Sequential changes from minimal pancreatic inflammation to advanced alcoholic pancreatitis.

PubMed

Noronha, M; Dreiling, D A; Bordalo, O

1983-11-01

A correlation of several clinical parameters and pancreatitis morphological alterations observed in chronic alcoholics with and without pancreatic is presented. Three groups of patients were studied: asymptomatic chronic alcoholics (24); non-alcoholic controls (10); and cases with advanced chronic pancreatitis (6). Clinical, biochemical and functional studies were performed. Morphological studies were made on surgical biopsy specimens in light and electron microscopy. The results of this study showed: 1) fat accumulates within pancreatic acinar cells in alcoholics drinking more than 80 g of ethanol per day; 2) ultrastructural changes found in acinar cells of the alcoholics are similar to those described for liver cells; 3) the alterations found in alcoholics without pancreatitis are also observed in those with advanced chronic pancreatitis. An attempt to correlate the sequential changes in the histopathology of alcoholic pancreatic disease with the clinical picture and secretory patterns was made. According to these observations, admitting the ultrastructural similarities between the liver and the pancreas and the recently demonstrated abnormalities of lipid metabolism in pancreatic cells in experimental animal research, the authors postulate a toxic-metabolic mechanism as a likely hypothesis for the pathogenesis of chronic alcoholic inflammation of the pancreas.

Dipeptidyl Peptidase-4 Inhibitor-Associated Pancreatic Carcinoma: A Review of the FAERS Database.

PubMed

Nagel, Angela K; Ahmed-Sarwar, Nabila; Werner, Paul M; Cipriano, Gabriela C; Van Manen, Robbert P; Brown, Jack E

2016-01-01

To date, there is limited literature regarding the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and pancreatic carcinoma. To describe the comparative incidence of DPP-4 inhibitors and pancreatic carcinoma as reportedly available in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. The goal was to provide health care practitioners a general understanding of the drug-disease occurrence. This is a case/noncase study utilizing Empirica Signal software to query FAERS from November 1968 to December 31, 2013. The software was used to calculate a disproportionality statistic--namely, the empirical Bayesian geometric mean (EBGM)--for reports of DPP-4 inhibitors-associated pancreatic carcinoma. The FDA considers an EBGM significant if the fifth percentile of the distribution is at least 2, defined as an EB05 ≥ 2. With use of a disproportionality analysis, DPP-4 inhibitors were compared with all agents listed in FAERS. A total of 156 patients experienced pancreatic carcinoma while receiving DPP-4 inhibitor therapy. An EB05 of 10.3 was determined for sitagliptin, 7.1 for saxagliptin, 4.9 for linagliptin, and 1.4 for alogliptin, compared with all other agents included in FAERS. Although an EB05 > 2 was achieved in 2 other antihyperglycemic agents, the findings were not consistent within their medication classes. There appears to be a statistical association between DPP-4 inhibitor use and pancreatic carcinoma. Causality cannot be inferred from the data provided. Additional clinical studies are needed to further explore this statistical association. © The Author(s) 2015.

Irreversible electroporation of locally advanced pancreatic neck/body adenocarcinoma

PubMed Central

2015-01-01

Objective Irreversible electroporation (IRE) of locally advanced pancreatic adenocarcinoma of the neck has been used to palliate appropriate stage 3 pancreatic cancers without evidence of metastasis and who have undergone appropriate induction therapy. Currently there has not been a standardized reported technique for pancreatic mid-body tumors for patient selection and intra-operative technique. Patients Subjects are patients with locally advanced pancreatic adenocarcinoma of the body/neck who have undergone appropriate induction chemotherapy for a reasonable duration. Main outcome measures Technique of open IRE of locally advanced pancreatic adenocarcinoma of the neck/body is described, with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open IRE of the pancreatic neck/body with bracketing of the celiac axis and superior mesenteric artery with continuous intraoperative ultrasound imaging and consideration of intraoperative navigational system is described. Conclusions IRE of locally advanced pancreatic adenocarcinoma of the body/neck is feasible for appropriate patients with locally advanced unresectable pancreatic cancer. PMID:26029461

Irreversible electroporation of stage 3 locally advanced pancreatic cancer: optimal technique and outcomes

PubMed Central

2015-01-01

Objective Irreversible electroporation (IRE) of stage 3 pancreatic adenocarcinoma has been used to provide quality of life time in patients who have undergone appropriate induction therapy. The optimal technique has been reported within the literature, but not in video form. IRE of locally advanced pancreatic cancer is technically demanding requiring precision ultrasound use for continuous imaging in multiple needle placements and during IRE energy delivery. Methods Appropriate patients with locally advanced pancreatic cancer should have undergone appropriate induction chemotherapy for a reasonable duration. The safe and effective technique for irreversible electroporation is preformed through an open approach with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open irreversible electroporation of the pancreas involves bracketing the target tumor with IRE probes and any and all invaded vital structures including the celiac axis, superior mesenteric artery (SMA), superior mesenteric-portal vein, and bile duct with continuous intraoperative ultrasound imaging through a caudal to cranial approach. Optimal IRE delivery requires a change in amperage of at least 12 amps from baseline tissue conductivity in order to achieve technical success. Multiple pull-backs are necessary since the IRE ablation probe lengths are 1 cm and thus needed to achieve technical success along the caudal to cranial plane. Conclusions Irreversible electroporation in combination with multi-modality therapy for locally advanced pancreatic carcinoma is feasible for appropriate patients with locally advanced cancer. Technical demands are high and require the highest quality ultrasound for precise spacing measurements and optimal delivery to ensure adequate change in tissue resistance. PMID:29075594

Novel agents for advanced pancreatic cancer

PubMed Central

Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

2015-01-01

Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

Pancreatic cancer: Advances in treatment

PubMed Central

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

2014-01-01

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

Pancreatic cancer: advances in treatment.

PubMed

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

2014-07-28

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

Pancreatic Carcinoma: the Disease that Kills.

