTrials.gov

    2015-10-20

    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

  1. Expression of Ki-67, p53, and K-ras in chronic pancreatitis and pancreatic ductal adenocarcinoma

    PubMed Central

    Jeong, Seok; Lee, Don Haeng; Lee, Jung Il; Lee, Jin-Woo; Kwon, Kye Sook; Kim, Pum-Soo; Kim, Hyung Gil; Shin, Yong Woon; Kim, Young Soo; Kim, Young Bae

    2005-01-01

    AIM: To examine surgical specimens of pancreas with either chronic pancreatitis or pancreatic cancer in order to study whether ductal hyperplasia and dysplasia in pancreas represent precursor lesions for pancreatic cancer. METHODS: We examined expression of Ki-67, CEA, p53, and K-ras, in the surgical specimens of pancreas with adenocarcinomas (n = 11) and chronic pancreatitis (n = 12). Cellular proliferation was assessed by Ki-67 proliferation index using the proliferation marker Ki-67. In specimens with pancreas cancer, we divided pancreas epithelium into normal (n = 7), ductal hyperplasia (n = 3), dysplasia (n = 4), and cancerous lesion (n = 11) after hematoxylin and eosin staining, Ki-67, and CEA immunohistochemical staining. In cases with chronic pancreatitis, the specimen was pathologically examined as in cases with pancreas cancer, and they were also determined as normal (n = 10), ductal hyperplasia (n = 4), or dysplasia (n = 5). p53 and K-ras expression were also studied by immunohistochemical staining. RESULTS: In pancreatic cancer, the Ki-67 index was 3.733.58 in normal site, 6.624.39 in ductal hyperplasia, 13.474.02 in dysplasia and 37.0310.05 in cancer tissue, respectively. Overall, p53 was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 14 (0%), 0 of 7 (0%), 7 of 9 (78%), and 10 of 11 (91%), respectively, and K-ras was positive in 0 of 8 (0%), 1 of 3 (33%), 4 of 6 (67%), 4 of 5 (80%), respectively. CONCLUSION: Our results favorably support the hypothesis that ductal hyperplasia and dysplasia of the pancreas might be precursor lesions for pancreas cancer. Further evaluation of oncogenes by the molecular study is needed. PMID:16425381

  2. Preoperative biliary drainage for pancreatic cancer.

    PubMed

    Van Heek, N T; Busch, O R; Van Gulik, T M; Gouma, D J

    2014-04-01

    This review is to summarize the current knowledge about preoperative biliary drainage (PBD) in patients with biliary obstruction caused by pancreatic cancer. Most patients with pancreatic carcinoma (85%) will present with obstructive jaundice. The presence of toxic substances as bilirubin and bile salts, impaired liver function and altered nutritional status due to obstructive jaundice have been characterized as factors for development of complications after surgery. Whereas PBD was to yield beneficial effects in the experimental setting, conflicting results have been observed in clinical studies. The meta-analysis from relative older studies as well as more importantly a recent clinical trial showed that PBD should not be performed routinely. PBD for patients with a distal biliary obstruction is leading to more serious complications compared with early surgery. Arguments for PBD have shifted from a potential therapeutic benefit towards a logistic problem such as patients suffering from cholangitis and severe jaundice at admission or patients who need extra diagnostic tests, or delay in surgery due to a referral pattern or waiting list for surgery as well as candidates for neoadjuvant chemo(radio)therapy. If drainage is indicated in these patients it should be performed with a metal stent to reduce complications after the drainage procedure such as stent occlusion and cholangitis. Considering a change towards more neoadjuvant therapy regimes improvement of the quality of the biliary drainage concept is still important. PMID:24727874

  3. Role of pancreatic stellate cells in chemoresistance in pancreatic cancer

    PubMed Central

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

    2014-01-01

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

  4. Molecular mechanisms of pancreatic stone formation in chronic pancreatitis.

    PubMed

    Ko, Shigeru B H; Azuma, Sakiko; Yoshikawa, Toshiyuki; Yamamoto, Akiko; Kyokane, Kazuhiro; Ko, Minoru S H; Ishiguro, Hiroshi

    2012-01-01

    Chronic pancreatitis (CP) is a progressive inflammatory disease in which the pancreatic secretory parenchyma is destroyed and replaced by fibrosis. The presence of intraductal pancreatic stone(s) is important for the diagnosis of CP; however, the precise molecular mechanisms of pancreatic stone formation in CP were left largely unknown. Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel expressed in the apical plasma membrane of pancreatic duct cells and plays a central role in [Formula: see text] secretion. In previous studies, we have found that CFTR is largely mislocalized to the cytoplasm of pancreatic duct cells in all forms of CP and corticosteroids normalizes the localization of CFTR to the proper apical membrane at least in autoimmune pancreatitis. From these observations, we could conclude that the mislocalization of CFTR is a cause of protein plug formation in CP, subsequently resulting in pancreatic stone formation. Considering our observation that the mislocalization of CFTR also occurs in alcoholic or idiopathic CP, it is very likely that these pathological conditions can also be treated by corticosteroids, thereby preventing pancreatic stone formation in these patients. Further studies are definitely required to clarify these fundamental issues. PMID:23133422

  5. Endoscopic Treatment of Recurrent Acute Pancreatitis and Smoldering Acute Pancreatitis.

    PubMed

    Das, Rohit; Yadav, Dhiraj; Papachristou, Georgios I

    2015-10-01

    Recurrent acute pancreatitis (RAP) is a challenging condition that can lead to chronic pancreatitis and long-term morbidity. Etiology-based treatment can potentially have an impact on the natural history of RAP and its progression to chronic pancreatitis. In cases of divisum-associated RAP and idiopathic RAP, several studies have been performed to evaluate the efficacy of endoscopic therapy in alleviation of symptoms and frequency of AP events. This review discusses the literature available on these topic as well as touching on the role of endoscopic therapy in smoldering acute pancreatitis. PMID:26431601

  6. Role of pancreatic stellate cells in chemoresistance in pancreatic cancer.

    PubMed

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

    2014-01-01

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

  7. Groove pancreatitis and pancreatic heterotopia in the minor duodenal papilla.

    PubMed

    Chatelain, Denis; Vibert, Eric; Yzet, Thierry; Geslin, Guillaume; Bartoli, Eric; Manaouil, David; Delcenserie, Richard; Brevet, Marie; Dupas, Jean-Louis; Regimbeau, Jean-Marc

    2005-05-01

    Groove pancreatitis is a rare form of segmental chronic pancreatitis that involves the anatomic space between the head of the pancreas, the duodenum, and the common bile duct. We report 2 cases of groove pancreatitis with pancreatic heterotopia in the minor papilla. Patients were a 44-year-old woman and a 47-year-old man. Both had a past history of alcohol consumption and presented with abdominal pain, vomiting, and weight loss caused by duodenal stenosis. Abdominal computed tomography revealed thickening of the duodenal wall and enlargement of the pancreatic head in both patients. In 1 patient, ultrasound endoscopy showed a dilated duct in the head of the pancreas. Pancreaticoduodenectomy was performed to rule out pancreatic adenocarcinoma and because of the severity of the symptoms. In both cases, gross and microscopic examinations showed fibrous scar of the groove area. The Santorini duct was dilated and contained protein plugs in both patients, with abscesses in 1 of them. In both cases, there were microscopic foci of heterotopic pancreas with mild fibrosis in the wall of the minor papilla. Groove pancreatitis is often diagnosed in middle-aged alcoholic men presenting with clinical symptoms caused by duodenal stenosis. The pathogenesis of this rare entity could be because of disturbance of the pancreatic secretion through the minor papilla. Pancreatitis in heterotopic pancreas located in the minor papilla and chronic consumption of alcohol seem to be important pathogenic factors. PMID:15841034

  8. 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

  9. Follicular pancreatitis: a distinct form of chronic pancreatitis-an additional mimic of pancreatic neoplasms.

    PubMed

    Gupta, Rajib K; Xie, Bill H; Patton, Kurt T; Lisovsky, Mikhail; Burks, Eric; Behrman, Stephen W; Klimstra, David; Deshpande, Vikram

    2016-02-01

    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, ? and ? light chains as well as IgG4 and IgG were performed. We found a total of 6 patients (male-female ratio, 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, 3 patients had a discrete solid mass, whereas 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-to-IgG ratio was <40% in 5 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

  10. Studies of pancreatic carcinogenesis in different animal models

    SciTech Connect

    Scarpelli, D.G.; Rao, M.S.; Reddy, J.K.

    1984-06-01

    Pancreatic carcinomas can be induced in rats, guinea pigs, and hamsters by a variety of carcinogens. The types of neoplasms which arise vary with the species of rodent. In the rat, they consist exclusively of acinar cells, in the other species the lesions are adenocarcinomas resembling those derived from pancreatic ductules and ducts, those in hamster more so than in guinea pigs. Careful sequential studies in the guinea pig and hamster suggest that acinar cells together with ductular and duct cells are involved in the genesis of duct adenocarcinomas. In each rodent model, the acinar cell appears to be quite sensitive to continued exposure to carcinogen. In each instance, acini undergo modulation, and in the guinea pig and hamster, permanent metaplastic transformation to ductlike structures. Such cells assume an enhanced capacity for cell proliferation which persists following cessation of carcinogen treatment. Other studies suggest that adult pancreatic acinar cells possess a surprising degree of plasticity. Their involvement in the pathogenesis of neoplasms resembling pancreatic ducts is not unlike other carcinogenic sequences where extensive cell modulation and metaplasia precede and are an integral part of the neoplastic transformation. 55 references, 9 figures, 4 tables.

  11. Histogenesis of exocrine pancreatic cancer in the hamster model.

    PubMed Central

    Pour, P M

    1984-01-01

    There is strong evidence that induced pancreatic adenomas and carcinomas derive from ductal and ductular cells in the pancreas. We base our beliefs on our knowledge of the embryology and histology of the pancreas in Syrian golden hamsters, along with the sequential alterations that occur during exocrine pancreatic tumor formation. This concept also has been supported by much experimental evidence, including autoradiographic, immunologic and in vitro studies. We also present other viewpoints on the origin of pancreatic cancer histogenesis and outline certain areas of disagreement. We report the development of acinar cell lesions under certain experimental dietary conditions in hamsters (the lesions resemble those commonly seen in the rat pancreatic tumor model) and the nature of these lesions. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 10. FIGURE 11. FIGURE 12. FIGURE 13. FIGURE 14. FIGURE 15. FIGURE 16. FIGURE 17. FIGURE 18. FIGURE 19. FIGURE 20. FIGURE 21. FIGURE 22. FIGURE 23. FIGURE 24. FIGURE 25. FIGURE 26. FIGURE 27. FIGURE 28. FIGURE 29. FIGURE 30. PMID:6236973

  12. PNMA1 promotes cell growth in human pancreatic ductal adenocarcinoma.

    PubMed

    Jiang, Shu-Heng; He, Ping; Ma, Ming-Ze; Wang, Yang; Li, Rong-Kun; Fang, Fang; Fu, Ying; Tian, Guang-Ang; Qin, Wen-Xin; Zhang, Zhi-Gang

    2014-01-01

    Paraneoplastic Ma1 (PNMA1) is a member of an expanding family of 'brain/testis' proteins involved in an autoimmune disorder defined as paraneoplastic neurological syndrome (PNS). Although it is widely studied in PNS, little is known about the underlying clinical significance and biological function of PNMA1 in tumors. Here, we find that elevated PNMA1 expression is more commonly observed in pancreatic ductal adenocarcinoma (PDAC) cell lines, compared with normal pancreatic cell and tissues from pancreatic ductal adenocarcinoma patient. Besides, higher PNMA1 expression is closely correlated with large tumor size. Suppression of endogenous PNMA1 expression decreases cell viability and promotes cell apoptosis. Subsequent studies reveal that the PI3K/AKT, MAPK/ERK pathway and members of the anti-apoptotic Bcl-2 family may be involved in the pro-survival and anti-apoptotic effect of PNMA1 on PDAC. Taken together, this study provides evidence that PNMA1 is involved in tumor growth of pancreatic carcinoma and PNMA1-related pathways might represent a new treatment strategy. PMID:25120759

  13. Current Knowledge on Pancreatic Cancer

    PubMed Central

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

    2012-01-01

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

  14. Pancreatic adenocarcinoma: epidemiology and genetics.

    PubMed Central

    Flanders, T Y; Foulkes, W D

    1996-01-01

    Pancreatic adenocarcinoma is an important cause of death from cancer throughout the developed world. There are few established environmental risk factors, but a previous history of pancreatitis and exposure to tobacco and salted food appear to be the most important. A family history of pancreatic adenocarcinoma is not common in patients with this disease, but recent research has shown that pancreatic adenocarcinoma can be a feature of cancer susceptibility syndromes associated with germline mutations in p16, BRCA1, BRCA2, and APC. This highlights the need for a full family history in apparently sporadic cases. Somatic mutations in p16, BRCA2, and APC have also been reported in pancreatic cancer; however, K-RAS mutations appear to be the commonest oncogenic alteration. Recent advances in our understanding of the basis of hereditary cancer syndromes may be applicable to the diagnosis, treatment, and possibly prevention of pancreatic adenocarcinoma in the future. PMID:8950667

  15. Molecular Signatures of Pancreatic Cancer

    PubMed Central

    Hong, Seung-Mo; Park, Jason Y.; Hruban, Ralph H.; Goggins, Michael

    2011-01-01

    Context The introduction of genome- and epigenome-wide screening techniques has dramatically improved our understanding of the molecular mechanisms underlying the development of pancreatic cancer. There are now 3 recognized histologic precursors of pancreatic cancer: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. Each of these precursor lesions is associated with specific molecular alterations. Objective To understand the molecular characteristics of pancreatic ductal adenocarcinoma and its precursor lesions. Data Sources PubMed (US National Library of Medicine). Conclusions In this review, we briefly summarize recent research findings on the genetics and epigenetics of pancreatic cancer. In addition, we characterize these molecular alterations in the context of the histologic subtypes of pancreatic cancer. PMID:21631264

  16. [The significance of beta2-microglobulin and carcinoembryonic antigen in the diagnosis of the carcinoma of the pancreas (author's transl)].

