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

    PubMed Central

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

    2014-01-01

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

  3. 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

  4. Clinical features of adenosquamous lung carcinoma in 127 patients.

    PubMed

    Sridhar, K S; Bounassi, M J; Raub, W; Richman, S P

    1990-07-01

    There has been increased recognition of adenosquamous lung carcinoma since the 1982 modification of World Health Organization (WHO) histologic criteria. However, data on clinical features of this histologic subtype were nonexistent. Medical records of 127 patients with adenosquamous lung carcinoma were reviewed to determine the clinical features, namely, age, race, sex, smoking history, asbestos exposure, symptoms present at the time of diagnosis, stage, treatments, and survival. The age distribution was: less than 40 yr, 3%; 40 to 49, 17%; 50 to 59, 28%; 60 to 69, 32%; 70 to 79, 18%; greater than or equal to 80, 2%. Men constituted 72%, and 90% were smokers. Four smokers had documented asbestos exposure. The symptoms in order of decreasing frequency were cough, weight loss, expectoration, anorexia, chest pain, dyspnea, weakness, hemoptysis, pneumonia, fever, nausea, vomiting, dizziness, and chills. Stage could be ascertained in 120 (95%) patients. Local stage constituted 10%, regional constituted 30%, and distant constituted 60%. Local stage had the best survival, with a projected 5-yr survival of 62%. Median survivals in regional and distant stages were 8 and 4 months, respectively. Symptoms of adenosquamous lung carcinoma were similar to other histologies. Most patients present in regional or distant stages. Local-stage patients had a good long-term survival after surgical excision of the tumor. PMID:2368969

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

    PubMed

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

    2014-03-01

    A 34 years old non-smoker male patient reported with growth of right maxillary region which on histopathology confirmed adenosquamous carcinoma of nose and paranasal sinus. Patient also had total situs inversus including dextrocardia, bronchiectasis and sinusitis. His blood group was AB negative. This association of Kartagener syndrome with adenosquamous carcinoma of paranasal sinuses has never been reported. Carcinoma of paranasal sinuses accounts only 0.3% of all cancers. Adenosquamous carcinoma makes only 2% of the nose and paranasal sinuses tumours. Kartagener syndrome, AB negative blood group and adenosquamous carcinoma of paranasal sinuses all are extremely rare clinical conditions found in populations and the combination of all three in the same patient have never been reported to the best of authors' knowledge. PMID:24718008

  6. Gallbladder Adenosquamous Carcinoma Associated with Biliopancreatic Maljunction and Cystic Metastases of the Liver Miming Abscess.

    PubMed

    Daldoul, Sami; Moussi, Amir

    2015-12-01

    Gallbladder adenosquamous carcinoma is a rare tumor with glandular and squamous malignant components. We report a special case of this rare tumor with cystic metastasis of the liver miming hepatic abscess and associated with biliopancreatic maljunction. PMID:27011570

  7. 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

  8. Adenosquamous carcinoma of the floor of the mouth and lower alveolus: a radiation-induced lesion

    SciTech Connect

    Siar, C.H.; Ng, K.H.

    1987-02-01

    A case of adenosquamous carcinoma of the floor of the mouth and alveolus that occurred following radiation therapy is described. The possible role of radiation in the etiology of this lesion is discussed, and the complex histopathologic features of this neoplasm are emphasized.

  9. Adenosquamous carcinoma arising from a thyroglossal duct cyst: A case report

    PubMed Central

    CHANG, YU-SUNG; SU, HSIN-HAO; HO, SZU-PEI

    2016-01-01

    The current study describes a case of adenosquamous carcinoma originating from a thyroglossal duct cyst (TGDC). A 77-year-old man presented with an asymptomatic mass in the left mid-neck, which was soft and mobile on palpation. Fine-needle aspiration was performed, but cytology did not detect any malignant cells. Computed tomography demonstrated a single cystic lesion in the left lobe of the thyroid gland; therefore, surgery was performed on the suspected thyroid cyst. However, it was identified intraoperatively that the lesion was separated from the thyroid gland and instead adhered to an additional hyoid bone; therefore, the Sistrunk procedure was performed. Histopathological examination of the resected tumor confirmed the diagnosis of adenosquamous carcinoma originating from a TGDC. Carcinoma arising from a TGDC is rare, and accounts for 1% of all TGDC cases. The most common subtype of carcinoma associated with TGDC is papillary carcinoma, whilst adenosquamous carcinoma developing from a TGDC is extremely rare, with only one case currently reported in the literature. Although a consensus for the management of this disease has not yet been established, adequate surgical excision with long-term follow-up is currently the preferred treatment. PMID:27073536

  10. Surgical resection of splenic metastasis from the adenosquamous gallbladder carcinoma: A case report

    PubMed Central

    Utsumi, Masashi; Aoki, Hideki; Kunitomo, Tomoyoshi; Mushiake, Yutaka; Kanaya, Nobuhiko; Yasuhara, Isao; Arata, Takashi; Katsuda, Kou; Tanakaya, Kohji; Takeuchi, Hitoshi

    2016-01-01

    Introduction Splenic metastasis of gallbladder carcinoma is extremely rare. Specific anatomical, histological, and functional properties of spleen are believed to be responsible for the rarity of solitary splenic metastasis. Presentation of case We present the case of a 62-year-old female who developed metachronous splenic metastasis of adenosquamous carcinoma of the gallbladder. We performed central bisegmentectomy of the liver for gallbladder carcinoma. The patient subsequently presented 3 months later with isolated splenic metastasis and liver metastasis. Splenectomy and partial hepatectomy was performed at this time. Histological examination confirmed metastatic adenosquamous carcinoma of the gallbladder. No signs of recurrence were observed at 3 months after the second surgery. Discussion Although splenectomy provides a potential means of radical treatment in patients with isolated splenic metastases, it should be performed with caution as splenic metastatic lesions may represent the initial clinical manifestation of systemic metastases at multiple sites. In this case, radical surgery was performed following the confirmation of no new unresectable metastatic lesions or systemic dissemination. Conclusion This is the first report on the adenosquamous splenic metastasis from the gallbladder carcinoma. Curative resection may be the treatment of choice for prolonging survival in patients with the splenic metastasis of gallbladder carcinoma. PMID:26852359

  11. 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

  12. 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

  13. 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

  14. Ciliated Adenosquamous Carcinoma: Expanding the Phenotypic Diversity of Human Papillomavirus-Associated Tumors.

    PubMed

    Radkay-Gonzalez, Lisa; Faquin, William; McHugh, Jonathan B; Lewis, James S; Tuluc, Madalina; Seethala, Raja R

    2016-06-01

    This study describes a unique subset of ciliated, human papillomavirus (HPV) related, adenosquamous carcinomas (AsqCA) of the head and neck that in contrast to most AsqCA, often show areas with lower grade cytonuclear features. They are comprised of largely non-keratinizing squamous cell carcinoma components with cystic change, gland formation, mucin production, and cilia in tumor cells. Seven cases of ciliated AsqCA were retrieved. Site distribution was as follows: palatine tonsil-3/7, base of tongue-1/7, and neck (unknown primary site)-3/7. Despite the occasional resemblance to mucoepidermoid carcinoma (MEC), the tumors showed focal keratinizing morphology and atypia, and all tumors were negative for MAML2 rearrangements. Oropharyngeal and neck tumors were uniformly p16 positive and showed punctate staining by in situ hybridization for high risk HPV DNA. There were two distant metastases (lung), and one tumor related death. Thus, ciliated AsqCA are HPV-associated lesions that pose unique pitfalls, closely mimicking MEC and other salivary gland tumors. These tumors add to the list of those which defy the dogma that ciliated epithelium always equates to a benign process. PMID:26411881

  15. [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

  16. 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

  17. 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 patient’s tumor. Further work should be pursued to better characterize this disease. PMID:26380056

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  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. 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

  6. 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

  7. Polyarthritis and pancreatic panniculitis associated with pancreatic carcinoma: review of the literature.

    PubMed

    Arbeláez-Cortés, Alvaro; Vanegas-García, Adriana L; Restrepo-Escobar, Mauricio; Correa-Londoño, Luis A; González-Naranjo, Luis A

    2014-12-01

    Pancreatic disorders, such as chronic or acute pancreatitis, and carcinoma may be infrequently accompanied or preceded by panniculitis or polyarthritis. This triad is known in the literature as the pancreatitis, panniculitis, and polyarthritis syndrome. Although the pancreatic disease of pancreatitis, panniculitis, and polyarthritis syndrome usually includes pancreatitis, here we review the literature with report of 1 additional case of polyarthritis and panniculitis occurring in the presence of pancreatic carcinoma. Given that the diagnosis is often difficult when abdominal symptoms are absent, knowledge of the association between panniculitis and polyarthritis with pancreatic disease may lead to a prompt diagnosis and management. The histopathology of the skin lesions can be a valuable clue for focusing attention to a pancreatic disease. PMID:25417680

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

    PubMed Central

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

    2010-01-01

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

  9. Isolated pancreatic metastases from a bronchogenic small cell carcinoma.

    PubMed

    Walshe, T; Martin, S T; Khan, M F; Egan, A; Ryan, R S; Tobbia, I; Waldron, R

    2009-04-01

    We describe the case of a 60 year old female smoker who presented with a three month history of weight loss (14 Kg), generalized abdominal discomfort and malaise. Chest radiography demonstrated a mass projected inferior to the hilum of the right lung. Computed Tomography of thorax confirmed a lobulated lesion in the right infrahilar region and subsequent staging abdominal CT demonstrated a low density lesion in the neck of the pancreas. Percutaneous Ultrasound guided pancreatic biopsy was performed, histology of which demonstrated pancreatic tissue containing a highly necrotic small cell undifferentiated carcinoma consistent with metastatic small cell carcinoma of the bronchus. PMID:19552294

  10. Successful pemetrexed-containing chemotherapy for epidermal growth factor receptor mutation-positive adenosquamous cell carcinoma of the lung: A case report

    PubMed Central

    WATANABE, HIROKO; TAMURA, TOMOHIRO; KAGOHASHI, KATSUNORI; KAWAGUCHI, MIO; KURISHIMA, KOICHI; SATOH, HIROAKI

    2016-01-01

    Pemetrexed-containing chemotherapy has shown promise in the treatment of non-small-cell lung cancer (NSCLC). However, although adenosquamous cell lung cancer (ASCLC) is a type of NSCLC, the availability of studies investigating its response to pemetrexed-containing chemotherapy is limited. A 66-year-old woman was referred to Mito Medical Center, University of Tsukuba with hemoptysis and a chest computed tomography (CT) scan revealed a large cavitary mass in the lower lobe of the left lung. The patient underwent left lower lobectomy and mediastinal lymph node dissection. The tumor was staged as pT2bN2M0. An epidermal growth factor receptor (EGFR) exon 19 deletion was identified in the adenocarcinomatous as well as the squamous cell carcinomatous components. Despite gefitinib therapy for pulmonary metastases, the patient developed cavitary metastases in both lungs. Therefore, treatment with pemetrexed-containing chemotherapy was initiated. A chest CT scan revealed significant regression of the metastatic lesions in both lungs, with thinning of the walls. The patient remains well and recurrence-free 19 months after the initiation of pemetrexed-containing chemotherapy. Therefore, the clinical response of EGFR mutation-positive ASCLC to pemetrexed-containing chemotherapy was promising, suggesting pemetrexed to be one of the key drugs for this subset of ASCLC patients.

  11. Photodynamic therapy for pancreatic and biliary tract carcinoma

    NASA Astrophysics Data System (ADS)

    Pereira, Stephen P.

    2009-02-01

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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. A Case of Pancreatic Cancer in the Setting of Autoimmune Pancreatitis with Nondiagnostic Serum Markers

    PubMed Central

    Chandrasegaram, Manju D.; Chiam, Su C.; Nguyen, Nam Q.; Neo, Eu L.; Chen, John W.; Worthley, Christopher S.; Brooke-Smith, Mark E.

    2013-01-01

    Background. Autoimmune pancreatitis (AIP) often mimics pancreatic cancer. The diagnosis of both conditions is difficult preoperatively let alone when they coexist. Several reports have been published describing pancreatic cancer in the setting of AIP. Case Report. The case of a 53-year-old man who presented with abdominal pain, jaundice, and radiological features of autoimmune pancreatitis, with a “sausage-shaped” pancreas and bulky pancreatic head with portal vein impingement, is presented. He had a normal serum IgG4 and only mildly elevated Ca-19.9. Initial endoscopic ultrasound-(EUS-) guided fine-needle aspiration (FNA) of the pancreas revealed an inflammatory sclerosing process only. A repeat EUS guided biopsy following biliary decompression demonstrated both malignancy and features of autoimmune pancreatitis. At laparotomy, a uniformly hard, bulky pancreas was found with no sonographically definable mass. A total pancreatectomy with portal vein resection and reconstruction was performed. Histology revealed adenosquamous carcinoma of the pancreatic head and autoimmune pancreatitis and squamous metaplasia in the remaining pancreas. Conclusion. This case highlights the diagnostic and management difficulties in a patient with pancreatic cancer in the setting of serum IgG4-negative, Type 2 AIP. PMID:23781378

  18. A case of pancreatic cancer in the setting of autoimmune pancreatitis with nondiagnostic serum markers.

    PubMed

    Chandrasegaram, Manju D; Chiam, Su C; Nguyen, Nam Q; Ruszkiewicz, Andrew; Chung, Adrian; Neo, Eu L; Chen, John W; Worthley, Christopher S; Brooke-Smith, Mark E

    2013-01-01

    Background. Autoimmune pancreatitis (AIP) often mimics pancreatic cancer. The diagnosis of both conditions is difficult preoperatively let alone when they coexist. Several reports have been published describing pancreatic cancer in the setting of AIP. Case Report. The case of a 53-year-old man who presented with abdominal pain, jaundice, and radiological features of autoimmune pancreatitis, with a "sausage-shaped" pancreas and bulky pancreatic head with portal vein impingement, is presented. He had a normal serum IgG4 and only mildly elevated Ca-19.9. Initial endoscopic ultrasound-(EUS-) guided fine-needle aspiration (FNA) of the pancreas revealed an inflammatory sclerosing process only. A repeat EUS guided biopsy following biliary decompression demonstrated both malignancy and features of autoimmune pancreatitis. At laparotomy, a uniformly hard, bulky pancreas was found with no sonographically definable mass. A total pancreatectomy with portal vein resection and reconstruction was performed. Histology revealed adenosquamous carcinoma of the pancreatic head and autoimmune pancreatitis and squamous metaplasia in the remaining pancreas. Conclusion. This case highlights the diagnostic and management difficulties in a patient with pancreatic cancer in the setting of serum IgG4-negative, Type 2 AIP. PMID:23781378

  19. 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.

  20. Pancreatic Metastasis from Mixed Adenoneuroendocrine Carcinoma of the Uterine Cervix: A Case Report

    PubMed Central

    Nishimura, Chihiro; Naoe, Hideaki; Hashigo, Shunpei; Tsutsumi, Hideharu; Ishii, Shotaro; Konoe, Takeyasu; Watanabe, Takehisa; Shono, Takashi; Sakurai, Kouichi; Takaishi, Kiyomi; Ikuta, Yoshiaki; Chikamoto, Akira; Tanaka, Motohiko; Iyama, Ken-ichi; Baba, Hideo; Katabuchi, Hidetaka; Sasaki, Yutaka

    2013-01-01

    Metastatic cancers of the pancreas are rare, accounting for approximately 2–4% of all pancreatic malignancies. Renal cell carcinoma is the most common solid tumor that metastasizes to the pancreas. Here, we present a case of uterine cervical carcinoma metastasizing to the pancreas and review the literature regarding this rare event. A 44-year-old woman with a uterine cervical tumor had undergone radical hysterectomy and had been diagnosed pathologically with stage Ib mixed adenoneuroendocrine carcinoma in 2004. She underwent concurrent radiotherapy and chemotherapy postoperatively. Pulmonary metastases subsequently appeared in 2008 and 2011, and she underwent complete resection of the lung tumors by video-assisted thoracic surgery. Although she was followed up without any treatment and with no other recurrences, positron emission tomography revealed an area of abnormal uptake within the pancreatic body in 2012. Enhanced computed tomography demonstrated a 20-mm lesion in the pancreatic body and upstream pancreatic duct dilatation. Endoscopic ultrasonography-guided fine needle aspiration was performed and pathological examination suggested neuroendocrine carcinoma (NEC). On the basis of these results and the patient's oncological background, lesions in the pancreatic body were diagnosed as secondary metastasis from the cervical carcinoma that had been treated 8 years earlier. No other distant metastases were visualized, and the patient subsequently underwent middle pancreatectomy. Pathological examination showed NEC consistent with pancreatic metastasis from the uterine cervical carcinoma. The patient has survived 7 months since the middle pancreatectomy without any signs of local recurrence or other metastatic lesions. PMID:23741220

  1. Pancreatic head carcinoma and right hepatic artery: embolization management-A case report.

    PubMed

    El Amrani, Mehdi; Leteurtre, Emmanuelle; Sergent, Géraldine; Ernst, Olivier; Maunoury, Vincent; Branche, Julien; Pruvot, François-René; Truant, Stéphanie

    2014-08-01

    A replaced right hepatic artery (RHA) is the most common anatomical variation in pancreatic surgery. The RHA is frequently encountered and can be problematic in pancreatic carcinoma. The preservation of the RHA is necessary to avoid ischemic complications but can impact margins resection in pancreaticoduodenectomy (PD). We report a case of a 53-year-old man with a head pancreatic carcinoma. There was a close contact between the tumor and the RHA arising from superior mesenteric artery (SMA). Preoperative embolization of the RHA was performed prior to PD. PMID:25083312

  2. A case of hyperfunctioning pancreatic mixed adenoneuroendocrine carcinoma (MANEC) arising from ectopic pancreatic tissue in the liver

    PubMed Central

    Steel, Christopher J.; Hostetler, Valerie; Dunn, Dell

    2015-01-01

    We report the case of a hyperfunctioning mixed adenoneuroendocrine carcinoma (MANEC) arising from ectopic pancreatic tissue in the liver. To our knowledge, the imaging appearance of a MANEC in the liver has never been reported. Literature on MANEC and its imaging features, including its appearance on the MR hepatobiliary phase and differential considerations, are reviewed and discussed. PMID:27190559

  3. Pancreatic metastases from ovarian carcinoma--diagnosis by endoscopic ultrasound-guided fine needle aspiration.

    PubMed

    Hadzri, M Hasmoni; Rosemi, Salleh

    2012-04-01

    Pancreatic metastases are very uncommon and originate most commonly from lung, colon, breast and kidney cancer. Ovarian adenocarcinoma has been reported as a primary site of pancreatic metastasis, but its diagnosis has rarely being reported by endoscopic ultrasound guided fine needle aspiration (EUS-FNA). We report a case of multiple metastases to the pancreas from ovarian carcinoma occurring four years after original resection of the primary tumour. Our patient presented with severe epigastric pain which was initially treated as acute pancreatitis. Further imaging modalities showed multiple large pseudocystic lesions in the pancreatic head and body. Subsequent EUS-FNA confirmed that the lesions were metastatic disease from an advanced ovarian carcinoma. She underwent palliative chemotherapy and the pancreatic lesion showed receding size. PMID:22822646

  4. 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

  5. A Synchronous Pancreatic Metastasis from Renal Clear Cell Carcinoma, with Unusual CT Characteristics, Completely Regressed after Therapy with Sunitinib

    PubMed Central

    Lauro, Salvatore; Onesti, Elisa Concetta; Righini, Riccardo; Cremona, Antonio; Marchetti, Paolo

    2014-01-01

    We present a case report of a 75-years-old woman affected by renal clear cell carcinoma with a synchronous pancreatic metastasis and a metachronous lung metastasis. This case has two peculiarities. First the pancreatic metastasis was treated just with medical therapy, that is, Sunitinib, instead of the surgical therapy that is mostly considered. Secondly, the pancreatic lesion showed different characteristics on the computed tomography scan compared to the usual pancreatic metastases from renal clear cell carcinoma. The pancreatic metastasis totally regressed after medical treatment and nowadays, four years after the diagnosis, the patient is disease-free. PMID:24707294

  6. 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

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

    SciTech Connect

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

    1991-06-01

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

  8. 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

  9. Pancreatitis

    MedlinePlus

    Pancreatitis What is the pancreas? What does it do? T he pancreas is an organ in the ... in maintaining normal blood sugar levels. What is pancreatitis? Pancreatitis is an inflammation, or swelling, of the ...

  10. 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

  11. 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.

  12. 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

  13. 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

  14. Effectiveness and security of CT-guided percutaneous implantation of 125I seeds in pancreatic carcinoma

    PubMed Central

    Guo, J-M; Jiang, H-T; Di, X-Y; Zhu, Y

    2014-01-01

    Objective: To assess the effectiveness and security of CT-guided percutaneous implantation of iodine-125 (125I)-labelled seeds in pancreatic carcinoma. Methods: A total of 36 patients (25 males and 11 females) with an average age of 57 years (range, 39–84 years) were enrolled and categorized into Stage III (27 cases) and Stage IV (9 cases) of pancreatic cancer. There were 3 tumours in the pancreatic head and 33 tumours in the pancreatic body or tail. The average diameter of the tumours was 37.1 mm (range, 15–65 mm). The implantation of 125I seeds was performed by using 18-G needles (length, 150–200 mm) through the anterior, lateral and posterior approaches. Then, 125I seeds were loaded and released into the lesions. Results: Implantations were performed via the anterior (23 patients), lateral (9 patients) and posterior (4 patients) approaches. During implantation, 3–14 punctures were performed for each patient, and a total of 164 punctures were recorded. Meanwhile, a total of 657 seeds were implanted with an average of 25.27 (range, 12–50) seeds per patient, and the success rate was 100%. The activity of each seed ranged from 0.55 to 0.65 mCi. A main adverse event occurred in one puncture and minor events in seven punctures. No significant relationship between the punctures or adverse events was identified. No serious complication was detected after the implantations during follow-up visits. Conclusion: This study suggested that CT-guided percutaneous implantation of 125I seeds in a pancreatic carcinoma was relatively safe and effective for treating unresectable pancreatic cancer. Advances in knowledge: The CT-guided percutaneous implantation of 125I seeds in unresectable pancreatic cancer showed highly successful rates without serious complications. PMID:24734936

  15. Incidental detection of pancreatic hemangioma mimicking a metastatic tumor of renal cell carcinoma

    PubMed Central

    Kim, Sung Hyun; Kim, Ji-Ye; Choi, Jin Young; Choi, Young Deuk

    2016-01-01

    Adult pancreatic hemangioma is a rare disease. We presented a case of a woman with pancreatic tail mass mimicking a distant metastasis from the kidney. A 68-year-old woman was found with a left kidney mass on medical checkup. Computed tomography scan showed a 4.3 cm-sized mass in the left kidney, suggesting renal cell carcinoma (RCC), and a strongly enhancing tiny nodule in the pancreatic tail. We could not rule the possibility of RCC metastasis, hence, surgical resection of the pancreatic mass simultaneously with radical nephrectomy for RCC was conducted. Gross pathologic examination revealed hemangioma. Immunohistochemistry revealed that the tumor was positive for CD34, CD31 and factor VIII-related antigen. There were no significant postoperative events, and the patient was discharged on postoperative day 7 without any complications. Treatment strategies for pancreatic hemangioma have not been established. To our knowledge, this was the first case report of asymptomatic pancreatic hemangioma. In previous literature, treatment differed on a case-by-case basis, ranging from observation to surgical resection. The most important factor in deciding whether to perform surgery is possibly risk-benefit effectiveness; however, tumor location, patient symptoms, and other factors are also important.

  16. Incidental detection of pancreatic hemangioma mimicking a metastatic tumor of renal cell carcinoma.

    PubMed

    Kim, Sung Hyun; Kim, Ji-Ye; Choi, Jin Young; Choi, Young Deuk; Kim, Kyung Sik

    2016-05-01

    Adult pancreatic hemangioma is a rare disease. We presented a case of a woman with pancreatic tail mass mimicking a distant metastasis from the kidney. A 68-year-old woman was found with a left kidney mass on medical checkup. Computed tomography scan showed a 4.3 cm-sized mass in the left kidney, suggesting renal cell carcinoma (RCC), and a strongly enhancing tiny nodule in the pancreatic tail. We could not rule the possibility of RCC metastasis, hence, surgical resection of the pancreatic mass simultaneously with radical nephrectomy for RCC was conducted. Gross pathologic examination revealed hemangioma. Immunohistochemistry revealed that the tumor was positive for CD34, CD31 and factor VIII-related antigen. There were no significant postoperative events, and the patient was discharged on postoperative day 7 without any complications. Treatment strategies for pancreatic hemangioma have not been established. To our knowledge, this was the first case report of asymptomatic pancreatic hemangioma. In previous literature, treatment differed on a case-by-case basis, ranging from observation to surgical resection. The most important factor in deciding whether to perform surgery is possibly risk-benefit effectiveness; however, tumor location, patient symptoms, and other factors are also important. PMID:27212999

  17. 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

  18. 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

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

    SciTech Connect

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

    1984-02-01

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

  20. Percutaneous irreversible electroporation of locally advanced pancreatic carcinoma using the dorsal approach: a case report.

    PubMed

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

    2015-06-01

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively. PMID:25288173

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

    SciTech Connect

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

    2015-06-15

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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Silencing of B7-H3 increases gemcitabine sensitivity by promoting apoptosis in pancreatic carcinoma.