PubMed

Kabashi, Serbeze; Dedushi, Kreshnike; Ramadani, Naser; Mucaj, Sefedin; Hoxhaj, Asrtrit; Jerliu, Naim

2016-02-01

The purpose of this case report is to demonstrate the clinical symptoms and laboratory changes that have occurred very late and were very few in number even the imaging studies performed at that time showed an intensive local tumor growth associated with the wide infiltration of the both adjacent and distant upper abdominal structures. A 71-year-old male patient who was a chronic alcohol abuser and ex smoker (quit smoking 8 years earlier) presented with symptoms of mild pain on epigastric region that irradiated toward the back and significant weight loss. The initial ultrasonography (US) examination was performed, followed by the lab tests and multidetector computed tomography (MDCT) examination. The diagnostic studies confirmed the presence of the pancreatic's body mass. The ordered laparoscopic evaluation established definitive diagnosis. Initial US examination showed heterogeneous pseudo-cystic changes and slight edema of the pancreatic parenchyma associated with the multiple oval hyperechogenic lesions of liver - the signs highly suggestive of secondary metastatic deposits. The other imaging findings that were obtained with the use of the MDCT confirmed the presence of an expansive primary process of the body of the pancreas associated with the secondary metastatic changes in liver. In addition, the consecutive lymphadenopathy was revealed along hepatoduodenal ligament, retropancreatic region and intraperitoneal compartment. Tumor markers resulted with the high values of the AFP of 2.3, CA19-9 of 423.0 U/mL, and CEA of 219.0 ng/mL. The specimen of the tumor tissue taken during laparoscopic biopsy was sent for histologic examination and the final result was "metastatic adenocarcinoma of pancreas". Pancreatic body carcinoma has always been associated with poor prognosis because diagnosis is made at the advanced stage of the disease. Therefore, poor prognosis might be improved if early diagnosis could be made. Recent researches confirmed genetic predisposition for

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

Treatment of pancreatic insufficiency using pancreatic extract in patients with advanced pancreatic cancer: a pilot study (PICNIC).

PubMed

Zdenkowski, Nicholas; Radvan, George; Pugliese, Leanna; Charlton, Julie; Oldmeadow, Christopher; Fraser, Allison; Bonaventura, Antonino

2017-06-01

Survival with advanced pancreatic cancer is less than 12 months. Pancreatic exocrine insufficiency may contribute to pancreatic cancer-related cachexia, via nutrient malabsorption. We aimed to determine the feasibility of prescribing pancreatic extract (Creon®) for patients with advanced pancreatic cancer. Patients with advanced pancreatic cancer, without frank malabsorption, were randomised in this feasibility study to pancreatic extract 50,000 units with meals and 25,000 units with snacks, or placebo. Standardised dietary advice was given. Anti-cancer and supportive care treatments were permitted. Outcomes included weight, body mass index (BMI), quality of life (QLQC30, PAN26), survival and nutritional assessment (PG-SGA). Eighteen patients were randomised before study closure due to slow recruitment. Baseline characteristics were well matched. Weight loss prior to randomisation was numerically greater in the pancreatic extract group (mean 0.7 vs 2.2 kg). Weight loss was numerically greater in the placebo group, however not significantly. No differences in BMI or nutrition score were seen. Quality of life did not differ between study groups. Median overall survival was 17 (95% CI 8.1-48.7) weeks in the control group, and 67.6 (95% CI 14.1-98.4) weeks in the pancreatic extract group (p = 0.1063). Only 17% (18/106) of potentially eligible patients were recruited, related to patient/family reluctance, rapid clinical deterioration and patients already prescribed pancreatic extract. A moderate pill burden was noted. Despite intriguing survival results, this study was not sufficiently feasible to proceed to a fully powered comparative study. A multi-centre study would be required to exclude a significant difference in outcomes.

CT guided interstitial therapy of pancreatic carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haaga, J.R.; Owens, D.B.; Kellermeyer, R.W.

1987-11-01

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

Pancreatic acinar cell carcinoma extending into the common bile and main pancreatic ducts.

PubMed

Yamaguchi, Rin; Okabe, Yoshinobu; Jimi, Atsuo; Shiota, Koji; Kodama, Takahito; Naito, Yoshiki; Yasunaga, Masafumi; Kinoshita, Hisafumi; Kojiro, Masamichi

2006-10-01

Acinar cell carcinoma (ACC) of the pancreas is relatively rare, accounting for only approximately 1% of all exocrine pancreatic tumors. A 69-year-old man was found to have a mass lesion measuring approximately 4 cm in diameter in the pancreatic head on ultrasound, abdominal dynamic CT, and percutaneous transhepatic cholangiography. Magnetic resonance cholangiopancreatography showed defect of the lower common bile duct (CBD) due to obstruction by the tumor cast. Histopathologically, the pancreatic head tumor invaded the main pancreatic duct (MPD) and CBD with extension into the CBD in a form of tumor cast. The tumor cells consisted of a solid proliferation with abundant eosinophilic cytoplasm and round nuclei in an acinar and trabecular fashion. A 55-year-old man with upper abdominal pain and nausea, had a cystic lesion approximately 3 cm in size in the pancreatic tail on CT. Histopathologically, the tumor was encapsulated by fibrous capsule and had extensive central necrosis with solid areas in the tumor periphery, and invaded with extension into the MPD in a form of tumor cast. The tumor cells resembled acinar cells in solid growths. Two resected cases of ACC with unusual tumor extension into the CBD and the MPD, respectively, are reported.

Alcohol and the pancreas. II. Pancreatic morphology of advanced alcoholic pancreatitis.

PubMed

Noronha, M; Bordalo, O; Dreiling, D A

1981-08-01

The histopathology of advanced chronic alcoholic pancreatitis is dominated by cellular degeneration, atrophy and fibrosis. Sequential changes in the histopathology of alcoholic pancreatic disease has been defined and traced from initial injury to end-stage disease. These sequential histopathologies have been correlated with clinical syndrome and secretory patterns. The data are more consistent with a toxic-metabolic pathogenesis of alcoholic pancreatitis than the previous Big Duct and Small Duct hypotheses.

[Results of surgical treatment in ampullary and pancreatic carcinoma and its prognostic parameters after R0-resection].