    PubMed

    Fateh-Moghadam, A; Mantel, W; Neumeier, D; Hannig, Ch; Kristin, H; Otte, M

    1978-03-15

    The concentration of beta2-microglobulin (beta2m) and carcinoembryonic antigen (CEA) was measured radioimmunologically in the sera of 79 patients with malignant disorders and 15 patients with chronic pancreatitis. Elevated levels of beta2m and CEA were found in 11 out of 22 patients with carcinoma of the pancreas, which sets off this malignancy from chronic pancreatitis and other malignant tumors. Only 3 patients with carcinoma of the pancreas exhibited serum levels within the normal range for both parameters and none of the patients with chronic pancreatitis was shown to have elevated levels of beta2m. The simultaneous determination of beta2m and CEA suggests itself for the diagnosis of pancreatic malignancy especially in the case of a tentative diagnosis of a pancreatic tumor. PMID:76694

  17. Early detection of pancreatic cancer.

    PubMed

    Kim, Victoria M; Ahuja, Nita

    2015-08-01

    Pancreatic adenocarcinoma is a low-incident but highly mortal disease. It accounts for only 3% of estimated new cancer cases each year but is currently the fourth common cause of cancer mortality. By 2030, it is expected to be the 2(nd) leading cause of cancer death. There is a clear need to diagnose and classify pancreatic cancer at earlier stages in order to give patients the best chance at a definitive cure through surgery. Three precursor lesions that distinctly lead to pancreatic adenocarcinoma have been identified, and we have increasing understanding the non-genetic and genetic risk factors for the disease. With increased understanding about the risk factors, the familial patters, and associated accumulation of genetic mutations involved in pancreatic cancer, we know that there are mutations that occur early in the development of pancreatic cancer and that improved genetic risk-based strategies in screening for pancreatic cancer may be possible and successful at saving or prolonging lives. The remaining challenge is that current standards for diagnosing pancreatic cancer remain too invasive and too costly for widespread screening for pancreatic cancer. Furthermore, the promises of noninvasive methods of detection such as blood, saliva, and stool remain underdeveloped or lack robust testing. However, significant progress has been made, and we are drawing closer to a strategy for the screening and early detection of pancreatic cancer. PMID:26361402

  18. [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. PMID:26520203

  19. Early detection of pancreatic cancer

    PubMed Central

    Ahuja, Nita

    2015-01-01

    Pancreatic adenocarcinoma is a low-incident but highly mortal disease. It accounts for only 3% of estimated new cancer cases each year but is currently the fourth common cause of cancer mortality. By 2030, it is expected to be the 2nd leading cause of cancer death. There is a clear need to diagnose and classify pancreatic cancer at earlier stages in order to give patients the best chance at a definitive cure through surgery. Three precursor lesions that distinctly lead to pancreatic adenocarcinoma have been identified, and we have increasing understanding the non-genetic and genetic risk factors for the disease. With increased understanding about the risk factors, the familial patters, and associated accumulation of genetic mutations involved in pancreatic cancer, we know that there are mutations that occur early in the development of pancreatic cancer and that improved genetic risk-based strategies in screening for pancreatic cancer may be possible and successful at saving or prolonging lives. The remaining challenge is that current standards for diagnosing pancreatic cancer remain too invasive and too costly for widespread screening for pancreatic cancer. Furthermore, the promises of noninvasive methods of detection such as blood, saliva, and stool remain underdeveloped or lack robust testing. However, significant progress has been made, and we are drawing closer to a strategy for the screening and early detection of pancreatic cancer. PMID:26361402

  20. [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. PMID:25294271

  1. Chemoprevention strategies for pancreatic cancer

    PubMed Central

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

    2010-01-01

    Pancreatic cancer has a poor prognosis and it is often diagnosed at advanced stages, which makes it very difficult to treat. The low survival rate of patients with pancreatic cancer points toward an increased need for novel therapeutic and chemopreventive strategies and early detection. Increased consumption of fruits and vegetables has been associated with a reduced risk of pancreatic cancer. Both synthetic as well as natural, diet-derived bioactive compounds have been evaluated as pancreatic cancer chemopreventive agents and have been shown to have various degrees of efficacy in cellular and in vivo animal models. Some chemopreventive agents (for example curcumin, resveratrol, B-DIM) have also been reported to sensitize pancreatic cancer cells to standard chemotherapeutic drugs (for example gemcitabine or erlotinib), which suggests the potential use of chemopreventive agents as potentiators of standard chemotherapy. Very few clinical trials with pancreatic cancer chemopreventive agents have been completed and some are in early phases. Further development of pancreatic cancer chemopreventive agents may prove to be tremendously valuable for individuals at high-risk of developing pancreatic cancer and patients who present with premalignant lesions. This Review discusses the current state of the pancreatic cancer chemoprevention field and highlights the challenges ahead. PMID:20440279

  2. Adrenocortical Carcinoma

    Cancer.gov

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

  3. Antibiosis of Necrotizing Pancreatitis

    PubMed Central

    Arlt, Alexander; Erhart, Wiebke; Schafmayer, Clemens; Held, Hanns-Christoph; Hampe, Jochen

    2014-01-01

    Summary Background Necrotizing pancreatitis is a life-threatening presentation of acute pancreatitis. The mortality of 20-80% initially depends on the persistence of organ failure and systemic inflammatory response syndrome (SIRS) and, in the later course of the disease, on secondary infection of the necrosis. The questions whether prophylactic antibiotics aiming to prevent this infection should be administered and which antibiotic is the best to use, as well as the problem of fungal infection under antibiotic treatment are still intriguing and insufficiently solved. Methods A search of the literature using PubMed was carried out, supplemented by a review of the programmes of the Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW). Results Despite the widely practised prophylactic antibiotic administration in severe pancreatitis, no evidence for the benefit of this strategy exists. One of the drawbacks might be a tendency for disastrous fungal infection under prophylactic antibiotics. Bacterial translocation from the gut in the second week after the onset of symptoms is the major source for infection of pancreatic necrosis and provides a clear indication for antibiotic treatment. However, routine fine-needle aspiration for a calculated antibiotic therapy cannot be recommended, and all other tests offer only indirect signs. Important factors such as enteral versus parenteral feeding and the method of necrosectomy are mostly neglected in the trials but seem to be essential for the outcome of the patient. Conclusions Even though most meta-analyses including the newer double-blind, placebo-controlled trials on prophylactic antibiotics showed no beneficial effects in the prevention of infection of necrosis and/or outcome of the patients, this strategy is still widely used in clinical routine. Since nearly all trials published so far show systematic problems (i.e. inaccurate definition of the severity of the disease, poor statistical testing, and neglect of differences in the route of nutrition), there is a need for randomized controlled prospective trials with exact definitions of the disease. PMID:26286761

  4. Hepatocyte Nuclear Factor 1A (HNF1A) as a Possible Tumor Suppressor in Pancreatic Cancer

    PubMed Central

    Luo, Zhaofan; Li, Yanan; Wang, Huamin; Fleming, Jason; Li, Min; Kang, Yaan; Zhang, Ran; Li, Donghui

    2015-01-01

    Background HNF1A (Hepatocyte nuclear factor 1 alpha) is a transcription factor that is known to regulate pancreatic differentiation and maintain homeostasis of endocrine pancreas. Recently, genome-wide association studies have implicated HNF1A as a susceptibility gene for pancreatic cancer. However, the functional significance and molecular mechanism of HNF1A in pancreatic carcinogenesis remains unclear. Methods Using RT-PCR, Western blot and immunohistochemistry methods, we examined HNF1A gene expression in eight pancreatic carcinoma cell lines and in paired tumor and normal tissue samples from patients with resected pancreatic ductal adenocarcinoma. We knocked down the HNF1A gene expression in two cancer cell lines using three siRNA sequences. The impacts on cell proliferation, apoptosis, and cell cycle as well as the phosphorylation of Akt signaling transduction proteins were examined using ATP assay, flow cytometry and Western blot. Results HNF1A was expressed in three out of eight pancreatic adenocarcinoma cell lines and the level of HNF1A mRNA and protein expression was significantly lower in tumors than in normal adjacent tissues by both RT-PCR and Western Blot analyses. Immunohistochemistry revealed that the level of HNF1A expression was significantly lower in tumor tissues than in non-tumor tissues. Selective blocking of HNF1A by specific siRNA conferred a 2-fold higher rate of cell proliferation, 20% increased S phase and G2 phase cells, and 30-40% reduced apoptosis in pancreatic cancer cell lines. We further demonstrated that HNF1A knockdown activated Akt and its downstream target, the mammalian target of rapamycin (mTOR) in pancreatic cancer cells. Conclusion These observations provide experimental evidence supporting a possible tumor suppressor role of HNF1A in pancreatic cancer. PMID:25793983

  5. Immunohistochemistry of Pancreatic Neoplasia

    PubMed Central

    Kaur, Sukhwinder; Shimizu, Tomohiro; Baine, Michael J.; Kumar, Sushil; Batra, Surinder K.

    2013-01-01

    Immunohistochemistry (IHC) is a valuable tool to visualize the distribution and localization of specific cellular components within morphologically preserved tissue sections or cell preparations. It combines the histologic morphology of tissues for detecting the actual antigen distribution, specificity of antibodyantigen interaction for optimal detection, and sensitivity of immunochemical methods for assessing the amount of antigen in tissues. It is routinely used clinically to diagnose type (benign or malignant), stage, and grade of cancer using specific tumor markers. The application of IHC ranges from disease diagnosis and prognosis to drug development and analysis of the pathobiological roles of various molecular players during disease development. Due to better availability of highly specific antibodies and optimal methodologies for performing immunohistochemical studies, IHC is being used at an expanding rate to understand pancreatic tumor biology as well as to study the fate of various molecular markers during the initiation, progression, and metastasis of pancreatic neoplasia. Herein, we describe the detailed protocol for IHC analyses of pancreatic intraepithelial neoplasia in tissues and fine needle aspirates from both human and mouse samples. PMID:23359148

  6. Nutrition in acute pancreatitis.

    PubMed

    Abou-Assi, S; O'Keefe, S J

    2001-03-01

    The majority of patients (80%) admitted with acute pancreatitis recovers after a few days of bowel rest and intravenous fluids. However, some cases progress to a fulminant disease complicated by a severe systemic inflammatory response and multiple organ failure, a condition in which mortality is related to the degree of negative nitrogen balance. The goal of nutrition support in this situation is to cover the increased metabolic demands without stimulating pancreatic secretion and exacerbating the "autodigestion" that characterizes the condition. Although human and animal studies have shown conflicting results regarding the effect of composition and location of feeding on pancreatic enzyme secretion, there is consensus that total parenteral nutrition (TPN), given at moderate infusion rates, does not significantly stimulate secretion in humans and that enteral diets stimulate enzyme secretion unless delivered below the jejunum. Consequently, until recently TPN has been the standard of therapy. The fact that the cost and complications of TPN can often outweigh its benefits (catheter sepsis, hyperglycemia) has led to a series of recent controlled clinical trials of modified enteral diets in which the diet is delivered by nasojejunal tube. Results have demonstrated that enteral nutrition, with either elemental or polymeric formulas, was cheaper, safer, and at the same time more effective in reducing the systemic inflammatory response. The pathophysiologic explanation for these observations needs further investigation. PMID:11246344

  7. [Acute pancreatitis and pregnancy].

    PubMed

    Scollo, P; Licitra, G

    1993-12-01

    Aetiologic factors (gallstones, hyperlipidemia I-IV, hypertriglyceridaemia) make their occurrence, mainly, in the third trimester of gestation. Two cases of acute pancreatitis in pregnancy are described; in both cases patients referred healthy diet, no habit to smoke and no previous episode of pancreatitis. An obstructive pathology of biliary tract was the aetiologic factor. Vomiting, upper abdominal pain are aspecific symptoms that impose a differential diagnosis with acute appendicitis, cholecystitis and obstructive intestinal pathology. Laboratory data (elevated serum amylase and lipase levels) and ultrasonography carry out an accurate diagnosis. The management of acute pancreatitis is based on the use of symptomatic drugs, a low fat diet alternated to the parenteral nutrition when triglycerides levels are more than 28 mmol/L. Surgical therapy, used only in case of obstructive pathology of biliary tract, is optimally collected in the third trimester or immediately after postpartum. Our patients, treated only medically, delivered respectively at 38th and 40th week of gestation. Tempestivity of diagnosis and appropriate therapy permit to improve prognosis of a pathology that, although really associated with pregnancy, presents high maternal mortality (37%) cause of complications (shock, coagulopathy, acute respiratory insufficiency) and fetal (37.9%) by occurrence of preterm delivery. PMID:8139793

  8. 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

  9. Pancreatic cancer: Classifying pancreatic cancer using gene expression profiling.

    PubMed

    Ayars, Michael; Goggins, Michael

    2015-11-01

    Despite some advances in our understanding of the molecular characteristics of pancreatic cancer, much more progress is needed. In a new study, RNA profiling of pancreatic cancers was used to identify gene signatures of tumour cells and stromal cells to help predict patient outcomes. PMID:26484444

  10. Pancreatic polypepetide inhibits pancreatic enzyme secretion via a cholinergic pathway

    SciTech Connect

    Jung, G.; Louie, D.S.; Owyang, C. )

    1987-11-01

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

  11. Pancreatic herniation: a rare cause of acute pancreatitis?

    PubMed Central

    Kumar, Prashant; Turp, Matthew; Fellows, Sarah; Ellis, Jonathan

    2013-01-01

    Acute pancreatitis is a common and potentially fatal condition, with several well-known causes including gallstones, excessive alcohol consumption and specific medications. We report a case of an 89-year-old man presenting with acute pancreatitis, which we believe to be secondary to a diaphragmatic herniation of the pancreas. This extremely rare anatomical abnormality can be found incidentally in the asymptomatic patient or may present with a variety of acute symptoms. However, there have been only isolated reports of these cases presenting as acute pancreatitis. While the majority of acute pancreatitis cases can be explained by common causes, it is important that clinicians be aware of and should consider investigating for other more unusual possibilities, such as pancreatic herniation, before labelling an episode as idiopathic. PMID:24343805

  12. GNAS mutation is a frequent event in pancreatic intraductal papillary mucinous neoplasms and associated adenocarcinomas.