    PubMed

    Zhao, Xin; Zhang, Guang-Bo; Gan, Wen-Juan; Xiong, Feng; Li, Zhi; Zhao, Hua; Zhu, Dong-Ming; Zhang, Bin; Zhang, Xue-Guang; Li, DE-Chun

    2013-03-01

    In numerous types of cancer, the expression of a novel member of the B7 ligand family, the B7-H3 immunoregulatory protein, has been correlated with a poor prognosis. In the present study, we investigated the role of B7-H3 in chemoresistance in pancreatic carcinoma. Silencing of B7-H3, through lentivirus-mediated delivery of stable short hairpin RNA, was observed to increase the sensitivity of the human pancreatic carcinoma cell line Patu8988 to gemcitabine as a result of enhanced drug-induced apoptosis. Overexpression of B7-H3 caused the cancer cells to be more resistant to the drug. Subsequently, we investigated the underlying mechanisms of B7-H3-mediated gemcitabine resistance, and found that the levels of survivin decreased in cells in which B7-H3 had been knocked down. In vivo animal experiments demonstrated that tumors in which B7-H3 had been knocked down displayed a slower growth rate compared with the control xenografts. Notably, gemcitabine treatment led to a strong antitumor activity in mice with tumors in which B7-H3 had been knocked down; however, this effect was only marginal in the control group. Furthermore, survivin expression was weak in gemcitabine-treated tumors in which B7-H3 had been knocked down and apoptosis was increased, as revealed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining. In summary, the present study demonstrated that B7-H3 induces gemcitabine resistance in pancreatic carcinoma cells, at least partially by downregulating survivin expression. These results provide novel insights into the function of B7-H3 and encourage the design and investigation of approaches targeting this protein in treating pancreatic carcinoma. PMID:23426281

  8. CT and MR imaging patterns for pancreatic carcinoma invading the extrapancreatic neural plexus (Part I): Anatomy, imaging of the extrapancreatic nerve

    PubMed Central

    Zuo, Hou-Dong; Zhang, Xiao-Ming; Li, Cheng-Jun; Cai, Chang-Ping; Zhao, Qiong-Hui; Xie, Xing-Guo; Xiao, Bo; Tang, Wei

    2012-01-01

    Pancreatic carcinoma is an extremely high-grade malignant tumor with fast development and high mortality. The incidence of pancreatic carcinoma continues to increase. Peripancreatic invasion and metastasis are the main characteristics and important prognostic factors in pancreatic carcinoma, especially invasion into the nervous system; pancreatic nerve innervation includes the intrapancreatic and extrapancreatic nerves. A strong grasp of pancreatic nerve innervation may contribute to our understanding of pancreatic pain modalities and the metastatic routes for pancreatic carcinomas. Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful techniques for depicting the anatomy of extrapancreatic nerve innervation. The purpose of the present work is to show and describe the anatomy of the extrapancreatic neural plexus and to elucidate its characteristics using CT and MRI, drawing on our own previous work and the research findings of others. PMID:22423316

  9. High-intensity focused ultrasound therapy in combination with gemcitabine for unresectable pancreatic carcinoma

    PubMed Central

    Lv, Wei; Yan, Tao; Wang, Guojin; Zhao, Wei; Zhang, Tao; Zhou, Dinghua

    2016-01-01

    Objective To investigate the therapeutic effect and safety of high-intensity focused ultrasound (HIFU) therapy combined with gemcitabine in treating unresectable pancreatic carcinoma. Methods The 45 patients suffering from pancreatic carcinoma were randomized into two groups. The patients in the experimental group (n=23) received HIFU in combination with gemcitabine and those in the control group (n=22) received gemcitabine alone. The effect and clinical benefit rates in the two groups were compared. The median survival time and 6-month and 12-month survival rates were calculated by Kaplan–Meier method and log-rank test. Results The median survival time and 6-month survival rate were significantly higher in the experimental group than in the control group (8.91 months vs 5.53 months, 73.9% vs 40.9%, respectively P<0.05), but 12-month survival rate was not statistically different between the two groups (13.0% vs 4.5%, P>0.05). The clinical benefit rates in the experimental group and the control group were 69.6% and 36.3%, respectively (P<0.05). The pain remission rate in the experimental group was significantly higher than that in the control group (65.2% vs 31.8%, P<0.05). Conclusion HIFU in combination with gemcitabine is better than gemcitabine alone. This combinatorial therapy may become a better and effective treatment for unresectable pancreatic carcinoma. PMID:27194912

  10. A malignant cause of hypoglycaemia: a metastatic insulin-secreting pancreatic neuroendocrine carcinoma.

    PubMed

    Sandoval, Mark Anthony; Pagsisihan, Daveric; Berberabe, A'Ericson; Palugod-Lopez, Elaine Gayle

    2016-01-01

    Most cases of insulinomas are benign. We report a case of a malignant form of insulinoma. A 46-year-old man presented with behavioural changes associated with hypoglycaemia. Diagnostic work up revealed high serum insulin, high C-peptide and low glucose levels, compatible with endogenous hyperinsulinaemic hypoglycaemia. CT imaging of the abdomen revealed a pancreatic head mass and multiple liver masses. Biopsy of the pancreatic mass revealed a grade three pancreatic neuroendocrine carcinoma. Histological analysis of a liver mass showed that it was identical to the pancreatic mass, confirming its metastatic nature. The patient underwent distal pancreatectomy with en bloc splenectomy. There was persistence of hypoglycaemic symptoms after removal of the pancreatic mass, suggesting that the liver metastases were also functioning. Symptoms were controlled by diazoxide and octreotide long-acting release. The patient is already 1 year postsurgery with no recurrence of severe hypoglycaemia, and he has good functional capacity and has returned to his office job. PMID:26994053

  11. 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.

  12. Pancreatitis

    MedlinePlus

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  13. 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

  14. 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

  15. 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

  16. Clinical Impact of Pancreatic Metastases from Renal Cell Carcinoma: A Multicenter Retrospective Analysis

    PubMed Central

    Grassi, Paolo; Doucet, Ludovic; Giglione, Palma; Grünwald, Viktor; Melichar, Bohuslav; Galli, Luca; De Giorgi, Ugo; Sabbatini, Roberto; Ortega, Cinzia; Santoni, Matteo; Bamias, Aristotelis; Verzoni, Elena; Derosa, Lisa; Studentova, Hana; Pacifici, Monica; Coppa, Jorgelina; Mazzaferro, Vincenzo; de Braud, Filippo; Porta, Camillo; Escudier, Bernard; Procopio, Giuseppe

    2016-01-01

    Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox’s proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54–142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10–14). Median overall survival was 73 months (95% CI 61–86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78–204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36–11.92; p<0.0001), Memorial Sloan Kettering/International Metastatic RCC Database Consortium prognostic score (HR 1.45, 95% CI 0.94–2.23 for intermediate vs good vs risk; HR 2.76 95%, CI 1.43–5.35 for poor vs good risk p = 0.0099) and pancreatic local treatment (HR 0.48; 95%CI 0.30–0.78 p = 0.0029) were associated with overall survival. Difference in median OS between patients with PM and that reported in a matched-control group of mRCC patients with extrapancreatic metastases was statistically significant (p < .0001). Pancreatic metastases from renal cell carcinoma usually occur years after nephrectomy, are associated with an indolent behavior and a prolonged survival. Targeted therapies and locoregional approaches are active and achieve high disease control rate. PMID:27064898

  17. Clinical Impact of Pancreatic Metastases from Renal Cell Carcinoma: A Multicenter Retrospective Analysis.

    PubMed

    Grassi, Paolo; Doucet, Ludovic; Giglione, Palma; Grünwald, Viktor; Melichar, Bohuslav; Galli, Luca; De Giorgi, Ugo; Sabbatini, Roberto; Ortega, Cinzia; Santoni, Matteo; Bamias, Aristotelis; Verzoni, Elena; Derosa, Lisa; Studentova, Hana; Pacifici, Monica; Coppa, Jorgelina; Mazzaferro, Vincenzo; de Braud, Filippo; Porta, Camillo; Escudier, Bernard; Procopio, Giuseppe

    2016-01-01

    Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox's proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54-142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10-14). Median overall survival was 73 months (95% CI 61-86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78-204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36-11.92; p<0.0001), Memorial Sloan Kettering/International Metastatic RCC Database Consortium prognostic score (HR 1.45, 95% CI 0.94-2.23 for intermediate vs good vs risk; HR 2.76 95%, CI 1.43-5.35 for poor vs good risk p = 0.0099) and pancreatic local treatment (HR 0.48; 95%CI 0.30-0.78 p = 0.0029) were associated with overall survival. Difference in median OS between patients with PM and that reported in a matched-control group of mRCC patients with extrapancreatic metastases was statistically significant (p < .0001). Pancreatic metastases from renal cell carcinoma usually occur years after nephrectomy, are associated with an indolent behavior and a prolonged survival. Targeted therapies and locoregional approaches are active and achieve high disease control rate. PMID:27064898

  18. 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.

  19. 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

  20. 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

  1. Metronomic temozolomide as second line treatment for metastatic poorly differentiated pancreatic neuroendocrine carcinoma.

    PubMed

    De Divitiis, C; von Arx, C; Grimaldi, A M; Cicala, D; Tatangelo, F; Arcella, A; Romano, G M; Simeone, E; Iaffaioli, R V; Ascierto, P A; Tafuto, S

    2016-01-01

    Neuroendocrine Neoplasms (NEN) are a group of heterogeneous malignancies derived from neuroendocrine cell compartment, with different roles in both endocrine and nervous system. Most NETs have gastroentero-pancreatic (GEP) origin, arising in the foregut, midgut, or hindgut. The 2010 WHO classification divides GEP-NETs into two main subgroups, neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC), according with Ki-67 levels. NET are tumors with low (<20 %) Ki-67 value, and NECs, including small cell lung carcinomas and Merkel Cell carcinomas, are all NETs with high Ki-67 levels (>20 %-G3). Poorly differentiated neuroendocrine carcinomas (NEC) are usually treated with cisplatin-based chemotherapy regimens. Here we present a case of a patient with pancreatic NEC progressing after cisplatin and etoposide, treated with temozolomide as palliative, second line treatment. According with the poor Performance Status (PS = 2) and to reduce the toxicity of the treatment was chosen an intermittent dosing regimen of metronomic temozolomide (75 mg/m(2)/day-one-week-on/on-week-off). MGMT resulted methylated. On July 2014 the patient started the treatment. On August 2014 the patient obtained a significant clinical benefit (PS = 0) and the total body CT scan performed on October 2014 showed a RECIST partial response on all the sites of disease. No drug-related side effects were reported by the patient. After 18 months of therapy the treatment continues without significant toxicity, and with further remission of the metastases. Treatment with metronomic "one-week-on/on-week-off" Temozolomide can be considered a good treatment option in patients with poor performance status, affected by pNEC with MGMT methylation. PMID:27142424

  2. 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

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

    PubMed

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

    2014-01-01

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

  4. Spiclomazine Induces Apoptosis Associated with the Suppression of Cell Viability, Migration and Invasion in Pancreatic Carcinoma Cells

    PubMed Central

    Liu, Zuojia; Zheng, Xiliang; Wang, Jin; Wang, Erkang

    2013-01-01

    The effective treatment for pancreatic carcinoma remains critically needed. Herein, this current study showed that spiclomazine treatment caused a reduction in viability in pancreatic carcinoma cell lines CFPAC-1 and MIA PaCa-2 in vitro. It was notable in this regard that, compared with pancreatic carcinoma cells, normal human embryonic kidney (HEK-293) and liver (HL-7702) cells were more resistant to the antigrowth effect of spiclomazine. Biochemically, spiclomazine treatment regulated the expression of protein levels in the apoptosis related pathways. Consistent with this effect, spiclomazine reduced the mitochondria membrane potential, elevated reactive oxygen species, and activated caspase-3/9. In addition, a key finding from this study was that spiclomazine suppressed migration and invasion of cancer cells through down-regulation of MMP-2/9. Collectively, the proposed studies did shed light on the antiproliferation effect of spiclomazine on pancreatic carcinoma cell lines, and further clarified the mechanisms that spiclomazine induced apoptosis associated with the suppression of migration and invasion. PMID:23840452

  5. 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.

  6. Successful palliative approach with high-intensity focused ultrasound in a patient with metastatic anaplastic pancreatic carcinoma: a case report.

    PubMed

    Ungaro, Antonio; Orsi, Franco; Casadio, Chiara; Galdy, Salvatore; Spada, Francesca; Cella, Chiara Alessandra; Tonno, Clementina Di; Bonomo, Guido; Vigna, Paolo Della; Murgioni, Sabina; Frezza, Anna Maria; Fazio, Nicola

    2016-01-01

    We report a case of a 74-year-old man with a metastatic anaplastic pancreatic carcinoma (APC). After an early tumour progression on first-line chemotherapy with cisplatin and gemcitabine, even though it was badly tolerated, he was treated with a combination of systemic modified FOLFIRI and high-intensity focused ultrasound (HIFU) on the pancreatic mass. A tumour showing partial response with a clinical benefit was obtained. HIFU was preferred to radiotherapy because of its shorter course and minimal side effects, in order to improve the patient's clinical conditions. The patient is currently on chemotherapy, asymptomatic with a good performance status. In referral centres, with specific expertise, HIFU could be safely and successfully combined with systemic chemotherapy for treatment of metastatic pancreatic carcinoma. PMID:27170835

  7. Successful palliative approach with high-intensity focused ultrasound in a patient with metastatic anaplastic pancreatic carcinoma: a case report

    PubMed Central

    Ungaro, Antonio; Orsi, Franco; Casadio, Chiara; Galdy, Salvatore; Spada, Francesca; Cella, Chiara Alessandra; Tonno, Clementina Di; Bonomo, Guido; Vigna, Paolo Della; Murgioni, Sabina; Frezza, Anna Maria; Fazio, Nicola

    2016-01-01

    We report a case of a 74-year-old man with a metastatic anaplastic pancreatic carcinoma (APC). After an early tumour progression on first-line chemotherapy with cisplatin and gemcitabine, even though it was badly tolerated, he was treated with a combination of systemic modified FOLFIRI and high-intensity focused ultrasound (HIFU) on the pancreatic mass. A tumour showing partial response with a clinical benefit was obtained. HIFU was preferred to radiotherapy because of its shorter course and minimal side effects, in order to improve the patient’s clinical conditions. The patient is currently on chemotherapy, asymptomatic with a good performance status. In referral centres, with specific expertise, HIFU could be safely and successfully combined with systemic chemotherapy for treatment of metastatic pancreatic carcinoma. PMID:27170835

  8. 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

  9. High-Dose Lanreotide in the Treatment of Poorly Differentiated Pancreatic Neuroendocrine Carcinoma: A Case Report

    PubMed Central

    Van Fraeyenhove, Frank; Meireson, Nathalie; Terriere, Luc; Willemsen, Paul; Kunnen, Jan; Mattelaer, Caroline; Van Acker, Frank; Schrijvers, Dirk

    2014-01-01

    Pancreatic neuroendocrine tumors (NETs), including poorly differentiated carcinomas (NECs), are rarely encountered. The majority of these tumors do not secrete excess hormones, but functioning NETs produce large amounts of vasoactive peptides and may cause carcinoid syndrome. Synthetic somatostatin analogs (SSAs) have been widely used in NETs for control of hormonal syndromes. Here, we present a case of poorly differentiated, grade 3 pancreatic NEC associated with carcinoid syndrome, for which adequate symptom control was achieved for 2 years and 4 months using the long-acting SSA lanreotide Autogel®. In February 2009, a 55-year-old woman presented with episodes of flushing, diarrhea and epigastric pain. Imaging techniques revealed the presence of a metabolically active mass expressing somatostatin receptors in the hilar area of the liver. Histopathological examination confirmed the malignant nature of the mass, which was identified as a poorly differentiated grade 3 pancreatic NEC (TNM staging: T4NxM0). Therapeutic options were limited for the patient because of the extent of the primary mass involving the celiac axis, severe gastrointestinal toxicity experienced as a side effect of chemotherapy with cisplatin-etoposide and, later in the course of the disease, extensive liver metastases and carcinoid heart syndrome. Along with a palliative debulking surgery and right portal vein embolization, biotherapy with a high dose of lanreotide Autogel (120 mg/14 days) contributed to alleviation of symptoms caused by hormone overproduction, even after the development of liver metastases. These results suggest that patients with poorly differentiated NECs who exhibit signs of carcinoid syndrome can benefit from treatment with somatostatin analogs. PMID:24707264

  10. 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

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

    PubMed Central

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

    2012-01-01

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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Sensitivity of cultured pancreatic carcinoma cells to Acinetobacter glutaminase-asparaginase.

    PubMed

    Wu, M C; Arimura, G K; Holcenberg, J S; Yunis, A A

    1982-09-01

    Cultured human pancreatic carcinoma cells (MIA PaCa-2) have been shown previously to be very sensitive to E. coli L-asparaginase (EC II). The present studies have demonstrated that another enzyme, Acinetobacter glutaminase-asparaginase (AGA) is much more effective in inhibiting cell growth. At the concentration of 0.0025 U/ml of AGA activity the enzyme totally inhibited cell growth, whereas the EC II with the same concentration did not show any effect. The inhibition of cell growth correlated well with inhibition of protein and glycoprotein synthesis. The addition of L-glutamine at the concentration of 1 mM completely reversed the inhibition of protein synthesis. Similarly, the addition of L-glutamine at the concentration of 3 mM daily on 3 successive days after adding AGA resulted in significant reversal of growth inhibition. The results of this study indicate that the action of AGA on MIA PaCa-2 is, to a great extent, exerted through its L-glutaminase activity. PMID:7173949

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

    PubMed Central

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

    2014-01-01

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

  20. 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

  1. Autoimmune pancreatitis mimicking pancreatic cancer

    PubMed Central

    Hammami, Mohamed; Noomen, Faouzi; Toumi, Omar; Harzallah, Olfa; Mahmoudi, Ammar; Kallel, Wassim; Zouari, Khadija; Hamdi, Abdelaziz

    2011-01-01

    Context: Autoimmune pancreatitis is a particular type of pancreatitis of presumed autoimmune etiology, it is an entity distinct from all others forms of chronic pancreatitis, characterized by clinical, histopathological, radiographic, serologic and therapeutic features. This benign disease resembles pancreatic carcinoma both clinically and radiographically. Case Report: A 27-year-old man presented with obstructive jaundice and evocative image of pancreatic tumor. A pancreaticoduodenectomy (Whipple operation) was performed and pathological examination of the specimen diagnosed AIP. Patient responded well to a course of corticosteroids with resolution of clinical and biological disorders. Conclusion: Accurate and timely diagnosis of autoimmune pancreatitis is particularly important because steroid therapy is effective and pancreatic resection is not necessary. PMID:22361500

  2. Pancreatic Exocrine Tumors

    MedlinePlus

    ... exocrine tumors. These tumors start in the exocrine cells of the pancreas. The following table describes the most common pancreatic exocrine tumors. TYPE DESCRIPTION Adenocarcinoma ... in the cells lining the pancreatic duct. Acinar Cell Carcinoma Acinar ...

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

    PubMed Central

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

    2016-01-01

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

  4. 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, Séverine; Stanzel, Sven; Schnölzer, 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

  5. 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.

  6. A case of long-term 24-month survival in pancreatic anaplastic carcinoma (giant cell type) after S1 postoperative adjuvant chemotherapy

    PubMed Central

    Nitta, Toshikatsu; Fujii, Kensuke; Kataoka, Jun; Tominaga, Tomo; Kawasaki, Hiroshi; Ishibashi, Takashi

    2016-01-01

    We herein describe the case of a 70-year-old female patient diagnosed with pancreatic carcinoma. An abdominal enhanced computed tomography scan revealed a poorly enhanced mass (17 mm × 15 mm in size) in the pancreatic head. Magnetic resonance cholangiopancreatography revealed stenosis of the main pancreatic and common bile ducts caused by a mass-neighboring cyst. Based on these findings, we performed subtotal stomach-preserving pancreaticoduodenectomy. The patient demonstrated a good postoperative course, and was discharged from our hospital in remission 49 days after the surgery. Pathological findings confirmed that it was anaplastic pancreas carcinoma (giant cell type). After the surgery, we performed S-1 adjuvant chemotherapy 100 mg/day for four weeks, repeated similarly every six weeks for a total of four courses. We have followed this case for over 2 years so far with adjuvant chemotherapy, and no recurrence or metastasis has been revealed. Adjuvant chemotherapy with S-1 in patients with resected anaplastic carcinoma of the pancreas is also recommended as a result of Japan Adjuvant Study Group of Pancreatic Cancer 01(JASPAC-01) like the ordinary pancreatic ductal carcinomas. There is a possibility to achieve long-term survival in cases in which multidisciplinary treatment such as a curative resection and adjuvant chemotherapy are performed. PMID:27111877

  7. 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

  8. 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

  9. 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

  10. 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

    2016-05-31

    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

  11. 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

  12. ACTH-secreting pancreatic neuroendocrine carcinoma with ovarian and pelvic metastases causing Cushing’s 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 Cushing’s 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

  13. Adenoviral p53 gene transfer and gemcitabine in three patients with liver metastases due to advanced pancreatic carcinoma

    PubMed Central

    Thiede, Christian; Fischer, Rainer; Ehninger, Gerhard; Haag, Cornelie

    2007-01-01

    Background. Current therapies for adenocarcinoma of the pancreas do not improve the life expectancy of patients. Methods. In a non-randomized pilot trail we tested whether a local therapy based upon an adenoviral gene transfer of wild type p53 in combination with gemcitabine administration would be safe in patients with liver metastases due to pancreatic carcinoma. We report on the clinical course of three patients with respect to safety, tolerability and tumor response. Results. Transient grade III toxicities occurred with fever, leucopenia, elevation of AP, ALT, AST, GGT, while grade IV toxicity occurred for bilirubin only. Laboratory tests suggested disseminated intravascular coagulation in all three patients, but fine needle biopsies of liver did not show any histological evidence of thrombus or clot formation. Progression of liver metastases was documented in one and stable disease in another patient two months after treatment. However, a major improvement with regression of the indexed lesion by 80% occurred in a third patient after a single administration of 7.5×1012 viral particles, and time to progression was extended to six months. Conclusion. The combination therapy of viral gene transfer and chemotherapy temporarily controls and diminishes tumor burden. Improvement of the toxicity profile is necessary. Further trials are warranted to improve treatment and life expectancy of patients suffering from fatal diseases such as pancreatic carcinoma. PMID:18333108

  14. Neuroendocrine differentiation in cervical carcinoma.

    PubMed Central

    Savargaonkar, P R; Hale, R J; Mutton, A; Manning, V; Buckley, C H

    1996-01-01

    AIMS: To examine neuroendocrine differentiation, as shown by chromogranin A (CGA) expression, in cervical carcinomas. METHODS: Sixty seven cervical carcinomas were studied and were classified as adenocarcinomas, adenosquamous carcinomas or squamous cell carcinomas based on the assessment of haematoxylin and eosin staining and stains for mucin. Where features of glandular differentiation were identified, sections were also stained for evidence of intestinal type mucin. CGA immunostaining was done and the results were graded on a three point scale: 0, + (1-5% of cells positive) and ++ (> 5% of cells positive). These findings were then analysed with respect to lymph node status, tumour differentiation and clinical outcome. RESULTS: There were 32 adenocarcinomas, 18 adenosquamous carcinomas and 17 squamous cell carcinomas. Positive staining was seen in 14 (20.9%) cases, of which four were strongly positive. All but one case were either adenocarcinomas or adenosquamous carcinomas. There was a trend for CGA positivity to be related to intestinal differentiation but this failed to reach statistical significance. No correlation could be demonstrated between CGA staining and lymph node status, tumour differentiation and clinical outcome. CONCLUSIONS: Neuroendocrine differentiation is common in cervical carcinomas where there is evidence of glandular differentiation. Whilst the numbers in this study are relatively small, the presence of neuroendocrine cells in otherwise typical carcinomas does not seem to have any association with clinical behaviour. Images PMID:8655680

  15. Annexin A1, A2, A4 and A5 play important roles in breast cancer, pancreatic cancer and laryngeal carcinoma, alone and/or synergistically

    PubMed Central

    DENG, SHISHAN; WANG, JIANGUO; HOU, LINGMI; LI, JINSUI; CHEN, GUO; JING, BAOQIAN; ZHANG, XIAOMING; YANG, ZHENGWEI

    2013-01-01

    Annexins are associated with metastasis and infiltration of cancer cells. Proteomic analysis and immunohistochemical staining were used to understand whether several annexins play important roles in cancer alone and/or synergistically. Seven fresh breast cancer samples with 23 paraffin specimens, three fresh pancreatic samples and five fresh laryngeal carcinoma samples with 25 paraffin specimens were obtained from humans, as well as ten golden hamster pancreatic cancer tissue samples, and they were used to observe differential expression of annexins compared with normal tissues using proteomics and immunohistochemical staining. Annexin A2, A4 and A5 were overexpressed in human breast cancer and laryngeal carcinoma tissues and in golden hamster pancreatic cancer tissue samples, respectively, as shown by proteomics and immunohistochemical staining. In addition, annexin A4 and A5 were expressed in breast cancer tissues, while annexin A1 was not expressed. Annexin A1, A2 and A4 were expressed in human laryngeal carcinoma tissues as shown by immunohistochemical staining. Annexin A1, A2, A4 and A5 played important roles in breast cancer, pancreatic cancer and laryngeal carcinoma, alone and/or synergistically, and they may be targets of therapy for malignant tumors. The choice of which annexins to target should depend on their respective biological behaviors. PMID:23255903

  16. 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.

  17. 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

  18. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1992-06-01

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

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

    PubMed Central

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

    2014-01-01

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

  1. [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

  2. 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

  3. Erlotinib-associated interstitial lung disease in advanced pancreatic carcinoma: a case report and literature review.

    PubMed

    Macerelli, Marianna; Mazzer, Micol; Foltran, Luisa; Cardellino, Giovanni Gerardo; Aprile, Giuseppe

    2015-01-01

    The combination of erlotinib and gemcitabine is a recognized option for patients with metastatic pancreatic cancer whose common adverse events such as skin rash, diarrhea, or fatigue are usually easily manageable. Interstitial lung disease (ILD) is a life-threatening toxicity reported in patients with non-small-cell lung cancers treated with epidermal growth factor receptor-tyrosine kinase inhibitors or gemcitabine. This side effect is extremely rare in patients with pancreatic cancer. We report fatal treatment-related ILD that occurred in a 67-year-old patient with metastatic pancreatic cancer. Risk factors and pathophysiology of ILD need further investigation but caution is highly recommended for patients with an underlying pulmonary disease when using erlotinib in monotherapy or combination therapy. PMID:25953445

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

    NASA Astrophysics Data System (ADS)

    Mang, Thomas S.; Wieman, Thomas J.

    1988-02-01

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

  5. Pancreatic islet cell carcinoma presenting with concurrent Cushing's and Zollinger-Ellison syndromes: case series and literature review.

    PubMed

    Said, Rabih; O'Reilly, Eileen M; Blumgart, Leslie; Shia, Jinru; Abou-Alfa, Ghassan K

    2010-02-01

    Cushing's syndrome and Zollinger-Ellison syndrome occur occasionally as a result of neuroendocrine cancers. The concurrence of the two syndromes has been considered to confer a poor clinical and therapeutic outcome. In this study, we are reviewing two patients with pancreatic islet cell carcinomas and with both Zollinger-Ellison and Cushing's syndromes, one followed up for more than 5 years, and the other still receiving therapy, 5 years since diagnosis. A literature review showed that surgery has limited utility as the majority of these patients had metastases at the time of diagnosis. Proton-pump inhibitors, ketoconazole, and somatostatin antagonists have a major role in controlling symptoms. Interferon and systemic chemotherapeutic agents play a role in the management of metastatic and fast-growing cases. Chemoembolization and bland embolization show encouraging results in controlling liver metastases. The latter was used effectively and more than once in the two patients presented herein. On the basis of recent molecular genetics studies, target therapy may be helpful, however, ongoing trials will define it's utility. As the data confers a worse prognosis versus other pancreatic neuroendocrine tumors, the relatively favorable outcome of the two patients reported herein may reflect the impact of multiple therapeutic modalities. PMID:19770666

  6. 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.

  7. 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

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

    PubMed Central

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

    2014-01-01

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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Combination of Two Targeted Medications (Bevacizumab Plus Cetuximab) Improve the Therapeutic Response of Pancreatic Carcinoma.

    PubMed

    Tai, Cheng-Jeng; Huang, Ming-Te; Wu, Chih-Hsiung; Wang, Chien-Kai; Tai, Chen-Jei; Chang, Chun-Chao; Hsieh, Cheng-I; Chang, Yu-Jia; Wu, Chang-Jer; Kuo, Li-Jen; Wei, Po-Lei; Chen, Ray-Jade; Chiou, Hung-Yi

    2016-04-01

    The objective of this study is to evaluate the efficacy and safety profiles of the targeted medications, bevacizumab and cetuximab, in combination with cytostatic drugs in patients with locally advanced or metastatic pancreatic cancer.In this retrospective phase 2 study, a total of 59 patients with pancreatic cancer were recruited and received conventional (gemcitabine, cisplatin, and fluorouracil) or targeted regimen (conventional plus bevacizumab and cetuximab for the first cycle) in 2-week intervals for four cycles. The primary end-point for this study was the overall response rate. Secondary end-points were progression-free survival and the safety profiles of the combined therapy.The median time-to-progression and overall survival were 3 and 7 months, respectively, in the conventional treatment group as well as 11 and 13 months, respectively, in the targeted medications treatment group. The most common adverse events in both treatment groups were nausea and vomiting. Moderate (Grade 2) nausea and vomiting were more common in the conventional group than the targeted group but severe (Grade 3) nausea and vomiting were more common in the targeted group.Bevacizumab and cetuximab in combination with gemcitabine, cisplatin, and fluorouracil may help lengthen overall survival up to six months for patients with pancreatic cancer. PMID:27082562

  14. 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

  15. 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)

  16. Targeting of XIAP combined with systemic mesenchymal stem cell-mediated delivery of sTRAIL ligand inhibits metastatic growth of pancreatic carcinoma cells.