PubMed

Ridwelski, K; Meyer, F; Schmidt, U; Lippert, H

2005-08-01

Resection is currently the only established reasonable therapeutic option with curative potential in pancreatic and ampullary carcinoma. The aim of the study was i) to analyze value and results of surgical therapy and ii) to detect the prognostic parameters, which determine significantly higher survival rates. Two-hundred-twenty patients with pancreatic and ampullary carcinoma (mean age, 61.4 years; 104 females/116 males) underwent surgery. Histologic investigation revealed 19 carcinomas of the papilla of Vater and 201 ductal pancreatic carcinomas. In 126 patients, stage IV a or b tumors were found, in addition, stage I (n =26), II (n = 17) and III (n = 51). Survival-rate was determined according to the method by Kaplan/Meier. Survival was compared using log-rank test. Association of several or multiple parameters with survival was tested using Cox model. Hundred-ten patients underwent tumor resection with primary curative intention (50 %): 96 resections of the pancreatic head, 2 total pancreatectomies and 12 left resections of the pancreas. R0-resection was achieved in 94 patients (42.7 %), whereas intervention was classified R1 in 10 and R2 in 6 cases. In addition, 60 palliative interventions (28 gastroenterostomies, 17 biliodigestive anastomoses, 15 anastomoses at both sites) and 50 explorative laparotomies were performed. In 42.3 % of patients, postoperative complications were found, but only 12/220 individuals died (overall letality, 5.4 %). Postoperative letality of curative pancreatic resections was 3.6 % (palliative intervention, 6.7 %; explorative laparotomy, 8.8 %). Five-year survival-rate of carcinoma of the papilla of Vater and pancreatic carcinoma was 73.3 % and 16.2 %, respectively (median survival time was 66.0 and 14.0 months, respectively). Taken together all other interventions, median survival time ranged between 4.0 (palliative intervention) to 10.0 months (R1-resection). No patient survived 5 years. Therefore, the most relevant prognostic

Does autoimmune pancreatitis increase the risk of pancreatic carcinoma?: a retrospective analysis of pancreatic resections.

PubMed

Gupta, Rajib; Khosroshahi, Arezou; Shinagare, Shweta; Fernandez, Carlos; Ferrone, Cristina; Lauwers, Gregory Y; Stone, John H; Deshpande, Vikram

2013-04-01

To estimate the risk of malignancy in autoimmune pancreatitis (AIP). We examined resected pancreata to compare the prevalence of pancreatic intraepithelial neoplasia (PanIN) in 28 cases of AIP and 30 cases of chronic pancreatitis not otherwise specified (CP-NOS). We also reviewed a cohort of 84 AIP cases. The mean age of the AIP cohort (57 years) was significantly higher than that of the cohort of CP-NOS (47 years) (P = 0.01). Twenty-three cases (82%) of AIP showed PanIN, and 7 cases (25%) showed grade 2 PanIN. Grade 3 PanIN was identified in one case of AIP. There was no statistically significant difference in the number of cases with high-grade PanIN lesions between the cases of type 1 as opposed to type 2 AIP. In comparison to CP-NOS, a comparable percentage of patients with AIP had PanIN (82% of AIP cases vs 63% of CP-NOS cases) (P = NS) and PanIN 2 (25% AIP vs 20% CP-NOS) (P = NS). Of the 84 AIP cases at our institution (mean follow-up, 49 months), 2 cases of pancreatic carcinoma were identified 6 and 10 years after the diagnoses of AIP. These findings raise concern that AIP is associated with an elevated risk of malignancy and should prompt additional studies.

Triple bypass for advanced pancreatic head cancer associated with biliary stricture, duodenal stenosis, and recurrent obstructive pancreatitis.

PubMed

Kudo, Yuzan; Sato, Norihiro; Tamura, Toshihisa; Hirata, Keiji

2016-12-01

Bypass surgery for cancer of the pancreatic head is usually done to palliate the obstructive symptoms in the biliary and/or digestive system. However, it is uncommon for patients to require pancreatic duct drainage for recurrent obstructive pancreatitis. In this article, we report a surgical technique of triple bypass consisting of Roux-en-Y hepaticojejunostomy, gastrojejunostomy, and pancreaticojejunostomy for advanced pancreatic cancer. A 76-year-old male patient with locally advanced and metastatic pancreatic head cancer was referred to our department for biliary stricture, duodenal stenosis, and recurrent obstructive pancreatitis associated with persistent pancreatic pseudocyst. In an attempt to resolve all these problems simultaneously, a triple bypass was performed. The patient survived and continued to receive chemotherapy for almost 1 year after surgery without any serious complications. Thus, triple bypass is a useful surgical technique that could relief symptoms and offer better quality of life to patients with advanced pancreatic cancer presenting with biliary stricture, duodenal stenosis, and severe obstructive pancreatitis difficult to treat by medication or endoscopic procedures.

Surgical and molecular pathology of pancreatic neoplasms.

PubMed

Hackeng, Wenzel M; Hruban, Ralph H; Offerhaus, G Johan A; Brosens, Lodewijk A A

2016-06-07

Histologic characteristics have proven to be very useful for classifying different types of tumors of the pancreas. As a result, the major tumor types in the pancreas have long been classified based on their microscopic appearance. Recent advances in whole exome sequencing, gene expression profiling, and knowledge of tumorigenic pathways have deepened our understanding of the underlying biology of pancreatic neoplasia. These advances have not only confirmed the traditional histologic classification system, but also opened new doors to early diagnosis and targeted treatment. This review discusses the histopathology, genetic and epigenetic alterations and potential treatment targets of the five major malignant pancreatic tumors - pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, acinar cell carcinoma and pancreatoblastoma.

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.

Expression levels of long non-coding RNA HOXA distal transcript antisense RNA and metabotropic glutamate receptor 1 in pancreatic carcinoma, and their prognostic values.

PubMed

Wang, Xiaoqing; Xiao, Lili; Yu, Haitao

2018-06-01

As a type of malignant tumor developed at the pancreas, the prognosis of pancreatic carcinoma is usually poor, and >90% patients will sucumb to this disease <5 years after diagnosis. Therefore, early detection and treatment of this disease are important for improving the prognosis of patients. Long non-coding RNAs (lncRNAs) have been proven to serve pivotal functions in the development and progression of various tumors. The lncRNA HOXA distal transcript antisense RNA (HOTTIP), which serves an oncogenic role in different types of malignant tumors, has also been reported to be closely correlated with the migration and invasion of pancreatic carcinoma. In addition, the metabotropic glutamate receptor 1 (mGluR1) is also associated with the progression of various types of human cancer; however, its functionality in pancreatic carcinoma is largely unknown. In the present study, the expression levels of HOTTIP and mGluR1 were compared between pancreatic carcinoma and adjacent normal healthy tissues, and the correlation between these expression levels was analyzed. The prognostic value of HOTTIP and mGluR1 in pancreatic carcinoma was also examined. It was observed that the expression levels of HOTTIP and mGluR1 were upregulated in pancreatic carcinoma tissues and pancreatic carcinoma cells, while the expression of HOTTIP was able to positively affect the expression of mGluR1. In addition, high expression levels of HOTTIP were significantly correlated with the tumor size and distant metastasis. These data suggested that HOTTIP and mGluR1 may potentially serve as biomarkers for the prognosis of pancreatic carcinoma.