    PubMed

    Hosoda, Waki; Sasaki, Eiichi; Murakami, Yoshiko; Yamao, Kenji; Shimizu, Yasuhiro; Yatabe, Yasushi

    2015-06-01

    In contrast to pancreatic ductal adenocarcinomas (PDAs), intraductal papillary mucinous neoplasms (IPMNs) frequently harbour GNAS mutations. To characterise GNAS-mutated pancreatic carcinomas, we examined mutations of GNAS and KRAS in 290 pancreatic adenocarcinomas and 77 pancreatic intraepithelial neoplasias (PanINs). In 64 % (39/61) of IPMNs and 37 % (11/30) of IPMN-associated adenocarcinomas, a GNAS mutation was found. GNAS mutations were frequent (78 %, 7/9) in mucinous carcinomas, with or without associated IPMN. In contrast, GNAS mutations were rarely observed in PDAs (1 %, 1/88) and PanINs (3 %, 2/77), and not at all in mucinous cystic neoplasms (MCNs) (0/10), neuroendocrine neoplasms (0/52), acinar cell neoplasms (0/16), serous cystadenomas (0/10), and solid-pseudopapillary neoplasms (0/14). We found GNAS mutations in 55/91 IPMNs with or without associated invasive carcinoma, solely in intestinal-type (78 %, 21/27) and gastric-type (62 %, 34/55) IPMNs. Of the IPMN-associated adenocarcinomas, mucinous-subtype tumours harboured GNAS mutations more frequently (83 %, 5/6) than tubular-subtype tumours (25 %, 6/24) (p?=?0.02). We separately analysed GNAS in the adenocarcinoma and the IPMN component in the IPMN-associated adenocarcinomas. In all mucinous-subtype tumours, the two components exhibited identical genotypes. In contrast, the two components in 8 of 24 tubular-subtype tumours exhibited different genotypes, indicating intratumour heterogeneity. In conclusion, mucinous carcinomas with or without associated IPMN as well as IPMNs frequently harbour a GNAS mutation, reinforcing the notion that these constitute a spectrum of pancreatic tumours. Clinically and pathologically, these tumours are associated, but GNAS mutation sheds further light on this spectrum. PMID:25796395

  13. 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 neither duodenal biopsies nor pancreatic head FNA confirm adenocarcinoma. PMID:26713302

  14. 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

  15. Diet and Pancreatic Cancer Prevention

    PubMed Central

    Casari, Ilaria; Falasca, Marco

    2015-01-01

    Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer. PMID:26610570

  16. Pancreatic involvement in Legionella pneumonia.

    PubMed

    Franchini, S; Marinosci, A; Ferrante, L; Sabbadini, M G; Tresoldi, M; Dagna, L

    2015-06-01

    Legionella-associated pancreatitis has been rarely reported. Since this condition is very rarely suspected and investigated in patients with Legionella pneumonia, its incidence is probably underestimated. Here we report a case of Legionella pneumonia-associated pancreatitis and review the relevant related literature. PMID:25575464

  17. Diet and Pancreatic Cancer Prevention.

    PubMed

    Casari, Ilaria; Falasca, Marco

    2015-01-01

    Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer. PMID:26610570

  18. 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.

  19. Myocardial function in acute pancreatitis.

    PubMed Central

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

    1981-01-01

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

  20. Familial pancreatic cancer: genetic advances.

    PubMed

    Rustgi, Anil K

    2014-01-01

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

  1. 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

  2. [Prolonged acute pancreatitis after bone marrow transplantation].

    PubMed

    De Singly, B; Simon, M; Bennani, J; Wittnebel, S; Zagadanski, A-M; Pacault, V; Gornet, J-M; Allez, M; Lmann, M

    2008-04-01

    Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids. PMID:18378104

  3. Sex differences in gallstone pancreatitis.

    PubMed Central

    Taylor, T V; Rimmer, S; Holt, S; Jeacock, J; Lucas, S

    1991-01-01

    From a computerized database comprising 28 pertinent items in each of a consecutive series of 664 patients with cholelithiasis, differences were studied between men and women. In 52 patients there was a documented attack of acute pancreatitis (7.8%). Twenty-five of 174 men had pancreatitis, compared with 27 of 490 women (p less than 0.0001). Men developed gallstones later in life than women, but suffered gallstone pancreatitis earlier in life and in the course of their gallstone-related disease. A history of flatulent dyspepsia, chronic cholecystitis, and biliary colic was less common in men than in women with pancreatitis (p less than 0.0001). Men with pancreatitis had fewer stones in their gallbladders than did women (p = 0.0002). The cystic duct and the common bile duct in the pancreatitic patient were more likely to be dilated (p less than 0.0001). In the nonpancreatic group, these ducts were larger in men. Pancreatic duct reflux on operative cholangiography was more common both in patients with pancreatitis 62% cf 14% (p less than 0.0001), and in men (p less than 0.001). Predisposition to pancreatitis relates to duct size rather than stone size per se. Men are more susceptible to gallstone migration at an early stage of their disease. In addition they have a larger diameter duct system and possibly a different anatomic disposition of the sphincter of Oddi, which predisposes them to a higher incidence of pancreatitis than women. The data suggest that it is cystic duct size that is critical in the pathogenesis of gallstone pancreatitis. PMID:1741646

  4. Alcohol consumption on pancreatic diseases

    PubMed Central

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

    2013-01-01

    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. PMID:23429423

  5. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor.

    PubMed

    Ceriolo, Paola; Fausti, Valentina; Cinotti, Elisa; Bonadio, Silvia; Raffaghello, Lizzia; Bianchi, Giovanna; Orcioni, Giulio Fraternali; Fiocca, Roberto; Rongioletti, Franco; Pistoia, Vito; Borgonovo, Giacomo

    2016-03-28

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokine-chemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10. PMID:27022231

  6. Ameloblastic Carcinoma

    PubMed Central

    Gunaratne, Dakshika Abeydeera; Coleman, Hedley G.; Lim, Lydia; Morgan, Gary J.

    2015-01-01

    Patient: Male, 66 Final Diagnosis: Ameloblastic carcinoma Symptoms: Jaw pain Medication: None Clinical Procedure: Surgical resection Specialty: Head and neck surgery Objective: Rare disease Background: Ameloblastic carcinoma secondary type is an extremely rare and aggressive odontogenic neoplasm that exhibits histological features of malignancy in primary and metastatic sites. It arises through carcinomatous de-differentiation of a pre-existing ameloblastoma or odontogenic cyst, typically following repeated treatments and recurrences of the benign precursor neoplasm. Identification of an ameloblastic carcinoma, secondary type presenting with histologic features of malignant transformation from an earlier untreated benign lesion remains a rarity. Herein, we report 1 such case. Case Report: A 66-year-old man was referred for management of a newly diagnosed ameloblastic carcinoma. He underwent radical surgical intervention comprising hemimandibulectomy, supraomohyoid neck dissection, and free-flap reconstruction. Final histologic analysis demonstrated features suggestive of carcinomatous de-differentiation for a consensus diagnosis of ameloblastic carcinoma, secondary type (de-differentiated) intraosseous. Conclusions: Ameloblastic carcinoma, secondary type represents a rare and challenging histologic diagnosis. Radical surgical resection with adequate hard and soft tissue margins is essential for curative management of localized disease. PMID:26126621

  7. 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

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

  9. 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

  10. Molecular pathology of pancreatic cancer.

    PubMed

    Saiki, Yuriko; Horii, Akira

    2014-01-01

    By genomic and epigenomic screening techniques, substantial progress has been made in our understanding of pancreatic cancer. The comprehensive studies of the pancreatic cancer genome have revealed that most genetic alterations are identified to be associated with specific core signaling pathways including high-frequency mutated genes such as KRAS, CDKN2A, TP53, and SMAD4 along with several low-frequency mutated genes. Three types of histological precursors of pancreatic cancer: pancreatic intraepithelial neoplasia, mucinous cystic neoplasm, and intraductal papillary mucinous neoplasm, had been recognized by morphological studies and the recent genomic screening techniques revealed that each of these precursor lesions were associated with specific molecular alterations. In the familial pancreatic cancer cases, several responsible genes were discovered. Epigenetic changes also play an important role in the progression of pancreatic cancer. Several tumor suppressor genes were silenced due to aberrant promoter CpG island hypermethylation. Several genetically engineered mouse models, based on the Kras mutation, were created, and provided reliable tools to identify the key molecules responsible for the development or progression of pancreatic cancer. PMID:24471965

  11. Vitamin D and pancreatic cancer.

    PubMed

    Barreto, Savio G; Neale, Rachel E

    2015-11-01

    Pancreatic cancer is currently the fourth leading cause of cancer-related death, and it is projected that within the next two decades it will become the second most common cause of death due to cancer. Few patients are diagnosed when surgical resection is feasible and the efficacy of existing chemotherapeutic agents for advanced/metastatic cancer is limited. Thus, there is a need to identify agents that can prevent pancreatic cancer or improve survival in those affected. Vitamin D and its analogues, with their ability to regulate cell growth, differentiation, apoptosis and angiogenesis, may be promising agents. This review explores the published literature about the potential role of vitamin D and its analogues in preventing or treating pancreatic cancer. The vitamin D system is altered in pancreatic cancer. Pancreatic cancer tissue expresses vitamin D receptors, but the calcitriol analogues may affect pancreatic cancer tissue by mechanisms that do not involve interaction with its receptors. Experimental evidence postulates multiple potential mechanisms by which calcitriol analogues may exert their anti-cancer effect, the most common being by action on cyclin-dependent kinases p21 and p27. Use of calcitriol analogues in pancreatic cancer remains largely underexplored and warrants further clinical trials. PMID:26276715

  12. Surgical Treatment of Necrotizing Pancreatitis

    PubMed Central

    Uhl, W.; Bchler, M.W.

    1997-01-01

    Surgical treatment in patients with severe acute pancreatitis is still a controversial subject, ranging from sole conservative to an aggressive approach. This article gives an overview of the literature with regard to indications for surgery, timing and techniques of operative treatment concepts in severe acute pancreatitis with special attention to the recommended necrosectomy and closed continuous lavage of the involved retroperitoneum. Taking into account recent findings from microbiological data we have developed a new algorithm in patients with acute pancreatitis. All patients with proven acute necrotizing pancreatitis receive an antibiotic therapy for 2 weeks beside the intensive care measures. So far only one third (33 percent) had infected pancreatic necroses in the 3rd week of the onset of the disease and were managed surgically. The delay resulted in optimal surgical conditions for necrosectomy and a mortality rate of 9 percent. This new concept and therapeutic approach with the early suitable antibiotic therapy in patients with proven necrotizing pancreatitis is recommended to (1) decrease the infection rate and (2) delay surgical intervention to the 3rd week of the disease with optimal surgical conditions. It seems that only patients with proven infected pancreatic necroses are candidates for surgical intervention.

  13. 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. PMID:25778551

  14. Dendritic cells pulsed with alpha-galactosylceramide induce anti-tumor immunity against pancreatic cancer in vivo.

    PubMed

    Nagaraj, S; Ziske, C; Strehl, J; Messmer, D; Sauerbruch, T; Schmidt-Wolf, I G H

    2006-08-01

    Ductal pancreatic adenocarcinoma is the fourth leading cause of cancer death in the Western world. Unfortunately, recent advances in diagnostics, staging and therapy have not resulted in significant improvements. Thus, new approaches are necessary to improve the outcome of patients with exocrine pancreatic cancer. We tested triggering of specific T lymphocytes in vivo by using the immunocompetent mouse strain C57BL/6. In the present study, we tried to enhance the anti-tumor effect against pancreatic carcinoma by supplementary triggering of NKT cells in vivo. We challenged Panc02 tumor-bearing mice by intratumoral vaccination with alpha-galactosylceramide (alpha-GalCer)-loaded dendritic cells (DCs). A significant expansion of IFNgamma-producing NKT cells was observed which also correlated with decrease in tumor growth in vivo. Hence, DCs loaded with alpha-GalCer could lead to a novel treatment option for patients with pancreatic cancer. PMID:16772371

  15. Pancreatic transplantation: a review.

    PubMed

    Cicalese, L; Giacomoni, A; Rastellini, C; Benedetti, E

    1999-01-01

    Pancreatic transplantation recently became a routine treatment for Type I diabetic patients with uremia or for those who previously received a kidney transplant with 1 year graft and patient survival of over 80% and 90%, respectively. Despite the life-long need for immunosuppression, this is clearly acceptable when compared to the need for dialysis and insulin therapy, and it reduces the evolution of diabetic complications. Isolated pancreatic transplant is less commonly applied because of the need for immunosuppression and the high rate of complications. However, this can still be an acceptable option for individual patients with brittle diabetes and hypoglycemic unawareness. Despite the fact that pancreas transplantation is an effective treatment for selected Type I diabetics, it remains a difficult surgical procedure with many potential complications and with several issues still subject to debate. In this article, the authors describe the procedure in all of its aspects and variations, and offer, through a review of the recent literature, insights on the current status of this transplant PMID:10667809

  16. [Hypertriglyceridemic pancreatitis and pregnancy].