    PubMed

    Mohr, Andrea; Albarenque, Stella Maris; Deedigan, Laura; Yu, Rui; Reidy, Mairead; Fulda, Simone; Zwacka, Ralf Michael

    2010-11-01

    Disseminating tumors are one of the gravest medical problems. Here, we combine the tumor-specific apoptosis-inducing activity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with the ability of mesenchymal stem cells (MSCs) to infiltrate both tumor and lymphatic tissues to target primary tumors as well as disseminated cancer cells in a human pancreatic cancer mouse model. Furthermore, we targeted X-linked inhibitor of apoptosis protein (XIAP) by RNA interference (RNAi) inside the cancer cells to make use of the apoptosis sensitization as well the antimetastatic effect that is afforded by XIAP silencing. We generated MSCs, termed MSC.sTRAIL, that express and secrete a trimeric form of soluble TRAIL (sTRAIL). MSC.sTRAIL triggered limited apoptosis in human pancreatic carcinoma cells that were resistant to soluble recombinant TRAIL, which is most likely due to the enhanced effect of the direct, cell-mediated delivery of trimeric TRAIL. MSC.sTRAIL-mediated cell death was markedly increased by concomitant knockdown of XIAP by RNAi in the cancer cells. These findings were confirmed in xenograft models, in which tumors from the parental pancreatic carcinoma cells showed only growth retardation on treatment with MSC.sTRAIL, whereas tumors with silenced XIAP that were treated with MSC.sTRAIL went into remission. Moreover, animals with XIAP-negative xenografts treated with MSC.sTRAIL were almost free of lung metastasis, whereas animals treated with control MSCs showed substantial metastatic growth in the lungs. In summary, this is the first demonstration that a combined approach using systemic MSC-mediated delivery of sTRAIL together with XIAP inhibition suppresses metastatic growth of pancreatic carcinoma. PMID:20882532

  17. Single Incision Laparoscopic Pancreas Resection for Pancreatic Metastasis of Renal Cell Carcinoma

    PubMed Central

    Sümer, Aziz; Demirel, Tugrul; Karakullukçu, Nazlι; Batman, Burçin; İçscan, Yalιn; Sarιçam, Gülay; Serin, Kürçsat; Loh, Wei-Liang; Dinççağ, Ahmet; Mercan, Selçuk

    2010-01-01

    Background: Transumbilical single incision laparoscopic surgery (SILS) offers excellent cosmetic results and may be associated with decreased postoperative pain, reduced need for analgesia, and thus accelerated recovery. Herein, we report the first transumbilical single incision laparoscopic pancreatectomy case in a patient who had renal cell cancer metastasis on her pancreatic corpus and tail. Methods: A 59-year-old female who had metastatic lesions on her pancreas underwent laparoscopic subtotal pancreatectomy through a 2-cm umbilical incision. Results: Single incision pancreatectomy was performed with a special port (SILS port) and articulated equipment. The procedure lasted 330 minutes. Estimated blood loss was 100mL. No perioperative complications occurred. The patient was discharged on the seventh postoperative day with a low-volume (20mL/day) pancreatic fistula that ceased spontaneously. Pathology result of the specimen was renal cell cancer metastases. Conclusion: This is the first reported SILS pancreatectomy case, demonstrating that even advanced surgical procedures can be performed using the SILS technique in well-experienced centers. Transumbilical single incision laparoscopic pancreatectomy is feasible and can be performed safely in experienced centers. SILS may improve cosmetic results and allow accelerated recovery for patients even with malignancy requiring advanced laparoscopic interventions. PMID:21605524

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

    ClinicalTrials.gov

    2016-05-03

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

  19. 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

  20. 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

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

    ClinicalTrials.gov

    2016-05-11

    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

  2. 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

  3. 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.

  4. Chronic pancreatitis

    MedlinePlus

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  5. Anaplastic Carcinoma Arising in a Mucinous Cystic Neoplasm Masquerading as Pancreatic Pseudocyst.

    PubMed

    Aldaoud, Najla; Joudeh, Amani; Al-Momen, Sami; Alnahawi, Mamdouh; Al-Abbadi, Mousa A

    2016-06-01

    Mucinous cystic neoplasms (MCN) of the pancreas can vary from benign to premalignant and malignant. Preoperative diagnosis is essential to offer the patient appropriate treatment. Occasionally these cases may harbor anaplastic carcinoma while clinically masquerade as a pseudocyst. Here in, we report an unusual case of a 37-year old female presented with recurrent abdominal pain that was suspected clinically and by imaging studies to have a pseudocyst. EUS-FNA with internal drainage of the cyst was performed. Cytological evaluation of the cyst fluid showed numerous inflammatory cells composed mainly of many neutrophils admixed with macrophages reminiscent of the usual pseudocyst content but there were scattered rare dyscohesive malignant cells which were highly pleomorphic with multinucleation. Immunostains on the cell block showed immunoreactivity of these cells including the multinucleated cells for Cam 5.2 and AE1/AE3 and focally for Ber-Ep4, Moc -31, and CA19-9. The subsequent resection confirmed the presence of anaplastic (undifferentiated) carcinoma (AC) arising in a MCN of the pancreas. Diagn. Cytopathol. 2016;44:538-542. © 2016 Wiley Periodicals, Inc. PMID:27028547

  6. Prolonged Clinical Benefit of Everolimus Therapy in the Management of High-Grade Pancreatic Neuroendocrine Carcinoma

    PubMed Central

    Fonseca, Paula J.; Uriol, Esther; Galván, José A.; Álvarez, Carlos; Pérez, Quionia; Villanueva, Noemi; Berros, José P.; Izquierdo, Marta; Viéitez, José M.

    2013-01-01

    Treatment options for patients with high-grade pancreatic neuroendocrine tumors (pNET) are limited, especially for those with progressive disease and for those who experience treatment failure. Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has been approved for the treatment of patients with low- or intermediate-grade advanced pNET. In the randomized phase III RADIANT-3 study in patients with low- or intermediate-grade advanced pNET, everolimus significantly increased progression-free survival (PFS) and decreased the relative risk for disease progression by 65% over placebo. This case report describes a heavily pretreated patient with high-grade pNET and liver and peritoneal metastases who achieved prolonged PFS, clinically relevant partial radiologic tumor response, and resolution of constitutional symptoms with improvement in Karnofsky performance status while receiving a combination of everolimus and octreotide long-acting repeatable (LAR). Radiologic and clinical responses were maintained for 19 months, with minimal toxicity over the course of treatment. This case supports the findings that the combination of everolimus plus octreotide LAR may be considered for use in patients with high-grade pNET and progressive disease. Although behavior and aggressiveness are different between low- or intermediate-grade and high-grade pNET, some high-grade pNET may express mTOR; hence, everolimus should be considered in a clinical trial. PMID:24019785

  7. 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

  8. Uncommon pancreatic tumors and pseudotumors.

    PubMed

    Lalwani, Neeraj; Mannelli, Lorenzo; Ganeshan, Dhakshina Moorthy; Shanbhogue, Alampady K; Dighe, Manjiri K; Tiwari, Hina Arif; Maximin, Suresh; Monti, Serena; Ragucci, Monica; Prasad, Srinivasa R

    2015-01-01

    A heterogeneous group of uncommon neoplastic and non-neoplastic pancreatic pathologies exists that can mimic pancreatic adenocarcinoma. These "imitators" are unique and may demonstrate characteristic clinical and imaging features. Imaging characteristics of some of these diverse lesions are not well described in the literature, and erroneous diagnoses of these entities as pancreatic carcinoma may be responsible for unnecessary surgeries. Knowledge of these selected pancreatic pathologies is essential to facilitate optimal patient management. PMID:25063236

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2006-05-01

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

  11. 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

  12. Diagnosis of pancreatic cancer

    PubMed Central

    Miura, Fumihiko; Amano, Hodaka; Yoshida, Masahiro; Furui, Shigeru; Takeshita, Koji

    2006-01-01

    The ability to diagnose pancreatic carcinoma has been rapidly improving with the recent advances in diagnostic techniques such as contrast-enhanced Doppler ultrasound (US), helical computed tomography (CT), enhanced magnetic resonance imaging (MRI), and endoscopic US (EUS). Each technique has advantages and limitations, making the selection of the proper diagnostic technique, in terms of purpose and characteristics, especially important. Abdominal US is the modality often used first to identify a cause of abdominal pain or jaundice, while the accuracy of conventional US for diagnosing pancreatic tumors is only 50–70%. CT is the most widely used imaging examination for the detection and staging of pancreatic carcinoma. Pancreatic adenocarcinoma is generally depicted as a hypoattenuating area on contrast-enhanced CT. The reported sensitivity of helical CT in revealing pancreatic carcinoma is high, ranging between 89% and 97%. Multi-detector-row (MD) CT may offer an improvement in the early detection and accurate staging of pancreatic carcinoma. It should be taken into consideration that some pancreatic adenocarcinomas are depicted as isoattenuating and that pancreatitis accompanied by pancreatic adenocarcinoma might occasionally result in the overestimation of staging. T1-weighted spin-echo images with fat suppression and dynamic gradient-echo MR images enhanced with gadolinium have been reported to be superior to helical CT for detecting small lesions. However, chronic pancreatitis and pancreatic carcinoma are not distinguished on the basis of degree and time of enhancement on dynamic gadolinium-enhanced MRI. EUS is superior to spiral CT and MRI in the detection of small tumors, and can also localize lymph node metastases or vascular tumor infiltration with high sensitivity. EUS-guided fine-needle aspiration biopsy is a safe and highly accurate method for tissue diagnosis of patients with suspected pancreatic carcinoma. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been suggested as a promising modality for noninvasive differentiation between benign and malignant lesions. Previous studies reported the sensitivity and specificity of FDG-PET for detecting malignant pancreatic tumors as being 71–100% and 64–90%, respectively. FDG-PET does not replace, but is complementary to morphologic imaging, and therefore, in doubtful cases, the method must be combined with other imaging modalities. PMID:18333085

  13. 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 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

  14. 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

  15. 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

  16. Pancreatitis - discharge

    MedlinePlus

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... You were in the hospital because you have pancreatitis. This is a swelling of the pancreas. You ...

  17. DNT cell inhibits the growth of pancreatic carcinoma via abnormal expressions of NKG2D and MICA in vivo.

    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-3 cells 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 in vivo, and the mechanism may be involved in abnormal expressions of MICA and NKG2D. PMID:26616050

  18. 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

  19. 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

  20. Elderly patients with pancreatic cancer.

    PubMed

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

    2014-07-01

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

  1. 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

  2. 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

  3. 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 Κ.; 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 4 cm). 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 (9 cm) 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

  4. APC haploinsufficiency coupled with p53 loss sufficiently induces mucinous cystic neoplasms and invasive pancreatic carcinoma in mice.

    PubMed

    Kuo, T-L; Weng, C-C; Kuo, K-K; Chen, C-Y; Wu, D-C; Hung, W-C; Cheng, K-H

    2016-04-28

    Adenomatous polyposis coli (APC), a tumor-suppressor gene critically involved in familial adenomatous polyposis, is integral in Wnt/β-catenin signaling and is implicated in the development of sporadic tumors of the distal gastrointestinal tract including pancreatic cancer (PC). Here we report for the first time that functional APC is required for the growth and maintenance of pancreatic islets and maturation. Subsequently, a non-Kras mutation-induced premalignancy mouse model was developed; in this model, APC haploinsufficiency coupled with p53 deletion resulted in the development of a distinct type of pancreatic premalignant precursors, mucinous cystic neoplasms (MCNs), exhibiting pathomechanisms identical to those observed in human MCNs, including accumulation of cystic fluid secreted by neoplastic and ovarian-like stromal cells, with 100% penetrance and the presence of hepatic and gastric metastases in >30% of the mice. The major clinical implications of this study suggest targeting the Wnt signaling pathway as a novel strategy for managing MCN. PMID:26411367

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

    NASA Astrophysics Data System (ADS)

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

    1987-03-01

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

  6. 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

  7. 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

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

    PubMed

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

    2015-11-01

    A man in his 40s was referred to our hospital with abdominal pain. A gastric submucosal tumor (SMT) was diagnosed nine years previously, but the patient was lost to follow-up. Upon our evaluation, the SMT had enlarged, as demonstrated by esophagogastroduodenoscopy and abdominal computed tomography. Endoscopic ultrasonography revealed a hypoechoic and isoechoic mosaic mass, which primarily occupied the third and fourth layers of the gastric wall. Aspiration cytodiagnosis was performed, the results of which led to a suspicion of adenocarcinoma arising from gastric ectopic pancreas. Next, we conducted segmental gastrectomy. Pathological examination showed adiponecrosis, a pancreatic stone, chronic inflammatory cell infiltration, and fibrosis. Thus, the patient was diagnosed with chronic pancreatitis occurring in a gastric aberrant pancreas. PMID:26537325

  9. 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

  10. 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.

  11. 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 ...

  12. A case of primary pancreatic non-Hodgkin B-cell lymphoma mimicking autoimmune pancreatitis.

    PubMed

    Anderloni, Andrea; Genco, Chiara; Ballarè, Marco; Carmagnola, Stefania; Battista, Serena; Repici, Alessandro

    2015-06-01

    Non Hodgkin lymphoma frequently involves the gastrointestinal tract, in particular the stomach and the small bowel. Rarely, it can also be a cause of pancreatic masses. Clinical presentation is often non-specific and may overlap with other pancreatic conditions such as carcinoma, neuroendocrine tumours and autoimmune pancreatitis. We report a case of primary pancreatic lymphoma in a young woman with jaundice, fever and abdominal pain mimicking autoimmune pancreatitis. Clinical evaluation included the abdominal Computed Tomography scan, Magnetic Resonance Imaging and an upper gastrointestinal endoscopy that revealed a large duodenal mass. Endoscopic biopsies were performed and eventually histological examination was coherent with a diagnosis of primary pancreatic lymphoma. PMID:26114186

  13. 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

  14. 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

  15. 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

  16. Hedgehog-EGFR cooperation response genes determine the oncogenic phenotype of basal cell carcinoma and tumour-initiating pancreatic cancer cells

    PubMed Central

    Eberl, Markus; Klingler, Stefan; Mangelberger, Doris; Loipetzberger, Andrea; Damhofer, Helene; Zoidl, Kerstin; Schnidar, Harald; Hache, Hendrik; Bauer, Hans-Christian; Solca, Flavio; Hauser-Kronberger, Cornelia; Ermilov, Alexandre N; Verhaegen, Monique E; Bichakjian, Christopher K; Dlugosz, Andrzej A; Nietfeld, Wilfried; Sibilia, Maria; Lehrach, Hans; Wierling, Christoph; Aberger, Fritz

    2012-01-01

    Inhibition of Hedgehog (HH)/GLI signalling in cancer is a promising therapeutic approach. Interactions between HH/GLI and other oncogenic pathways affect the strength and tumourigenicity of HH/GLI. Cooperation of HH/GLI with epidermal growth factor receptor (EGFR) signalling promotes transformation and cancer cell proliferation in vitro. However, the in vivo relevance of HH-EGFR signal integration and the critical downstream mediators are largely undefined. In this report we show that genetic and pharmacologic inhibition of EGFR signalling reduces tumour growth in mouse models of HH/GLI driven basal cell carcinoma (BCC). We describe HH-EGFR cooperation response genes including SOX2, SOX9, JUN, CXCR4 and FGF19 that are synergistically activated by HH-EGFR signal integration and required for in vivo growth of BCC cells and tumour-initiating pancreatic cancer cells. The data validate EGFR signalling as drug target in HH/GLI driven cancers and shed light on the molecular processes controlled by HH-EGFR signal cooperation, providing new therapeutic strategies based on combined targeting of HH-EGFR signalling and selected downstream target genes. PMID:22294553

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

    PubMed

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

    2016-01-26

    Adoptive immunotherapy using cytokine-induced killer (CIK) cells is a promising cancer treatment, but its efficacy is restricted by various factors, including the accumulation of myeloid-derived suppressor cells (MDSCs). In this study, we determine whether chemotherapeutic drugs that reduce MDSC levels enhance the efficacy of CIK cell therapy in the treatment of solid tumors. Fifty-three patients were included in this study; 17 were diagnosed with metastatic renal cell carcinoma (MRCC), 10 with advanced pancreatic cancer (PC), and 26 with metastatic melanoma (MM). These patients were divided into two groups: CIK cell therapy alone and CIK cell therapy combined with chemotherapy. Combining CIK cell therapy and chemotherapy increased 1-year survival rates and median survival times in MRCC and PC patients, but not in MM patients. The disease control rate did not differ between treatment groups for MRCC or MM patients, but was higher in PC patients receiving combined treatment than CIK cell treatment alone. These data suggest that addition of MDSC-decreasing chemotherapy to CIK cell therapy improves survival in MRCC and PC patients. PMID:26716894

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

    PubMed Central

    Zhang, Yong; Shang, Yiman; Gao, Quanli

    2016-01-01

    Adoptive immunotherapy using cytokine-induced killer (CIK) cells is a promising cancer treatment, but its efficacy is restricted by various factors, including the accumulation of myeloid-derived suppressor cells (MDSCs). In this study, we determine whether chemotherapeutic drugs that reduce MDSC levels enhance the efficacy of CIK cell therapy in the treatment of solid tumors. Fifty-three patients were included in this study; 17 were diagnosed with metastatic renal cell carcinoma (MRCC), 10 with advanced pancreatic cancer (PC), and 26 with metastatic melanoma (MM). These patients were divided into two groups: CIK cell therapy alone and CIK cell therapy combined with chemotherapy. Combining CIK cell therapy and chemotherapy increased 1-year survival rates and median survival times in MRCC and PC patients, but not in MM patients. The disease control rate did not differ between treatment groups for MRCC or MM patients, but was higher in PC patients receiving combined treatment than CIK cell treatment alone. These data suggest that addition of MDSC-decreasing chemotherapy to CIK cell therapy improves survival in MRCC and PC patients. PMID:26716894

  19. 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

  20. 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

  1. Mucins and Pancreatic Cancer

    PubMed Central

    Jonckheere, Nicolas; Skrypek, Nicolas; Van Seuningen, Isabelle

    2010-01-01

    Pancreatic cancer is characterized by an often dramatic outcome (five year survival < 5%) related to a late diagnosis and a lack of efficient therapy. Therefore, clinicians desperately need new biomarkers and new therapeutic tools to develop new efficient therapies. Mucins belong to an ever increasing family of O-glycoproteins. Secreted mucins are the main component of mucus protecting the epithelia whereas membrane-bound mucins are thought to play important biological roles in cell-cell and cell-matrix interactions, in cell signaling and in modulating biological properties of cancer cells. In this review, we will focus on the altered expression pattern of mucins in pancreatic cancer, from the early neoplastic lesion Pancreatic Intraepithelial Neoplasia (PanIN) to invasive pancreatic carcinomas, and the molecular mechanisms (including genetic and epigenetic regulation) and signaling pathways known to control their expression. Moreover, we will discuss the recent advances about the biology of both secreted and membrane-bound mucins and their key roles in pancreatic carcinogenesis and resistance to therapy. Finally, we will discuss exciting opportunities that mucins offer as potential therapeutic targets in pancreatic cancer. PMID:24281201

  2. 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

  3. Predictive value of metabolic 18FDG-PET response on outcomes in patients with locally advanced pancreatic carcinoma treated with definitive concurrent chemoradiotherapy

    PubMed Central

    2011-01-01

    Background We aimed to study the predictive value of combined 18F-fluoro-deoxy-D-glucose positron emission tomography and computerized tomography (FDG-PET-CT), on outcomes in locally advanced pancreatic carcinoma (LAPC) patients treated with concurrent chemoradiotherapy (C-CRT). Methods Thirty-two unresectable LAPC patients received 50.4 Gy (1.8 Gy/fr) of RT and concurrent 5-FU followed by 4 to 6 cycles of gemcitabine consolidation. Response was evaluated by FDG-PET-CT at post-C-CRT 12-week. Patients were stratified into two groups according to the median difference between pre- and post-treatment maximum standard uptake values (SUVmax) as an indicator of response for comparative analysis. Results At a median follow-up of 16.1 months, 16 (50.0%) patients experienced local/regional failures, 6 of which were detected on the first follow-up FDG-PET-CT. There were no marginal or isolated regional failures. Median pre- and post-treatment SUVmax and median difference were 14.5, 3.9, and -63.7%, respectively. Median overall survival (OS), progression-free survival (PFS), and local-regional progression-free survival (LRPFS) were 14.5, 7.3, and 10.3 months, respectively. Median OS, PFS, and LRPFS for those with greater (N = 16) versus lesser (N = 16) SUVmax change were 17.0 versus 9.8 (p = 0.001), 8.4 versus 3.8 (p = 0.005), and 12.3 versus 6.9 months (p = 0.02), respectively. On multivariate analysis, SUVmax difference was predictive of OS, PFS, and LRPFS, independent of existing covariates. Conclusions Significantly higher OS, PFS, and LRPFS in patients with greater SUVmax difference suggest that FDG-PET-CT-based metabolic response assessment is an independent predictor of clinical outcomes in LAPC patients treated with definitive C-CRT. PMID:22074002

  4. A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.

    PubMed Central

    Rigg, A.; Cunningham, D.; Gore, M.; Hill, M.; O'Brien, M.; Nicolson, M.; Chang, J.; Watson, M.; Norman, A.; Hill, A.; Oates, J.; Moore, H.; Ross, P.

    1997-01-01

    Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5). PMID:9000605

  5. Acute Pancreatitis and Pregnancy

    MedlinePlus

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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Pancreatic Cystic Neoplasms

    PubMed Central

    Limaiem, Faten; Khalfallah, Tahar; Farhat, Leila Ben; Bouraoui, Saâdia; 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

  12. 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

  13. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

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

  14. [Hereditary pancreatitis].

    PubMed

    Dyrla, Przemysław; Nowak, Tomasz; Gil, Jerzy; Adamiec, Cezary; Bobula, Mariusz; Saracyn, Marek

    2016-02-01

    Hereditary pancreatitis (HP) is a rare, heterogeneous familial disease and should be suspected in any patient who has suffered at least two attacks of acute pancreatitis for which there is no underlying cause and unexplained chronic pancreatitis with a family history in a first- or second degree relative. with an early onset, mostly during childhood. Genetic factors have been implied in cases of familial chronic pancreatitis. The most common are mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). The inflammation results in repeated DNA damage, error-prone repair mechanisms and the progressive accumulation of genetic mutations. Risk of pancreatic adenocarcinoma is a major concern of many patients with hereditary chronic pancreatitis, but the individual risk is poorly defined. Better risk models of pancreatic cancer in individual patients based on etiology of pancreatitis, family history, genetics, smoking, alcohol, diabetes and the patient's age are needed. PMID:27000817

  15. 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

  16. Advances in cryoablation for pancreatic cancer.

    PubMed

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

    2016-01-14

    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

  17. Evaluation of the Lundh test in the diagnosis of pancreatic disease.

    PubMed

    Levin, G E; Youngs, G R; Bouchier, I A

    1972-02-01

    The Lundh test meal was administered to 32 normal subjects and 53 patients with suspected pancreatic disease. Tryptic activity was measured in the recovered duodenal juice. The level of activity distinguished the normal subjects from those with independently confirmed pancreatic disease, particularly chronic pancreatitis and carcinoma of the pancreas. The advantages and disadvantages of the test are discussed. PMID:5017441

  18. Chronic Pancreatitis in Children

    MedlinePlus

    ... Children/Pediatric > Chronic Pancreatitis in Children test Chronic Pancreatitis in Children What symptoms would my child have? ... will develop diabetes in adolescence. Who gets chronic pancreatitis? Those at risk for chronic pancreatitis are children ...

  19. 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

  20. A suspicious pancreatic mass in chronic pancreatitis: pancreatic actinomycosis.

    PubMed

    de Clerck, F; Laukens, P; De Wilde, V; Vandeputte, L; Cabooter, M; Van Huysse, J; Orlent, H

    2015-01-01

    Introduction. Pancreatic actinomycosis is a chronic infection of the pancreas caused by the suppurative Gram-positive bacterium Actinomyces. It has mostly been described in patients following repeated main pancreatic duct stenting in the context of chronic pancreatitis or following pancreatic surgery. This type of pancreatitis is often erroneously interpreted as pancreatic malignancy due to the specific invasive characteristics of Actinomyces. Case. A 64-year-old male with a history of chronic pancreatitis and repeated main pancreatic duct stenting presented with weight loss, fever, night sweats, and abdominal pain. CT imaging revealed a mass in the pancreatic tail, invading the surrounding tissue and resulting in splenic vein thrombosis. Resectable pancreatic cancer was suspected, and pancreatic tail resection was performed. Postoperative findings revealed pancreatic actinomycosis instead of neoplasia. Conclusion. Pancreatic actinomycosis is a rare type of infectious pancreatitis that should be included in the differential diagnosis when a pancreatic mass is discovered in a patient with chronic pancreatitis and prior main pancreatic duct stenting. Our case emphasizes the importance of pursuing a histomorphological confirmation. PMID:25705533

  1. Pancreatic Diseases

    MedlinePlus

    ... and in front of your spine. It produces juices that help break down food and hormones that help control blood sugar levels. Problems with the pancreas can lead to many health problems. These include Pancreatitis, or inflammation of the ...

  2. 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 ...

  3. Acute pancreatitis

    MedlinePlus

    ... of acute pancreatitis may include: Acute kidney failure Acute respiratory distress syndrome (ARDS) Buildup of fluid in the abdomen ( ascites ) Cysts or abscesses in the pancreas Heart failure Low blood pressure Repeat episodes of acute ...

  4. Long-term survival with peritoneal mucinous carcinomatosis from intraductal mucinous papillary pancreatic carcinoma treated with complete cytoreduction and hyperthermic intraperitoneal chemotherapy.

    PubMed

    Arjona-Sanchez, Alvaro; Muñoz-Casares, Cristobal; Ortega-Salas, Rosa; Casado-Adam, Angela; Sanchez-Hidalgo, Juan Manuel; Rufián-Peña, Sebastián

    2014-09-01

    Traditionally, peritoneal carcinomatosis (PC) was regarded as an untreatable condition; however, the introduction of locoregional therapies combining cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) approximately two decades ago has changed this view. There is controversy, however, when a PC arises from pancreatic cancer. We have reported on an extraordinary case of an aggressive pseudomixoma peritonei arising from an invasive intraductal papillary mucinous neoplasm (IPMN) treated with complete cytoreduction and HIPEC. This combination of treatments has not been previously described. Moreover, a very long-term disease-free survival of up to 70 months has been achieved by this combined approach. This approach may provide some optimism for considerable life extension in selected patients who present with an aggressive peritoneal mucinous carcinomatosis of pancreatic origin considered suitable only for palliative care. PMID:25256894

  5. 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-κB) 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-κB 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

  6. Acute pancreatitis.

    PubMed

    Hotz, H G; Reber, H A

    1999-09-01

    Efforts to unravel the intracellular processes that occur in acute pancreatitis continue. In cerulein pancreatitis, new evidence supports the idea that a very early event is premature trypsinogen activation triggered by lysosomal cathepsin B. Clinicians persist in trying to identify more sensitive and specific prognostic signs of the severity of attacks of pancreatitis; one study suggests that computer-based neural networks may be an alternative to biochemical markers and clinical scoring systems. The systemic severity of episodes of pancreatitis seems to be related to a multitude of proinflammatory cytokines and chemokines acting at sites distant from the pancreas. Selective blockade of some of these peptides (eg, endothelin-1 and platelet-activating factor) has decreased mortality and distant organ damage in animal models and may deserve clinical evaluation. Gene therapy may be more efficient than pharmacologic therapy in increasing anti-inflammatory cytokine (interleukin-10) levels. Clinical studies have further underlined the usefulness of prophylactic antibiotics in severe acute pancreatitis. Radiologic and endoscopic techniques may be alternatives to surgery for certain complications of pancreatitis (eg, infected necrosis and pseudocysts) in particular subsets of patients. PMID:17023979

  7. 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

  8. Acute Pancreatitis (Beyond the Basics)

    MedlinePlus

    ... pancreatitis. (See "Patient information: Gallstones (Beyond the Basics)" .) Alcoholic pancreatitis — Alcohol is a common cause of acute pancreatitis. Alcoholic pancreatitis is more common in individuals who have ...