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

Metastatic tonsillar squamous cell carcinoma masquerading as a pancreatic cystic tumor and diagnosed by EUS-guided FNA.

PubMed

Glass, Ryan; Andrawes, Sherif A; Hamele-Bena, Diane; Tong, Guo-Xia

2017-11-01

Metastatic carcinoma to the pancreas is uncommon and head and neck squamous carcinoma metastatic to the pancreas is extremely rare. Metastatic squamous cell carcinoma to the pancreas presents a unique diagnostic challenge: in addition to mimicking the rare primary squamous cell carcinoma of the pancreas based on cytologic, histologic, and immunohistochemical features, it may be mistaken for a cystic neoplasm of the pancreas because of its high predilection for cystic degeneration in metastatic sites. Herein, we report a case of tonsillar squamous cell carcinoma with a cystic pancreatic metastasis diagnosed by ultrasound-guided fine needle aspiration biopsy (EUS-FNA). This represents a third reported case of metastatic squamous cell carcinoma to the pancreas from the head and neck region. Metastatic squamous cell carcinoma should be considered in the differential diagnosis of EUS-FNA during evaluation of pancreatic cystic lesion. © 2017 Wiley Periodicals, Inc.

Surgical resection after TNFerade therapy for locally advanced pancreatic cancer.

PubMed

Chadha, Manpreet K; Litwin, Alan; Levea, Charles; Iyer, Renuka; Yang, Gary; Javle, Milind; Gibbs, John F

2009-09-04

Treatment of pancreatic cancer remains a major oncological challenge and survival is dismal. Most patients, present with advanced disease at diagnosis and are not candidates for curative resection. Preoperative chemoradiation may downstage and improve survival in locally advanced pancreatic cancer. This has prompted investigators to look for novel neoadjuvant therapies. Gene therapy for pancreatic cancer is a novel investigational approach that may have promise. TNFerade is a replication deficient adenovirus vector carrying the human tumor necrosis factor (TNF)-alpha gene regulated under control of a radiation-inducible gene promoter. Transfection of tumor cells with TNFerade maximizes the antitumor effect of TNF-alpha under influence of radiation leading to synergistic effects in preclinical studies. We describe a case of locally advanced unresectable pancreatic cancer treated with a novel multimodal approach utilizing gene therapy with TNFerade and concurrent chemoradiation that was followed by successful surgical resection. Neoadjuvant TNFerade based chemoradiation therapy may be a useful adjunct to treatment of locally advanced pancreatic cancer.

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

PubMed Central

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

1995-01-01

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

High-intensity focused ultrasound (HIFU) for pancreatic carcinoma: evaluation of feasibility, reduction of tumour volume and pain intensity.

PubMed

Marinova, Milka; Rauch, Maximilian; Mücke, Martin; Rolke, Roman; Gonzalez-Carmona, Maria A; Henseler, Jana; Cuhls, Henning; Radbruch, Lukas; Strassburg, Christian P; Zhang, Lian; Schild, Hans H; Strunk, Holger M

2016-11-01

Prognosis of patients with locally advanced pancreatic adenocarcinoma is extremely poor. They often suffer from cancer-related pain reducing their quality of life. This prospective observational study aimed to evaluate feasibility, local tumour response, and changes in quality of life and symptoms in Caucasian patients with locally advanced pancreatic cancer treated by ultrasound-guided high-intensity focused ultrasound (HIFU). Thirteen patients underwent HIFU, five with stage III, eight with stage IV UICC disease. Ten patients received simultaneous palliative chemotherapy. Postinterventional clinical assessment included evaluation of quality of life and symptom changes using standardized questionnaires. CT and MRI follow-up evaluated the local tumour response. HIFU was successfully performed in all patients. Average tumour reduction was 34.2 % at 6 weeks and 63.9 % at 3 months. Complete or partial relief of cancer-related pain was achieved in 10 patients (77 %), five of whom required less analgesics for pain control. Quality of life was improved revealing increased global health status and alleviated symptoms. HIFU treatment was well tolerated. Eight patients experienced transient abdominal pain directly after HIFU. HIFU ablation of pancreatic carcinoma is a feasible, safe and effective treatment with a crucial benefit in terms of reduction of tumour volume and pain intensity. • US-guided HIFU is feasible and safe for patients with unresectable pancreatic cancer. • HIFU can considerably reduce tumour volume and cancer-related pain. • Patients treated with HIFU experienced significant and lasting reduction of pain intensity. • HIFU has a crucial clinical benefit for patients with pancreatic cancer.

Metastatic pancreatic carcinoma and bronchioloalveolar adenomas in an Egyptian fruit bat (Rousettus aegyptiacus).

PubMed

Cushing, Andrew C; Ossiboff, Robert; Buckles, Elizabeth; Abou-Madi, Noha

2013-09-01

An adult female, intact Egyptian fruit bat (Rousettus aegyptiacus) was presented for lethargy, anorexia, and markedly reduced flying activity. Physical and ultrasound examinations were suggestive of an abdominal mass with free fluid within the abdomen. Based on the poor and deteriorating clinical condition of the animal, euthanasia was elected. Gross necropsy revealed an irregular thickening at the root of the mesentery and a diffusely, dark-red liver with rounded hepatic margins. Histologic examination revealed extensive neoplastic effacement of the pancreas with invasion into the surrounding mesentery and mesenteric lymph nodes and metastatic spread to the liver. Based on the morphology of the neoplastic cells, the involvement of the pancreas, and immunohistochemistry, a diagnosis of metastatic pancreatic carcinoma was made. Additionally, two small neoplasms were identified in the lungs. These masses were distinct from the carcinoma, and their morphology was consistent with bronchioloalveolar adenomas. This is the first known report of either benign pulmonary lesions or pancreatic carcinomas in the order Chiroptera.