    PubMed

    Sanduende Otero, Y; Figueira Moure, A; Rama-Maceiras, P; Bautista Guilln, A; Diguez Fernndez, M

    2003-11-01

    A 33-year-old secundipara with a history of gestational diabetes and familial hypertriglyceridemia exacerbated during her previous pregnancy was admitted in the 36th week of gestation with diffuse abdominal pain, vomiting, low-grade fever, and general malaise. A blood sample had a lipemic, milky-pink appearance and plasma concentrations were as follows: triglycerides 2173 mg/dL, cholesterol 320 mg/dL, amylase 801 U/L, lactate dehydrogenase 650 U/L, creatinine 1.5 mg/dL, glucose 380 mg/dL, and left-shifted white cells. Acute pancreatitis was diagnosed and owing to signs of fetal distress, a cesarean was performed under light general anesthesia with propofol, succinylcholine, and sevoflurane. After the umbilical cord was cut, rocoronium and fentanyl were administered. The neonate was healthy and the patient's condition evolved favorably with conservative treatment. The incidence of pancreatitis during pregnancy is low but related morbidity and mortality are high. The usual cause is biliary tract disease, although rare metabolic alterations such as hyperlipidemia may occasionally act as the trigger. Early diagnosis and treatment are the keys to successful surgery and postoperative recovery. PMID:14753142

  17. Pathophysiology of chronic pancreatitis

    PubMed Central

    Brock, Christina; Nielsen, Lecia Mller; Lelic, Dina; Drewes, Asbjrn Mohr

    2013-01-01

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

  18. Pancreatic insulinomas: Laparoscopic management

    PubMed Central

    Antonakis, Pantelis T; Ashrafian, Hutan; Martinez-Isla, Alberto

    2015-01-01

    Insulinomas are rare pancreatic neuroendocrine tumors that are most commonly benign, solitary, and intrapancreatic. Uncontrolled insulin overproduction from the tumor produces neurological and adrenergic symptoms of hypoglycemia. Biochemical diagnosis is confirmed by the presence of Whipples triad, along with corroborating measurements of blood glucose, insulin, proinsulin, C-peptide, ?-hydroxybutyrate, and negative tests for hypoglycemic agents during a supervised fasting period. This is accompanied by accurate preoperative localization using both invasive and non-invasive imaging modalities. Following this, careful preoperative planning is required, with the ensuing procedure being preferably carried out laparoscopically. An integral part of the laparoscopic approach is the application of laparoscopic intraoperative ultrasound, which is indispensable for accurate intraoperative localization of the lesion in the pancreatic region. The extent of laparoscopic resection is dependent on preoperative and intraoperative findings, but most commonly involves tumor enucleation or distal pancreatectomy. When performed in an experienced surgical unit, laparoscopic resection is associated with minimal mortality and excellent long-term cure rates. Furthermore, this approach confers equivalent safety and efficacy rates to open resection, while improving cosmesis and reducing hospital stay. As such, laparoscopic resection should be considered in all cases of benign insulinoma where adequate surgical expertise is available. PMID:26566426

  19. What's New in Pancreatic Cancer Research and Treatment?

    MedlinePLUS

    ... Next Topic Additional resources for pancreatic cancer What’s new in pancreatic cancer research and treatment? Research into ... area of research in many types of cancer. New treatments for pancreatic neuroendocrine tumors (NETs) Many pancreatic ...

  20. Chronic pancreatitis: A diagnostic dilemma

    PubMed Central

    Duggan, Sinead N; Ní Chonchubhair, Hazel M; Lawal, Oladapo; O’Connor, Donal B; Conlon, Kevin C

    2016-01-01

    Typical clinical symptoms of chronic pancreatitis are vague and non-specific and therefore diagnostic tests are required, none of which provide absolute diagnostic certainly, especially in the early stages of disease. Recently-published guidelines bring much needed structure to the diagnostic work-up of patients with suspected chronic pancreatitis. In addition, novel diagnostic modalities bring promise for the future. The assessment and diagnosis of pancreatic exocrine insufficiency remains challenging and this review contests the accepted perspective that steatorrhea only occurs with > 90% destruction of the gland. PMID:26900292

  1. Severe Acute Pancreatitis in Pregnancy

    PubMed Central

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

    2015-01-01

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

  2. 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

  3. Acute mediastinitis arising from pancreatic mediastinal fistula in recurrent pancreatitis.

    PubMed

    Choe, In Soo; Kim, Yong Seok; Lee, Tae Hee; Kim, Sun Moon; Song, Kyung Ho; Koo, Hoon Sup; Park, Jung Ho; Pyo, Jin Sil; Kim, Ji Yeong; Choi, In Seok

    2014-10-28

    Acute mediastinitis is a fatal disease that usually originates from esophageal perforation and surgical infection. Rare cases of descending necrotizing mediastinitis can occur following oral cavity and pharynx infection or can be a complication of pancreatitis. The most common thoracic complications of pancreatic disease are reactive pleural effusion and pneumonia, while rare complications include thoracic conditions, such as pancreaticopleural fistula with massive pleural effusion or hemothorax and extension of pseudocyst into the mediastinum. There have been no reports of acute mediastinitis originating from pancreatitis in South Korea. In this report, we present the case of a 50-year-old female suffering from acute mediastinitis with pleural effusion arising from recurrent pancreatitis that improved after surgical intervention. PMID:25356062

  4. Acute mediastinitis arising from pancreatic mediastinal fistula in recurrent pancreatitis

    PubMed Central

    Choe, In Soo; Kim, Yong Seok; Lee, Tae Hee; Kim, Sun Moon; Song, Kyung Ho; Koo, Hoon Sup; Park, Jung Ho; Pyo, Jin Sil; Kim, Ji Yeong; Choi, In Seok

    2014-01-01

    Acute mediastinitis is a fatal disease that usually originates from esophageal perforation and surgical infection. Rare cases of descending necrotizing mediastinitis can occur following oral cavity and pharynx infection or can be a complication of pancreatitis. The most common thoracic complications of pancreatic disease are reactive pleural effusion and pneumonia, while rare complications include thoracic conditions, such as pancreaticopleural fistula with massive pleural effusion or hemothorax and extension of pseudocyst into the mediastinum. There have been no reports of acute mediastinitis originating from pancreatitis in South Korea. In this report, we present the case of a 50-year-old female suffering from acute mediastinitis with pleural effusion arising from recurrent pancreatitis that improved after surgical intervention. PMID:25356062

  5. Primary Lymphoepithelioma-Like Carcinoma of the Prostate Gland: A Review of the Literature

    PubMed Central

    Venyo, Anthony Kodzo-Grey

    2016-01-01

    Background. Primary lymphoepithelioma-like carcinoma of the prostate gland (PLELCP) is rare with hardly any information on its diagnostic features and biological behaviour. Aim. To review the literature. Method. Various Internet data bases were searched. Literature Review. PLELCP is extremely rare and there are hardly any pictures of the tumour involving the prostate; hence it would appear that clinicians would need to use their knowledge of the microscopic and immunohistochemical characteristics of the tumour in the nasopharynx and urinary bladder as diagnostic aid. PLELCP on microscopy mimics nasopharyngeal LELC. The LELC component of the tumour is characterized by indistinct cytoplasmic borders and a syncytial growth pattern. The stroma may be densely infiltrated by lymphoid cells admixed with some plasma cells and neutrophils and at times prominent infiltration of eosinophils. PLELCPs tend to have adenocarcinoma, either as the only pattern or with additional ductal components or adenosquamous carcinoma. PLELCPs stain positively with PSA, PSAP, AMACR/P504S, EMA, and cytokeratins AE1/AE3, 7, 8, and 20. There is no consensus on treatment of PLECP. The reported prognosis has been poor. Conclusions. PLELCPs should be entered into a multicenter trial to determine the biological behaviour and to find the best treatment option that would improve the prognosis. PMID:26881187

  6. Heterogeneity and targeting of pancreatic cancer stem cells

    PubMed Central

    Penchev, Vesselin R.; Rasheed, Zeshaan A.; Maitra, Anirban; Matsui, William

    2012-01-01

    Cancer stem cells (CSCs) have been identified in an ever-increasing number of human malignancies based on the ability to recapitulate tumors in the ectopic setting and maintain long-term tumorigenic potential. In pancreatic adenocarcinoma, CSCs may also display additional properties, such as relative drug resistance and enhanced invasive and migratory potential that implicate a role in disease pathogenesis spanning initial tumor formation to metastatic disease progression. Importantly, these findings also suggest that the development of novel therapeutic strategies capable of inhibiting or eliminating CSCs will improve clinical outcomes. Preclinical studies have already described a wide array of potential targeting approaches that target CSC-specific surface antigens and cellular pathways involved in cell survival, adhesion, self-renewal and differentiation. Furthermore, progress in this area should continue to move forward as the unique biology of CSCs is better understood. All preclinical studies to date have focused on targeting specific and phenotypically defined CSCs, but multiple cell populations with the ability to form tumors and self-renew have been identified in pancreatic carcinoma. Since the clinical efficacy of CSC-directed therapies will depend on the inhibition of all sources of tumor self-renewal, better understanding how specific CSC populations are related to one another and whether each possesses specific functional properties will be critical. In this review, we will discuss the potential relationships between different pancreatic CSC populations and strategies to identify novel targeting approaches. PMID:22896694

  7. 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

  8. P62/Ubiquitin IHC Expression Correlated with Clinicopathologic Parameters and Outcome in Gastrointestinal Carcinomas

    PubMed Central

    Mohamed, Amr; Ayman, Alkhoder; Deniece, Johnson; Wang, Tengteng; Kovach, Charles; Siddiqui, Momin T.; Cohen, Cynthia

    2015-01-01

    P62 and ubiquitin are small regulatory proteins demonstrated to have implications in the prognosis and survival of various malignancies including: hepatocellular, breast, ovarian, and some gastrointestinal carcinomas. Several trials studied the link of their activity to the extrinsic apoptosis pathway and showed that their autophagy modification has a critical stand point in tumorigenesis. These findings explain their vital role in controlling the process of cell death and survival. It has been shown recently that p62 and ubiquitin overexpression in different types of cancers, such as triple negative breast and ovarian cancers, have directly correlated with incidence of distant metastases. We aim to evaluate p62/ubiquitin expression in gastrointestinal carcinomas of gastric, colonic, and pancreatic origin, and correlate with annotated clinicopathologic data. In gastric carcinoma (61), positive p62 nuclear expression was noted in 57% and cytoplasmic in 61%, while positive ubiquitin was nuclear expressed in 68.8%, and cytoplasmic in 29.5%. In colon carcinoma (45), positive p62 nuclear expression was noted in 29% and cytoplasmic in 71%, while positive ubiquitin was nuclear in 58% and cytoplasmic in 44%. In pancreatic cancer (18), positive p62 nuclear expression was noted in 78% and cytoplasmic in 56%, while positive ubiquitin was nuclear in 83% and cytoplasmic in 72%. Normal gastric (6), colon (4), and pancreatic (4) tissues were negative for both P62 and ubiquitin (nuclear and cytoplasmic staining <20%). Ubiquitin high expression was associated with more lymph node metastases in colon (4.14 vs 1.70, P?=?0.04), and pancreatic adenocarcinomas (3.07 vs 0.33, P?=?0.03). Also, ubiquitin high expression was associated with worse pancreatic adenocarcinoma overall survival (1.37 vs 2.26 mos, P?=?0.04). In addition, gastric cancer patients with high p62 expression tend to have more poorly differentiated grade when compared to those with low expression (21 vs 17, P?=?0.04) but less lymph node metastases (2.77 vs 5.73, P?=?0.01). P62 and ubiquitin expression did not correlate with other clinicopathologic parameters in gastric, colon or pancreatic denocarcinomas. The results suggest that p62 and ubiquitin are highly expressed in gastric, colonic, and pancreatic carcinomas. High ubiquitin expression was noted to have an impact on number of lymph node metastases in patients with colon and pancreatic adenocarcinomas, but on overall survival only in patients with pancreatic adenocarcinoma. Also, P62 high expression is correlated with poor differentiation, but less lymph node metastases, in gastric carcinoma. PMID:25870850

  9. P62/Ubiquitin IHC Expression Correlated with Clinicopathologic Parameters and Outcome in Gastrointestinal Carcinomas.

    PubMed

    Mohamed, Amr; Ayman, Alkhoder; Deniece, Johnson; Wang, Tengteng; Kovach, Charles; Siddiqui, Momin T; Cohen, Cynthia