  9. A retrospective study of pancreatic tumors in slaughter cattle.

    PubMed

    Kelley, L C; Harmon, B G; McCaskey, P C

    1996-07-01

    Sixteen primary pancreatic tumors were found in a retrospective study of bovine pancreatic lesions detected in slaughtered cattle. Eleven islet cell tumors and three pancreatic exocrine carcinomas were identified based on light microscopy and immunohistochemistry. Nine of 11 islet cell tumors were classified as malignant. Metastatic sites included iliac, mediastinal, hepatic, and mesenteric lymph nodes, peritoneum, mesentery, and liver. Six cows with multiple islet cell tumors also had pheochromocytomas. All 11 islet cell tumors had positive immunoreactivity to insulin and somatostatin. Three tumors also contained cells immunoreactive for glucagon and two tumors contained pancreatic polypeptide immunoreactive cells. Immunoreactivity of tumor cells in metastatic sites was similar to their respective primary tumors. All exocrine pancreatic carcinomas metastasized widely and were immunonegative for insulin, somatostatin, glucagon, and pancreatic polypeptide. No mixed endocrine-exocrine tumors were identified. None of the endocrine or exocrine tumors contained amyloid. Additional primary tumors of the bovine pancreas included one neurofibroma and one neurofibrosarcoma. Additional cases with lesions of the bovine pancreas included nodular hyperplasia in 15 cows, exocrine acinar atrophy and fibrosis in four cows (two of which also had pancreatic lithiasis), pancreatitis in one cow, peripancreatic fibrosis in two cows, pancreatic steatosis in one animal, and pancreatic hemorrhages in one cow. PMID:8817837

  10. Pancreatic cancer

    PubMed Central

    Güngör, C; Hofmann, B T; Wolters-Eisfeld, G; Bockhorn, M

    2014-01-01

    In recent years, it has become clear that the current standard therapeutic options for pancreatic cancer are not adequate and still do not meet the criteria to cure patients suffering from this lethal disease. Although research over the past decade has shown very interesting and promising new therapeutic options for these patients, only minor clinical success was achieved. Therefore, there is still an urgent need for new approaches that deal with early detection and new therapeutic options in pancreatic cancer. To provide optimal care for patients with pancreatic cancer, we need to understand better its complex molecular biology and thus to identify new target molecules that promote the proliferation and resistance to chemotherapy of pancreatic cancer cells. In spite of significant progress in curing cancers with chemotherapy, pancreatic cancer remains one of the most resistant solid tumour cancers and many studies suggest that drug-resistant cancer cells are the most aggressive with the highest relapse and metastatic rates. In this context, activated Notch signalling is strongly linked with chemoresistance and therefore reflects a rational new target to circumvent resistance to chemotherapy in pancreatic cancer. Here, we have focused our discussion on the latest research, current therapy options and recently identified target molecules such as Notch-2 and the heparin-binding growth factor midkine, which exhibit a wide range of cancer-relevant functions and therefore provide attractive new therapeutic target molecules, in terms of pancreatic cancer and other cancers also. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 PMID:24024905

  11. Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis.

    PubMed

    Kadota, Kyuichi; Nitadori, Jun-ichi; Rekhtman, Natasha; Jones, David R; Adusumilli, Prasad S; Travis, William D

    2015-09-01

    Currently, non-small cell lung carcinomas are primarily classified by light microscopy. However, recent studies have shown that poorly differentiated tumors are more accurately classified by immunohistochemistry. In this study, we investigated the use of immunohistochemical analysis in reclassifying lung carcinomas that were originally diagnosed as squamous cell carcinoma. Tumor slides and blocks were available for histologic evaluation, and tissue microarrays were constructed from 480 patients with resected lung carcinomas originally diagnosed as squamous cell carcinoma between 1999 and 2009. Immunohistochemical analyses for p40, p63, thyroid transcription factor-1 (TTF-1; clones SPT24 and 8G7G3/1), napsin A, chromogranin A, synaptophysin, and CD56 were performed. Staining intensity (weak, moderate, or strong) and distribution (focal or diffuse) were also recorded. Of all, 449 (93.5%) patients were confirmed as having squamous cell carcinomas; the cases were mostly diffusely positive for p40 and negative for TTF-1 (8G7G3/1). Twenty cases (4.2%) were reclassified as adenocarcinoma, as they were positive for TTF-1 (8G7G3/1 or SPT24) with either no or focal p40 expression, and all of them were poorly differentiated with squamoid morphology. In addition, 1 case was reclassified as adenosquamous carcinoma, 4 cases as large cell carcinoma, 4 cases as large cell neuroendocrine carcinoma, and 2 cases as small cell carcinoma. In poorly differentiated non-small cell lung carcinomas, an accurate distinction between squamous cell carcinoma and adenocarcinoma cannot be reliably determined by morphology alone and requires immunohistochemical analysis, even in resected specimens. Our findings suggest that TTF-1 8G7G3/1 may be better suited as the primary antibody in differentiating adenocarcinoma from squamous cell carcinoma. PMID:25871623

  12. 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.

  13. Pancreatic pseudocysts.

    PubMed

    Apostolou, C; Krige, J E J; Bornman, P C

    2006-11-01

    Improvements in imaging studies and a better understanding of the natural history of pancreatic fluid collections (PFCs) have allowed the different types to be clarified. Stratification of PFCs into subgroups should help in selecting from the increasing current available treatment options, which include percutaneous, endoscopic and surgical drainage. Percutaneous catheter drainage is safe and effective and should be the treatment of choice in poor-risk patients, and for infected pseudocysts related to acute pancreatitis. Endoscopic drainage should be the first management option in suitable pseudocysts related to chronic pancreatitis, if the necessary expertise is available. The high success rate and current low morbidity of elective open surgery mean that it is still the standard of management in this disease. Laparoscopic approaches are gaining favour, predominantly in drainage of collections in the lesser sac, and long-term data are awaited. The precise application of this modality will need to be critically compared with the low morbidity of mini-laparotomy, which is the current standard after non-operative treatment fails in these patients. It is essential to clearly stratify the different types of pancreatic pseudocysts, in particular with relation to acute or chronic pancreatitis, and perform a valid comparison of the different treatment modalities within groups. In this capacity a precise and transparent classification may provide valuable answers, in particular relating to optimal management according to pseudocyst type. PMID:17330634

  14. [Pancreatic ultrasonography].

    PubMed

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

    2015-04-01

    Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%. PMID:24950816

  15. 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

  16. 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

  17. [The L.A.I. test and tumor markers (Ca 19-9 and TPA) in the diagnosis of pancreatic carcinoma].

    PubMed

    Meduri, F; Bizzarini, M; Diana, F; Merenda, R; Gerunda, G E; Doni, M G; Maffei Faccioli, A

    1989-08-31

    A particular cell-mediated immune response is tested in this work: the leukocyte adherence inhibition (L.A.I.) in the presence of organ tumor antigens. Forty-two patients suspected of having pancreatic cancer were submitted to the L.A.I. test and Ca 19.9 and TPA determination. The diagnosis of pancreatic cancer was eventually surgically confirmed and staged in 30 patients. The most important features of the L.A.I. test were good specificity (94%) and the ability to diagnose stage I cancers (3/4 cases, 75%), while the other markers are more likely to diagnose more advanced stages. The L.A.I. test seems to be also useful during the follow-up period since its positivity may even be some months previous to the clinical symptoms. During follow-up the L.A.I. test proved useful in supervising the neoplastic disease course from the moment of relapse to advanced clinical symptoms. PMID:2682370

  18. Computed Tomography of Pancreatitis and Pancreatic Cancer.

    PubMed

    Furlow, Bryant

    2015-01-01

    Pancreatic disease often is asymptomatic until tissue damage and complications occur or until malignancies have reached advanced stages and have metastasized. Contrast-enhanced multidetector computed tomography plays a central role in diagnosing, staging, and treatment planning for pancreatitis and pancreatic cancer. This article introduces the functional anatomy of the pancreas and common bile duct and the epidemiology, pathobiology, and computed tomography imaging of pancreatitis, calculi, and pancreatic cancer. PMID:26199449

  19. Prognostic significance of Ki-67 antigen and p53 protein expression in pancreatic duct carcinoma: a study of the monoclonal antibodies MIB-1 and DO-7 in formalin-fixed paraffin-embedded tumour material.

    PubMed Central

    Linder, S.; Parrado, C.; Falkmer, U. G.; Blåsjö, M.; Sundelin, P.; von Rosen, A.

    1997-01-01

    Formalin-fixed paraffin-embedded material from 57 patients in whom curative resection of pancreatic carcinoma had been attempted was analysed by an immunohistochemical procedure to estimate proliferation and p53 protein expression. Using the monoclonal antibody (MAb) MIB-1, which recognizes a Ki-67 epitope, the proliferating cell index (PCI, percentage of immunoreactive tumour nuclei) and proliferating cell area (PCA, percentage of immunoreactive tumour nuclear area) were calculated using an interactive image analysis system and were compared with semiquantitative scoring of stainability. MAb DO-7, which recognizes both wild- and mutant-type p53 protein, was used to assess p53 expression in the same material. MIB-1 stainings were of high quality in 53 tumours. The median PCI was 29.7% (range 0.5-82.1%) and the median PCA was 10.6% (range 0.0-36.5%). There was a close correlation between PCI and PCA (P < 0.0001). PCI and PCA values were in conformity with the semiquantitative scoring (P < 0.0001). The p53 immunohistochemical stainings were successful in 48 tumours and the protein was expressed in 22 (46%). High PCI values (> 45%, n = 14) correlated with shorter survival time (P < 0.01). PCA (P < 0.05) and the expression of p53 protein (P < 0.001) were independent prognostic variables. Images Figure 1 Figure 2 PMID:9218733

  20. Paraneoplastic leukemoid reaction in pancreatic cancer: A case report

    PubMed Central

    Dos Santos, Mélanie; Bouhier, Karine; Dao, Manh-Thong

    2015-01-01

    Paraneoplastic leukemoid reaction is a rare syndrome defined by a leukocyte count exceeding 50 Giga/Liter (G/L), mostly described with progressive lung or renal carcinoma. We report a case of a 68-year-old man with recurrent pancreatic carcinoma presenting a leukemoid reaction with a white blood cell count of 63.87 G/L without identified infectious, iatrogenic or hematologic causes. His overall condition quickly degraded and he died three weeks after the discovery of the leukemoid reaction. This is the first case in French literature of leukemoid reaction in a patient with pancreatic carcinoma with poor prognostic value. PMID:26483880

  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. Pancreatic cancer.

    PubMed

    Kleeff, Jorg; Korc, Murray; Apte, Minoti; La Vecchia, Carlo; Johnson, Colin D; Biankin, Andrew V; Neale, Rachel E; Tempero, Margaret; Tuveson, David A; Hruban, Ralph H; Neoptolemos, John P

    2016-01-01

    Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumours do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4 - none of which are currently druggable. Indeed, therapeutic options are limited and progress in drug development is impeded because most pancreatic cancers are complex at the genomic, epigenetic and metabolic levels, with multiple activated pathways and crosstalk evident. Furthermore, the multilayered interplay between neoplastic and stromal cells in the tumour microenvironment challenges medical treatment. Fewer than 20% of patients have surgically resectable disease; however, neoadjuvant therapies might shift tumours towards resectability. Although newer drug combinations and multimodal regimens in this setting, as well as the adjuvant setting, appreciably extend survival, ∼80% of patients will relapse after surgery and ultimately die of their disease. Thus, consideration of quality of life and overall survival is important. In this Primer, we summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of this disease. In addition, we present an outline of potential future directions for pancreatic cancer research and patient management. PMID:27158978

  3. 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 ...

  4. 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 ...

  5. Is Pancreatic Cancer Hereditary?

    MedlinePlus

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

  6. 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

  7. 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.

  8. 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

  9. 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

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

    SciTech Connect

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

    2010-03-01

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

  11. 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

  12. Complications of pancreatic surgery

    PubMed Central

    Andrén-Sandberg, Åke

    2011-01-01

    Many diseases, including pancreatitis benign tumors and cancer, may require pancreas surgery. Pancreatic resection can lead to a prolonged survival in pancreatic cancer and even a potential chance for cure. However, the pancreatic surgery can result in complications, and high postoperative morbidity rates are still presence. This article reviews the pancreatic abstracts of American Pancreas Club 2011, which involves the more common complications, their prevention and treatment. PMID:22363072

  13. [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

  14. 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, Béatrice; Péoc'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

  15. 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 (PPARγ) 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-κB and TGFβ. Regulation of pathways involved in pancreatic carcinogenesis is effectuated by the Ubiquitin Proteasome System (UPS). This paper will examine PPARγ in pancreatic cancer, the regulation of this nuclear receptor by the UPS, and their relationship to other pathways important in pancreatic carcinogenesis. PMID:23049538

  16. 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

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

    PubMed

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

    The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas. PMID:27232353

  18. [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

  19. 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.

  20. 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 in vitro and in vivo. In our in vitro 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

  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. Middle segment-preserving pancreatectomy for recurrent metastasis of renal cell carcinoma after pancreatoduodenectomy: a case report.

    PubMed

    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

  6. 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

  7. 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

  8. Receptor strategies in pancreatitis.

    PubMed Central

    Grendell, J. H.

    1992-01-01

    A variety of receptors on pancreatic acinar and duct cells regulate both pancreatic exocrine secretion and intracellular processes. These receptors are potential sites of action for therapeutic agents in the treatment of pancreatitis. Cholecystokinin (CCK) receptor antagonists, which may reduce the level of metabolic "stress" on acinar cells, have been shown to mitigate the severity of acute pancreatitis in a number of models. Not all studies have shown a benefit, however, and differences may exist between different structural classes of antagonists. Because increased pancreatic stimulation due to loss of feedback inhibition of CCK has been proposed to contribute to the pain of some patients with chronic pancreatitis, CCK receptor antagonists could also be of benefit in this setting. Somatostatin and its analogs diminish pancreatic secretion of water and electrolytes and have been effective in treating pancreatic fistulas and pseudocysts. These agents are also being evaluated for their ability to reduce pain in chronic pancreatitis (perhaps by reducing ductal pressure by diminishing secretory volume) and mitigating the severity of acute pancreatitis (possibly by reducing the metabolic load on acinar cells). Recently described secretin receptor antagonists may also have therapeutic value as a means of selectively inhibiting pancreatic secretion of water and electrolytes. PMID:1340060

  9. 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

  10. Pancreatic Cancer Genetics.

    PubMed

    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

  11. 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

  12. Inherited pancreatic cancer syndromes.

    PubMed

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

    2012-01-01

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

  13. Pancreatic cancer genomics: insights and opportunities for clinical translation

    PubMed Central

    2013-01-01

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

  14. Vitamin D Receptor Signaling and Pancreatic Cancer Cell EMT

    PubMed Central

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

    2016-01-01

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

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

    2015-01-01

    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

  16. [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

  17. 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

  18. Human papillomavirus-related carcinomas of the sinonasal tract.

    PubMed

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

    2013-02-01

    High-risk human papillomavirus (HPV) is an established cause of head and neck carcinomas arising in the oropharynx. The presence of HPV has also been reported in some carcinomas arising in the sinonasal tract, but little is known about their overall incidence or their clinicopathologic profile. The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. p16 immunohistochemical analysis and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcome data were extracted from patient medical records. Of 161 sinonasal carcinomas, 34 (21%) were positive for high-risk HPV DNA, including type 16 (82%), type 31/33 (12%), and type 18 (6%). HPV-positive carcinomas consisted of 28 squamous cell carcinomas and variants (15 nonkeratinizing or partially keratinizing, 4 papillary, 5 adenosquamous, 4 basaloid), 1 small cell carcinoma, 1 sinonasal undifferentiated carcinoma, and 4 carcinomas that were difficult to classify but exhibited adenoid cystic carcinoma-like features. Immunohistochemistry for p16 was positive in 59/161 (37%) cases, and p16 expression strongly correlated with the presence of HPV DNA: 33 of 34 (97%) HPV-positive tumors exhibited high p16 expression, whereas only 26 of 127 (20%) HPV-negative tumors were p16 positive (P<0.0001). The HPV-related carcinomas occurred in 19 men and 15 women ranging in age from 33 to 87 years (mean, 54 y). A trend toward improved survival was observed in the HPV-positive group (hazard ratio=0.58, 95% confidence interval [0.26, 1.28]). The presence of high-risk HPV in 21% of sinonasal carcinomas confirms HPV as an important oncologic agent of carcinomas arising in the sinonasal tract. Although nonkeratinizing squamous cell carcinoma is the most common histologic type, there is a wide morphologic spectrum of HPV-related disease that includes a variant that resembles adenoid cystic carcinoma. The distinctiveness of these HPV-related carcinomas of the sinonasal tract with respect to risk factors, clinical behavior, and response to therapy remains to be clarified. PMID:23095507

  19. 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 ...

  20. 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 ...

  1. Pancreatic exocrine insufficiency after pancreatic surgery.

    PubMed

    Goess, Ruediger; Ceyhan, Güralp O; Friess, Helmut

    2016-06-01

    Pancreatic exocrine insufficiency is an often-underestimated complication following pancreatic surgery. After recent advances in managing acute postoperative complications the focus of current research is now shifting onto the long-term complications following pancreatectomy. Weight loss and steatorrhea as typical symptoms have high influence on the quality of life in the postoperative period. Malnutrition-related symptoms occur late and are often misinterpreted. Enzyme replacement therapy is more or less the only possible treatment option, even though not many controlled trials have been performed in this field. In this review we summarized the pathophysiology, diagnosis, risk factors and treatment options of exocrine insufficiency and focus mainly on patients with pancreaticoduodenectomy (classical Whipple), pylorus-preserving pancreaticoduodenectomy (ppWhipple) or distal pancreatectomy. Incidence of pancreatic exocrine insufficiency after surgery depends mainly on the initial diagnosis, the preoperative exocrine function and is associated with the extent of parenchyma resection. Diagnosing exocrine failure after surgery can be difficult and specific function tests are commonly not routinely performed. Starting and monitoring of enzyme replacement treatment is more based on clinical symptoms, than on objective markers. To improve the performance status of postsurgical patients it is important to consider pancreatic exocrine function as one aspect of quality of life. Further clinical trials should be initiated to gain more specific knowledge about the influence of the different pancreatic resections on pancreatic exocrine function to initialize proper treatment even before major clinical symptoms occur. PMID:27058237

  2. Spontaneous Primary Squamous Cell Carcinoma of the Lung in a Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Jean, Sherrie M; Morales, Pablo R; Paul, Katherine; Garcia, AnaPatricia

    2011-01-01

    A 3-y-old male rhesus macaque (Macaca mulatta) was noticed to be lethargic in the compound. Physical exam revealed cyanotic mucous membranes, dyspnea, bilateral harsh lung sounds, wheezing on expiration, and a firm mass possibly associated with the liver. Radiographs revealed bilateral soft tissue opacities in the thorax. Due to poor prognosis, the rhesus was euthanized, and a necropsy was performed. Both right and left lung lobes were consolidated and had multifocal white–tan masses. On cut section, the masses were firm, had areas of necrosis, hemorrhage, and often contained a tenacious exudate. Masses were identified in the liver and both kidneys. Given the morphologic features of the neoplasm, a diagnosis of squamous cell carcinoma was made. Immunohistochemistry staining for thyroid transcription factor, a nuclear transcription factor normally found in lung, thyroid, and tumors arising from either of those tissues, confirmed that the masses originated from the lung. Malignant primary lung tumors are divided into 8 main histologic subtypes: squamous cell carcinoma, small-cell carcinoma, large-cell carcinoma, adenocarcinoma, adenosquamous carcinoma, sarcomatoid carcinoma, carcinoid tumor, and salivary gland tumors. Clinical signs associated with lung tumors include, but are not limited to, dyspnea, coughing, hemoptysis, lethargy, anorexia, and weight loss. Although squamous cell carcinoma will be low on the differential list for these clinical signs, we encourage clinicians and researchers to not rule it out solely based on incidence and age of the animal. PMID:21640039

  3. Human papillomavirus-related head and neck squamous cell carcinoma variants.

    PubMed

    El-Mofty, Samir K

    2015-01-01

    During the last few decades, a phenotypically distinct type of head and neck squamous cell carcinoma (SCC), which is etiologically related to human papillomavirus (HPV), has emerged, and its prevalence continues to increase. The tumors are site-specific with special predilection for the oropharynx. They are morphologically and molecularly distinct and are responsive to different types of treatment modalities, with excellent clinical outcome, in spite of early lymph node metastasis. Microscopically, the carcinomas are nonkeratinizing SCCs. More recently, other variants that are believed to be etiologically related to HPV are reported. As a result, several clinical and pathologic questions have emerged. Importantly, whether the virus is biologically active in these tumors and involved in their pathogenesis, and second, what are the clinical implications with regard to patient management and outcome in these HPV-related variants. This review is an attempt to answer some of these questions based on information derived from available yet limited number of publications. The variants to be discussed include nonkeratinizing SCC (NKSCC), NKSCC with maturation (hybrid type), keratinizing SCC (KSSC), basaloid squamous carcinoma (BSCC), undifferentiated carcinoma (UC), papillary SCC (PSCC), small cell carcinoma, adenosquamous carcinoma (AdSCC), and spindle cell (sarcomatoid) carcinoma. PMID:25804342

  4. Identification of cystatin SN as a novel biomarker for pancreatic cancer.

    PubMed

    Jiang, Jie; Liu, Hui-Ling; Liu, Zhi-Hao; Tan, Si-Wei; Wu, Bin

    2015-05-01

    Cystatin SN (cystatin 1, CST1) is a member of the cystatin superfamily that inhibits the proteolytic activity of cysteine proteases. CST1 is a tumor biomarker that provides useful information for the diagnosis of esophageal, gastric, and colorectal carcinomas. However, the significance of CST1 in pancreatic cancer is unknown. The aim of this study was to assess whether CST1 is a potential biomarker for early diagnosis of malignant pancreatic neoplasms. Microarray analysis of mRNA extracted from pancreatic cancer and pancreatic normal tissues was performed. Bioinformatics revealed that CST1 was one of the highest expressed genes on the array in pancreatic cancer, compared with normal tissue. In addition, the upregulation of CST1 in pancreatic cancer and several pancreatic cancer cell lines was confirmed using real-time PCR (RT-PCR), immunohistochemistry, and Western blotting. Next, CST1 knockdown using siRNA reduced the expression of the proliferation-related proteins p-AKT and PCNA significantly, as well as colony formation and xenograft development in vitro. Consistent with this, CST1 mRNA overexpression was correlated closely with malignancy-associated proteins such as PCNA, cyclin D1, cyclin A2, and cyclin E in pancreatic cancer cell lines. In conclusion, our data suggest that CST1 might contribute to the proliferation of pancreatic cancer cells and could be a potential biomarker for the early detection of pancreatic cancer. PMID:25577248

  5. 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

  6. 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

  7. TLR9 ligation in pancreatic stellate cells promotes tumorigenesis

    PubMed Central

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

    2015-01-01

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

  8. 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.

  9. K-ras and p53 mutations in hamster pancreatic ductal adenocarcinomas and cell lines.

    PubMed Central

    Erill, N.; Cuatrecasas, M.; Sancho, F. J.; Farré, A.; Pour, P. M.; Lluís, F.; Capellá, G.

    1996-01-01

    K-ras and p53 gene alterations are frequently found in human pancreatic carcinomas and cell lines. The aim of this study was to analyze for the presence of K-ras and p53 gene mutations in hamster pancreatic tumors and cell lines. Mutations at the first coding exon of the K-ras gene and in exons V to VIII of the hamster p53 gene were analyzed in six cell lines (H2T, PC1, PC1.2, PC1.0, WD, and PD) and in N-nitroso-bis(2-oxopropyl)amine-induced pancreatic (n = 9) and extra-pancreatic (n = 4) tumors. K-ras mutations were present in seven of the nine pancreatic tumors and in all extra-pancreatic tumors. No p53 mutations were detected in the tumors. All cell lines analyzed contained K-ras mutations. Moreover, four of the six cell lines contained single amino acid substitutions in the p53 gene. Cell lines derived from nitrosamine-induced pancreatic tumors in the hamster contained K-ras and p53 alterations similar to those found in cell lines derived from human pancreatic carcinomas. Images Figure 1 Figure 2 Figure 3 PMID:8863680

  10. 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

  11. 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

  12. 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

  13. [Robotic Pancreatic Surgery].

    PubMed

    Kirchberg, J; Weitz, J

    2016-04-01

    Pancreatic surgery is one of the most challenging fields in visceral surgery. However, laparoscopic pancreatic surgery has not become the standard of care as yet, especially because of the very demanding reconstruction of anastomoses in pancreaticoduodenectomy. Robotic surgery has been a recent advance in laparoscopy. Its benefits are a better 3D view, a greater degree of freedom corresponding to that of the human hand, and tremor elimination. These factors greatly facilitate the intracorporeal suturing and knot-tying, which offers a technical advantage in performing pancreaticojejunostomy as compared with laparoscopic resections. However, only a few centres are offering this procedure for pancreatic resections. Retrospective analyses show that robotic pancreatic resections are safe und oncologically adequate if performed by experienced surgeons. Prospective, randomised trials comparing laparoscopic and robotic pancreatic resection techniques are not available to date. PMID:27074213

  14. 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 patient’s tumor are also discussed. PMID:23416985

  15. 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

  16. 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

  17. Inhibition of pancreatic tumoral cells by snake venom disintegrins

    PubMed Central

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

    2014-01-01

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

  18. Inhibition of pancreatic tumoral cells by snake venom disintegrins.

    PubMed

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

    2015-01-01

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

  19. 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

  20. 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

  1. Expression and Diagnostic Value of HE4 in Pancreatic Adenocarcinoma

    PubMed Central

    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

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

    SciTech Connect

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

    1982-04-01

    Positron emission tomography (PET) was used to assess possible pancreatic disease in 100 patients. Following injection of 10-15 mCi (370-740 MBq) of 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.

  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 /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.

  4. 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

  5. Pancreatitis after renal transplantation.

    PubMed Central

    Corrodi, P; Knoblauch, M; Binswanger, U; Schölzel, E; Largiader, F

    1975-01-01

    Pancreatitis is seldom seen as a severe complication of renal transplantation. In a review on 1321 renal transplants, 23 cases with 12 deaths are reported (Johnson and Nabseth, 1970). Single case reports may be added. In our departments pancreatitis has proved to be a fairly frequent complication. It developed in 10 (7 percent) of 147 patients with renal transplantation one week to seven and a half years after transplantation (patients with primary hyperparathyroidism excluded). Three of the eight acute cases had haemorrhagic pancreatitis, in two of them leading to death. Two patients had chronic calcifying pancreatitis. Pancreatitis was complicated in one case by abscess formation and in two by severe haemorrhage into a pseudo-cyst. In two patients the diagnosis was made at necropsy only and death was probably not related to the acute pancreatitis. The exact pathogenesis of pancreatitis after renal transplantation cannot be precisely assessed. Possible contributing factors are treatment with corticosteroids, azathioprin, and L-asparaginase, early hypercalcaemia after transplantation, surgery, infections of bacterial or viral origin, and unknown immunological processes. PMID:1093948

  6. Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C

    PubMed Central

    Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

    2016-01-01

    Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea. PMID:27044768

  7. 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

  8. [Primary pancreatic plasmacytoma].

    PubMed

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

    2014-01-01

    Extramedullary plasmacytomas are uncommon malignant plasma cell tumors that present outside the bone marrow; 80% of extramedullary plasmacytomas are located in the upper respiratory tract, and gastrointestinal plasmacytomas are rare. We present the case of an asymptomatic 65-year-old man in whom a pancreatic mass was found incidentally. The lesion was determined to be a pancreatic plasmacytoma after fine-needle aspiration cytology and surgical resection. No clinical, laboratory, or imaging findings indicative of multiple myeloma or association with other plasmacytomas were found, so the tumor was considered to be a primary pancreatic plasmacytoma. PMID:22738942

  9. Common and unusual CT and MRI manifestations of pancreatic adenocarcinoma: a pictorial review

    PubMed Central

    Yang, Min-Jie; Li, Su; Liu, Yong-Guang; Jiao, Na

    2013-01-01

    Pancreatic adenocarcinoma is the most common malignancy of the pancreas with high death rate. Preoperative imaging is crucial for the assessment of the disease and the planning of treatment. In this review, we discussed the common and unusual findings of pancreatic carcinoma. The common CT and MR findings include hypovascular mass, dilataion of upstream biliary and pancreatic ducts, invasion to adjacent structures and metastasis. The uncommon CT and MR findings include: a cystic mass, a mass without dilataion of upstream ducts, multiple masses or a lesion diffusively infiltrating most parts of the pancreas without distorting its configuration. PMID:23630658

  10. 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

  11. 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

  12. 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

  13. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez Muñoz, J Enrique

    2015-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis. The multimodal dynamic endoscopic ultrasound-guided secretin-stimulated evaluation of the pancreas provides relevant morphological and functional information for the diagnosis of chronic pancreatitis at early stages. Extracorporeal shock wave lithotripsy in patients with calcifying pancreatitis and endoscopic pancreatic stent placement are effective alternatives for pain therapy in patients with chronic pancreatitis. Presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significantly increase of mortality rate. Despite that, pancreatic enzyme replacement therapy is not prescribed in the majority of patients with pancreatic exocrine insufficiency, or it is prescribed at a low dose. The newly developed and commercialized needles for endoscopic ultrasound-guided pancreatic biopsy are effective in retrieving appropriate tissue samples for the histological diagnosis of autoimmune pancreatitis. Maintenance therapy with azathioprine is effective and safe to prevent relapses in patients with autoimmune pancreatitis. PMID:26520201

  14. 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

  15. 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

  16. [Diagnosis of chronic pancreatitis].