Imaging Characteristics and Prevalence of Pancreatic Carcinoma in Kosovo During 2011-2015 - Diagnostic Method as Choice.

PubMed

Dedushi, Kreshnike; Kabashi, Serbeze; Mucaj, Sefedin; Hasbahta, Gazmed; Ramadani, Naser; Hoxhaj, Astrit

2016-06-01

Pancreatic cancer is the 10(th)most common malignancy and the 4(th)largest cancer killer in adults. The purpose of this paper is to evaluate the number of cases presented with pancreatic carcinoma during the years 2011-2015, our experience of the imaging characteristics of pancreatic carcinoma. We evaluated prevalence of the pancreatic cancers, distant metastases and other local infiltration signs among the total cases of the pancreatic cancers diagnosed in the University Clinical Center of Kosovo, with the aim to compare these research findings to similar studies made in the developed countries. This is a retrospective research study done during the period of 2011-2015. This retrospective research study includes 362 patients recently diagnosed with pancreatic cancer, examined in the period of 2011-2015 at the University Clinical Center of Kosovo. The imaging diagnostics are performed with MSCT Sensation 64 Siemens, MSCT Emotion 6 Siemens, and 1.5T MRI Symphony Siemens, biopsy guide with MSCT Sensation 64 Siemens in the Radiologic Clinic of UCCK; while the histopathology diagnostics has been performed in Clinic of Pathology at UCCK and prevalence is taken from the number of cases Reported at the Institute of Oncology Institute of Statistics and NIPH (National Institute of Public Health of Kosovo). Out of a total of the 362 patients diagnosed with pancreas cancer, results is female 39.5% (n=143) and male 61.5% (n=219), report M: F (1: 1.6), 286 cases resulted in head and neck 79 % (n=286), 76 cases resulted in body and tail cancers (21%), distant metastases in first imaging modality were found in(n=155) patients 43 %, local infiltration was found in patients: gastric infiltration 15 % (n=54), duodenal and papilla infiltration 26% (n=94), local infiltration spleen 16% (n=57), local infiltration mesentery 43 % (n= 155), dilated biliary tree 34 % (n=123), regional lymph node infiltration 83 % (n= 300). Out of a total of the 362 patients diagnosed with pancreas cancer

Primary Pancreatic Head Tuberculosis: Great Masquerader of Pancreatic Adenocarcinoma

PubMed Central

Gupta, Dhaval; Patel, Jatin; Rathi, Chetan; Ingle, Meghraj; Sawant, Prabha

2015-01-01

Isolated pancreatic tuberculosis (TB) is considered an extremely rare condition, even in the developing countries. Most reported cases of pancreatic TB are diagnosed after exploratory laparotomy or autopsy. Pancreatic TB is a potential mimic of invasive pancreatic malignancy and the presence of vascular invasion does not distinguish one condition from the other. Every effort should be made for the earliest diagnosis of this condition as TB is a treatable condition and it avoids unnecessary management of pancreatic carcinoma. Here we report a rare case of primary pancreatic head TB in a 58-year-old male who presented with hypodense lesion in head of pancreas with double duct sign and portal vein invasion mimicking non-resectable pancreatic carcinoma. PMID:27785295

Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

ClinicalTrials.gov

2017-07-10

Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

Advances in Hereditary Colorectal and Pancreatic Cancer

PubMed Central

Underhill, Meghan L.; Germansky, Katharine A.; Yurgelun, Matthew B.

2017-01-01

Purpose Innovations in genetic medicine have lead to improvements in the early detection, prevention, and treatment of cancer for patients with inherited risks of gastrointestinal cancer, particularly hereditary colorectal cancer and hereditary pancreatic cancer. Methods This review provides an update on recent data and key advances that have improved the identification, understanding, and management of patients with hereditary colorectal cancer and hereditary pancreatic cancer. Findings This review details recent and emerging data that highlight the developing landscape of genetics in hereditary colorectal and pancreatic cancer risk. A summary is provided of the current state-of-the-art practices for identifying, evaluating, and managing patients with suspected hereditary colorectal cancer and pancreatic cancer risk. The impact of next-generation sequencing technologies in the clinical diagnosis of hereditary gastrointestinal cancer and also in discovery efforts of novel genes linked to familial cancer risk are discussed. Emerging targeted therapies that may play a particularly important role in the treatment of patients with hereditary forms of colorectal cancer and pancreatic cancer are also reviewed. Current approaches for pancreatic cancer screening and the psychosocial impact of such procedures are also detailed. Implications Given the availability of novel diagnostic, risk-reducing, and therapeutic strategies that exist for patients with hereditary risk for colorectal or pancreatic cancer, it is imperative that clinicians be vigilant about evaluating patients for hereditary cancer syndromes. Continuing to advance genetics research in hereditary gastrointestinal cancers will allow for more progress to be made in personalized medicine and prevention. PMID:27045993

Lymphocytic mural folliculitis and pancreatic carcinoma in a cat.

PubMed

Lobetti, Remo

2015-06-01

A 9-year-old castrated domestic shorthair cat was presented with a 6 week history of progressive non-pruritic alopecia, polyphagia and weight loss. A diagnosis of lymphocytic mural folliculitis was made and the cat was treated with a combination of prednisolone and ciclosporin; this produced an improvement in the alopecia but no resolution. Sixteen months after the initial assessment and diagnosis, the cat was re-evaluated for intermittent vomiting and weight loss with normal appetite. On examination the dermatopathy was still evident and a mass involving the duodenum and pancreas was present, which was diagnosed as a pancreatic carcinoma. From this case it would appear that lymphocytic mural folliculitis might be an early dermatological manifestation of pancreatic neoplasia. © ISFM and AAFP 2014.

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

2016-03-18

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. 2016 BMJ Publishing Group Ltd.

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

PubMed Central

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

Case report: Irreversible electroporation for locally advanced pancreatic cancer.