    2015-01-01

    P62 and ubiquitin are small regulatory proteins demonstrated to have implications in the prognosis and survival of various malignancies including: hepatocellular, breast, ovarian, and some gastrointestinal carcinomas. Several trials studied the link of their activity to the extrinsic apoptosis pathway and showed that their autophagy modification has a critical stand point in tumorigenesis. These findings explain their vital role in controlling the process of cell death and survival. It has been shown recently that p62 and ubiquitin overexpression in different types of cancers, such as triple negative breast and ovarian cancers, have directly correlated with incidence of distant metastases. We aim to evaluate p62/ubiquitin expression in gastrointestinal carcinomas of gastric, colonic, and pancreatic origin, and correlate with annotated clinicopathologic data. In gastric carcinoma (61), positive p62 nuclear expression was noted in 57% and cytoplasmic in 61%, while positive ubiquitin was nuclear expressed in 68.8%, and cytoplasmic in 29.5%. In colon carcinoma (45), positive p62 nuclear expression was noted in 29% and cytoplasmic in 71%, while positive ubiquitin was nuclear in 58% and cytoplasmic in 44%. In pancreatic cancer (18), positive p62 nuclear expression was noted in 78% and cytoplasmic in 56%, while positive ubiquitin was nuclear in 83% and cytoplasmic in 72%. Normal gastric (6), colon (4), and pancreatic (4) tissues were negative for both P62 and ubiquitin (nuclear and cytoplasmic staining <20%). Ubiquitin high expression was associated with more lymph node metastases in colon (4.14 vs 1.70, P?=?0.04), and pancreatic adenocarcinomas (3.07 vs 0.33, P?=?0.03). Also, ubiquitin high expression was associated with worse pancreatic adenocarcinoma overall survival (1.37 vs 2.26 mos, P?=?0.04). In addition, gastric cancer patients with high p62 expression tend to have more poorly differentiated grade when compared to those with low expression (21 vs 17, P?=?0.04) but less lymph node metastases (2.77 vs 5.73, P?=?0.01). P62 and ubiquitin expression did not correlate with other clinicopathologic parameters in gastric, colon or pancreatic denocarcinomas. The results suggest that p62 and ubiquitin are highly expressed in gastric, colonic, and pancreatic carcinomas. High ubiquitin expression was noted to have an impact on number of lymph node metastases in patients with colon and pancreatic adenocarcinomas, but on overall survival only in patients with pancreatic adenocarcinoma. Also, P62 high expression is correlated with poor differentiation, but less lymph node metastases, in gastric carcinoma. PMID:25870850

  10. Vascular and ductal elastotic changes in pancreatic cancer.

    PubMed

    Lakiotaki, Eleftheria; Sakellariou, Stratigoula; Evangelou, Kostantinos; Liapis, George; Patsouris, Efstratios; Delladetsima, Ioanna

    2016-03-01

    This study aims to identify and define the type and frequency of elastotic alterations of vessels and ducts in pancreatic ductal carcinoma (PDAC) and evaluate its diagnostic significance. Representative tissue from 36 Whipple specimens, stained with Verhoeff's Van-Gieson, was studied focusing on the density and distribution of elastic fibers in walls of vessels and ducts, in perivascular and periductal tissue and in tumor stroma. Vessels and ducts within the carcinoma, at tumor periphery and in non-tumoral pancreas were grouped and examined separately. Vimentin and ?-SMA immunostains were used for the depiction of fibroblasts and myofibroblasts. Histochemistry revealed mild to severe elastotic changes of vessels and ducts in all examined cases. Vascular and ductal elastosis was more prominent within the tumor and diminished at tumor periphery. In tumor stroma and non-tumoral pancreatic tissue mild or no elastosis was identified. ?-SMA+ cells were observed in large numbers in tumor stroma and as a ring around carcinomatous structures. There were scant ?-SMA+ cells around elastotic and non-elastotic vessels. Conclusively, vascular and ductal elastosis is a tumor-associated phenomenon in PDAC. Its presence is indicative of benignity acquiring a possible diagnostic role. PMID:26619815

  11. Surgery for pancreatic cancer - discharge

    MedlinePLUS

    Claudius C, Lillemoe KD. Palliative Therapy for Pancreatic Cancer. In: Cameron JL, Cameron AM, eds. Current Surgical Therapy . 11th ed. Philadelphia, PA: Saunders Elsevier; 2014: 481-487. Jensen EH, Borja-Cacho D, ...

  12. 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.

  13. Overview of Exocrine Pancreatic Pathobiology

    PubMed Central

    Pandiri, Arun R

    2014-01-01

    Exocrine pancreas is a source of several enzymes that are essential for the digestive process. The exocrine pancreatic secretion is tightly regulated by the neuroendocrine system. The endocrine pancreas is tightly integrated anatomically and physiologically with the exocrine pancreas and modulates its function. Compound-induced pancreatitis is not a common event in toxicology or drug development but it becomes a significant liability when encountered. Understanding the species-specific differences in physiology is essential to understand the underlying pathobiology of pancreatic disease in animal models and its relevance to human disease. This review will mainly focus on understanding the morphology and physiology of the pancreas, unique islet-exocrine interactions, and pancreatitis. PMID:24190915

  14. Canagliflozin-Associated Acute Pancreatitis.

    PubMed

    Verma, Rajanshu

    2014-09-01

    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. PMID:25187092

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

    PubMed Central

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

    2014-01-01

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

  16. 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

  17. 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

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

    ClinicalTrials.gov

    2016-02-09

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

  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. Pancreaticoduodenectomy. Does it have a role in the palliation of pancreatic cancer?

    PubMed Central

    Lillemoe, K D; Cameron, J L; Yeo, C J; Sohn, T A; Nakeeb, A; Sauter, P K; Hruban, R H; Abrams, R A; Pitt, H A

    1996-01-01

    OBJECTIVE: The authors define the role of palliative pancreaticoduodenectomy in patients with pancreatic carcinoma. BACKGROUND: Decreases in perioperative morbidity and mortality and improved long-term survival associated with pancreaticoduodenectomy for patients with pancreatic carcinoma have clearly established a role for this operation when performed with curative intent. However, most surgeons remain hesitant to perform pancreaticoduodenectomy unless surgical margins are widely clear, choosing rather to perform palliative biliary and gastric bypass. METHODS: A single-institution retrospective review was performed comparing the outcome of 64 consecutive patients undergoing pancreaticoduodenectomy for pancreatic carcinoma with gross or microscopic evidence of adenocarcinoma at the surgical resection margins, and 62 consecutive patients found to be unresectable at the time of laparotomy because of local invasion without evidence of metastatic disease (stage III). Combined biliary and gastric bypass were performed in 87% of patients not resected. RESULTS: The two groups were similar with respect to age, gender, race, and presenting symptoms. The hospital mortality rate was identical in both groups (1.6%). Fifty-eight percent of patients undergoing pancreaticoduodenectomy had an uncomplicated postoperative course compared with 68% of patients undergoing palliative bypass (not significant). The length of postoperative hospital stay after pancreaticoduodenectomy was 18.4 days, which was significantly longer (p < 0.05) than for patients undergoing palliative bypass (15.0 days). The overall actuarial survival (Kaplan-Meier) was improved significantly in patients undergoing pancreaticoduodenectomy (p < 0.02). Postoperative chemotherapy and radiation therapy improved survival in both groups. CONCLUSIONS: Pancreaticoduodenectomy can be performed with a similar perioperative morbidity and mortality and only a minimal increase in hospital stay when compared with traditional surgical palliation. Pancreaticoduodenectomy with postoperative chemotherapy and radiation therapy is associated with improved long-term survival when compared with patients treated with surgical bypass. These data support the role of palliative pancreaticoduodenectomy in patients with pancreatic carcinoma and with local residual disease. PMID:8645045

  1. Pancreatic cancer stem cells

    PubMed Central

    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. PMID:26045976

  2. Pancreatic cancer: Advances in treatment

    PubMed Central

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

    2014-01-01

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

  3. Pancreatic Cancer, Inflammation and Microbiome

    PubMed Central

    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 for pancreatic cancer development. Yet only in the past two 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 into 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 in order to both prevent and treat pancreatic cancer more efficiently. Further studies towards this direction are urgently needed. PMID:24855007

  4. [Surgical management of pancreatic cancer].

    PubMed

    Kim, Song Cheol

    2008-02-01

    Pancreatic cancer is a major problematic concern among all forms of gastrointestinal malignancies because of its poor prognosis. Although significant progress has been made in the surgical treatment in terms of increased resection rate and decreased treatment-related morbidity and mortality, the true survival rate still remains below 5% today. Surgical options for pancreatic cancer are based on the its unique anatomy and physiology, catastrophic tumor biology, experience of surgeon, and status of patients. Four main options exist for the surgical treatment of pancreatic cancer. These include standard "Whipple" pancreaticoduodenectomy (PD), pylorus preserving PD (PPPD), distal pancreatectomy (left-side pancreatectomy), and total pancreatectomy according to the location of tumor. Portal vein involvement by tumor is regarded as an anatomical extension of disease, and en bloc resection of portal vein with tumor is recommended if technically feasible, which is stated in 2002 AJCC tumor staging for pancreatic cancer. In comparison of the survival rates between standard and extended resection of pancreatic head cancer, no significant survival benefit was demonstrated from the prospective reports. PPPD may be superior to standard PD in respect to nutrition and quality of life without any deleterious effect upon long term survival or tumor recurrence. New surgical treatment modalities including modified extended pancreatectomy, neoadjuvant chemotherapy, and radical antegrade modular distal pancreatectomy have been tried to improve the patients' survival. However, early diagnosis and treatment remain as key factors for the cure of pancreatic cancer irrespective of various surgical trials. PMID:18349571

  5. Oncolytic virotherapy for pancreatic cancer

    PubMed Central

    Wennier, Sonia; Li, Shoudong; McFadden, Grant

    2011-01-01

    Within the past decade, many oncolytic viruses (OVs) have been studied as potential treatments for pancreatic cancer and some of these are currently under clinical trials. The applicability of certain OVs, such as adenoviruses, herpesviruses and reoviruses, for the treatment of pancreatic cancer has been intensively studied for several years, whereas the applicability of other more recently investigated OVs, such as poxviruses and parvoviruses, is only starting to be determined. At the same time, studies have identified key characteristics of pancreatic cancer biology that provide a better understanding of the important factors or pathways involved in this disease. This review aims to summarise the different replication-competent OVs proposed as therapeutics for pancreatic cancer. It also focuses on the unique biology of these viruses that makes them exciting candidate virotherapies for pancreatic cancer and discusses how they could be genetically manipulated or combined with other drugs to improve their efficacy based on what is currently known about the molecular biology of pancreatic cancer. PMID:21676289

  6. Canine inflammatory mammary carcinoma: histopathology, immunohistochemistry and clinical implications of 21 cases.

    PubMed

    Pea, Laura; Perez-Alenza, M Dolores; Rodriguez-Bertos, Antonio; Nieto, Ana

    2003-03-01

    Human inflammatory breast carcinoma (IBC) is the most malignant type of breast cancer with an extremely poor prognosis. The dog is the unique animal species in which spontaneous inflammatory mammary carcinoma (IC) has been reported, although it is not well documented. The purpose of this study was to characterize histopathologically and immunohistochemically the canine IC, considering associated clinical features. Twenty-one dogs diagnosed with IC and with known clinical and necropsy data were included in the study. Tissue samples from necropsies underwent a histopathological review and an immunohistochemical study (Ki-67, estrogen receptor (ER), progesterone receptor (PR), and P53 tumor suppressor protein). The histological study revealed several types of carcinomas (solid, tubular, papillary, and adenosquamous) and three lipid-rich carcinomas. All tumors were ER negative. Two histological patterns of neoplastic dermal infiltration were observed: tubular/papillary and sarcomatous-like. Dermal sarcomatous-like infiltration was significantly related to previous treatments with progestagens (p = 0.006), primary type of IC (p = 0.03), extreme local pain (p = 0.02), reduced observation of emboli in dermal lymphatic vessels (p = 0.01), and increased expression of p53 (p = 0.001). PR expression was significantly higher in secondary post-surgical IC (p = 0.04). The absence of PR was related to the existence of pulmonary metastases at necropsy (p = 0.04). Canine primary IC is the most aggressive form of this disease with distinct histopathological and immunohistochemical characteristics. Progestins and endocrine-related mechanisms seem to be involved in canine IC development. Canine IC could serve as a spontaneous model for human IBC, particularly in studies concerned with new therapeutics approaches. PMID:12725414

  7. [Malignant pancreatic non-hodgkin's lymphoma manifesting as severe acute pancreatitis].

    PubMed

    Mofredj, A; Cadranel, J F; Cazier, A; Traor, I; Coutarel, P; Levy, P

    1999-04-01

    Primary non-Hodgkin's lymphoma of the pancreas is a rare disease. Its diagnosis is difficult without histological examination. In fact, clinical and imaging findings are not pathognomonic. Acute pancreatitis associated with pancreatic lymphoma is extremely rare. We have found only 7 case reports in literature. We report herein a new case of pancreatic lymphoma which was revealed by a severe pancreatitis. PMID:10416118

  8. Efficacy of minimally invasive therapies on unresectable pancreatic cancer.

    PubMed

    Huang, Zhi-Mei; Pan, Chang-Chuan; Wu, Pei-Hong; Zhao, Ming; Li, Wang; Huang, Zi-Lin; Yi, Rui-Yang

    2013-06-01

    For patients with unresectable pancreatic cancer, current chemotherapies have negligible survival benefits. Thus, developing effective minimally invasive therapies is currently underway. This study was conducted to evaluate the efficacy of transarterial chemoembolization plus radiofrequency ablation and/or 125I radioactive seed implantation on unresectable pancreatic cancer. We analyzed the outcome of 71 patients with unresectable pancreatic carcinoma who underwent chemoembolization plus radiofrequency ablation and/or radioactive seed implantation. Of the 71 patients, the median survival was 11 months, and the 1-, 2-, and 3-year overall survival rates were 32.4%, 9.9%, and 6.6%, respectively. Patients who had no metastasis, who had oligonodular liver metastases (?3 lesions), and who had multinodular liver metastases (>3 lesions) had median survival of 12, 18, and 8 months, respectively, and 1-year overall survival rates of 50.0%, 68.8%, and 5.7%, respectively. Although the survival of patients without liver metastases was worse than that of patients with oligonodular liver metastasis, the result was not significant (P = 0.239). In contrast, the metastasis-negative patients had significantly better survival than did patients with multinodular liver metastases (P < 0.001). Patients with oligonodular liver lesions had a significant longer median survival than did patients with multinodular lesions (P < 0.001). In conclusion, combined minimally invasive therapies had good efficacy on unresectable pancreatic cancer and resulted in a good control of liver metastases. In addition, the number of liver metastases was a significant factor in predicting prognosis and response to treatment. PMID:22958741

  9. Somatostatin prevents acute pancreatitis after pancreatic duct sphincter hydrostatic balloon dilation in patients with idiopathic recurrent pancreatitis.