    PubMed

    Löser, C

    1998-11-11

    Chronic pancreatitis is typically characterized by clinical (abdominal pain, steatorrhea, loss of body weight), morphological (calcifications, dilated ductus pancreaticus) as well as functional (maldigestion, diabetes mellitus) parameters. Since the diagnosis of chronic pancreatitis is hampered by the inavailability of early histological confirmation, it is therefore based on morphological (ultrasound, ERP, EUS, CT) and functional (faecal elastase) criteria. Due to the poor correlation between morphological and functional parameters in the early phase of the disease, both are complementary at this stage. While the diagnosis of severe cases of chronic pancreatitis with steatorrhea is hardly a challenge in clinical practice, the differential diagnostic evaluation of mild and moderate cases remains a major clinical problem. ERP remains to be the most sensitive morphological procedure, while determination of faecal elastase is the most sensitive and specific "tubeless" pancreatic function test available today and in the future prove to be rapid, easy to handle and highly practicable in clinical routine. PMID:9857766

  17. 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

  18. 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

  19. Pancreatic Islet Transplantation

    MedlinePlus

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

  20. Acute Pancreatitis in Children

    MedlinePlus

    ... Patient Education Events Helpful Links Stories of Courage Cycle of Courage Share Your Story State Chapters Northern ... acute pancreatitis. These include gallstone disease, high blood calcium, high blood triglycerides, and abnormalities of the bile ...

  1. 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

  2. [Nutrition in acute pancreatitis].

    PubMed

    Mössner, J; Teich, N

    2008-08-01

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

  3. 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

  4. Gastrointestinal cancer-associated antigen CA 19-9 in histological specimens of pancreatic tumours and pancreatitis.

    PubMed Central

    Haglund, C.; Lindgren, J.; Roberts, P. J.; Nordling, S.

    1986-01-01

    The expression of the gastrointestinal cancer associated antigen CA 19-9, defined by the monoclonal antibody 1116 NS 19-9, was studied by immunoperoxidase staining in routine formalin-fixed, paraffin-embedded tissue sections from normal pancreata, pancreata with pancreatitis and from benign and malignant pancreatic neoplasms. The formalin-fixed specimens were treated with pepsin, which enhanced the staining intensity. Eighty-five per cent of well to moderately differentiated adenocarcinomas were positive. The staining was most intense in the apical border of cells lining the lumina of malignant glands, and in mucus inside the lumina, but cytoplasmic staining was also seen. In poorly differentiated adenocarcinomas the number of positive cells was smaller and in anaplastic carcinomas only occasional cells were stained. All mucinous cystadenomas and cystadenocarcinomas stained intensely, whereas serous cystadenomas, and all benign and malignant islet cell tumours were negative. Ducts in chronic pancreatitis and in normal pancreata were positive in 96% and 79%, respectively, but the staining was focal and usually weaker than in carcinomas. In acute pancreatitis (92% positive) the staining was more intense, and the CA 19-9 expression was seen predominantly in small terminal ducts and in centroacinar cells. There was an apparent correlation between the degree of differentiation of the ductal adenocarcinomas and the expression of CA 19-9, whereas the correlation between tissue expression and serum levels of CA 19-9 was poor. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:3513813

  5. 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.

  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. Peutz-Jeghers syndrome with small intestinal malignancy and cervical carcinoma

    PubMed Central

    Li, Lian-Jie; Wang, Zhi-Qing; Wu, Bao-Ping

    2008-01-01

    We report a case of 30-year-old woman with Peutz-Jeghers syndrome (PJS). Because of small intestinal obstruction, she received the small intestinal polypectomy in 2001, and the pathological diagnosis was Peutz-Jeghers polyp canceration (mucinous adenocarcinoma, infiltrating full-thickness of the intestine). The patient did not feel uncomfortable after 6 mo of chemotherapy and other management. We kept a follow-up study on her and found that she suffered from cervical cancer in 2007, with a pathological diagnosis of cervical adenosquamous carcinoma.The patient presented with typical features of PJS, but without a family history. The PJS accompanied with both small intestinal and cervical malignancies has not been reported so far in the world. PMID:19109876

  8. Hypocalcemia in acute pancreatitis revisited

    PubMed Central

    Ahmed, Armin; Azim, Afzal; Gurjar, Mohan; Baronia, Arvind Kumar

    2016-01-01

    Hypocalcemia is a frequent finding in acute pancreatitis. Severe hypocalcemia can present with neurological as well as cardiovascular manifestations. Correction of hypocalcemia by parenteral calcium infusion remains a controversial topic as intracellular calcium overload is the central mechanism of acinar cell injury in pancreatitis. The current article deals with the art and science of calcium correction in pancreatitis patients. PMID:27076730

  9. Clinical pancreatic disorder I: Acute pancreatitis.

    PubMed

    Andrén-Sandberg, Ake

    2011-07-01

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

  10. Pharmacogenetics in pancreatic cancer.

    PubMed

    Tourkantonis, Ioannis S; Peponi, Evangelia; Syrigos, Konstantinos N; Saif, Muhammad Wasif

    2014-07-01

    Pancreatic cancer is an aggressive malignancy with a poor overall survival rate. Given advances in pharmacogenomics, numerous gene mutations have been identified that could be potential targets for drug development. Therefore, future research strategies may identify prognostic and predictive markers aiming to improve outcome by maximizing efficacy whilst lowering toxicity. In this commentary, we summarize several interesting results regarding pancreatic cancer pharmacogenetics that have been presented in the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting. In particular, we focus on Abstract #4124, which investigated the potential predictive role of human equilibrative nucleoside transporter 1 (hENT1) in patients treated with adjuvant gemcitabine for pancreatic cancer, on Abstract #4125, which examined the tolerability of a modified FOLFORINOX study based on UGT1A1*28 genotype guided dosing of IRI in patients with advanced pancreatic cancer, and on Abstract #4130, which confirmed the predictive role of circulating tumor and invasive cells (CTICs) from patients with unresectable pancreatic cancer in second-line chemotherapy treatment setting. PMID:25076337

  11. 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

  12. Borderline resectable pancreatic cancer.

    PubMed

    Hackert, Thilo; Ulrich, Alexis; Büchler, Markus W

    2016-06-01

    Surgery followed by adjuvant chemotherapy remains the only treatment option for pancreatic ductal adenocarcinoma (PDAC) with the chance of long-term survival. If a radical tumor resection is possible, 5-year survival rates of 20-25% can be achieved. Pancreatic surgery has significantly changed during the past years and resection approaches have been extended beyond standard procedures, including vascular and multivisceral resections. Consequently, borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC), which has recently been defined by the International Study Group for Pancreatic Surgery (ISGPS), has become a controversial issue with regard to its management in terms of upfront resection vs. neoadjuvant treatment and sequential resection. Preoperative diagnostic accuracy to define resectability of PDAC is a keypoint in this context as well as the surgical and interdisciplinary expertise to perform advanced pancreatic surgery and manage complications. The present mini-review summarizes the current state of definition, management and outcome of BR-PDAC. Furthermore, the topic of ongoing and future studies on neoadjuvant treatment which is closely related to borderline resectability in PDAC is discussed. PMID:26970276

  13. 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

  14. 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

  15. [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

  16. Regulation of neutrophil gelatinase-associated lipocalin expression by C/EBPβ in lung carcinoma cells

    PubMed Central

    ZHANG, PI-XIAN; CHANG, JING-XIA; XIE, JIAN-JUN; YUAN, HUA-MIN; DU, ZE-PENG; ZHANG, FA-REN; LÜ, ZHUO; XU, LI-YAN; LI1, EN-MIN

    2012-01-01

    Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin family, has been found to be overexpressed in a variety of tumors, including lung adenocarcinomas. However, the mechanism by which NGAL expression is regulated in lung carcinoma needs further evaluation. In this study, immunohistochemistry was employed to analyze the expression of NGAL in lung carcinoma tissue samples, including lung squamous carcinomas, adenocarcinomas, adenosquamous carcinomas and bronchial alveolar cell carcinomas. The results showed that NGAL was expressed in 82.61% (19/23) of the samples. RT-PCR and immunofluorescent staining showed that NGAL was localized to the cytoplasm in lung carcinoma cell lines. To explore the transcriptional regulation mechanism of NGAL basal expression in lung carcinoma, a 1515-bp fragment (−1431 to +84) of the NGAL promoter region was cloned and a series of deletion and mutation constructs were generated. These constructs were analyzed using the luciferase reporter assay. The results indicated that the cis-acting elements important for the basal activity of NGAL transcription were likely located between −152 and −141. Further analysis using site-directed mutagenesis and the luciferase reporter assay suggested that the C/EBP binding sites were responsible for the activity of the NGAL promoter. Finally, the binding ability and specificity of the transcription factors were determined by electrophoretic mobility-shift assay (EMSA). The results showed that C/EBPβ was able to bind to the −152 and −141 segments. Taken together, these findings suggest that NGAL is expressed in lung carcinomas and that NGAL expression is mediated by the binding of C/EBPβ to the −152 and −141 segment of the NGAL promoter. PMID:23162623

  17. 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.

  18. Enzymatic debridement in necrotizing pancreatitis.

    PubMed

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

    2015-05-01

    Multiple organ failure and pancreatic necrosis are the factors that determine prognosis in acute pancreatitis attacks. We investigated the effects of collagenase on the debridement of experimental pancreatic necrosis. The study covered 4 groups; each group had 10 rats. Group I was the necrotizing pancreatitis group. Group II was the collagenase group with pancreatic loge by isotonic irrigation following necrotizing pancreatitis. Group III was the collagenase group with pancreatic loge following necrotizing pancreatitis. Group IV was the intraperitoneal collagenase group following necrotizing pancreatitis. The progress of the groups was compared hematologically and histopathologically. There was no difference among the groups regarding the levels of leukocyte, hemogram, and urea. The differences in AST levels between Group I and II; and differences in glucose, calcium, LDH, AST, and amylase between Group II and III; between Group II and IV; between Group I and III; and between Group I and IV were statistically significant (P < 0.05). There were statistically significant differences between Group II and III, and Group II and IV regarding edema, acinar necrosis, inflammatory cell infiltration, hemorrhage, and fat necrosis (P < 0.05). In conclusion, the collagenase preparation used in this experimental pancreatitis model was found to be effective in the debridement of pancreatic necrosis. PMID:26011212

  19. Enzymatic Debridement in Necrotizing Pancreatitis

    PubMed Central

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

    2015-01-01

    Multiple organ failure and pancreatic necrosis are the factors that determine prognosis in acute pancreatitis attacks. We investigated the effects of collagenase on the debridement of experimental pancreatic necrosis. The study covered 4 groups; each group had 10 rats. Group I was the necrotizing pancreatitis group. Group II was the collagenase group with pancreatic loge by isotonic irrigation following necrotizing pancreatitis. Group III was the collagenase group with pancreatic loge following necrotizing pancreatitis. Group IV was the intraperitoneal collagenase group following necrotizing pancreatitis. The progress of the groups was compared hematologically and histopathologically. There was no difference among the groups regarding the levels of leukocyte, hemogram, and urea. The differences in AST levels between Group I and II; and differences in glucose, calcium, LDH, AST, and amylase between Group II and III; between Group II and IV; between Group I and III; and between Group I and IV were statistically significant (P < 0.05). There were statistically significant differences between Group II and III, and Group II and IV regarding edema, acinar necrosis, inflammatory cell infiltration, hemorrhage, and fat necrosis (P < 0.05). In conclusion, the collagenase preparation used in this experimental pancreatitis model was found to be effective in the debridement of pancreatic necrosis. PMID:26011212

  20. 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

  1. 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

  2. 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

  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. [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

  7. 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

  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. 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

  10. 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

  11. Metastases of esophageal carcinoma to skeletal muscle: single center experience.

    PubMed

    Cincibuch, Jan; Mysliveček, Miroslav; Melichar, Bohuslav; Neoral, Cestmír; Metelková, Iva; Zezulová, Michaela; Procházková-Študentová, Hana; Flodr, Patrik; Zlevorová, Miloslava; Aujeský, René; Cwiertka, Karel

    2012-09-21

    Metastases of esophageal carcinoma to the skeletal muscle are rare, but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT). A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases. Four patients had skeletal muscle metastases of esophageal carcinoma, including two patients with squamous cell carcinoma. In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases, muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma. In all cases, skeletal muscle metastases were the first manifestation of systemic disease. In three patients palliation was obtained with the combination of external beam radiation therapy, systemic chemotherapy or surgical resection. Skeletal muscle metastases are a rare complication of esophageal carcinoma. PMID:23002370

  12. 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

  13. Periampullary and Pancreatic Incidentaloma

    PubMed Central

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

    2006-01-01

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

  14. 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

  15. 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

  16. 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

  17. 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

  18. Chinese herb derived-Rocaglamide A is a potent inhibitor of pancreatic cancer cells

    PubMed Central

    Wang, Baochun; Li, Yixiong; Tan, Fengbo; Xiao, Zhanxiang

    2016-01-01

    Pancreatic cancer ranks No.1 in mortality rate worldwide. This study aims to identify the novel anti-pancreatic cancer drugs. Human pancreatic carcinoma cell lines were purchased from ATCC. CPE-based screening assay was used to examine the cell viability. Patient derived tumor xenografts in SCID mice was established. The Caspase-3 and 7 activities were measured using the Caspase Glo 3/7 Assay kit. Soft agar colony formation assay was used to evaluate the colony formation. Wound healing assay was employed to determine the cell migration. We screened a Chinese herbal product library and found three “hits” that kill cancer cells at nanomolar to micromolar concentrations. One of these compounds, rocaglamide, was found to be potent inhibitors of a wide spectrum of pancreatic cancer cell lines. Furthermore, Rocaglamide reduced the tumor size in a patient-derived pancreatic cancer xenograft mouse model without noticeable toxicity in vivo. Rocaglamide also inhibits pancreatic cancer cell migration and invasion. In conclusion, these data support that Rocaglamide may be a promising anti-pancreatic cancer drug. PMID:27158390

  19. GSH2 promoter methylation in pancreatic cancer analyzed by quantitative methylation-specific polymerase chain reaction

    PubMed Central

    GAO, FEI; HUANG, HAO-JIE; GAO, JUN; LI, ZHAO-SHEN; MA, SHU-REN

    2015-01-01

    Tumor suppressor gene silencing via promoter hypermethylation is an important event in pancreatic cancer pathogenesis. Aberrant DNA hypermethylation events are highly tumor specific, and may provide a diagnostic tool for pancreatic cancer patients. The objective of the current study was to identify novel methylation-related genes that may potentially be used to establish novel therapeutic and diagnostic strategies against pancreatic cancer. The methylation status of the GS homeobox 2 (GSH2) gene was analyzed using the sodium bisulfite sequencing method. The GSH2 methylation ratio was examined in primary carcinomas and corresponding normal tissues derived from 47 patients with pancreatic cancer, using quantitative methylation-specific polymerase chain reaction. Methylation ratios were found to be associated with the patient's clinicopathological features. GSH2 gene methylation was detected in 26 (55.3%) of the 47 pancreatic cancer patients, indicating that it occurs frequently in pancreatic cancer. A significant association with methylation was observed for tumor-node-metastasis stage (P=0.031). GSH2 may be a novel methylation-sensitive tumor suppressor gene in pancreatic cancer and may be a tumor-specific biomarker of the disease. PMID:26171036

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

    ClinicalTrials.gov

    2016-05-10

    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. 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

  2. Computed tomography of pancreatic trauma

    SciTech Connect

    Jeffrey, R.B. Jr.; Federle, M.P.; Crass, R.A.

    1983-05-01

    In a review of over 300 CT scans of abdominal trauma, we encountered 13 patients with surgically proved pancreatic injuries. CT correctly diagnosed pancreatic fractures, contusions, or posttraumatic pseudocysts in 11 of these patients. There were two false positive and two false negative diagnoses. The CT diagnosis of pancreatic trauma may be difficult in selected patients who are scanned soon after injury. Acutely, the actual plane of a pancreatic fracture may be difficult to identify with CT, and the peripancreatic soft-tissue changes of traumatic pancreatitis are often subtle. Eight of 11 correctly diagnosed pancreatic injuries showed thickening of the left anterior renal fascia on CT scans. This sign should prompt a critical evaluation of the pancreas of the traumatized patient.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Squamous Cell Carcinoma

    MedlinePlus

    ... care Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin has ... has a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a common ...

  9. 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

  10. 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

  11. Molecular biology of pancreatic cancer.

    PubMed

    Belda-Iniesta, Cristóbal; Ibáñez de Cáceres, Immaculada; Barriuso, Jorge; de Castro Carpeño, Javier; González Barón, Manuel; Feliú, Jaime

    2008-09-01

    Pancreatic cancer is a leading cause of cancer death. This devastating disease has the horrible honour of close to equal incidence and mortality rates. Late diagnosis and a constitutive resistance to every chemotherapy approach are responsible for this scenario. However, molecular biology tools in cooperation with translational efforts have dissected several secrets that underlie pancreatic cancer. Progressive acquisition of malignant, invasive phenotypes from pre-malignant lesions, recent revelations on core signalling pathways and new targeted designed trials offer a better future for pancreatic cancer patients. This review will summarise recent advances in the molecular biology of pancreatic cancer. PMID:18796369

  12. [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

  13. [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

  14. 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

  15. Primary pancreatic echinococcosis.

    PubMed

    Yarlagadda, Padmaja; Yenigalla, Bindu Madhav; Penmethsa, Uma; Myneni, Ramesh Babu

    2013-07-01

    Hydatid disease is an endemic and common zoonosis in India. Liver is the most common site of infection. However, extra hepatic primary pancreatic hydatid cyst is rare. We report a case of primary hydatid cyst in the tail of pancreas compressing the adjacent organs in a 43-year-old male who presented with abdominal mass and was diagnosed as pancreatic cyst/splenic cyst by ultrasonography. Computed tomography of abdomen revealed a large cystic lesion in the tail of pancreas suggestive of a pseudocyst of pancreas. The case was managed surgically by splenectomy and distal pancreatectomy with albendazole therapy. Microbiological Investigations of aspirated fluid revealed free hooklets and invaginated scolices of Echinococcus granulosus, which was correlated with histopathological findings. PMID:24471002

  16. Primary pancreatic echinococcosis

    PubMed Central

    Yarlagadda, Padmaja; Yenigalla, Bindu Madhav; Penmethsa, Uma; Myneni, Ramesh Babu

    2013-01-01

    Hydatid disease is an endemic and common zoonosis in India. Liver is the most common site of infection. However, extra hepatic primary pancreatic hydatid cyst is rare. We report a case of primary hydatid cyst in the tail of pancreas compressing the adjacent organs in a 43-year-old male who presented with abdominal mass and was diagnosed as pancreatic cyst/splenic cyst by ultrasonography. Computed tomography of abdomen revealed a large cystic lesion in the tail of pancreas suggestive of a pseudocyst of pancreas. The case was managed surgically by splenectomy and distal pancreatectomy with albendazole therapy. Microbiological Investigations of aspirated fluid revealed free hooklets and invaginated scolices of Echinococcus granulosus, which was correlated with histopathological findings. PMID:24471002

  17. 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

  18. [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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. Pancreatic cancer: chemotherapy and radiotherapy

    PubMed Central

    Andrén-Sandberg, Åke

    2011-01-01

    Pancreatic cancer in many cases appears in a non-curatively resectable stage when the diagnosis is made. Palliative treatment become an option in the patients with advanced stage. The present article reviewed chemotherapy and radiotherapy in various advanced stage of pancreatic cancer. PMID:22540056

  6. 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

  7. Two cases of pancreatic neoplasia in British ferrets (Mustela putorius furo).

    PubMed

    Lloyd, C G; Lewis, W G V

    2004-11-01

    Two six-year-old male neutered polecat ferrets (Mustela putorius furo) were presented for the investigation of acute collapse or periodic weakness and weight loss. While blood biochemistry revealed hypoglycaemia in both cases, diagnosis of an insulin-secreting neoplasia was confirmed by exploratory surgery in one case and supported by the use of an insulin assay in the other. Subsequent histopathological examination showed the former to be a pancreatic islet cell carcinoma and the latter to be a pancreatic islet cell adenoma. While neoplasia of the pancreas commonly affects ferrets in the USA, there appears to be only one previous report from the UK. PMID:15553194

  8. 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

  9. 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

  10. [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; Lémann, 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

  11. Cystic dystrophy of the duodenal wall is not always associated with chronic pancreatitis

    PubMed Central

    Pezzilli, Raffaele; Santini, Donatella; Calculli, Lucia; Casadei, Riccardo; Morselli-Labate, Antonio Maria; Imbrogno, Andrea; Fabbri, Dario; Taffurelli, Giovanni; Ricci, Claudio; Corinaldesi, Roberto

    2011-01-01

    Cystic dystrophy of the duodenal wall is a rare form of the disease which was described in 1970 by French authors who reported the presence of focal pancreatic disease localized in an area comprising the C-loop of the duodenum and the head of the pancreas. German authors have defined this area as a “groove”. We report our recent experience on cystic dystrophy of the paraduodenal space and systematically review the data in the literature regarding the alterations of this space. A MEDLINE search of papers published between 1966 and 2010 was carried out and 59 papers were considered for the present study; there were 19 cohort studies and 40 case reports. The majority of patients having groove pancreatitis were middle aged. Mean age was significantly higher in patients having groove carcinoma. The diagnosis of cystic dystrophy of the duodenal wall can now be assessed by multidetector computer tomography, magnetic resonance imaging and endoscopic ultrasonography. These latter two techniques may also add more information on the involvement of the remaining pancreatic gland not involved by the duodenal malformation and they may help in differentiating “groove pancreatitis” from “groove adenocarcinoma”. In conclusion, chronic pancreatitis involving the entire pancreatic gland was present in half of the patients with cystic dystrophy of the duodenal wall and, in the majority of them, the pancreatitis had calcifications. PMID:22110260

  12. 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. PMID:27022231

  13. Pancreatic intraepithelial neoplasia-can we detect early pancreatic cancer?

    PubMed

    Haugk, Beate

    2010-10-01

    Haugk B
(2010) Histopathology 57, 503-514
Pancreatic intraepithelial neoplasia - can we detect early pancreatic cancer? Pancreatic cancer is one of the most lethal cancers, with an incidence equalling mortality. Pancreatic cancer is a heterogeneous group in which pancreatic ductal adenocarcinoma (PDAC) is the most common. It is now established that PDAC develops through stepwise progression from precursor lesions. Detection and treatment of these precursor lesions would allow curative treatment. Three precursor lesions for PDAC have been identified. Two of these - mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) - are rare, radiologically detectable, cystic precursor lesions which can be cured if treated at the preinvasive stage. The third and most common precursor lesion has recently been defined as pancreatic intraepithelial neoplasia (PanIN). PanINs are microscopic lesions with no clinical correlate. They display a spectrum of cyto-architectural changes (PanIN-1, PanIN-2 and PanIN-3) mirrored in an increasing accumulation of molecular genetic changes, with PanIN-3 sharing many of the alterations with PDAC. Great advances in the understanding of pancreatic carcinogenesis have opened avenues for diagnosis and chemoprevention. However, access to the pancreas is limited, molecular tests are at the early stages and too little is known about the natural history of early PanINs to justify resection. Currently, screening focuses upon high-risk individuals only. PMID:20875068

  14. 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

  15. 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

  16. Tissue expression of the tumour associated antigen CA242 in benign and malignant pancreatic lesions. A comparison with CA 50 and CA 19-9.

    PubMed Central

    Haglund, C.; Lindgren, J.; Roberts, P. J.; Kuusela, P.; Nordling, S.

    1989-01-01

    The expression of a novel tumour associated antigen CA 242, defined by the monoclonal antibody C 242, was studied by immunoperoxidase staining in formalin-fixed, paraffin-embedded tissue sections from normal pancreata, pancreata with pancreatitis and benign and malignant pancreatic neoplasms. The antigenic determinant of the C 242 antibody is a sialylated carbohydrate structure, related but chemically different from tumour marker antigens CA 19-9 and CA 50. Thirty-eight of 41 (93%) well to moderately differentiated ductal adenocarcinomas of the pancreas and all cystadenocarcinomas were positive for CA 242. The staining was most intense in the apical border of the cells, and in the intraluminal mucus. Only two out of seven poorly differentiated adenocarcinomas stained, and the number of positive cells was smaller than in well differentiated carcinomas. Only occasional cells were stained in one out of five anaplastic carcinomas. Part of large ducts were positive in 91% (21/23) specimens of chronic pancreatitis. In acute pancreatitis small terminal ducts, centro-acinar cells and some large ducts stained for CA 242. In normal pancreas only a few small terminal ducts were CA 242 positive. Carcinomas always stained more strongly for CA 242 than normal pancreatic tissue adjacent to the carcinoma. The results of CA 242 are compared with those of tumour marker antigens CA 50 and CA 19-9. Serum CA 242 levels were determined in 23 of the patients with pancreatic cancer using a fluoroimmunoassay. Fifteen (65%) patients had an elevated value. There was no clear-cut correlation between the serum levels and the immunohistochemical expression of the CA 242 antigen. The expression of CA 242 in pancreatic tissue resembles that of CA 50 and is similar to CA 19-9. The antigen is expressed in serum of many patients with pancreatic cancer and, therefore, is a potential candidate for a serum tumour marker. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:2557879

  17. 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

  18. 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

  19. 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

  20. 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

  1. Genomic Loss of DUSP4 Contributes to the Progression of Intraepithelial Neoplasm of Pancreas to Invasive Carcinoma.

    PubMed

    Hijiya, Naoki; Tsukamoto, Yoshiyuki; Nakada, Chisato; Tung Nguyen, Lam; Kai, Tomoki; Matsuura, Keiko; Shibata, Kohei; Inomata, Masafumi; Uchida, Tomohisa; Tokunaga, Akinori; Amada, Kohei; Shirao, Kuniaki; Yamada, Yasunari; Mori, Hiromu; Takeuchi, Ichiro; Seto, Masao; Aoki, Masahiro; Takekawa, Mutsuhiro; Moriyama, Masatsugu

    2016-05-01

    The progression from precursor lesions of pancreatic cancer, including pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm (IPMN), to invasive disease is characterized by stepwise accumulation of genetic alterations. However, it remains unclear whether additional alterations are required for the progression of high-grade neoplasms to invasive pancreatic carcinoma. We compared the genomic profiles of paired noninvasive and invasive carcinoma tissues collected from patients with IPMN. We demonstrate that the frequency of genomic copy-number aberrations significantly increased during the course of invasion, and the loss of 8p11.22-ter was more often associated with invasive tissues. Expression profiling in pancreatic cancer cell lines with and without 8p11.22-ter revealed that DUSP4, an MAPK phosphatase, was significantly downregulated in cells lacking 8p11.22-ter as well as in invasive carcinomas due to genomic loss. Restoration of DUSP4 expression in pancreatic cancer cells significantly suppressed invasiveness and anoikis resistance via ERK inactivation. Accordingly, we found that blockade of ERK signaling by MEK inhibition was effective in an orthotopic xenograft model and significantly extended survival. Collectively, our findings demonstrate a genetic mechanism by which pancreatic precursor lesions progress to invasive carcinomas and highlight DUSP4 as a novel invasion suppressor that can be therapeutically exploited through manipulation of ERK signaling. Cancer Res; 76(9); 2612-25. ©2016 AACR. PMID:26941286

  2. 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

  3. 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 Whipple’s triad, along with corroborating measurements of blood glucose, insulin, proinsulin, C-peptide, β-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

  4. 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

  5. Pancreatic exocrine insufficiency: diagnosis and treatment.

    PubMed

    Domínguez-Muñoz, J Enrique

    2011-03-01

    Pancreatic insufficiency is a major consequence of pancreatic diseases leading to a loss of pancreatic parenchyma, obstruction of the main pancreatic duct, decreased pancreatic stimulation, or acid-mediated inactivation of pancreatic enzymes. In addition, gastrointestinal and pancreatic surgical resections are frequent causes. Clinical manifestations include abdominal cramps, steatorrhea and malnutrition. Malnutrition, the main contributing factor of weight loss, has been related to a high morbidity and mortality secondary to an increased risk of malnutrition-related complications and cardiovascular events. Assessments of exocrine pancreatic function, such as fecal fat quantification and (13) C-triglyceride breath test, are the method of choice for diagnosis. In clinical practice, high-risk patient populations include those with severe necrotizing pancreatitis, gastrointestinal and pancreatic surgery, cancer of pancreas head, and those with pancreatic calcifications. Apart from relief of maldigestion-related symptoms, the main goal of pancreatic enzyme substitution therapy is to ensure a normal nutritional status. Therapy of pancreatic insufficiency is based on the oral administration of exogenous pancreatic enzymes. Restriction of fat intake, though traditionally important in conventional treatment, should be reconsidered. Enzyme substitution therapy should ideally mimic the physiological pattern of pancreatic exocrine secretion, and pancreatic enzymes in the form of enteric-coated minimicrospheres are considered as the most elaborated commercially available enzyme preparations. In general, pancreatic exocrine insufficiency in patients after surgery may be managed similarly to patients with chronic pancreatitis. This review focuses on current perspectives in diagnosis and treatment of pancreatic exocrine insufficiency and practical suggestions on its clinical management. PMID:21323992

  6. Merkel Cell Carcinoma

    MedlinePlus

    ... genital warts Melanoma Merkel cell carcinoma Sebaceous carcinoma Squamous cell carcinoma Skin cancer in people of color Why see ... et al . “Lack of evidence for basal or squamous cell carcinoma infection with Merkel cell polyomavirus in immunocompetent patients ...