PubMed

Orcutt, Sonia; Kis, Bela; Malafa, Mokenge

2017-01-01

For patients with pancreatic adenocarcinoma who are not candidates for surgical resection, long-term survival is poor, even with currently available systemic and radiation therapy options. However, for those with locally advanced disease who do not have distant metastasis, locoregional control of the tumor has the potential to improve long-term outcomes. A newly developed technology, irreversible electroporation, has advantages over traditional thermal ablation with unresectable cancers in this location. In our case report, we describe the first patient treated with irreversible electroporation at our institution for locally advanced pancreatic cancer. The patient is a 63-year-old man who had a partial response to standard chemotherapy and radiation, but was found on operative assessment to have persistently unresectable disease. He therefore underwent irreversible electroporation to the pancreatic mass. His postoperative course was complicated by delayed gastric emptying and wound infection. Three months after surgery, he had no evidence of distant or recurrent disease. Irreversible electroporation for locally advanced pancreatic cancer is an emerging technique which attempts to improve local control of locally advanced, non-metastatic pancreatic cancer. Early data have demonstrated the potential for improved long-term survival in these patients, although further studies are needed to confirm safety and efficacy of this technique. While there is a positive outlook for the use of irreversible electroporation for locally advanced pancreas cancer, there remain some uncertainties surrounding this therapy, which underscores the importance of future research in this area. Copyright © 2017. Published by Elsevier Ltd.

Pancreatic Carcinoma: the Disease that Kills

PubMed Central

Kabashi, Serbeze; Dedushi, Kreshnike; Ramadani, Naser; Mucaj, Sefedin; Hoxhaj, Asrtrit; Jerliu, Naim

2016-01-01

The purpose of this case report is to demonstrate the clinical symptoms and laboratory changes that have occurred very late and were very few in number even the imaging studies performed at that time showed an intensive local tumor growth associated with the wide infiltration of the both adjacent and distant upper abdominal structures. A 71-year-old male patient who was a chronic alcohol abuser and ex smoker (quit smoking 8 years earlier) presented with symptoms of mild pain on epigastric region that irradiated toward the back and significant weight loss. The initial ultrasonography (US) examination was performed, followed by the lab tests and multidetector computed tomography (MDCT) examination. The diagnostic studies confirmed the presence of the pancreatic’s body mass. The ordered laparoscopic evaluation established definitive diagnosis. Initial US examination showed heterogeneous pseudo-cystic changes and slight edema of the pancreatic parenchyma associated with the multiple oval hyperechogenic lesions of liver - the signs highly suggestive of secondary metastatic deposits. The other imaging findings that were obtained with the use of the MDCT confirmed the presence of an expansive primary process of the body of the pancreas associated with the secondary metastatic changes in liver. In addition, the consecutive lymphadenopathy was revealed along hepatoduodenal ligament, retropancreatic region and intraperitoneal compartment. Tumor markers resulted with the high values of the AFP of 2.3, CA19-9 of 423.0 U/mL, and CEA of 219.0 ng/mL. The specimen of the tumor tissue taken during laparoscopic biopsy was sent for histologic examination and the final result was “metastatic adenocarcinoma of pancreas”. Pancreatic body carcinoma has always been associated with poor prognosis because diagnosis is made at the advanced stage of the disease. Therefore, poor prognosis might be improved if early diagnosis could be made. Recent researches confirmed genetic

Gene expression analysis of pancreatic cell lines reveals genes overexpressed in pancreatic cancer.

PubMed

Alldinger, Ingo; Dittert, Dag; Peiper, Matthias; Fusco, Alberto; Chiappetta, Gennaro; Staub, Eike; Lohr, Matthias; Jesnowski, Ralf; Baretton, Gustavo; Ockert, Detlef; Saeger, Hans-Detlev; Grützmann, Robert; Pilarsky, Christian

2005-01-01

Pancreatic cancer is one of the leading causes of cancer-related death. Using DNA gene expression analysis based on a custom made Affymetrix cancer array, we investigated the expression pattern of both primary and established pancreatic carcinoma cell lines. We analyzed the gene expression of 5 established pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-1, Capan-2 and HPAF II) and 5 primary isolates, 1 of them derived from benign pancreatic duct cells. Out of 1,540 genes which were expressed in at least 3 experiments, we found 122 genes upregulated and 18 downregulated in tumor cell lines compared to benign cells with a fold change >3. Several of the upregulated genes (like Prefoldin 5, ADAM9 and E-cadherin) have been associated with pancreatic cancer before. The other differentially regulated genes, however, play a so far unknown role in the course of human pancreatic carcinoma. By means of immunohistochemistry we could show that thymosin beta-10 (TMSB10), upregulated in tumor cell lines, is expressed in human pancreatic carcinoma, but not in non-neoplastic pancreatic tissue, suggesting a role for TMSB10 in the carcinogenesis of pancreatic carcinoma. Using gene expression profiling of pancreatic cell lines we were able to identify genes differentially expressed in pancreatic adenocarcinoma, which might contribute to pancreatic cancer development. Copyright 2005 S. Karger AG, Basel.

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

ClinicalTrials.gov

2018-04-24

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

Negative methylation status of Vimentin predicts improved prognosis in pancreatic carcinoma

PubMed Central

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

2014-01-01

AIM: To determine the existence of a potential relationship between the methylation state of the Vimentin gene and its prognostic value in pancreatic cancer. METHODS: Sixty-four primary tumor specimens and normal tissues were collected consecutively from pancreatic cancer patients during surgery at Hangzhou First People’s Hospital and Affiliated Hospital of the Logistics University of the Chinese People’s Armed Police Force. DNA was extracted from the samples and subsequently quantitative methylation-specific polymerase chain reaction was used to detect the Vimentin methylation status of the samples. All of the patients were followed up to December 2012. χ2 test, Kaplan-Meier survival and Cox regression statistical models were used. RESULTS: Out of 64 pancreatic cancer tissues, 21 were marked as Vimentin methylation-positive, and 43 were marked as Vimentin methylation-negative. The location of pancreatic carcinoma was related to the Vimentin methylation state. The pathological T staging (P < 0.001), adjuvant chemotherapy (P = 0.003) and the Vimentin methylation state (P = 0.037) were independent prognostic factors. CONCLUSION: In our study, Vimentin methylation status can predict the prognosis of pancreatic cancer patients. However, additional experiments and clinical trials are needed to accurately validate this observation. PMID:25278713

Imaging Characteristics and Prevalence of Pancreatic Carcinoma in Kosovo During 2011-2015 - Diagnostic Method as Choice

PubMed Central

Dedushi, Kreshnike; Kabashi, Serbeze; Mucaj, Sefedin; Hasbahta, Gazmed; Ramadani, Naser; Hoxhaj, Astrit