    PubMed

    Guelrud, M; Mendoza, S; Viera, L; Gelrud, D

    1991-01-01

    The purpose of this study was to determine whether prophylactic somatostatin infusion can prevent pancreatitis after hydrostatic balloon dilation of the pancreatic duct sphincter segment in 16 patients with idiopathic recurrent pancreatitis. This study demonstrated that prophylactic administration of somatostatin before, during, and after the procedure diminished the incidence and severity of acute pancreatitis. We recommend consideration of such prophylaxis in patients undergoing this procedure. PMID:1672278

  10. [Double sphincterostomy of pancreatic and choledochal sphincters in the treatment of chronic recurrent pancreatitis].

    PubMed

    Guelrud, M; Mendoza, S; Plaz, J; Mujica, V

    1991-01-01

    The treatment of recurrent chronic pancreatitis is controversial. Some patients may have sphincter of Oddi motor abnormalities. Although widely used in the biliary tree, little data is available on endoscopic sphincterotomy of the pancreatic sphincter. This report describes 5 patients with recurrent chronic pancreatitis, who had pancreatic sphincterotomy for hypertensive sphincter of Oddi. Four patients continue long-term follow-up with marked reduction of chronic pain of attacks of recurrent pancreatitis. It is concluded that endoscopic sphincterotomy of the pancreatic sphincter may improve pain in chronic pancreatitis and may obviate the need for surgery. PMID:1688212

  11. Loss of Periostin Results in Impaired Regeneration and Pancreatic Atrophy after Cerulein-Induced Pancreatitis.

    PubMed

    Hausmann, Simone; Regel, Ivonne; Steiger, Katja; Wagner, Nadine; Thorwirth, Manja; Schlitter, Anna M; Esposito, Irene; Michalski, Christoph W; Friess, Helmut; Kleeff, Jrg; Erkan, Mert

    2016-01-01

    The extracellular matrix molecule periostin (POSTN, encoded by POSTN), which is secreted by activated pancreatic stellate cells, has important functions in chronic pancreatitis and pancreatic cancer. However, the role of POSTN in acute pancreatitis and subsequent regeneration processes has not been addressed so far. We analyzed the function of POSTN in pancreatic exocrine regeneration after the induction of a severe acute pancreatitis. Postn-deficient mice and wild-type control animals received repetitive cerulein injections, and a detailed histologic analysis of pancreatic tissues was performed. Although there was no difference in pancreatitis severity in the acute inflammatory phase, the recovery of the exocrine pancreas was massively impaired in Postn-deficient mice. Loss of Postn expression was accompanied by strong pancreatic atrophy and acinar-to-adipocyte differentiation, which was also reflected in gene expression patterns. Our data suggest that POSTN is a crucial factor for proper exocrine lineage-specific regeneration after severe acute pancreatitis. PMID:26632158

  12. Lipolysis of visceral adipocyte triglyceride by pancreatic lipases converts mild acute pancreatitis to severe pancreatitis independent of necrosis and inflammation.

    PubMed

    Patel, Krutika; Trivedi, Ram N; Durgampudi, Chandra; Noel, Pawan; Cline, Rachel A; DeLany, James P; Navina, Sarah; Singh, Vijay P

    2015-03-01

    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

  13. Application of Neural Networks to the Classification of Pancreatic Intraductal Proliferative Lesions

    PubMed Central

    Oko?, Krzysztof; Tomaszewska, Romana; Nowak, Krystyna; Stachura, Jerzy

    2001-01-01

    The aim of the study was to test applycability of neural networks to classification of pancreatic intraductal proliferative lesions basing on nuclear features, especially chromatin texture. Material for the study was obtained from patients operated on for pancreatic cancer, chronic pancreatitis and other tumours requiring pancreatic resection. Intraductal lesions were classified as low and high grade as previously described. The image analysis system consisted of a microscope, CCD camera combined with a PC and AnalySIS v. 2.11 software. The following texture characteristics were measured: variance of grey levels, features extracted from the grey levels correlation matrix and mean values, variance and standard deviation of the energy obtained from Laws matrices. Furthermore we used moments derived invariants and basic geometric data such as surface area, the minimum and maximum diameter and shape factor. The sets of data were randomly divided into training and testing groups. The training of the network using the back?propagation algorithm, and the final classification of data was carried out with a neural network simulator SNNS v. 4.1. We studied the efficacy of networks containing from one to three hidden layers. Using the best network, containing three hidden layers, the rate of correct classification of nuclei was 73%, and the rate of misdiagnosis was 3%; in 24% the network response was ambiguous. The present findings may serve as a starting point in search for methods facilitating early diagnosis of ductal pancreatic carcinoma. PMID:12082293

  14. Intraductal papillary mucinous neoplasm involving pancreaticobiliary maljunction and an aberrant pancreatic duct draining into the stomach: A case report and review of the literature.

    PubMed

    Kinowaki, Yuko; Takazawa, Yutaka; Yamamoto, Noriko; Ishikawa, Yuichi

    2016-02-01

    Intraductal papillary mucinous neoplasms (IPMN) are characterized by the growth of epithelial components with mucin production in the main pancreatic duct, or a large branch. We report a case of intraductal papillary mucinous carcinoma (IPMC) of the pancreatic head, complicated by pancreaticobiliary maljunction (PBM) and an aberrant pancreatic duct draining into the stomach. A 50-year-old man with malaise and jaundice was found to have a mass in the pancreatic head at a local hospital. He was clinically diagnosed with IPMC with invasion to the stomach and duodenum after extensive endoscopic and radiological evaluation and a pancreaticoduodenectomy was performed. Histologically, most of the lesion exhibited proliferation of atypical glands, with irregular papillary and villoglandular structures lined by mucinous columnar epithelium, which extended intraepithelially along the dilated pancreatic duct wall. Tumor cells spread into the duodenal wall formed mucous nodules. The pancreatic ducts of this lesion uniquely showed two malformations; PBM, and an aberrant pancreatic duct opening to the gastric wall. This case was rare in the sense that IPMC extended into such unique structures. We report a case of IPMC with rare localization. The pathogenesis of this type of tumor in an abnormal pancreatic duct will be discussed. PMID:26611763

  15. ROLE OF PANCREATIC FAT IN THE OUTCOMES OF PANCREATITIS

    PubMed Central

    Acharya, Chathur; Navina, Sarah; Singh, Vijay P.

    2014-01-01

    The role of obesity in relation to various disease processes is being increasingly studied, with reports over the last several years increasingly mentioning its association with worse outcomes in acute disease. Obesity has also gained recognition as a risk factor for severe acute pancreatitis (SAP) [18]. The mortality in SAP may be as high as 30% and is usually attributable to multi system organ failure (MSOF) earlier in the disease, and complications of necrotizing pancreatitis later [911]. To date there is no specific treatment for acute pancreatitis (AP) and the management is largely expectant and supportive. Obesity in general has also been associated with poor outcomes in sepsis and other pathological states including trauma and burns [1214]. With the role of unsaturated fatty acids (UFA) as propagators in SAP having recently come to light [15] and with the recognition of acute lipotoxicity, there is now an opportunity to explore different strategies to reduce the mortality and morbidity in SAP and potentially other disease states associated with such a pathophysiology. In this review we will discuss the role of fat and implications of the consequent acute lipotoxicity on the outcomes of acute pancreatitis in lean and obese states and during acute on chronic pancreatitis. PMID:25278311

  16. Concurrent acute pancreatitis and pericardial effusion

    PubMed Central

    Kayar, Yusuf; Turkdogan, Kenan Ahmet; Baysal, Birol; Gultekin, Nigar; Danalioglu, Ahmet; Ince, Ali Tuzun; Senturk, Hakan

    2015-01-01

    While pleural effusion and ascites secondary to acute pancreatitis are common, clinically relevant pericardial effusion and cardiac tamponade are observed rarely. In a study by Pezzilli et al., pleural effusion was noted in 7 of the 21 patients with acute pancreatitis whereas the authors detected pericardial effusion development in only three. The authors asserted that pleural effusion was associated with severe acute pancreatitis, while pericardial effusion and the severity of acute pancreatitis were not significantly related. PMID:26327959

  17. Lysates of S. pyogenes serotype M49 induce pancreatic tumor growth delay by specific and unspecific antitumor immune responses.

    PubMed

    Linnebacher, Michael; Maletzki, Claudia; Emmrich, Jrg; Kreikemeyer, Bernd

    2008-10-01

    Treatment of pancreatic cancer by active unspecific bacterial immunotherapy is a promising new strategy. Recently, we showed that a single intratumoral injection of wildtype Streptococcus pyogenes M49 results in complete regression of pancreatic carcinoma in mice mediated both by unspecific cytotoxicity and by specific immune reactions against tumor cells. As for potential clinical use, conditioning and especially inactivation of bacteria would abolish the risk of systemic bacterial infections; we here explored the potential of a streptococcal lysate prepared by bacteriophage lysine to affect pancreatic carcinoma growth in vivo. Application of the lysate into established Panc02 tumors resulted in pronounced growth cessation accompanied by raises in levels of circulating monocytes, granulocytes, and natural killer cells. Detailed analysis of splenocyte subsets revealed lysate-induced transient increases in pre-B cells followed by raised levels of activated T cells. Moreover, blood levels of proinflammatory, T helper-1-type cytokines were significantly elevated. These systemic immunologic effects were accompanied by massive infiltrations of cytotoxic T cells into the tumors. Concomitantly, lymphocytes obtained from treated mice specifically recognized Panc02 tumor cells in IFN-gamma-enzyme-linked immunosorbent spot and in cellular cytotoxicity assays. In rechallenge experiments, these immunologic effector cells were found to delay, but not completely prevent growth of secondary tumors. However, when considering the notoriously depressed immune status of individuals suffering from pancreatic carcinoma, the orchestrated antitumoral immune responses we analyzed here in detail significantly strengthen the potential usefulness of microbial compounds as active unspecific immunotherapeutic agent for treatment of pancreatic carcinoma. PMID:18779749

  18. 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

  19. Stress kinase inhibition modulates acute experimental pancreatitis

    PubMed Central

    Fleischer, F.; Dabew, R.; ke, B. G; Wagner, ACC

    2001-01-01

    AIM: To examine the role of p38 during acute experimental cerulein pancreatitis. METHODS: Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347) and/or a specific p38 inhbitor (SB203580) and pancreatic stress kinase activity was determined. Parameters to assess pancreatitis included trypsin, amylase, lipase, pancreatic weight and histology. RESULTS: JNK inhibition with CEP1347 ameliorated pancreatitis, reducing pancreatic edema. In contrast, p38 inhibition with SB203580 aggravated pancreatitis with higher trypsin levels and, with induction of acinar necrosis not normally found after cerulein hyperstimulation. Simultaneous treatment with both CEP1347 and SB203580 mutually abolished the effects of either compound on cerulein pancreatitis. CONCLUSION: Stress kinases modulate pancreatitis differentially. JNK seems to promote pancreatitis development, possibly by supporting inflammatory reactions such as edema formation while its inhibition ameliorates pancreatitis. In contrast, p38 may help reduce organ destruction while inhibition of p38 during induction of cerulein pancreatitis leads to the occurrence of acinar necrosis. PMID:11819771

  20. Blunt pancreatic trauma: A persistent diagnostic conundrum?

    PubMed

    Kumar, Atin; Panda, Ananya; Gamanagatti, Shivanand

    2016-02-28

    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

  1. Diagnosis and treatment of pancreatic exocrine insufficiency

    PubMed Central

    Lindkvist, Bjrn

    2013-01-01

    Pancreatic exocrine insufficiency is an important cause of maldigestion and a major complication in chronic pancreatitis. Normal digestion requires adequate stimulation of pancreatic secretion, sufficient production of digestive enzymes by pancreatic acinar cells, a pancreatic duct system without significant outflow obstruction and adequate mixing of the pancreatic juice with ingested food. Failure in any of these steps may result in pancreatic exocrine insufficiency, which leads to steatorrhea, weight loss and malnutrition-related complications, such as osteoporosis. Methods evaluating digestion, such as fecal fat quantification and the 13C-mixed triglycerides test, are the most accurate tests for pancreatic exocrine insufficiency, but the probability of the diagnosis can also be estimated based on symptoms, signs of malnutrition in blood tests, fecal elastase 1 levels and signs of morphologically severe chronic pancreatitis on imaging. Treatment for pancreatic exocrine insufficiency includes support to stop smoking and alcohol consumption, dietary consultation, enzyme replacement therapy and a structured follow-up of nutritional status and the effect of treatment. Pancreatic enzyme replacement therapy is administered in the form of enteric-coated minimicrospheres during meals. The dose should be in proportion to the fat content of the meal, usually 40-50000 lipase units per main meal, and half the dose is required for a snack. In cases that do not respond to initial treatment, the doses can be doubled, and proton inhibitors can be added to the treatment. This review focuses on current concepts of the diagnosis and treatment of pancreatic exocrine insufficiency. PMID:24259956

  2. Low E-cadherin and beta-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas.

    PubMed

    Akimoto, T; Kawabe, S; Grothey, A; Milas, L

    1999-03-01

    This study examined the relationship between the expression of E-cadherin or beta-catenin in murine adenocarcinomas and their hematogenous metastatic propensity, assessed by both spontaneous and artificial lung metastasis. Seven different carcinomas, syngeneic to C3Hf/Kam mice were used: 4 mammary carcinomas (MCa-4, MCa-29, MCa-35, and MCa-K), ovarian carcinoma OCa-I, hepatocarcinoma HCa-I, and adenosquamous carcinoma ACa-SG. These tumors vary widely in their ability to spontaneously metastasize to the lung (from 0 to 100% metastatic incidence), and their cells greatly differ in their ability to form artificial lung nodules when injected i.v. Primary tumors in the leg were assessed for E-cadherin and beta-catenin expression by western blotting. The expression of both proteins showed wide variation among the tumors; however, the expression of E-cadherin correlated well with that of beta-catenin. There was significant inverse correlation between the expression of E-cadherin, as well as beta-catenin, and the incidence of both spontaneous and artificial lung metastases from these tumors. Spontaneous metastases of highly metastatic HCa-I and moderately metastatic MCa-35 were significantly lower in E-cadherin and beta-catenin expression than their corresponding primary tumors were. Thus, the propensity of murine carcinomas for hematogenous spread is highly related to E-cadherin and beta-catenin levels in primary tumors. The inverse correlation between the expression of these molecules and spontaneous and artificial metastases implies that tumor cells with low E-cadherin and beta-catenin content have increased ability to enter the vascular circulation at the primary tumor site and to colonize distant tissues. PMID:10411110

  3. Podocalyxin-like protein 1 expression is useful to differentiate pancreatic ductal adenocarcinomas from adenocarcinomas of the biliary and gastrointestinal tracts.