  7. Basal Cell Carcinoma

    MedlinePlus

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  8. What Are the Key Statistics about Pancreatic Cancer?

    MedlinePlus

    ... cancer? Next Topic Pancreatic cancer risk factors Key statistics for pancreatic cancer How common is pancreatic cancer? ... can be affected by certain risk factors . For statistics related to survival, see Pancreatic cancer survival rates ...

  9. 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

  10. 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

  11. 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

  12. 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. PMID:26365583

  13. 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

  14. 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

  15. Computerized tomography in acute and chronic pancreatitis

    SciTech Connect

    Kalmar, J.A.; Matthews, C.C.; Bishop, L.A.

    1984-11-01

    Modern imaging techniques have revolutionized the diagnostic evaluation of pancreatitis, primarily demonstrating its complications. Computerized tomography (CT) is a more sensitive method than ultrasonography and pancreatic ductography. A chart review revealed 214 patients at our hospital with a discharge diagnosis of pancreatitis. Sixty patients had CT for evaluation of possible complications. Only five scans were normal. Of 37 cases of acute pancreatitis, 92% demonstrated localized or diffuse enlargement, and 65% showed loss of pancreatic outline. Other frequent findings included thickening of perirenal fascia (49%), ileus (43%), edema of mesentery (35%), and inflammatory exudate (32%). Abscess and pseudocyst were each detected in 8% of cases. In chronic pancreatitis 65% of patients showed localized or diffuse pancreatic enlargement. Atrophy of the gland (30%), calcification (30%), pseudocyst (26%), and dilated pancreatic ducts (17%) were also seen. CT is effective in evaluating pancreatitis and its complications. 14 references, 5 figures, 2 tables.

  16. Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation.

    PubMed

    Okuyama, Noriko; Ide, Yoshihito; Nakano, Miyako; Nakagawa, Tsutomu; Yamanaka, Kanako; Moriwaki, Kenta; Murata, Kohei; Ohigashi, Hiroaki; Yokoyama, Shigekazu; Eguchi, Hidetoshi; Ishikawa, Osamu; Ito, Toshifumi; Kato, Michio; Kasahara, Akinori; Kawano, Sunao; Gu, Jianguo; Taniguchi, Naoyuki; Miyoshi, Eiji

    2006-06-01

    Changes in oligosaccharide structures have been reported in certain types of malignant transformations and, thus, could be used for tumor markers in certain types of cancer. In the case of pancreatic cancer cell lines, a variety of fucosylated proteins are secreted into their conditioned media. To identify fucosylated proteins in the serum of patients with pancreatic cancer, we performed western blot analyses using Aleuria Aurantica Lectin (AAL), which is specific for fucosylated structures. An approximately 40 kD protein was found to be highly fucosylated in pancreatic cancer and an N-terminal analysis revealed that it was the beta chain of haptoglobin. While the appearance of fucosylated haptoglobin has been reported in other diseases such as hepatocellular carcinoma, liver cirrhosis, gastric cancer and colon cancer, the incidence was significantly higher in the case of pancreatic cancer. Fucosylated haptoglobin was observed more frequently at the advanced stage of pancreatic cancer and disappeared after an operation. A mass spectrometry analysis of haptoglobin purified from the serum of patients with pancreatic cancer and the medium from a pancreatic cancer cell line, PSN-1, showed that the alpha 1-3/alpha 1-4/alpha 1-6 fucosylation of haptoglobin was increased in pancreatic cancer. When a hepatoma cell line, Hep3B, was cultured with the conditioned media from pancreatic cancer cells, haptoglobin secretion was dramatically increased. These findings suggest that fucosylated haptoglobin could serve as a novel marker for pancreatic cancer. Two possibilities were considered in terms of the fucosylation of haptoglobin. One is that pancreatic cancer cells, themselves, produce fucosylated haptoglobin; the other is that pancreatic cancer produces a factor, which induces the production of fucosylated haptoglobin in the liver. PMID:16385567

  17. Constitutively Active Akt1 Cooperates with KRasG12D to Accelerate In Vivo Pancreatic Tumor Onset and Progression☆☆☆

    PubMed Central

    Albury, Toya M.; Pandey, Veethika; Gitto, Sarah B.; Dominguez, Lisette; Spinel, Lina P.; Talarchek, Jacqueline; Klein-Szanto, Andres J.; Testa, Joseph R.; Altomare, Deborah A.

    2015-01-01

    BACKGROUND AND AIMS: Pancreatic adenocarcinoma is a deadly disease characterized by metastatic progression and resistance to conventional therapeutics. Mutation of KRAS is the most frequent early event in pancreatic tumor progression. AKT isoforms are frequently activated in pancreatic cancer, and reports have implicated hyperactivation of AKT1, as well as AKT2, in pancreatic tumor formation. The objective here is to delineate the role of AKT in facilitating in vivo pancreatic tumor progression in the context of KRAS mutation and predisposition to pancreatic cancer. METHODS: Mice with Akt1 and KRas mutant alleles expressed using the pancreas Pdx promoter were mated to characterize the incidence and frequency of histologic and genetic alterations known to occur commonly in human pancreatic ductal adenocarcinoma. RESULTS: Active Akt1 (Akt1Myr, containing a myristoylation sequence) cooperated with active mutant KRasG12D to accelerate pancreatic carcinoma onset and progression and increase phosphorylation of downstream effectors in the Akt pathway. Mucin and smooth muscle actin expression was found in and around pancreatic intraepithelial neoplasms (PanINs), and accelerated time to metastasis was found in Akt1Myr/KRasG12D mice. CONCLUSIONS: In contrast to prior reports of pancreatic KRas mutant mice mated with mice deficient for various tumor suppressor genes, which resulted in aggressive disease within a few months of age, Akt1Myr/KRasG12D mice enabled the study of PanINs and spontaneous pancreatic transformation more characteristic of human pancreatic progression in elderly individuals. The Akt1Myr/KRasG12D model holds promise for delineating the tumor biology and biomarkers critical for understanding their cooperation in cancer oncogenesis and future targeting in therapeutic strategies. PMID:25748236

  18. 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

  19. Neoadjuvant strategy as initial treatment in resectable pancreatic cancer: concrete evidence of benefit.

    PubMed

    DE Felice, Francesca; Musio, Daniela; Raffetto, Nicola; Tombolini, Vincenzo

    2014-09-01

    Pancreatoduodenectomy remains the recommended treatment in potentially curative strategies for pancreatic carcinoma. Due to high local failure rates even after complete resection, a multi-modality treatment approach is paramount in the management of resectable disease. Despite there being insufficient evidence to recommend a specific neoadjuvant strategy, several studies have tested the use of preoperative chemoradiotherapy in this sub-group of patients, achieving promising results. The treatment is well-tolerated, with higher rates of negative margins and lower rates of lymph node positivity at resection, a decrease in local failure and benefit in overall survival. Considering the poor oncological results after primary surgical treatment, neoadjuvant strategy should be considered as a valid alternative in resectable pancreatic carcinoma. PMID:25202043

  20. 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.

  1. 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

  2. Valsartan-induced acute pancreatitis.

    PubMed

    Can, Burak; Sali, Mursel; Batman, Adnan; Yilmaz, Hasan; Korkmaz, Ugur; Celebi, Altay; Senturk, Omer; Hulagu, Sadettin

    2014-01-01

    Gastrointestinal toxicity is uncommon among patients treated with angiotensin II receptor antagonists. A 58-year-old man presented with nausea, vomiting and constant pain in the epigastrium that radiated to the flanks. He received treatment with valsartan (160 mg daily) for hypertension. The clinical, biochemical and radiological findings were compatible with a diagnosis of acute pancreatitis. After the patient achieved a clinical and biochemical recovery, the valsartan therapy was started again. Six weeks later, he returned to the hospital with an attack of pancreatitis. Subsequently, he returned with repeated attacks of pancreatitis twice, and the valsartan was discontinued. Ten months after the treatment, the patient had no complaints. When severe abdominal symptoms occur for no apparent reason during treatment with valsartan, a diagnosis of pancreatitis should be considered. PMID:24694480

  3. How Is Pancreatic Cancer Diagnosed?

    MedlinePlus

    ... of cancer coming back after treatment Computed tomography (CT) scan The CT scan makes detailed cross-sectional images ... special type of CT known as a multiphase CT scan or a pancreatic protocol CT scan . During this ...

  4. Vaccine therapy for pancreatic cancer

    PubMed Central

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

    2013-01-01

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

  5. 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 α-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. α-SMA+ cells were observed in large numbers in tumor stroma and as a ring around carcinomatous structures. There were scant α-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

  6. Effects of dietary fat on virus-induced pancreatic carcinogenesis in guinea fowl.

    PubMed

    Kirev, T; Woutersen, R A; Kril, A

    2002-01-01

    The present study was performed to assess the effects of diets supplemented with low (5%) and high (20%) corn oil on a Pts 56 retrovirus-induced model of pancreatic carcinogenesis in guinea fowl. The early microscopic lesions appear after 3 mo after virus treatment and progress over time. Eight to 10 mo after initiation, up to 100% of virus-inoculated birds develop multiple hyperplastic and neoplastic pancreatic lesions of duct/ductular phenotype. Short-term (1-4 mo) feeding of low- or high-fat diets, beginning at Month 3, had no significant effects on body and pancreatic weight. However, the incidence, multiplicity, and areas of the pancreatic tissue occupied by intra- and interlobular aggregates of hyperplastic ducts with mucinous metaplasia of the lining cells were significantly increased compared with the birds fed the common diet. At the same time, development of ductular neoplasms, particularly carcinomas, was retarded compared with the common diet-fed controls. Long-term (5-7 mo) fat intake resulted in an increase in body weight gain, while absolute pancreatic weights remained relatively constant. Furthermore, the high- and low-fat diets caused a significant increase in areas of retrovirus-induced pancreatic lesions, as well as an increase in multiplicity of ductular neoplasms compared with short-term fat feeding. It is concluded that short-term feeding of diets supplemented with 5% or 20% corn oil delayed the development of the common virus-induced ductular neoplasms, particularly carcinomas, and had an enhancing effect on development of hyperplastic inter- and intralobular aggregates of ducts. This finding was not observed, however, during the long-term feeding period of the study. PMID:12235656

  7. Canagliflozin-Associated Acute Pancreatitis.

    PubMed

    Verma, Rajanshu

    2016-01-01

    Canagliflozin is a new drug in class of sodium-glucose cotransporter 2 inhibitors used for treatment of type 2 diabetes mellitus. We describe a patient who developed moderately severe acute pancreatitis as an untoward consequence after being initiated on this drug. To the best of our knowledge, this is the first reported case of canagliflozin-associated acute pancreatitis in clinical literature. PMID:25187092

  8. Acute Scorpion Pancreatitis in Trinidad

    PubMed Central

    Bartholomew, Courtenay

    1970-01-01

    Over a two-month period 30 patients were admitted to hospital following stings of the scorpion of Trinidad, the Tityus trinitatis. In 24 cases acute pancreatitis developed soon after the sting, but in nine of these no abdominal pain occurred. All the patients made an uneventful recovery. Although such complications have been reported no pseudocyst formations or acute haemorrhagic pancreatitis occurred in this series. PMID:5443968

  9. [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

  10. Mimics of pancreatic ductal adenocarcinoma

    PubMed Central

    Kaza, Ravi K.; Azar, Shadi F.; Ruma, Julie A.; Francis, Isaac R.

    2013-01-01

    Abstract Several uncommon primary pancreatic tumors, inflammatory conditions, metastasis to the pancreas and peripancreatic masses can mimic the appearance of pancreatic ductal adenocarcinoma (PDA). Differentiation between these lesions and PDA can be challenging, due to the overlap in imaging features; however, familiarity with their typical imaging features and clinical presentation may be helpful in their differentiation, as in some cases, invasive diagnostic tests or unnecessary surgery can be avoided. The different pathologies that can mimic PDA include inflammatory conditions such as the various forms of pancreatitis (chronic-focal mass-forming, autoimmune and groove pancreatitis), pancreatic neuroendocrine tumors, solid pseudopapillary tumors, metastasis (solid non-lymphomatous and hematologic), congenital variants (annular pancreas), as well as peripancreatic lesions (accessory spleen, adrenal masses, duodenal masses, lymph nodes and vascular lesions), and certain rare pancreatic tumors (e.g., acinar cell tumors, solid serous tumors, hamartoma and solitary fibrous tumors). The clinical presentation and imaging features of the most commonly encountered mimics of PDA are discussed in this presentation with representative illustrations. PMID:24060833

  11. Pancreatic tumors imaging: An update.

    PubMed

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

    2016-04-01

    Currently, ultrasound (US), computed tomography (CT) and Magnetic Resonance imaging (MRI) represent the mainstay in the evaluation of pancreatic solid and cystic tumors affecting pancreas in 80-85% and 10-15% of the cases respectively. Integration of US, CT or MR imaging is essential for an accurate assessment of pancreatic parenchyma, ducts and adjacent soft tissues in order to detect and to stage the tumor, to differentiate solid from cystic lesions and to establish an appropriate treatment. The purpose of this review is to provide an overview of pancreatic tumors and the role of imaging in their diagnosis and management. In order to a prompt and accurate diagnosis and appropriate management of pancreatic lesions, it is crucial for radiologists to know the key findings of the most frequent tumors of the pancreas and the current role of imaging modalities. A multimodality approach is often helpful. If multidetector-row CT (MDCT) is the preferred initial imaging modality in patients with clinical suspicion for pancreatic cancer, multiparametric MRI provides essential information for the detection and characterization of a wide variety of pancreatic lesions and can be used as a problem-solving tool at diagnosis and during follow-up. PMID:26777740

  12. 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

  13. 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

  14. 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

  15. 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

  16. EZH2 Is Associated with Malignant Behavior in Pancreatic IPMN via p27Kip1 Downregulation

    PubMed Central

    Kuroki, Hideyuki; Hayashi, Hiromitsu; Okabe, Hirohisa; Hashimoto, Daisuke; Takamori, Hiroshi; Nakahara, Osamu; Nakagawa, Shigeki; Fukushima, Yukiko; Chikamoto, Akira; Beppu, Toru; Hirota, Masahiko; Iyama, Ken-ichi; Baba, Hideo

    2014-01-01

    Background The epigenetic mechanism of tumorigenesis in pancreatic intraductal papillary mucinous neoplasm (IPMN) remains largely unknown. The aim of this study is to examine the role of enhancer of zeste homologue 2 (EZH2) alteration in pancreatic IPMN progression. Methods Fifty-four surgically resected pancreatic IPMN specimens, including a total of 181 lesions (normal duct in 48, adenoma in 50, borderline atypia in 53, carcinoma in situ (CIS) in 19, and invasive carcinoma in 11) were analyzed by immunohistochemical staining (EZH2, Ki-67, p27Kip1). Using paraffin embedded sections, total RNA was successfully extracted from 20 IPMN lesions (borderline IPMN in 9, CIS in 6, invasive carcinoma in 5) and 7 pancreatic normal ducts, and then levels of EZH2 and p27Kip1 mRNA were analyzed by real time PCR. Results In immunohistochemical analysis, cell proliferative activity revealed by Ki-67 positive nuclei was increased during IPMN progression (normal ductcarcinoma). EZH2 expression displayed a similar pattern (normal ductcarcinoma) with cell proliferative activity. EZH2 expression in malignant (CIS and invasive carcinoma) IPMNs was significantly higher than that in adenoma and borderline-atypia IPMNs. EZH2 expression level in IPMN lesions was positively correlated with the Ki-67 positive nuclear ratio (p<0.0001). EZH2-positive cells in malignant IPMN did not express p27Kip1. EZH2 mRNA expressions in malignant lesions were significantly higher than those in benign lesions (p<0.0001). In contrast, p27Kip1 mRNA in malignant lesions was significantly decreased compared to those in benign lesion (p<0.05), and there was an inverse correlation between EZH2 and p27Kip1 mRNA levels (p = 0.0109). Conclusion EZH2 is associated with the accelerated cell proliferation and malignant step in pancreatic IPMN via the downregulation of p27Kip1. PMID:25084021

  17. Diagnosis of pancreatitis in dogs and cats.

    PubMed

    Xenoulis, P G

    2015-01-01

    Pancreatitis is the most common disorder of the exocrine pancreas in both dogs and cats. Ante-mortem diagnosis of canine and feline pancreatitis can be challenging. The clinical picture of dogs and cats with pancreatitis varies greatly (from very mild to severe or even fatal) and is characterised by non-specific findings. Complete blood count, serum biochemistry profile and urinalysis should always be performed in dogs and cats suspected of having pancreatitis, although findings are not-specific for pancreatitis. Serum amylase and lipase activities and trypsin-like immunoreactivity (TLI) concentrations have no or only limited clinical value for the diagnosis of pancreatitis in either dogs or cats. Conversely, serum pancreatic lipase immunoreactivity (PLI) concentration is currently considered to be the clinicopathological test of choice for the diagnosis of canine and feline pancreatitis. Abdominal radiography is a useful diagnostic tool for the exclusion of other diseases that may cause similar clinical signs to those of pancreatitis. Abdominal ultrasonography can be very useful for the diagnosis of pancreatitis, but this depends largely on the clinician's experience. Histopathological examination of the pancreas is considered the gold standard for the diagnosis and classification of pancreatitis, but it is not without limitations. In clinical practice, a combination of careful evaluation of the animal's history, serum PLI concentration and abdominal ultrasonography, together with pancreatic cytology or histopathology when indicated or possible, is considered to be the most practical and reliable means for an accurate diagnosis or exclusion of pancreatitis compared with other diagnostic modalities. PMID:25586803

  18. [Early diagnosis and staging of pancreatic cancer].

    PubMed

    Shiratori, Keiko

    2006-07-01

    Case of pancreatic cancer have increased in number, and the number of deaths from that disease has reached 20,000 in recent years in Japan. Only a few patients with pancreatic cancer can be cured. However, the prognosis in small pancreatic cancer such as TS1 less than 2 cm is relatively good if radical surgical resection is performed. Therefore early diagnosis of pancreatic cancer is important to improve the dismal prognosis. Although clinical symptoms are not reliable for the diagnosis of pancreatic cancer, 30% of TS1 patients have abdominal or back pain. Recent epidemiologic studies have shown that familial history of pancreatic cancer, chronic pancreatitis, diabetes, obesity, and smoking are possible high-risk factors for pancreatic cancer. Serum pancreatic enzyme and tumor markers in terms of CA19-9 and CEA are measured first. Ultrasonography (US) should be performed as soon as possible. Not only tumors but also slightly dilated main pancreatic ducts and/or small simple cysts that may represent indirect changes due to pancreatic cancer can be detected with US. Enhanced computed tomography, magnetic resonance cholangiopancreatography and endoscopic US are also useful. Endoscopic retrograde cholangiopancreatography yields more detailed images of branch ducts, and the cytology of pancreatic juice can be determined following examination. Unfortunately, position-emission tomography is not a reliable method for the diagnosis of small tumors in the pancreas. Finally, TNM staging of pancreatic cancer is performed based on the results of these imaging examinations. PMID:16878407

  19. ESPGHAN and NASPGHAN Report on the Assessment of Exocrine Pancreatic Function and Pancreatitis in Children.

    PubMed

    Taylor, Christopher J; Chen, Kathy; Horvath, Karoly; Hughes, David; Lowe, Mark E; Mehta, Devendra; Orabi, Abrahim I; Screws, Jeremy; Thomson, Mike; Van Biervliet, Stephanie; Verkade, Henkjan J; Husain, Sohail Z; Wilschanski, Michael

    2015-07-01

    The purpose of this clinical report is to discuss several recent advances in assessing exocrine pancreatic insufficiency (EPI) and pancreatitis in children, to review the array of pancreatic function tests, to provide an update on the inherited causes of EPI, with special emphasis on newly available genetic testing, and to review newer methods for evaluating pancreatitis. PMID:25915425

  20. Parathyroid carcinoma.

    PubMed

    Butt, Waqas Tariq; Azim, Asad; Abbas, Ansab; Gauhar, Tooba Mahmud; Afzal, Ameer; Azim, Khawaja Muhammad

    2012-09-01

    Parathyroid carcinoma is a rare endocrine malignancy accounting for less than 1% of all cases of hyperparathyroidism. We present a case of a middle-aged woman who was undiagnosed for 3 years before presenting with renal stones and advanced musculoskeletal disease. Investigations revealed primary hyperparathyroidism. Focused cervical exploration and left inferior parathyroidectomy was carried out based on the pre-operative localization studies. Parathyroid carcinoma was diagnosed on histopathology postoperatively. Subsequent en bloc resection was not performed and the patient is being monitored with serial parathyroid hormone levels which have not shown any increase in 6 months of follow-up. Only two previous cases of parathyroid carcinoma have been reported from Pakistan. PMID:22980615

  1. 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

  2. [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

  3. 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

  4. 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

  5. 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

  6. 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

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

    PubMed Central

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

    1996-01-01

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

  8. 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

  9. A genetically engineered mouse model developing rapid progressive pancreatic ductal adenocarcinoma.

    PubMed

    Yamaguchi, Takashi; Ikehara, Sanae; Nakanishi, Hayao; Ikehara, Yuzuru

    2014-10-01

    The premalignant lesions of pancreatic cancer, pancreatic intraepithelial neoplasia (PanIN), have a high frequency of mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS), and genetic alterations in the retinoblastoma (Rb)-E2 factor (E2F) and transformed 3T3 cell double minute 2 (MDM2)-p53 pathways accelerate development of pancreatic ductal adenocarcinoma. The viral oncoprotein SV40 large T antigen (TAg) can inhibit the effects of the Rb family of molecules and of p53 on these pathways, and targeted expression of TAg in mouse pancreas is associated with the development of endocrine or acinar cell tumours. In this study, to determine whether the viral oncoprotein promotes pancreatic duct carcinogenesis initiated by oncogenic KRAS, we generated mice expressing temperature-sensitive SV40 large T antigen (tsTAg) on pancreatic epithelial cells in the presence or absence of Kras(G12D) . Mice with pancreas-specific tsTAg expression developed acinar cell dysplasia by 22 weeks without PanIN formation, while mice expressing both tsTAg and Kras(G12D) developed highly aggressive adenocarcinoma with a ductal cell phenotype within a short period, and died within 3 weeks. The tumours resembled human pancreatic ductal adenocarcinoma (PDAC) at the histological level, and oncogenic Kras and tsTAg synergistically activated E2f and Sre transcription in established PDAC cell lines. These results suggest that tsTAg synergistically promotes Kras(G12D) -associated PDAC formation, and our study identifies a new mouse model of PDAC that may allow a better understanding of the mechanism of carcinogenesis in pancreatic carcinoma, which shows a catastrophic clinical course. PMID:25042889

  10. Genetics of pancreatitis: the 2014 update.

    PubMed

    Masamune, Atsushi

    2014-01-01

    Chronic pancreatitis is a progressive inflammatory disease in which pancreatic secretory parenchyma is destroyed and replaced by fibrous tissue, eventually leading to malnutrition and diabetes. Alcohol is the leading cause in Western countries, but genetic factors are also implicated. Since the identification of mutations in the cationic trypsinogen (PRSS1) gene as a cause of hereditary pancreatitis in 1996, we have seen great progress in our understanding of the genetics of pancreatitis. It has been established that mutations in the genes related to the activation and inactivation of trypsin(ogen) such as PRSS1, serine protease inhibitor Kazal type 1 (SPINK1) and chymotrypsin C (CTRC) genes are associated with pancreatitis. In 2013, carboxypeptidase A1 (CPA1) was identified as a novel pancreatitis susceptibility gene. Endoplasmic reticulum stress in pancreatic acinar cells resulting from the mis-folding of mutated pancreatic enzymes has been shown to act as a novel mechanism underlying the susceptibility to pancreatitis. In Japan, the nationwide survey revealed 171 patients (96 males and 75 females) with hereditary pancreatitis in 59 families based on the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer criteria. Because about 30% of families with hereditary pancreatitis do not carry mutations in any of the known pancreatitis susceptibility genes, other yet unidentified genes might be involved. Next generation sequencers can perform billions of sequencing reactions with a read length of 150-250 nucleotides. Comprehensive analysis using next generation sequencers will be a promising strategy to identify novel pancreatitis-associated genes and further clarify the pathogenesis of pancreatitis. PMID:24522117

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

    PubMed

    Peña, 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

  12. Role of bacterial infections in pancreatic cancer

    PubMed Central

    Michaud, Dominique S.