2016-01-01

Introduction: Pancreatic cancer is the 10thmost common malignancy and the 4thlargest cancer killer in adults. Aim: The purpose of this paper is to evaluate the number of cases presented with pancreatic carcinoma during the years 2011-2015, our experience of the imaging characteristics of pancreatic carcinoma. We evaluated prevalence of the pancreatic cancers, distant metastases and other local infiltration signs among the total cases of the pancreatic cancers diagnosed in the University Clinical Center of Kosovo, with the aim to compare these research findings to similar studies made in the developed countries. This is a retrospective research study done during the period of 2011-2015. Materials and Methodology: This retrospective research study includes 362 patients recently diagnosed with pancreatic cancer, examined in the period of 2011-2015 at the University Clinical Center of Kosovo. The imaging diagnostics are performed with MSCT Sensation 64 Siemens, MSCT Emotion 6 Siemens, and 1.5T MRI Symphony Siemens, biopsy guide with MSCT Sensation 64 Siemens in the Radiologic Clinic of UCCK; while the histopathology diagnostics has been performed in Clinic of Pathology at UCCK and prevalence is taken from the number of cases Reported at the Institute of Oncology Institute of Statistics and NIPH (National Institute of Public Health of Kosovo). Results: Out of a total of the 362 patients diagnosed with pancreas cancer, results is female 39.5% (n=143) and male 61.5% (n=219), report M: F (1: 1.6), 286 cases resulted in head and neck 79 % (n=286), 76 cases resulted in body and tail cancers (21%), distant metastases in first imaging modality were found in(n=155) patients 43 %, local infiltration was found in patients: gastric infiltration 15 % (n=54), duodenal and papilla infiltration 26% (n=94), local infiltration spleen 16% (n=57), local infiltration mesentery 43 % (n= 155), dilated biliary tree 34 % (n=123), regional lymph node infiltration 83 % (n= 300). Out of a total

Metastatic pancreatic adenocarcinoma and renal cell carcinoma treated with gemcitabine and sunitinib malate. A case report.

PubMed

Bharthuar, Anubha; Pearce, Lori; Litwin, Alan; LeVea, Charles; Kuvshinoff, Boris; Iyer, Renuka

2009-09-04

Pancreatic adenocarcinoma and renal cell carcinoma are relatively frequent cancers that have been rarely reported as synchronous primary malignancies. When present simultaneously, they pose a therapeutic challenge given the many available targeted agents with reported efficacy in renal cell cancer and limited options for metastatic pancreatic cancer. We report the case of a 43-year-old Caucasian gentleman diagnosed simultaneously with metastatic pancreatic adenocarcinoma and localized renal cell carcinoma treated with combination chemotherapy, consisting of gemcitabine and sunitinib. Patient had a radiographic response and prolonged progression free survival of twenty six weeks; side effects were manageable and included grade 3 neutropenia and grade 2 hypertension. This encouraging response, safety profile and progression free survival response suggest that we should further examine this and other such regimens to improve clinical outcomes for maximum efficacy with minimal side-effects.

Pancreatic resection for renal cell carcinoma metastasis: An exceptionally rare coexistence.

PubMed

Boussios, Stergios; Zerdes, Ioannis; Batsi, Ourania; Papakostas, Vasilios P; Seraj, Esmeralda; Pentheroudakis, George; Glantzounis, George K

2016-01-01

Pancreatic metastases are uncommon and only found in a minority of patients with widespread metastatic disease at autopsy. The most common primary cancer site resulting in pancreatic metastases is the kidney, followed by colorectal cancer, melanoma, breast cancer, lung carcinoma and sarcoma. Herein, we report a 63-year-old male patient who presented -3.5 years after radical nephrectomy performed for renal cell carcinoma (RCC)-with a well-defined lobular, round mass at the body of the pancreas demonstrated by abdominal Magnetic Resonance Imaging (MRI). The patient underwent distal pancreatectomy combined with splenectomy and cholecystectomy. Histopathological examination revealed clusters of epithelial clear cells, immunohistochemically positive for RCC marker, and negative for CD10 and CA19-9. A final diagnosis of clear RCC metastasizing to pancreas was obtained in view of the past history of RCC, microscopy and the immunoprofile. This was the second metachronous disease recurrence after a previous metastatic involvement of the liver, developed 19 months from the initial diagnosis. The patient has remained well at a 6 month follow up post-resection. Solitary pancreatic metastases may be misdiagnosed as primary pancreatic cancer. However, imaging including computed tomography (CT) and MRI, may discriminate between them. Surgical procedures could differentiate solitary metastasis from neuroendocrine neoplasms. The optimal resection strategy involves adequate resection margins and maximal tissue preservation of the pancreas. Recently, an increasing number of surgical resections have been performed in selected patients with limited metastatic disease to the pancreas. In addition, a rigid follow-up scheme, including endoscopic ultrasound (EUS) and CT is essential give patients a chance for a prolonged life. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Advances in pancreatic cancer research: moving towards early detection.

PubMed

He, Xiang-Yi; Yuan, Yao-Zong

2014-08-28

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients (nearly 80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC. However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide clues for its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.

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

ClinicalTrials.gov

2018-05-02

BRCA1 Gene Mutation; BRCA2 Gene Mutation; Metastatic Pancreatic Adenocarcinoma; PALB2 Gene Mutation; Pancreatic Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IV Pancreatic Cancer AJCC v6 and v7

Challenges and advances in mouse modeling for human pancreatic tumorigenesis and metastasis

PubMed Central

Qiu, Wanglong

2013-01-01

Pancreatic cancer is critical for developed countries, where its rate of diagnosis has been increasing steadily annually. In the past decade, the advances of pancreatic cancer research have not contributed to the decline in mortality rates from pancreatic cancer—the overall 5-year survival rate remains about 5% low. This number only underscores an obvious urgency for us to better understand the biological features of pancreatic carcinogenesis, to develop early detection methods, and to improve novel therapeutic treatments. To achieve these goals, animal modeling that faithfully recapitulates the whole process of human pancreatic cancer is central to making the advancements. In this review, we summarize the currently available animal models for pancreatic cancer and the advances in pancreatic cancer animal modeling. We compare and contrast the advantages and disadvantages of three major categories of these models: (1) carcinogen-induced; (2) xenograft and allograft; and (3) genetically engineered mouse models. We focus more on the genetically engineered mouse models, a category which has been rapidly expanded recently for their capacities to mimic human pancreatic cancer and metastasis, and highlight the combinations of these models with various newly developed strategies and cell-lineage labeling systems. PMID:23114842

Coexistent Ampullary Squamous Cell Carcinoma with Adenocarcinoma of the Pancreatic Duct

PubMed Central

Pathak, Gayatri S.; Deshmukh, Sanjay D.; Yavalkar, Prasanna A.; Ashturkar, Amrut V.