    PubMed

    Ney, Jasmin Teresa; Zhou, Hui; Sipos, Bence; Bttner, Reinhard; Chen, Xin; Klppel, Gnter; Gtgemann, Ines

    2007-02-01

    Metastases of adenocarcinomas from the pancreas, liver, and gastrointestinal tract are difficult to distinguish from each other because of their similar morphological and immunohistochemical features. So far, no specific marker for pancreatic ductal adenocarcinomas has been described. Podocalyxin-like protein 1 (PODXL-1) is expressed on vascular endothelium, hematopoietic precursor cells, and renal podocytes. We found that 44% (71/160) of pancreatic ductal adenocarcinomas expressed PODXL-1 in a membranous pattern. There was no expression in intrahepatic cholangiocarcinomas (0/18, P < .001), rarely in adenocarcinomas of the extrahepatic bile ducts (1/13, P = .009), and none in duodenal adenocarcinomas (0/5, P = .070). PODXL-1 expression was seen in only 9% of hepatocellular carcinomas (5/56, P < .001), 9% (4/47, P < .001) of gastric carcinomas, 10% of esophageal adenocarcinomas (2/20, P = .003), and 6% of colonic adenocarcinomas (1/17, P = .001). When used as a differential diagnostic marker, ampullary carcinoma needs to be excluded, as 30% (6/20, P = .24) of ampullary carcinomas stain positive, especially those of the signet-ring type (3/3). Adenocarcinomas of the lung and prostate, and liver metastases of colorectal carcinomas lacked PODXL-1 expression. It is concluded that immunoreactivity for PODXL-1 favors a pancreatic origin if ampullary carcinoma is excluded. PMID:17137615

  4. Clear cell carcinoma of exocrine pancreas: a rare tumor with an unusual presentation.

    PubMed

    Ray, Biswajit; New, Norman E; Wedgwood, Kevin R

    2005-03-01

    Metastatic clear cell carcinomas are relatively common from primary tumors arising in the kidney, female genital tract, adrenal cortex, and lung, but they rarely occur from primary tumors of the pancreas. We report a case of metastatic pancreatic tumor with marked clear cell changes in a 46-year-old white man presenting with a pseudocyst of the pancreas. At laparotomy, there was a hard area in the head of the pancreas and another hard nodule was present in the omentum. The histologic and immunohistochemical test of the excised omental nodule exhibited features consistent with clear cell carcinoma from pancreatic primary. To our knowledge, this is the first report of a metastatic clear cell pancreatic tumor with such an unusual presentation. PMID:15714142

  5. A Case of Tumor Lysis Syndrome in a Patient with Pancreatic Adenocarcinoma Treated with Low-Dose Gemcitabine

    PubMed Central

    Brinton, Taylor; Yousuf, Tariq; Steinecker, Gary; Rydel, James

    2015-01-01

    Background Tumor lysis syndrome (TLS) is a common adverse consequence of treatment of high-grade hematologic malignancies that has been known to occur rarely in some solid tumors, including small cell lung cancer, breast cancer, colorectal cancer, neuroblastoma, ovarian cancer, and hepatocellular carcinoma. Case Report We present a case of TLS in a patient with pancreatic adenocarcinoma treated with one small dose of gemcitabine. To our knowledge, this phenomenon has only been described once prior in the medical literature and never with a reduced dose of chemotherapy. Conclusion This case reveals the need for heightened awareness of TLS in patients with solid tumors, especially in patients with pancreatic adenocarcinoma.

  6. 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

  7. Pharmacologic therapy for acute pancreatitis

    PubMed Central

    Kambhampati, Swetha; Park, Walter; Habtezion, Aida

    2014-01-01

    While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

  8. 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.

  9. 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. PMID:26081808

  10. Innovative treatments for pancreatic cancer.

    PubMed

    Lieberman, S M; Hrig, H; Kaufman, H L

    2001-06-01

    Pancreatic cancer is the fifth leading cause of cancer deaths in the United States with little or no impact from conventional treatment options. Significant advances in understanding basic immunology have renewed interest in using immunotherapy to treat pancreatic cancer. Cancer immunotherapy, including humanized MAbs, cytokines, and potent vaccine strategies, has been successful in animal models and is being evaluated in clinical trials. Gene therapy is also being explored using methods to inactivate oncogenes, replace defective tumor suppressor genes, confer enhanced chemosensitivity to tumor cells, and increase immunogenicity of tumor cells. Angiogenesis, an essential step in the growth and metastasis of pancreatic cancer, has been targeted by many antiangiogenic agents. Several clinical trials have been initiated to evaluate the role of these innovative strategies in patients with pancreatic cancer with increasingly sophisticated correlative studies to learn more about the mechanisms of tumor rejection with these agents. The rapid translation of basic science discoveries to clinical trials should result in the development of new effective treatments for patients with pancreatic cancer. PMID:11459285

  11. Cystic Lesions in Autoimmune Pancreatitis

    PubMed Central

    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. PMID:26675058

  12. Basal Cell Carcinoma (BCC)

    MedlinePLUS

    ... carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive than other types of basal ... to treat them early and with slightly more aggressive techniques. Excision – The basal cell carcinoma is cut ...

  13. Medullary carcinoma of thyroid

    MedlinePLUS

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

  14. Nasopharyngeal carcinoma.

    PubMed

    Kamran, Sophia C; Riaz, Nadeem; Lee, Nancy

    2015-07-01

    Nasopharyngeal carcinoma is uncommon in the United States, with only 0.2 to 0.5 cases per 100,00 people; this is in contrast to southern China and Hong Kong, where the incidence is 25 to 50 per 100,000 people. There is a potential link between Epstein-Barr virus and the development of nasopharyngeal carcinoma. Radiotherapy alone as a single modality leads to similar 10-year survival rates in United States, Denmark, and Hong Kong (34%, 37%, and 43%, respectively). Multiple studies have shown an advantage to concurrent chemoradiation in the treatment of advanced disease. Radiation therapy remains the mainstay of salvage therapy, and modern techniques have allowed clinicians to achieve adequate local control without excessive toxicity. PMID:25979399

  15. 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

  16. [Urothelial carcinoma].

    PubMed

    Rbben, H; Vom Dorp, F

    2011-09-01

    Various study groups are working on the WHO classification of 2004 which eliminates the previous grades of differentiation G1, G2, and G3 and classifies non-muscle-invasive bladder cancer into genetically stable low-grade and genetically unstable high-grade urothelial carcinomas. In muscle-invasive bladder cancer, extended lymph node dissection as part of radical cystectomy should remain the standard procedure for now. PMID:21837494

  17. Shock and terminal pancreatitis.

    PubMed

    Becker, V; Stollhoff, K

    1985-03-01

    63% of 523 lethal cases of shock showed a DIC-syndrome. First of all the lung was affected with 69% of the cases with DIC-syndrome, followed by the pancreas with 52%. In search of disseminated intravascular coagulation, the pancreas is a very favourable organ since other acute superimposed findings normally don't exist. 18% of the cases with DIC-syndrome showed in addition to the DIC-syndrome a terminal pancreatitis resp. a tryptic necrosis. The pathogenesis of the tryptic necrosis can be explained by a decrease of blood supply in shock, which makes autodigestion possible. The tryptic necrosis differs from the hypoxic necrosis phenomenologically. The hypoxia as pathogenetic principle (Franz Bchner) causes the tryptic necrosis in an indirect way: it provides the conditions for autodigestion. This study aims to encourage to examine the pancreas of lethal cases of shock more regularly since this examination is an enrichment as well for the anatomic diagnosis of shock as for the comprehension of the pancreas. PMID:4001028

  18. Pancreatic pleomorphic rhabdomyosarcoma

    PubMed Central

    Shirafkan MD, Ali; Boroumand MD, Nahal; Komak MD, Spogmai; Duchini MD, Andrea; Cicalese MD, Luca

    2015-01-01

    Introduction Rhabdomyosarcoma (RMS) is a primary malignancy that arises from the embryonic mesenchyme with the potential to differentiate into skeletal muscle. RMS of the biliary tree is extremely rare. We report a case of an undifferentiated pleomorphic RMS involving the liver and pancreas. Presentation of case A 62 year old Caucasian woman with rapidly growing abdominal mass and a history of endometrial adenocarcinoma underwent laparotomy due to compression symptoms and concerns of malignancy. A large mass arising from the pancreas and extending into the liver was identified and resected with a distal pancreatectomy associated with a left lateral liver segmentectomy. A diagnosis of pleomorphic RMS was made from the pathology specimen. Chemotherapy and radiotherapy were also performed. Unfortunately the patient died 2 years following treatment due to recurrence of the disease. Discussion P-RMS in the biliary tree is extremely rare (0.5%) and mostly seen in infants and children. Preoperative diagnosis is challenging since the symptoms are unspecific. Preoperative imaging rarely contributes to the final diagnosis. The only possible treatment for adult RMS is surgical resection of the tumor followed by chemotherapy and radiotherapy. Long-term prognosis of P-RMS reported (predominantly of limbs) is poor. To our knowledge, no previous cases of RMS originating from the pancreas have been reported. Conclusion However RMS is an extremely rare tumor in adults, it should be included in the differential diagnosis of patients with atypical pancreatic and liver lesions. PMID:26092712

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

  20. Hepatocellular carcinoma.

    PubMed

    Hussain, S A; Ferry, D R; El-Gazzaz, G; Mirza, D F; James, N D; McMaster, P; Kerr, D J

    2001-02-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer of men and eleventh most common cancer of women world-wide. However, because almost every individual who develops liver cancer dies of the disease, HCC is the third most common cause of the cancer deaths in men and seventh most common in women. The treatment of choice for hepatocellular carcinoma remains surgical resection or liver transplantation, in carefully selected cases. In patients with hepatocellular carcinoma not amenable to surgical intervention a variety of different therapeutic interventions have been investigated. These include direct ablation of the tumour using agents such as ethanol or acetic acid, transcatheter arterial chemoembolization, or systemic chemotherapy. The evaluation of their efficacy is compromised by the paucity of adequately powered randomised clinical trials. The main challenge facing the research community over the next decade is to prioritise the most promising treatments and take these forward into multicentre controlled trials. Even if these fail to improve results, they will help reduce the variation in clinical practice by eliminating anecdotal treatment. PMID:11300318

  1. Pancreas-preserving biliary amputation with pancreatic diversion: a new surgical technique for complete resection of the intrapancreatic biliary system.