    2013-01-01

    Established risk factors for pancreatic cancer, including tobacco smoking, chronic pancreatitis, obesity and type 2 diabetes, collectively account for less than half of all pancreatic cancer cases. Inflammation plays a key role in pancreatic carcinogenesis, but it is unclear what causes local inflammation, other than pancreatitis. Epidemiological data suggest that Helicobacter pylori may be a risk factor for pancreatic cancer, and more recently, data suggest that periodontal disease, and Porphyromonas gingivalis, a pathogen for periodontal disease, may also play a role in pancreatic carcinogenesis. Individuals with periodontal disease have elevated markers of systemic inflammation, and oral bacteria can disseminate into the blood, stomach, heart and even reach the brain. These infections may contribute to the progression of pancreatic cancer by acting jointly with other pancreatic cancer risk factors that impact the inflammation and immune response, such as smoking and obesity, and the ABO genetic variant, recently linked to pancreatic cancer through genome-wide association studies. The complex interplay between bacteria, host immune response and environmental factors has been examined closely in relation to gastric cancer, but new research suggests bacteria may be playing a role in other gastrointestinal cancers. This review will summarize the literature on epidemiological studies examining infections that have been linked to pancreatic cancer and propose mechanistic pathways that may tie infections to pancreatic cancer. PMID:23843038

  13. Role of bacterial infections in pancreatic cancer.

    PubMed

    Michaud, Dominique S

    2013-10-01

    Established risk factors for pancreatic cancer, including tobacco smoking, chronic pancreatitis, obesity and type 2 diabetes, collectively account for less than half of all pancreatic cancer cases. Inflammation plays a key role in pancreatic carcinogenesis, but it is unclear what causes local inflammation, other than pancreatitis. Epidemiological data suggest that Helicobacter pylori may be a risk factor for pancreatic cancer, and more recently, data suggest that periodontal disease, and Porphyromonas gingivalis, a pathogen for periodontal disease, may also play a role in pancreatic carcinogenesis. Individuals with periodontal disease have elevated markers of systemic inflammation, and oral bacteria can disseminate into the blood, stomach, heart and even reach the brain. These infections may contribute to the progression of pancreatic cancer by acting jointly with other pancreatic cancer risk factors that impact the inflammation and immune response, such as smoking and obesity, and the ABO genetic variant, recently linked to pancreatic cancer through genome-wide association studies. The complex interplay between bacteria, host immune response and environmental factors has been examined closely in relation to gastric cancer, but new research suggests bacteria may be playing a role in other gastrointestinal cancers. This review will summarize the literature on epidemiological studies examining infections that have been linked to pancreatic cancer and propose mechanistic pathways that may tie infections to pancreatic cancer. PMID:23843038

  14. Blunt pancreatic trauma: A persistent diagnostic conundrum?

    PubMed Central

    Kumar, Atin; Panda, Ananya; Gamanagatti, Shivanand

    2016-01-01

    Blunt pancreatic trauma is an uncommon injury but has high morbidity and mortality. In modern era of trauma care, pancreatic trauma remains a persistent challenge to radiologists and surgeons alike. Early detection of pancreatic trauma is essential to prevent subsequent complications. However early pancreatic injury is often subtle on computed tomography (CT) and can be missed unless specifically looked for. Signs of pancreatic injury on CT include laceration, transection, bulky pancreas, heterogeneous enhancement, peripancreatic fluid and signs of pancreatitis. Pan-creatic ductal injury is a vital decision-making parameter as ductal injury is an indication for laparotomy. While lacerations involving more than half of pancreatic parenchyma are suggestive of ductal injury on CT, ductal injuries can be directly assessed on magnetic resonance imaging (MRI) or encoscopic retrograde cholangio-pancreatography. Pancreatic trauma also shows temporal evolution with increase in extent of injury with time. Hence early CT scans may underestimate the extent of injures and sequential imaging with CT or MRI is important in pancreatic trauma. Sequential imaging is also needed for successful non-operative management of pancreatic injury. Accurate early detection on initial CT and adopting a multimodality and sequential imaging strategy can improve outcome in pancreatic trauma. PMID:26981225

  15. 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

  16. Pancreatic Lesion: Malignancy or Abscess?

    PubMed

    Shulik, Oleg; Cavanagh, Yana; Grossman, Matthew

    2016-01-01

    BACKGROUND Pancreatic abscesses are rare. They may be seen in patients with pancreatic inflammation or pancreatitis. Patients with pancreatic abscesses may have abdominal pain, fever, chills, and nausea/vomiting or an inability to eat. Presentation with alternate symptomatology is extremely unusual. CASE REPORT A 67-year-old Asian male presented with painless, afebrile obstructive jaundice and a CA 19-9 of 1732 IU. He was found to have a 3.1×2.4 cm low-density lesion in the head of the pancreas and the right lobe of the liver, suggesting malignancy. Surgical management was considered, however additional diagnostic workup, including an endoscopic retrograde cholangiopancreatography (ERCP), was performed to complete staging of the presumed mass. A smooth, 3-cm-long, tapering stricture was found it the common bile duct. It was stented from the common hepatic duct to the duodenum. Subsequent endoscopic ultrasound (EUS) evaluation of the pancreatic head lesion revealed a drainable fluid collection that was aspirated and found to contain pyogenic material on pathology. The patient's symptoms resolved, and he was subsequently managed conservatively. A repeat ERCP confirmed complete resolution of the previously visualized cystic lesion. Interestingly, laboratory values showed concomitant normalization of CA 19-9 to 40 IU. CONCLUSIONS EUS-guided biopsy is not widely regarded as a required step before surgery, in the management of patients with pancreatic masses. It is generally reserved for determination of resectability or staging, and only utilized when clinically indicated. However, this practice may be associated with an inherently significant risk of misdiagnosis and subsequent unnecessary surgery, as illustrated by this case. Malignancy was initially suspected in our patient and surgical resection was recommended. Endoscopic measures were only pursued to complete staging. We propose that EUS-guided biopsy may be a crucial diagnostic step in the management algorithm of pancreatic lesions in selected patients. In addition, we encourage consideration of nonmalignant pancreatic collections in the differential diagnosis of pancreatic masses, especially when present in patients with diabetes mellitus. PMID:27188399

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. Ureteral Metastasis as the Presenting Manifestation of Pancreatic Carcinoma

    PubMed Central

    Arvind, Nand Kishore; Singh, Onkar; Gupta, Shilpi; Ali, Qutub

    2013-01-01

    We recently cared for a patient with adenocarcinoma of the pancreas who presented with ureteral metastasis followed by hydroureteronephrosis long before the appearance of any symptoms related to the primary lesion. The entity is extremely rare; only seven similar cases are on record in the scientific literature. No recent review exists on this topic. This encouraged us to present our case along with the previous cases of adenocarcinoma of the pancreas with ureteral metastasis that have been reported. PMID:24223025

  4. 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

  5. Radiographic findings in recurrent parathyroid carcinoma

    SciTech Connect

    Krudy, A.G.; Doppman, J.L.; Marx, S.J.; Brennan, M.F.; Spiegel, A.; Aurback, G.D.

    1982-03-01

    Seven cases of recurrent parathyroid carcinoma were reviewed. Subperiosteal resorption was seen in 6, pulmonary nodules in 4, renal calculi in 5, brown tumors in 5, and pancreatic calcifications in 1. Angiography was performed in 5 patients, showing 1 definite and 2 probable cervical recurrences, 1 mediastinal lesion, and 1 case of possible bone metastases. Venous sampling for parathyroid hormone was carried out in 4 patients and suggested residual disease in 2; in addition, there were 1 false and 1 true negative. CT was performed in 4 patients and was useful in delineating metastatic pulmonary nodules, cervical recurrence, and hepatic metastases. The radiographic approach to recurrent parathryoid carcinoma and the use of CT and angiography are discussed.

  6. Recurrent acute pancreatitis and its relative factors

    PubMed Central

    Zhang, Wei; Shan, Hong-Chao; Gu, Yan

    2005-01-01

    AIM: To evaluate the causes and the relative factors of recurrent acute pancreatitis. METHODS: From 1997 to 2000, acute pancreatitis relapsed in 77 of 245 acute pancreatitis patients. By reviewing the clinical treatment results and the follow-up data, we analyzed the recurrent factors of acute pancreatitis using univariate analysis and multivariate analysis. RESULTS: Of the 245 acute pancreatitis patients, 77 were patients with recurrent acute pancreatitis. Of them, 56 patients relapsed two times, 19 relapsed three times, each patient relapsed three and four times. Forty-seven patients relapsed in hospital and the other 30 patients relapsed after discharge. Eighteen patients relapsed in 1 year, eight relapsed in 1-3 years, and four relapsed after 3 years. There were 48 cases of biliary pancreatitis, 3 of alcohol pancreatitis, 5 of hyperlipidemia pancreatitis, 21 of idiopathic pancreatitis. Univariate analysis showed that the patients with local complications of pancreas, obstructive jaundice and hepatic function injury were easy to recur during the treatment period of acute pancreatitis (P = 0.022<0.05, P = 0.012<0.05 and P = 0.002<0.05, respectively). Multivariate analysis showed that there was no single factor related to recurrence. Of the 47 patients who had recurrence in hospital, 16 had recurrence in a fast period, 31 after refeeding. CONCLUSION: Acute pancreatitis is easy to recur even during treatment. The factors such as changes of pancreas structure and uncontrolled systemic inflammatory reaction are responsible for the recurrence of acute pancreatitis. Early refeeding increases the recurrence of acute pancreatitis. Defining the etiology is essential for reducing the recurrence of acute pancreatitis. PMID:15902746

  7. Adjuvant treatment for pancreatic cancer.

    PubMed

    Daoud, Vladimir; Saif, Muhammad Wasif; Goodman, Martin

    2014-07-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in both men and women. Surgical resection has been shown to be the only curable treatment available. Unfortunately only 20% of all patients diagnosed with pancreatic cancer are surgical candidates due to the aggressive biology of this disease. There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. The survival of these patients, even status post resection and adjuvant therapy, remains poor and therefore the need for alternative adjuvant therapies is needed. We will therefore discuss Abstracts #4124, #TPS4162, #4120 and #E15191 in this paper which are relevant to the issues described above. PMID:25076340

  8. Fluid resuscitation in acute pancreatitis

    PubMed Central

    Aggarwal, Aakash; Manrai, Manish; Kochhar, Rakesh

    2014-01-01

    Acute pancreatitis remains a clinical challenge, despite an exponential increase in our knowledge of its complex pathophysiological changes. Early fluid therapy is the cornerstone of treatment and is universally recommended; however, there is a lack of consensus regarding the type, rate, amount and end points of fluid replacement. Further confusion is added with the newer studies reporting better results with controlled fluid therapy. This review focuses on the pathophysiology of fluid depletion in acute pancreatitis, as well as the rationale for fluid replacement, the type, optimal amount, rate of infusion and monitoring of such patients. The basic goal of fluid epletion should be to prevent or minimize the systemic response to inflammatory markers. For this review, various studies and reviews were critically evaluated, along with authors’ recommendations, for predicted severe or severe pancreatitis based on the available evidence. PMID:25561779

  9. Advances in Surgical Management of Pancreatic Diseases.

    PubMed

    Datta, Jashodeep; Vollmer, Charles M

    2016-03-01

    The surgical management of pancreatic diseases is rapidly evolving, encompassing advances in evidence-driven selection of patients amenable for surgical therapy, preoperative risk stratification, refinements in the technical conduct of pancreatic operations, and quantification of postoperative morbidity. These advances have resulted in dramatic reductions in mortality following pancreatic surgery, particularly at high-volume pancreatic centers. Surgical decision making is complex, and requires an intimate understanding of disease pathobiology, host physiology, technical considerations, and evolving trends. This article highlights key developments in the contemporary surgical management of pancreatic diseases. PMID:26895685

  10. Pancreatic surgery: evolution and current tailored approach

    PubMed Central

    Mužina Mišić, Dubravka; Glavčić, 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

  11. Inflammasomes in pancreatic physiology and disease

    PubMed Central

    Hoque, Rafaz

    2015-01-01

    In this review we summarize the role of inflammasomes in pancreatic physiology and disease with a focus on acute pancreatitis where much recent progress has been made. New findings have identified inducers of and cell specificity of inflammasome component expression in the pancreas, the contribution of inflammasome-regulated effectors to pancreatitis, and metabolic regulation of inflammasome activation, which are strong determinants of injury in pancreatitis. New areas of pancreatic biology will be highlighted in the context of our evolving understanding of gut microbiome- and injury-induced inflammasome priming, pyroptosis, and innate immune-mediated regulation of cell metabolism. PMID:25700081

  12. 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

  13. 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

  14. [Supportive care in pancreatic cancer].

    PubMed

    Capodano, Géraldine

    2015-03-01

    Pancreatic cancer is one of the most aggressive malignancy with an expected overall survival of less than one year in metastatic canes. Many refmactory symptoms may be present at diagnosis and must be adequaty managed to improve quality of life (and survival ?) of these patients This includes dedicated supportive care but also an early introduction of palliative care methods. The current manuscript details the mast common and problematic maaifestatiaas of pancreatic cancer including weight loss, anorexia, cachexia syndrome, pain management, venous thromboembolism, malignant biliary and gastric outlet obstruction. PMID:26016203

  15. 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

  16. 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 ...

  17. 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 radiation therapy to the neck given ...

  18. 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

  19. 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

  20. Ultrasonography in diagnosing chronic pancreatitis: New aspects

    PubMed Central

    Dimcevski, Georg; Erchinger, Friedemann G; Havre, Roald; Gilja, Odd Helge

    2013-01-01

    The course and outcome is poor for most patients with pancreatic diseases. Advances in pancreatic imaging are important in the detection of pancreatic diseases at early stages. Ultrasonography as a diagnostic tool has made, virtually speaking a technical revolution in medical imaging in the new millennium. It has not only become the preferred method for first line imaging, but also, increasingly to clarify the interpretation of other imaging modalities to obtain efficient clinical decision. We review ultrasonography modalities, focusing on advanced pancreatic imaging and its potential to substantially improve diagnosis of pancreatic diseases at earlier stages. In the first section, we describe scanning techniques and examination protocols. Their consequences for image quality and the ability to obtain complete and detailed visualization of the pancreas are discussed. In the second section we outline ultrasonographic characteristics of pancreatic diseases with emphasis on chronic pancreatitis. Finally, new developments in ultrasonography of the pancreas such as contrast enhanced ultrasound and elastography are enlightened. PMID:24259955

  1. 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

  2. Bronchiolar Carcinoma

    PubMed Central

    Quinlan, J. J.; Schaffner, V. D.; Hiltz, J. E.

    1966-01-01

    Bronchiolar carcinoma is a malignant tumour which apparently arises in a terminal bronchiole from which it spreads either by bronchial embolization or by lymphogenous and/or hematogenous dissemination. It is not a common neoplasm. Histologically, the tumour bears a striking resemblance to the disease of sheep, jagziekte, which is of virus etiology. A very common finding in reported cases is preexisting pulmonary fibrosis. At the Nova Scotia Sanatorium, Kentville, 80 cases of primary lung cancer have been encountered within the past 25 years. Six of these were bronchiolar carcinomas. Five patients had co-existing chronic pulmonary disease, bronchiectasis in one and tuberculosis in four. One patient died of a rapidly progressive bilateral lesion and five were explored. Lobectomy was done in all five, but in one for palliation only. Three patients are alive and well three, six and 14 years, respectively, after their operations. PMID:4285258

  3. Nasopharyngeal carcinoma

    SciTech Connect

    Ho, J.H.C.

    1985-07-01

    In this editorial comment, the author presents a review of recent achievements in the diagnosis and treatment of squamous cell carcinoma of the nasopharynx. The value of the use of CT scans for differentiating between cranial nerve involvement by recurring tumors and irradiation neuropathy, and between temporal lobe irradiation encephalopathy and other nonneoplastic neurologic disorders and meningeal metastasis is discussed. Magnetic resonance imaging is said to be superior to CT for finding soft tissue involvement or abnormalities in the brain. 13 references.

  4. 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

  5. Serum Protein Signatures Differentiating Autoimmune Pancreatitis versus Pancreatic Cancer

    PubMed Central

    Fritz, Stefan; Hinz, Ulf; Schnölzer, Martina; Kempf, Tore; Warnken, Uwe; Michel, Angelika; Pawlita, Michael; Werner, Jens

    2013-01-01

    Autoimmune pancreatitis (AIP) is defined by characteristic lymphoplasmacytic infiltrate, ductal strictures and a pancreatic enlargement or mass that can mimic pancreatic cancer (PaCa). The distinction between this benign disease and pancreatic cancer can be challenging. However, an accurate diagnosis may pre-empt the misdiagnosis of cancer, allowing the appropriate medical treatment of AIP and, consequently, decreasing the number of unnecessary pancreatic resections. Mass spectrometry (MS) and two-dimensional differential gel electrophoresis (2D-DIGE) have been applied to analyse serum protein alterations associated with AIP and PaCa, and to identify protein signatures indicative of the diseases. Patients' sera were immunodepleted from the 20 most prominent serum proteins prior to further 2D-DIGE and image analysis. The identity of the most-discriminatory proteins detected, was performed by MS and ELISAs were applied to confirm their expression. Serum profiling data analysis with 2D-DIGE revealed 39 protein peaks able to discriminate between AIP and PaCa. Proteins were purified and further analysed by MALDI-TOF-MS. Peptide mass fingerprinting led to identification of eleven proteins. Among them apolipoprotein A-I, apolipoprotein A-II, transthyretin, and tetranectin were identified and found as 3.0-, 3.5-, 2-, and 1.6-fold decreased in PaCa sera, respectively, whereas haptoglobin and apolipoprotein E were found to be 3.8- and 1.6-fold elevated in PaCa sera. With the exception of haptoglobin the ELISA results of the identified proteins confirmed the 2D-DIGE image analysis characteristics. Integration of the identified serum proteins as AIP markers may have considerable potential to provide additional information for the diagnosis of AIP to choose the appropriate treatment. PMID:24349355

  6. Respiratory failure in acute pancreatitis.

    PubMed Central

    Banerjee, A. K.; Haggie, S. J.; Jones, R. B.; Basran, G. S.

    1995-01-01

    There are a number of important pulmonary complications of acute pancreatitis which make a significant contribution to the morbidity and mortality of the condition. The pathophysiology and management guidelines are given for each and approaches towards better treatment in the future are discussed. PMID:7644392

  7. Fictitious pancreatitis in choledochal cyst.

    PubMed

    Stringel, G; Filler, R M

    1982-08-01

    The classical presentation of choledocal cyst has been regarded as a triad of abdominal pain, jaundice and a palpable abdominal mass; unusual presentations include rupture of the choledocal cyst with bile peritonitis, pancreatitis and bleeding esophageal varices. We are reporting 3 children presenting clinically as recurrent acute pancreatitis with elevated serum amylase and found to have type I choledocal cyst. Despite elevated serum amylase there was no evidence of pancreatic inflammation at laparotomy. High amylase concentration was found in fluid contained within the cyst. This was probably responsible for the elevated serum amylase and also the inflammatory reaction seen in the wall of the choledocal cyst. These cases support the hypothesis that pancreatic reflux into the bile ducts is the etiological factor in the development of choledocal cyst. Our 3 cases were treated by cyst excision and have remained asymptomatic. The presence of hyperamylasemia should not delay appropriate surgical management. The treatment of choice is cyst excision, since it will eliminate factors contributing to the development of cholangitis and hyperamylasemia. PMID:6181241

  8. Endoscopic treatment of pancreatic calculi.

    PubMed

    Kim, Yong Hoon; Jang, Sung Ill; Rhee, Kwangwon; Lee, Dong Ki

    2014-05-01

    Chronic pancreatitis is a progressive inflammatory disease that destroys pancreatic parenchyma and alters ductal stricture, leading to ductal destruction and abdominal pain. Pancreatic duct stones (PDSs) are a common complication of chronic pancreatitis that requires treatment to relieve abdominal pain and improve pancreas function. Endoscopic therapy, extracorporeal shock wave lithotripsy (ESWL), and surgery are treatment modalities of PDSs, although lingering controversies have hindered a consensus recommendation. Many comparative studies have reported that surgery is the superior treatment because of reduced duration and frequency of hospitalization, cost, pain relief, and reintervention, while endoscopic therapy is effective and less invasive but cannot be used in all patients. Surgery is the treatment of choice when endoscopic therapy has failed, malignancy is suspected, or duodenal stricture is present. However, in patients with the appropriate indications or at high-risk for surgery, endoscopic therapy in combination with ESWL can be considered a first-line treatment. We expect that the development of advanced endoscopic techniques and equipment will expand the role of endoscopic treatment in PDS removal. PMID:24944986

  9. Pancreatic Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  10. Chronic Pancreatitis (Beyond the Basics)

    MedlinePlus

    ... chronic pancreatitis can have difficulty digesting fats in foods; this can lead to weight loss and occasionally diarrhea. In severe cases, the pancreas loses its ability to produce enough insulin, leading to diabetes. Abdominal pain — Abdominal pain usually occurs in the ...

  11. Redox Homeostasis in Pancreatic ? Cells

    PubMed Central

    Jeek, Petr; Dlaskov, Andrea; Plecit-Hlavat, Lydie

    2012-01-01

    We reviewed mechanisms that determine reactive oxygen species (redox) homeostasis, redox information signaling and metabolic/regulatory function of autocrine insulin signaling in pancreatic ? cells, and consequences of oxidative stress and dysregulation of redox/information signaling for their dysfunction. We emphasize the role of mitochondrion in ? cell molecular physiology and pathology, including the antioxidant role of mitochondrial uncoupling protein UCP2. Since in pancreatic ? cells pyruvate cannot be easily diverted towards lactate dehydrogenase for lactate formation, the respiration and oxidative phosphorylation intensity are governed by the availability of glucose, leading to a certain ATP/ADP ratio, whereas in other cell types, cell demand dictates respiration/metabolism rates. Moreover, we examine the possibility that type 2 diabetes mellitus might be considered as an inevitable result of progressive self-accelerating oxidative stress and concomitantly dysregulated information signaling in peripheral tissues as well as in pancreatic ? cells. It is because the redox signaling is inherent to the insulin receptor signaling mechanism and its impairment leads to the oxidative and nitrosative stress. Also emerging concepts, admiting participation of redox signaling even in glucose sensing and insulin release in pancreatic ? cells, fit in this view. For example, NADPH has been firmly established to be a modulator of glucose-stimulated insulin release. PMID:23304259

  12. General Information about Pancreatic Cancer

    MedlinePlus

    ... quality of life by controlling the symptoms and complications of this disease. Stages of Pancreatic Cancer Key ... and drain the bile into the small intestine. Gastric bypass: If the tumor is blocking ... therapy is a cancer treatment that uses high-energy x-rays or ...

  13. Nutrition in the management of necrotizing pancreatitis.

    PubMed

    O'Keefe, Stephen J D; Broderick, Timothy; Turner, Maryann; Stevens, Stacie; O'Keefe, J Sebastian

    2003-07-01

    Comparative trials have shown that enteral feeding (EN) is better than total parenteral nutrition (TPN) in acute pancreatitis. However, the following case report of a 64-year-old man with necrotizing pancreatitis suggests that EN may cause complications in patients with ductular damage. In the second week, this patient with acute pancreatitis developed >50% pancreatic necrosis, resulting in gastroduodenal obstruction and pain, leading to the use of TPN. A trial of EN delivered past the obstruction was associated with increased abdominal pain, leukocytosis, and pancreatic fluid accumulation. Measurement of the pancreatic response to feeding showed a 90% reduction in enzyme secretion compared to healthy volunteers, but no change in the uptake of stable isotope labeled amino acids into secreted trypsin. This suggests that enzymes were being synthesized by the remaining pancreatic tissue, but that some of the secretions were leaking into the inflammatory mass. Symptoms resolved after reinstitution of TPN and bowel rest. A further trial of EN was successful when the tube was advanced to the distal jejunum to avoid pancreatic stimulation. After 3 weeks of home EN, he was readmitted for surgical evacuation of an infected fluid collection. Although enteral feeding is generally better than TPN in the nutritional management of acute pancreatitis, there may be a subgroup of patients with ductular damage due to necrotizing disease in whom TPN and pancreatic rest may be safer. PMID:15017674

  14. Acute pancreatitis in children and adolescents

    PubMed Central

    Suzuki, Mitsuyoshi; Sai, Jin Kan; Shimizu, Toshiaki

    2014-01-01

    In this Topic Highlight, the causes, diagnosis, and treatment of acute pancreatitis in children are discussed. Acute pancreatitis should be considered during the differential diagnosis of abdominal pain in children and requires prompt treatment because it may become life-threatening. The etiology, clinical manifestations, and course of acute pancreatitis in children are often different than in adults. Therefore, the specific features of acute pancreatitis in children must be considered. The etiology of acute pancreatitis in children is often drugs, infections, trauma, or anatomic abnormalities. Diagnosis is based on clinical symptoms (such as abdominal pain and vomiting), serum pancreatic enzyme levels, and imaging studies. Several scoring systems have been proposed for the assessment of severity, which is useful for selecting treatments and predicting prognosis. The basic pathogenesis of acute pancreatitis does not greatly differ between adults and children, and the treatments for adults and children are similar. In large part, our understanding of the pathology, optimal treatment, assessment of severity, and outcome of acute pancreatitis in children is taken from the adult literature. However, we often find that the common management of adult pancreatitis is difficult to apply to children. With advances in diagnostic techniques and treatment methods, severe acute pancreatitis in children is becoming better understood and more controllable. PMID:25400985

  15. HER2 overexpression correlates with survival after curative resection of pancreatic cancer.

    PubMed

    Komoto, Masahiro; Nakata, Bunzo; Amano, Ryosuke; Yamada, Nobuya; Yashiro, Masakazu; Ohira, Masaichi; Wakasa, Kenichi; Hirakawa, Kosei

    2009-07-01

    HER2 overexpression has been linked to clinical outcomes in several solid tumors, such as breast cancer. However, the correlation between HER2 overexpression and survival in pancreatic carcinoma remains unclear. The impact of HER2 overexpression on survival in pancreatic ductal cancer was examined. Immunohistochemical staining of 129 pancreatic cancers without hematogenous metastases or peritoneal dissemination treated by macroscopically curative resection were analyzed in association with survival data. To determine HER2 overexpression in this pancreatic cancer series, the polyclonal antibody included in HercepTest, which is used worldwide for clinical examination of HER2 overexpression in breast cancer, was used. Immunoreactivity was classified according to the scale presented in the HercepTest Scoring Guidelines. Twenty-two cases (17.1%) had a score of 0, 28 cases (21.7%) had of a score of 1+, 41 cases (31.8%) had a score of 2+, and 38 cases (29.4%) had a score of 3+. Therefore, HER2 overexpression (score 2+ or 3+) was observed in 79 cases (61.2%). Patients with HER2 overexpression tumors had significantly shorter survival times than those with HER2 normal expression (score 0 or 1+) tumors (median survival time, 14.7 vs 20.7 months, respectively; P = 0.0078 on the log-rank test). On multivariate survival analysis, HER2 overexpression remained an independent prognostic factor (hazard ratio, 1.806; P = 0.0258). A significant percentage of pancreatic cancers were demonstrated to have HER2 overexpression, and overexpression of this tyrosine kinase receptor proved to be an independent factor for a worse prognosis. These results should encourage further investigation of treatments using new molecular targeting agents against HER2 protein to improve the survival of pancreatic cancer patients. PMID:19432892

  16. Eflornithine (DFMO) Prevents Progression of Pancreatic Cancer by Modulating Ornithine Decarboxylase Signaling

    PubMed Central

    Mohammed, Altaf; Janakiram, Naveena B.; Madka, Venkateshwar; Ritchie, Rebekah L.; Brewer, Misty; Biddick, Laura; Patlolla, Jagan Mohan R.; Sadeghi, Michael; Lightfoot, Stan; Steele, Vernon E.; Rao, Chinthalapally V.