    PubMed

    Kondo, Satoshi; Hirano, Satoshi; Ambo, Yoshiyasu; Tanaka, Eiichi; Morikawa, Toshiaki; Okushiba, Shunichi; Katoh, Hiroyuki

    2004-01-01

    Pancreatoduodenectomy is not optimal for organ preservation in patients with mucosal carcinoma of the choledochus. When the lesion spreads near the papilla of Vater, pancreas-preserving biliary amputation may be indicated to achieve complete resection of the biliary system. The first successful case is reported here with technical considerations. First, the pancreatic neck was divided and a tube was inserted into the main pancreatic duct beyond the papilla. The choledochus was dissected downward with division of the posterior pancreatoduodenal vessels. The main pancreatic duct was isolated with the aid of palpation of the tube, and was then ligated and divided. Subsequent dissection was performed to the level of the duodenal mucosa, which was incised circularly. The duodenal defect was then closed. The elevated jejunum was interposed between the pancreatic stumps and bilateral pancreaticojejunostomies were created. The procedure was successfully performed in a patient with superficially spreading cholangiocarcinoma. Postoperative bile leak and pancreatic fistula were controlled with medical management. The patient is currently well without tumor recurrence 19 months after surgery. Her glucose tolerance, which was moderately impaired preoperatively, has been maintained. Pancreas-preserving biliary amputation has been developed as an organ-preserving procedure alternative to pancreatoduodenectomy. Indications, methods of pancreatic reconstruction, and long-term results require further study. PMID:15362726

  2. Metabolism addiction in pancreatic cancer.

    PubMed

    Blum, R; Kloog, Y

    2014-01-01

    Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains largely elusive. Renewed research interest in longstanding doctrines of tumor metabolism has led to the emergence of aberrant signaling pathways as critical factors modulating central metabolic networks that fuel pancreatic tumors. Such pathways, including those of Ras signaling, glutamine-regulatory enzymes, lipid metabolism and autophagy, are directly affected by genetic mutations and extreme tumor microenvironments that typify pancreatic tumor cells. Elucidation of these metabolic networks can be expected to yield more potent therapies against this deadly disease. PMID:24556680

  3. Pancreatic pathophysiology in cystic fibrosis.

    PubMed

    Gibson-Corley, Katherine N; Meyerholz, David K; Engelhardt, John F

    2016-01-01

    The pancreas is one of the earliest, and most commonly affected, organs in patients with cystic fibrosis (CF). Studying the pathogenesis of pancreatic disease is limited in CF patients, due to its early clinical onset, co-morbidities and lack of tissue samples from the early phases of disease. In recent years, several new CF animal models have been developed that have advanced our understanding of both CF exocrine and endocrine pancreatic disease. Additionally, these models have helped us to better define the influence of pancreatic lesions on CF disease progression in other organs, such as the gastrointestinal tract and lung. Copyright Copyright 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26365583

  4. Pancreatic surgery: evolution and current tailored approach

    PubMed Central

    Muina Mii?, Dubravka; Glav?i?, Goran

    2014-01-01

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

  5. Transpapillary drainage of pancreatic parenchymal necrosis

    PubMed Central

    Smoczy?ski, Marian; Adrych, Krystian

    2015-01-01

    In the last two decades the strategy of treatment of necrotizing pancreatitis has changed. Endoscopic therapy of patients with symptomatic walled-off pancreatic necrosis has a high rate of efficiency. Here we present a description of a patient with parenchymal limited necrosis of the pancreas and a disruption of the main pancreatic duct. In the treatment, active transpapillary drainage of the pancreatic necrosis (through the major duodenal papilla) was performed and insertion of an endoprosthesis into the main pancreatic duct (through the minor duodenal papilla) was applied, which enabled a bypass over the infiltration and resulted in complete resolution. PMID:26649102

  6. A Case of Recurrent Acute Pancreatitis due to Pancreatic Arteriovenous Malformation

    PubMed Central

    Choi, Jong Kyoung; Kwak, Min Sun; Kim, Jai Hwan; Jang, Eun Sun; Hwang, Sung Wook; Hwang, Jin Hyeok; Joo, Li Jin; Yoon, Yoo Seok; Kim, Hae Ryoung

    2010-01-01

    Pancreatic arteriovenous malformation (AVM) is an extremely rare condition with various clinical manifestations. We report herein a case of recurrent acute pancreatitis due to pancreatic AVM in a 49-year-old man. This patient presented with epigastric pain that had developed after consuming alcohol 2 days prior to admission. Serum amylase and lipase levels were elevated and computed tomography revealed focal low-attenuation lesions with peripancreatic infiltrations in the pancreatic tail and multiple collateral vessels around the low-attenuation lesions. He was diagnosed with acute pancreatitis and pancreatic AVM. Although he had stopped drinking after the first attack of acute pancreatitis, his pancreatitis recurred twice within 3 months. He underwent a distal pancreatectomy after the third attack of acute pancreatitis. He was free of symptoms for 2 years after the pancreatectomy. PMID:20479928

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

    PubMed Central

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

    2010-01-01

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

  8. Gemcitabine suppresses malignant ascites of human pancreatic cancer: correlation with VEGF expression in ascites.

    PubMed

    Kuwahara, Kenichi; Sasaki, Tamito; Kobayashi, Kensou; Noma, Bunjirou; Serikawa, Masahiro; Iiboshi, Tomohiro; Miyata, Hideki; Kuwada, Yukio; Murakami, Masateru; Yamasaki, Souichirou; Kariya, Kenji; Morinaka, Kenji; Chayama, Kazuaki

    2004-01-01

    It has been reported that vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also has the ability to increase vascular permeability. VEGF plays an important role in the development of malignant ascites in various cancers. Gemcitabine has been prescribed for patients with inoperable human pancreatic ductal carcinoma as a first-line chemotherapy. However, the response rates of patients with malignant ascites who were undergoing systemic chemotherapy were extremely limited. In the present study, we investigated the role of VEGF and the effects of gemcitabine on malignant ascites of human pancreatic ductal carcinoma. As an in vitro assay, the human pancreatic cancer cell line (SUIT-2) was incubated in DMEM supplemented with serially diluted concentrations of gemcitabine for 24 h. The expression levels of VEGF in culture media were assayed using an enzyme-linked immunosorbent assay (ELISA). As an in vivo assay, a cell suspension (1 x 10(7) cells in 100 microliters PBS) was injected into the intraperitoneal region. The mice were randomly divided into two groups (control and treated with gemcitabine). The mice were sacrificed four weeks after inoculation, the ascites volume was measured, and the extent of peritoneal dissemination was examined. The expression levels of VEGF and CD31 in peritoneal nodules were examined by immunohistochemistry. In addition, secreted VEGF protein levels were quantified using ELISA. The results show that VEGF levels in the culture medium decreased in response to gemcitabine in a dose-dependent manner. The ascites formation and peritoneal dissemination within mice were suppressed by the treatment with gemcitabine. Immunohistochemical analysis suggested that expression of VEGF and CD31 in peritoneal nodules was suppressed by gemcitabine treatment, and the VEGF protein level in ascites was significantly decreased by gemcitabine (p<0.05). These results suggest that gemcitabine controls malignant ascites and peritoneal dissemination, either directly or indirectly, via VEGF. Moreover, intraperitoneal administration of gemcitabine may be a useful therapeutic approach for patients with malignant ascites in pancreatic carcinoma. PMID:14654905

  9. Notch Signaling in Pancreatic Development.

    PubMed

    Li, Xu-Yan; Zhai, Wen-Jun; Teng, Chun-Bo

    2016-01-01

    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

  10. 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

  11. New Insights into the Pathogenesis of Pancreatitis

    PubMed Central

    Sah, Raghuwansh P.; Dawra, Rajinder K.; Saluja, Ashok K.

    2014-01-01

    Purpose of review In this article, we review important advances in our understanding of the mechanisms of pancreatitis. Recent Findings The relative contribution of intra-pancreatic trypsinogen activation and NF?B activation, the two major early independent cellular events in the etiology of pancreatitis, have been investigated using novel genetic models. Trypsinogen activation has traditionally held the spotlight for many decades as it is believed to be the central pathogenic event of pancreatitis However, recent experimental evidence points to the role of trypsin activation in early acinar cell damage but not in the inflammatory response of acute pancreatitis through NF?B activation. Further, chronic pancreatitis in the caerulein model develops independently of typsinogen activation. Sustained activation of the NF?B pathway, but not persistent intra-acinar expression of active trypsin, was shown to result in chronic pancreatitis. Calcineurin-NFAT signaling was shown to mediate downstream effects of pathologic rise in intracellular calcium. IL-6 was identified as a key cytokine mediating pancreatitis-associated lung injury. Summary Recent advances challenge the long-believed trypsin-centered understanding of pancreatitis. It is becoming increasingly clear that activation of intense inflammatory signaling mechanisms in acinar cells is crucial to the pathogenesis of pancreatitis, which may explain the strong systemic inflammatory response in pancreatitis. PMID:23892538

  12. Molecular mechanisms of alcohol associated pancreatitis

    PubMed Central

    Clemens, Dahn L; Wells, Mark A; Schneider, Katrina J; Singh, Shailender

    2014-01-01

    Alcohol abuse is commonly associated with the development of both acute and chronic pancreatitis. Despite this close association, the fact that only a small percentage of human beings who abuse alcohol develop pancreatitis indicates that alcohol abuse alone is not sufficient to initiate clinical pancreatitis. This contention is further supported by the fact that administration of ethanol to experimental animals does not cause pancreatitis. Because of these findings, it is widely believed that ethanol sensitizes the pancreas to injury and additional factors trigger the development of overt pancreatitis. How ethanol sensitizes the pancreas to pancreatitis is not entirely known. Numerous studies have demonstrated that ethanol and its metabolites have a number of deleterious effects on acinar cells. Important acinar cells properties that are affected by ethanol include: calcium signaling, secretion of zymogens, autophagy, cellular regeneration, the unfolded protein response, and mitochondrial membrane integrity. In addition to the actions of ethanol on acinar cells, it is apparent that ethanol also affects pancreatic stellate cells. Pancreatic stellate cells have a critical role in normal tissue repair and the pathologic fibrotic response. Given that ethanol and its metabolites affect so many pancreatic functions, and that all of these effects occur simultaneously, it is likely that none of these effects is THE effect. Instead, it is most likely that the cumulative effect of ethanol on the pancreas predisposes the organ to pancreatitis. The focus of this article is to highlight some of the important mechanisms by which ethanol alters pancreatic functions and may predispose the pancreas to disease. PMID:25133017

  13. Novel therapeutic targets for pancreatic cancer

    PubMed Central

    Tang, Shing-Chun; Chen, Yang-Chao

    2014-01-01

    Pancreatic cancer has become the fourth leading cause of cancer death in the last two decades. Only 3%-15% of patients diagnosed with pancreatic cancer had 5 year survival rate. Drug resistance, high metastasis, poor prognosis and tumour relapse contributed to the malignancies and difficulties in treating pancreatic cancer. The current standard chemotherapy for pancreatic cancer is gemcitabine, however its efficacy is far from satisfactory, one of the reasons is due to the complex tumour microenvironment which decreases effective drug delivery to target cancer cell. Studies of the molecular pathology of pancreatic cancer have revealed that activation of KRAS, overexpression of cyclooxygenase-2, inactivation of p16INK4A and loss of p53 activities occurred in pancreatic cancer. Co-administration of gemcitabine and targeting the molecular pathological events happened in pancreatic cancer has brought an enhanced therapeutic effectiveness of gemcitabine. Therefore, studies looking for novel targets in hindering pancreatic tumour growth are emerging rapidly. In order to give a better understanding of the current findings and to seek the direction in future pancreatic cancer research; in this review we will focus on targets suppressing tumour metastatsis and progression, KRAS activated downstream effectors, the relationship of Notch signaling and Nodal/Activin signaling with pancreatic cancer cells, the current findings of non-coding RNAs in inhibiting pancreatic cancer cell proliferation, brief discussion in transcription remodeling by epigenetic modifiers (e.g., HDAC, BMI1, EZH2) and the plausible therapeutic applications of cancer stem cell and hyaluronan in tumour environment. PMID:25152585

  14. Precise Classification of Cervical Carcinomas Combined with Somatic Mutation Profiling Contributes to Predicting Disease Outcome

    PubMed Central

    Spaans, Vivian M.; Trietsch, Marjolijn D.; Peters, Alexander A. W.; Osse, Michelle; ter Haar, Natalja; Fleuren, Gert J.; Jordanova, Ekaterina S.

    2015-01-01

    Introduction Squamous cell carcinoma (SCC), adenocarcinoma (AC), and adenosquamous carcinoma (ASC) are the most common histological subtypes of cervical cancer. Differences in the somatic mutation profiles of these subtypes have been suggested. We investigated the prevalence of somatic hot-spot mutations in three well-defined cohorts of SCC, AC, and ASC and determined the additional value of mutation profiling in predicting disease outcome relative to well-established prognostic parameters. Materials and Methods Clinicopathological data were collected for 301 cervical tumors classified as SCC (n=166), AC (n=55), or ASC (n=80). Mass spectrometry was used to analyze 171 somatic hot-spot mutations in 13 relevant genes. Results In 103 (34%) tumors, 123 mutations were detected (36% in SCC, 38% in AC, and 28% in ASC), mostly in PIK3CA (20%) and KRAS (7%). PIK3CA mutations occurred more frequently in SCC than AC (25% vs. 11%, P=0.025), whereas KRAS mutations occurred more frequently in AC than SCC (24% vs. 3%, P<0.001) and ASC (24% vs. 3%, P<0.001). A positive mutation status correlated with worse disease-free survival (HR 1.57, P=0.043). In multivariate analysis, tumor diameter, parametrial infiltration, and lymph node metastasis, but not the presence of a somatic mutation, were independent predictors of survival. Conclusion Potentially targetable somatic mutations occurred in 34% of cervical tumors with different distributions among histological subtypes. Precise classification of cervical carcinomas in combination with mutation profiling is valuable for predicting disease outcome and may guide the development and selection of tumor-specific treatment approaches. PMID:26197069

  15. Clear Cell Carcinoma of the Pancreas -A Case Report and Review of the Literature-

    PubMed Central

    Lee, Hui-Young; Lee, Dong-Gyu; Chun, Kwangjin; Lee, Seungkoo

    2009-01-01

    Most of the malignant neoplasms of the pancreas demonstrate features that are consistent with adenocarcinoma. According to the WHO classification, primary clear cell carcinoma of the pancreas is rare and it is classified as a "miscellaneous" carcinoma. In addition, there is not an adequate systematic overview that can demonstrate its true existence as a definable entity. We report here on an unusual case of primary pancreatic clear cell carcinoma, which is the first such reported case in Korea. A 66 year old woman presented with abdominal pain and significant weight loss over the previous three weeks. On the abdominal computed tomography (CT), we detected an abdominal mass involving the pancreas tail and liver, and clear cell carcinoma with rhabdoid feature was seen on the histologic evaluation. The tumor cells showed well defined cell membranes, clear cytoplasm and prominent cell boundaries. The immunohistochemical stains showed positive reactions to antibodies against pan-cytokeratin, cytokeratin 7, carcinoemb