    2015-01-01

    Ornithine decarboxylase (ODC) is the key rate limiting enzyme in the polyamine synthesis pathway and it is overexpressed in a variety of cancers. We found that polyamine synthesis and modulation of ODC signaling occurs at early stages of pancreatic precursor lesions and increases as the tumor progresses in Kras activated p48Cre/+-LSL-KrasG12D/+ mice. Interest in use of the ODC inhibitor Eflornithine (DFMO) as a cancer chemopreventive agent has increased in recent years since ODC was shown to be transactivated by the c-myc oncogene and to cooperate with the ras oncogene in malignant transformation of epithelial tissues. We tested the effects of DFMO on pancreatic intraepithelial neoplasms (PanINs) and their progression to pancreatic ductal adenocarcinoma (PDAC) in genetically engineered Kras mice. The KrasG12D/+ mice fed DFMO at 0.1 and 0.2 % in the diet showed a significant inhibition (p<0.0001) of PDAC incidence compared with mice fed control diet. Pancreatic tumor weights were decreased by 3143% (p<0.030.001) with both doses of DFMO. DFMO at 0.1 and 0.2 % caused a significant suppression (27 and 31%, P<0.020.004) of PanIN 3 lesions (carcinoma in situ). DFMO-treated pancreas exhibited modulated ODC pathway components along with decreased proliferation and increased expression of p21/p27 as compared with pancreatic tissues derived from mice fed control diet. In summary, our preclinical data indicate that DFMO has potential for chemoprevention of pancreatic cancer and should be evaluated in other PDAC models and in combination with other drugs in anticipation of future clinical trials. PMID:25248858

  17. Autoimmune pancreatitis--recent advances.

    PubMed

    Novotný, I; Díte, P; Lata, J; Nechutová, H; Kianicka, B

    2010-01-01

    Autoimmune pancreatitis (AIP) is recognized as a distinct clinical entity, identified as a chronic inflammatory process of the pancreas in which the autoimmune mechanism is involved. Clinically and histologically, AIP has two subsets: type 1--lymphoplasmatic sclerosing pancreatitis with abundant infiltration of the pancreas and other affected organs with immunoglobulin G4-positive plasma cells, and type 2--duct centric fibrosis, characterized by granulocyte epithelial lesions in the pancreas without systemic involvement. In the diagnosis of AIP, two diagnostic criterions are used--the HISORt criteria and Asian Diagnostic Criteria. In the differential diagnosis, the pancreatic cancer must be excluded by endosonographically guided pancreatic biopsy. Typical signs of AIP are concomitant disorders in other organs (kidney, liver, biliary tract, salivary glands, colon, retroperitoneum, prostate). Novel clinicopathological entity was proposed as an 'IgG4-related sclerosing disease' (IgG4-RSC). Extensive IgG4-positive plasma cells and T lymphocyte infiltration is a common characteristics of this disease. Recently, IgG4-RSC syndrome was extended to a new entity, characterized by IgG4 hypergammaglobulinemia and IgG4-positive plasma cell infiltration, this being considered an expression of a lymphoproliferative disease, 'IgG4-positive multiorgan lymphoproliferative syndrome'. This syndrome includes Mikulicz's disease, mediastinal fibrosis, autoimmune hypophysitis, and inflammatory pseudotumor--lung, liver, breast. In the therapy of AIP, steroids constitute first-choice treatment. High response to the corticosteroid therapy is an important diagnostic criterion. In the literature, there are no case-control studies that determine if AIP predisposes to pancreatic cancer. Undoubtedly, AIP is currently a hot topic in pancreatology. PMID:20814208

  18. Recent Advances in Autoimmune Pancreatitis.

    PubMed

    Hart, Phil A; Zen, Yoh; Chari, Suresh T

    2015-07-01

    Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that is characterized clinically by frequent presentation with obstructive jaundice, histologically by a dense lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response to corticosteroid therapy. Two distinct diseases, type 1 and type 2 AIP, share these features. However, these 2 diseases have unique pancreatic histopathologic patterns and differ significantly in their demographic profiles, clinical presentation, and natural history. Recognizing the popular and long-standing association of the term "AIP" with what is now called "type 1 AIP," we suggest using "AIP" solely for type 1 AIP and to acknowledge its own distinct disease status by using "idiopathic duct-centric chronic pancreatitis" (IDCP) for type 2 AIP. AIP is the pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). The etiopathogenesis of AIP and IgG4-RD is largely unknown. However, the remarkable effectiveness of B-cell depletion therapy with rituximab in patients with AIP and IgG4-RD highlights the crucial role of B cells in its pathogenesis. IDCP is less commonly recognized, and little is known about its pathogenesis. IDCP has no biomarker but is associated with inflammatory bowel disease in ~25% of patients. Recently, the international consensus diagnostic criteria for AIP identified combinations of features that are diagnostic of both diseases. Both AIP and IDCP are corticosteroid responsive; however, relapses are common in AIP and rare in IDCP. Therefore, maintenance therapy with either an immunomodulator (eg, azathioprine, 6-mercaptopurine, or mycophenolate mofetil) or rituximab is often necessary for patients with AIP. Long-term survival is excellent for both patients with AIP and patients with IDCP. PMID:25770706

  19. Long-term culture and immortalization of epithelial cells from normal adult human pancreatic ducts transfected by the E6E7 gene of human papilloma virus 16.

    PubMed Central

    Furukawa, T.; Duguid, W. P.; Rosenberg, L.; Viallet, J.; Galloway, D. A.; Tsao, M. S.

    1996-01-01

    Pancreatic cancer is one of the most lethal cancers in humans. The majority of these cancers arise from the pancreatic duct epithelium. Research into the pathogenesis of pancreatic carcinoma has largely relied on animal models. In vitro models of pancreatic carcinogenesis using propagable cultured epithelial cells derived from the pancreatic ducts of rats and hamsters have been described. A human model, however, has been nonexistent due to the unavailability of propagable cultured duct epithelial cells derived from normal human pancreas. We report here a reproducible method for the long-term culture of pancreatic duct epithelial cells derived from normal and benign adult human pancreata by infection with a retrovirus containing the E6 and E7 genes of the human papilloma virus 16. One of these cell lines has become immortal and has propagated continuously for more than 20 passages. They remain anchorage dependent in their growth and nontumorigenic in nude mice. These cell lines and the methodology described here to establish them may provide new avenues for in vitro studies of the roles played by duct epithelium in human pancreatic diseases and cancers. Images Figure 1 Figure 2 Figure 3 PMID:8669463

  20. PanScan, the Pancreatic Cancer Cohort Consortium, and the Pancreatic Cancer Case-Control Consortium

    Cancer.gov

    The Pancreatic Cancer Cohort Consortium consists of more than a dozen prospective epidemiologic cohort studies within the NCI Cohort Consortium, whose leaders work together to investigate the etiology and natural history of pancreatic cancer.

  1. Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery

    ClinicalTrials.gov

    2016-01-29

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

  2. Hexon Modification to Improve the Activity of Oncolytic Adenovirus Vectors against Neoplastic and Stromal Cells in Pancreatic Cancer

    PubMed Central

    Lucas, Tanja; Benihoud, Karim; Vigant, Frédéric; Schmidt, Christoph Q. Andreas; Simmet, Thomas; Kochanek, Stefan

    2015-01-01

    Primary pancreatic carcinoma has an unfavourable prognosis and standard treatment strategies mostly fail in advanced cases. Virotherapy might overcome this resistance to current treatment modalities. However, data from clinical studies with oncolytic viruses, including replicating adenoviral (Ad) vectors, have shown only limited activity against pancreatic cancer and other carcinomas. Since pancreatic carcinomas have a complex tumor architecture and frequently a strong stromal compartment consisting of non-neoplastic cell types (mainly pancreatic stellate cells = hPSCs) and extracellular matrix, it is not surprising that Ad vectors replicating in neoplastic cells will likely fail to eradicate this aggressive tumor type. Because the TGFβ receptor (TGFBR) is expressed on both neoplastic cells and hPSCs we inserted the TGFBR targeting peptide CKS17 into the hypervariable region 5 (HVR5) of the capsid protein hexon with the aim to generate a replicating Ad vector with improved activity in complex tumors. We demonstrated increased transduction of both pancreatic cancer cell lines and of hPSCs and enhanced cytotoxicity in co-cultures of both cell types. Surface plasmon resonance analysis demonstrated decreased binding of coagulation factor X to CKS17-modified Ad particles and in vivo biodistribution studies performed in mice indicated decreased transduction of hepatocytes. Thus, to increase activity of replicating Ad vectors we propose to relax tumor cell selectivity by genetic hexon-mediated targeting to the TGFBR (or other receptors present on both neoplastic and non-neoplastic cells within the tumor) to enable replication also in the stromal cell compartment of tumors, while abolishing hepatocyte transduction, and thereby increasing safety. PMID:25692292

  3. CpG island methylation profile of pancreatic intraepithelial neoplasia

    PubMed Central

    Sato, Norihiro; Fukushima, Noriyoshi; Hruban, Ralph H; Goggins, Michael

    2009-01-01

    Infiltrating adenocarcinoma of the pancreas is thought to develop through well-defined precursor lesions called pancreatic intraductal neoplasia (PanIN). Despite the exponential growth in our understanding of genetic events that characterize the progression of PanINs to invasive carcinoma, little is known about the role of epigenetic alterations in these precursor lesions. To define the timing and prevalence of methylation abnormalities during early pancreatic carcinogenesis, we investigated the CpG island methylation profile in the various grades of PanINs. Using methylation-specific PCR, we analyzed DNA samples from 65 PanIN lesions for methylation status of eight genes recently identified by microarray approach as aberrantly hypermethylated in invasive pancreatic cancer. Aberrant methylation at any of the eight genes was identified in 68% of all the PanIN lesions examined, and, notably, aberrant methylation was identified in more than 70% of the earliest lesions (PanIN-1A). The average number of methylated loci was 1.1 in PanIN-1A, 0.8 in PanIN-1B, 1.1 in PanIN-2, and 2.9 in PanIN-3 lesions (P = 0.01 for PanIN -3 vs earlier PanINs). Among the genes analyzed, NPTX2 demonstrated an increase in methylation prevalence from PanIN-1 to PanIN-2 (P = 0.0008), and from PanIN-2 to PanIN-3 for SARP2 (P = 0.001), Reprimo (P = 0.01), and LHX1 (P = 0.03). These results suggest that aberrant CpG island hypermethylation begins in early stages of PanINs, and its prevalence progressively increases during neoplastic progression. PMID:18157091

  4. Update on surgical treatment of pancreatic neuroendocrine neoplasms

    PubMed Central

    D’Haese, Jan G; Tosolini, Chiara; Ceyhan, Güralp O; Kong, Bo; Esposito, Irene; Michalski, Christoph W; Kleeff, Jörg

    2014-01-01

    Pancreatic neuroendocrine neoplasms (PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential (neurendocrine tumors PNETs) or overt (neuroendocrine carcinomas PNECs) malignant, but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimally-invasive approaches which should be tailored to the individual patient. Generally, surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs, indications for tumor resection are much wider than for pancreatic adenocarcinoma, in many cases due to the relatively benign tumor biology. Thus, patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands, even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However, poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly single-center series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable, ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review, we summarize recent advances in the surgical treatment of PNENs. PMID:25320524

  5. Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

    NASA Astrophysics Data System (ADS)

    Hu, Wenyan; Fu, Ling

    2013-05-01

    Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, primarily based on multichannel detection of intrinsic optical emissions and cell morphology. Fresh rat pancreatic tissues harvested at 1 day, 7 days, and 28 days after induction of chronic pancreatitis were imaged, respectively. PSCs, inflammatory cells, blood vessels, and collagen fibers were identified simultaneously. The PSCs at day 1 of chronic pancreatitis showed significant enlargement compared with those in normal pancreas (p<0.001, analysis of variance linear contrast; n=8 for each group). Pathological events relating to these components were observed, including presence of inflammatory cells, deposited collagen, and phenotype conversion of PSCs. We demonstrate that label-free nonlinear optical microscopy is an efficient tool for dissecting PSCs and other pancreatic components coincidently within 3-D pancreatic tissues. It is a prospect for intravital observation of dynamic events under natural physiological conditions, and might help uncover the key mechanisms of exocrine pancreatic diseases, leading to more effective treatments.

  6. Current status of endotherapy for chronic pancreatitis

    PubMed Central

    Kwek, Andrew Boon Eu; Ang, Tiing Leong; Maydeo, Amit

    2014-01-01

    Chronic pancreatitis is associated with varied morphological complications, including intraductal stones, main pancreatic ductal strictures, distal biliary strictures and pseudocysts. Endoscopic therapy provides a less invasive alternative to surgery. In addition, extracorporeal shockwave lithotripsy improves the success rate of endoscopic clearance of intraductal stones. However, recent data from randomised trials have shown better long-term outcomes with surgical drainage for obstructive pancreatic ductal disease. In patients with distal biliary strictures, stent insertion leads to good immediate drainage, but after stent removal, recurrent narrowing is common. Endoscopic drainage of pancreatic pseudocysts has excellent outcome and should be accompanied by pancreatic ductal stenting when a ductal communication is evident. In those who remain symptomatic, endoscopic ultrasonography-guided coeliac plexus block may provide effective but short-term pain relief. In this review, we present the current evidence for the role of endotherapy in the management of patients with chronic pancreatitis. PMID:25630314

  7. Pancreatic cancer: Pathogenesis, prevention and treatment

    SciTech Connect

    Sarkar, Fazlul H. Banerjee, Sanjeev; Li, Yiwei

    2007-11-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States with a very low survival rate of 5 years. To better design new preventive and/or therapeutic strategies for the fight against pancreatic cancer, the knowledge of the pathogenesis of pancreatic cancer at the molecular level is very important. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways among which the EGFR, Akt, and NF-{kappa}B pathways appear to be most relevant. Therefore, the strategies targeting EGFR, Akt, NF-{kappa}B, and their downstream signaling could be promising for the prevention and/or treatment of pancreatic cancer. In this brief review, we will summarize the current knowledge regarding the pathogenesis, prevention, and treatment of pancreatic cancer.

  8. [Laboratory and instrumental diagnostics of pancreatic diseases].

    PubMed

    2011-01-01

    The review focuses on the potential of modern laboratory and instrumental diagnostics ofpancreatic diseases including various forms of chronic pancreatitis, pancreatic cancer, cysts and pseudocysts, calcificators and concrements, abscesses, neuroendocrine tumours, etc. Diagnostic criteria for exocrine pancreatic disorders, such as hyper- and hyposecretory (hyper- and hypoenzymatic) forms of chronic pancreatitis are described along with direct and indirect, invasive and non-invasive, probe-based and probe-free methods for their study. Special attention is given to instrumental visualization of structural and morphological changes in the pancreas under different pathological conditions. The description of methods for the study of pancreatic endocrine functions and diagnostics of pancreatic diseases is preceded by a brief anatomo-physiologic essay. PMID:22420188

  9. Transcatheter Embolization of Pseudoaneurysms Complicating Pancreatitis

    SciTech Connect

    Golzarian, Jafar; Nicaise, Nicole; Deviere, Jacques; Ghysels, Marc; Wery, Didier; Dussaussois, Luc; Gansbeke, Daniel van; Struyven, Julien

    1997-11-15

    Purpose: To evaluate the therapeutic role of angiography in patients with pseudoaneurysms complicating pancreatitis. Methods: Thirteen symptomatic pseudoaneurysms were treated in nine patients with pancreatitis. Eight patients had chronic pancreatitis and pseudocyst and one had acute pancreatitis. Clinical presentation included gastrointestinal bleeding in seven patients and epigastric pain without bleeding in two. All patients underwent transcatheter embolization. Results: Transcatheter embolization resulted in symptomatic resolution in all patients. Rebleeding occurred in two patients, 18 and 28 days after embolization respectively, and was successfully treated by repeated emnbolization. One patient with severe pancreatitis died from sepsis 28 days after embolization. Follow-up was then available for eight patients with no relapse of bleeding after a mean follow-up of 32 months (range 9-48 months). Conclusion: Transcatheter embolization is safe and effective in the management of pseudoaneurysms complicating pancreatitis.

  10. Potential targets for pancreatic cancer immunotherapeutics

    PubMed Central

    Dodson, Lindzy F; Hawkins, William G; Goedegebuure, Peter

    2011-01-01

    Pancreatic adenocarcinoma is the fourth leading cause of cancer death with an overall 5-year survival of less than 5%. As there is ample evidence that pancreatic adenocarcinomas elicit antitumor immune responses, identification of pancreatic cancer-associated antigens has spurred the development of vaccination-based strategies for treatment. While promising results have been observed in animal tumor models, most clinical studies have found only limited success. As most trials were performed in patients with advanced pancreatic cancer, the contribution of immune suppressor mechanisms should be taken into account. In this article, we detail recent work in tumor antigen vaccination and the recently identified mechanisms of immune suppression in pancreatic cancer. We offer our perspective on how to increase the clinical efficacy of vaccines for pancreatic cancer. PMID:21463193

  11. Pancreatic Cancer: Pathogenesis, Prevention and Treatment

    PubMed Central

    Sarkar, Fazlul H.; Banerjee, Sanjeev; Li, Yiwei

    2007-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States with a very low survival rate of 5 years. To better design new preventive and/or therapeutic strategies for the fight against pancreatic cancer, the knowledge of the pathogenesis of pancreatic cancer at the molecular level is very important. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways among which the EGFR, Akt, and NF-κB pathways appear to be most relevant. Therefore, the strategies targeting EGFR, Akt, NF-κB, and their downstream signaling could be promising for the prevention and/or treatment of pancreatic cancer. In this brief review, we will summarize the current knowledge regarding the pathogenesis, prevention, and treatment of pancreatic cancer. PMID:17174370

  12. Acute recurrent pancreatitis: An autoimmune disease?

    PubMed Central

    Pezzilli, Raffaele

    2008-01-01

    In this review article, we will briefly describe the main characteristics of autoimmune pancreatitis and then we will concentrate on our aim, namely, evaluating the clinical characteristics of patients having recurrence of pain from the disease. In fact, the open question is to evaluate the possible presence of autoimmune pancreatitis in patients with an undefined etiology of acute pancreatitis and for this reason we carried out a search in the literature in order to explore this issue. In cases of recurrent attacks of pain in patients with “diopathic”pancreatitis, we need to keep in mind the possibility that our patients may have autoimmune pancreatitis. Even though the frequency of this disease seems to be quite low, we believe that in the future, by increasing our knowledge on the subject, we will be able to diagnose an ever-increasing number of patients having acute recurrence of pain from autoimmune pancreatitis. PMID:18286678

  13. Current status of endotherapy for chronic pancreatitis.

    PubMed

    Kwek, Andrew Boon Eu; Ang, Tiing Leong; Maydeo, Amit

    2014-12-01

    Chronic pancreatitis is associated with varied morphological complications, including intraductal stones, main pancreatic ductal strictures, distal biliary strictures and pseudocysts. Endoscopic therapy provides a less invasive alternative to surgery. In addition, extracorporeal shockwave lithotripsy improves the success rate of endoscopic clearance of intraductal stones. However, recent data from randomised trials have shown better long-term outcomes with surgical drainage for obstructive pancreatic ductal disease. In patients with distal biliary strictures, stent insertion leads to good immediate drainage, but after stent removal, recurrent narrowing is common. Endoscopic drainage of pancreatic pseudocysts has excellent outcome and should be accompanied by pancreatic ductal stenting when a ductal communication is evident. In those who remain symptomatic, endoscopic ultrasonography-guided coeliac plexus block may provide effective but short-term pain relief. In this review, we present the current evidence for the role of endotherapy in the management of patients with chronic pancreatitis. PMID:25630314

  14. The Clinical Utility of CA 19-9 in Pancreatic Adenocarcinoma: Diagnostic and Prognostic Updates

    PubMed Central

    Poruk, Katherine E.; Gay, David Z.; Brown, Kurt; Mulvihill, Jeffrey D.; Boucher, Kenneth M.; Scaife, Courtney L.; Firpo, Matthew A.; Mulvihill, Sean J.

    2015-01-01

    CA 19-9 and CEA are the most commonly used biomarkers for diagnosis and management of patients with pancreatic cancer. Since the original compendium by Steinberg in 1990, numerous studies have reported the use of CA 19-9 and, to a lesser extent, CEA in the diagnosis of pancreatic cancer. Here we update an evaluation of the accuracy of CA 19-9 and CEA, and, unlike previous reviews, focus on discrimination between malignant and benign disease instead of normal controls. In 57 studies involving 3,285 pancreatic carcinoma cases, the combined sensitivity of CA 19-9 was 78.2% and in 37 studies involving 1,882 cases with benign pancreatic disease the specificity of CA 19-9 was 82.8%. From the combined analysis of studies reporting CEA, the sensitivity was 44.2% (1,324 cases) and the specificity was 84.8% (656 cases). These measurements more appropriately reflect the expected biomarker accuracy in the differential diagnosis of patients with periampullary diseases. We also present a summary of the use of CA 19-9 as a prognostic tool and evaluate CA 19-9 diagnostic and prognostic utility in a 10-year, single institution experience. PMID:23331006

  15. The clinical utility of CA 19-9 in pancreatic adenocarcinoma: diagnostic and prognostic updates.

    PubMed

    Poruk, Katherine E; Gay, D Z; Brown, K; Mulvihill, J D; Boucher, K M; Scaife, C L; Firpo, M A; Mulvihill, S J

    2013-03-01

    CA 19-9 and CEA are the most commonly used biomarkers for diagnosis and management of patients with pancreatic cancer. Since the original compendium by Steinberg in 1990, numerous studies have reported the use of CA 19-9 and, to a lesser extent, CEA in the diagnosis of pancreatic cancer. Here we update an evaluation of the accuracy of CA 19-9 and CEA, and, unlike previous reviews, focus on discrimination between malignant and benign disease instead of normal controls. In 57 studies involving 3,285 pancreatic carcinoma cases, the combined sensitivity of CA 19-9 was 78.2% and in 37 studies involving 1,882 cases with benign pancreatic disease the specificity of CA 19-9 was 82.8%. From the combined analysis of studies reporting CEA, the sensitivity was 44.2% (1,324 cases) and the specificity was 84.8% (656 cases). These measurements more appropriately reflect the expected biomarker accuracy in the differential diagnosis of patients with periampullary diseases. We also present a summary of the use of CA 19-9 as a prognostic tool and evaluate CA 19-9 diagnostic and prognostic utility in a 10-year, single institution experience. PMID:23331006

  16. Enhanced antitumor effect of combined gemcitabine and proton radiation in the treatment of pancreatic cancer

    PubMed Central

    Galloway, Nicholas R.; Aspe, Jonathan R.; Sellers, Chelsey; Wall, Nathan R.

    2009-01-01

    OBJECTIVES This study evaluates the efficacy of combining proton irradiation with gemcitabine and the role the inhibitor of apoptosis proteins (IAP) survivin & XIAP play in the radiosensitive vs. radioresistant status of pancreatic cancer. METHODS The radioresistant (PANC-1) and radiosensitive (MIA PaCa-2) pancreatic carcinoma cells response to combined gemcitabine and proton irradiation was compared. Cells were treated with 0.1 - 500 ?-M gemcitabine and 0 - 15 Gy proton irradiation after which Trypan blue and flow cytometry were utilized to determine changes in the cell cycle and apoptosis. Expression levels of survivin were measured using Western blotting. Combination therapy with 24 h gemcitabine followed by 10-Gy proton irradiation proved most effective. RESULTS Gemcitabine and proton irradiation, resulted in increased survivin levels, with little apoptosis. However, combination therapy resulted in robust apoptotic induction with a concomitant survivin & XIAP reduction in the MIA PaCa-2 cells with little effect in the PANC-1 cells. siRNA studies confirmed a role for XIAP in the radioresistance of PANC-1 cells. CONCLUSIONS Our data demonstrate that combining gemcitabine and proton irradiation enhances apoptosis in human pancreatic cancer cells when XIAP levels decrease. Therefore, XIAP may play an important role in human pancreatic cancer proton radioresistance. PMID:19506533

  17. Learning experiences with sunitinib continuous daily dosing in patients with pancreatic neuroendocrine tumours

    PubMed Central

    Raymond, E.; Faivre, S.

    2014-01-01

    Molecular strategies to improve outcomes for patients with pancreatic neuroendocrine tumours (nets) have focused on targeting vascular endothelial growth factor, platelet-derived growth factor, and mtor (the mammalian target of rapamycin). This approach has led to the regulatory approval of two molecularly targeted agents for advanced pancreatic nets: sunitinib, a multi-targeted tyrosine kinase inhibitor, and everolimus, an mtor inhibitor. Initial experience with sunitinib in advanced pancreatic net was gained from the phase iii registration trial, which used a continuous daily dosing (cdd) schedule instead of daily drug administration for 4 consecutive weeks every 6 weeks (schedule 4/2), the approved schedule for advanced renal cell carcinoma (rcc) and gastrointestinal stromal tumour (gist). Clinical experience gained with schedule 4/2 in rcc and gist shows that, using a therapy management approach, patients can start and be maintained on the recommended dose and schedule, thus optimizing treatment outcomes. Here, we discuss challenges that can potentially be faced by physicians who use sunitinib on the cdd schedule, and we use clinical data and real-life clinical experience to present therapy management approaches that support cdd in advanced pancreatic net. PMID:25489258

  18. Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and progression

    PubMed Central

    Li, Ying-Yi; Mukaida, Naofumi

    2014-01-01

    Pim-3 is a member of the provirus integration site for Moloney murine leukemia virus (Pim) family proteins that exhibit serine/threonine kinase activity. Similar to the other Pim kinases (Pim-1 and Pim-2), Pim-3 is involved in many cellular processes, including cell proliferation, survival, and protein synthesis. Although Pim-3 is expressed in normal vital organs, it is overexpressed particularly in tumor tissues of endoderm-derived organs, including the liver, pancreas, and colon. Silencing of Pim-3 expression can retard in vitro cell proliferation of hepatocellular, pancreatic, and colon carcinoma cell lines by promoting cell apoptosis. Pim-3 lacks the regulatory domains similarly as Pim-1 and Pim-2 lack, and therefore, Pim-3 can exhibit its kinase activity once it is expressed. Pim-3 expression is regulated at transcriptional and post-transcriptional levels by transcription factors (e.g., Ets-1) and post-translational modifiers (e.g., translationally-controlled tumor protein), respectively. Pim-3 could promote growth and angiogenesis of human pancreatic cancer cells in vivo in an orthotopic nude mouse model. Furthermore, a Pim-3 kinase inhibitor inhibited cell proliferation when human pancreatic cancer cells were injected into nude mice, without inducing any major adverse effects. Thus, Pim-3 kinase may serve as a novel molecular target for developing targeting drugs against pancreatic and other types of cancer. PMID:25071334

  19. Valproic Acid Limits Pancreatic Recovery after Pancreatitis by Inhibiting Histone Deacetylases and Preventing Acinar Redifferentiation Programs.

    PubMed

    Eisses, John F; Criscimanna, Angela; Dionise, Zachary R; Orabi, Abrahim I; Javed, Tanveer A; Sarwar, Sheharyar; Jin, Shunqian; Zhou, Lili; Singh, Sucha; Poddar, Minakshi; Davis, Amy W; Tosun, Akif Burak; Ozolek, John A; Lowe, Mark E; Monga, Satdarshan P; Rohde, Gustavo K; Esni, Farzad; Husain, Sohail Z

    2015-12-01

    The mechanisms by which drugs induce pancreatitis are unknown. A definite cause of pancreatitis is due to the antiepileptic drug valproic acid (VPA). On the basis of three crucial observations-that VPA inhibits histone deacetylases (HDACs), HDACs mediate pancreas development, and aspects of pancreas development are recapitulated during recovery of the pancreas after injury-we hypothesized that VPA does not cause injury on its own, but it predisposes patients to pancreatitis by inhibiting HDACs and provoking an imbalance in pancreatic recovery. In an experimental model of pancreatic injury, we found that VPA delayed recovery of the pancreas and reduced acinar cell proliferation. In addition, pancreatic expression of class I HDACs (which are the primary VPA targets) increased in the midphase of pancreatic recovery. VPA administration inhibited pancreatic HDAC activity and led to the persistence of acinar-to-ductal metaplastic complexes, with prolonged Sox9 expression and sustained β-catenin nuclear activation, findings that characterize a delay in regenerative reprogramming. These effects were not observed with valpromide, an analog of VPA that lacks HDAC inhibition. This is the first report, to our knowledge, that VPA shifts the balance toward pancreatic injury and pancreatitis through HDAC inhibition. The work also identifies a new paradigm for therapies that could exploit epigenetic reprogramming to enhance pancreatic recovery and disorders of pancreatic injury. PMID:26476347

  20. Abnormal expression levels of sMICA and NKG2D are correlated with poor prognosis in pancreatic cancer

    PubMed Central

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

    2016-01-01

    Soluble major histocompatibility complex class I-related chain A molecules (sMICA) and natural-killer group 2 member D (NKG2D) not only correlate with tumorigenesis and progression, but also with tumor invasion and metastasis. In this study, we used immunohistochemistry to investigate the correlation and prognostic significance of the differential expression of sMICA and NKG2D in pancreatic carcinoma and paracarcinoma tissues from 70 patients with pancreatic carcinomas. The results showed that sMICA expression was significantly (P<0.05) higher in tumor tissues (67.1%) than that in adjacent nontumor tissues (31.4%), whereas NKG2D expression was significantly (P<0.001) lower in tumor tissues (32.9%) than that in adjacent nontumor tissues (60.0%). Spearman’s rank correlation test showed a negative correlation between the expression of sMICA and that of NKG2D (r=−0.676, P<0.001). Kaplan–Meier survival analysis showed that a high sMICA expression was significantly correlated with decreased disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001), while a high NKG2D expression was significantly associated with increased DFS (P=0.001) and OS (P=0.001) of the patients. Multivariate analysis showed that a high sMICA expression was an independent predictive factor for poor DFS (P<0.001) and OS (P=0.012); but low NKG2D expression was not an independent prognostic factor for poor DFS (P=0.238) and OS (P=0.574). In conclusion, our findings suggest that the expression levels of sMICA and NKG2D are abnormal and negatively correlated with one another in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for the prognosis of pancreatic carcinoma. PMID:26730197