2011-01-01

Primary squamous cell carcinoma (SCC) of ampulla has seldom been reported. However, metastatic SCC to ampulla of Vater is well known. We report a case of primary SCC of ampulla of Vater coexistent with well-differentiated adenocarcinoma of the distal pancreatic duct. A 50-year-old female presented with evidence of obstructive jaundice. Endoscopic retrograde cholangio-pancreatography revealed bulging papilla with ulcero-infiltrative growth at the ampulla of Vater. An initial endoscopic biopsy of the ampullary mass showed a well-differentiated SCC. The patient underwent Whipple's operation. Thorough sampling of the dilated portion of the pancreatic duct showed presence of well-differentiated adenocarcinoma of the distal pancreatic duct. Immunohistochemical study with synaptophysin and chromogranin was done with negative result, ruling out neuroendocrine differentiation. Also, a detailed clinical, endoscopic and radiological examination was carried out, that excluded the presence of primary SCC elsewhere. PMID:22064341

Expression of EGF and EGFR strongly correlates with metastasis of pancreatic ductal carcinoma.

PubMed

Pryczynicz, Anna; Guzińska-Ustymowicz, Katarzyna; Kemona, Andrzej; Czyzewska, Jolanta

2008-01-01

The epidermal growth factor family members: EGF, EGFR and the c-erbB-2(HER-2/neu) gene product have been found to play a role in carcinomas of the stomach, liver, breast, ovary and lungs. Recent reports have indicated that they are also involved in the growth of pancreatic ductal carcinoma, its invasiveness and metastasis. Thirty-six patients with pancreatic ductal carcinoma were analysed with respect to sex, age, histological type, malignancy grade (G), pTN status (pTN), local lymph node involvement and distant metastasis. The tumor levels of EGF, EGFR and c-erbB-2 expression were determined immunohistochemically. Expression of c-erbB-2 was observed in 24/36 cases, EGF in 13/36 cases and EGFR in 18/36 cases. Overexpression of EGF and EGFR was associated with metastasis to lymph nodes and other organs. A correlation was also found between EGF expression and the presence of EGFR in the tumour. The expression of c-erbB-2 protein was not found to correlate with any parameters. EGF and EGFR play a key role in neoplastic spread through lymph node involvement and metastasis to other organs.

Analysis of the cytochrome c-dependent apoptosis apparatus in cells from human pancreatic carcinoma

PubMed Central

Gerhard, M C; Schmid, R M; Häcker, G

2002-01-01

Defects in the apoptotic system are likely to play a role in tumorigenesis. Pancreatic carcinoma cells are extremely resistant to apoptosis induction by chemotherapy suggesting that the apoptosis machinery is faulty. We investigated the integrity of the cytochrome c-dependent apoptotic apparatus in 10 human pancreatic carcinoma cell lines. Expression of Apaf-1, caspase-3, -6, -7, -8 and -9, Hsp-70 and XIAP was detected in all cell lines. The expression levels of Apaf-1 and caspase-8 were homogenous in all cell lines whereas differences in expression of other caspases were seen. In cytosolic fractions, all investigated caspases were processed in response to cytochrome c but the extent of processing varied between the cell lines. No stringent correlation between the amount of processing of caspase-9 and effector caspases was seen. Cytochrome c-induced effector caspase activity was quantitated by enzyme assay. Especially at low concentrations of added cytochrome c, this response varied greatly between the cell lines. These data demonstrate that the apoptotic system downstream of the mitochondria is qualitatively intact in pancreatic carcinoma. They further show that the response to cytochrome c can be quantitated in a cell-free system and that determinants other than mere expression of apoptotic molecules can regulate cytochrome c-induced apoptosis. British Journal of Cancer (2002) 86, 893–898. DOI: 10.1038/sj/bjc/6600171 www.bjcancer.com © 2002 Cancer Research UK PMID:11953820

Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial.

PubMed

Tröger, Wilfried; Galun, Danijel; Reif, Marcus; Schumann, Agnes; Stanković, Nikola; Milićević, Miroslav

2014-07-21

The treatment of cancer patients with mistletoe extract is said to prolong their survival and, above all, improve their quality of life. We studied whether the quality of life of patients with advanced pancreatic cancer could be improved by mistletoe extract. An open, single-center, group-sequential, randomized phase III trial (ISRCTN70760582) was conducted. From January 2009 to December 2010, 220 patients with locally advanced or metastatic pancreatic cancer who were receiving no further treatment for pancreatic cancer other than best supportive care were included in this trial. They were stratified by prognosis and randomly allocated either to a group that received mistletoe treatment or to one that did not. Mistletoe extract was given in escalating doses by subcutaneous injection three times a week. The planned interim evaluation of data from 220 patients indicated that mistletoe treatment was associated with longer overall survival, and the trial was terminated prematurely. After termination of the study, the results with respect to quality of life (assessed with the QLO-C30 scales of the European Organisation for Research and Treatment of Cancer) and trends in body weight were evaluated. Data on quality of life and body weight were obtained from 96 patients treated with mistletoe and 72 control patients. Those treated with mistletoe did better on all 6 functional scales and on 7 of 9 symptom scales, including pain (95% confidence interval [CI] -29 to -17), fatigue (95% CI -36.1 to -25.0), appetite loss (95% CI -51 to -36.7), and insomnia (95% CI -45.8 to -28.6). This is reflected by the trend in body weight during the trial. In patients with locally advanced or metastatic pancreatic carcinoma, mistletoe treatment significantly improves the quality of life in comparison to best supportive care alone. Mistletoe is an effective second-line treatment for this disease.

Distribution of type IV collagen in pancreatic adenocarcinoma and chronic pancreatitis.

PubMed Central

Lee, C. S.; Montebello, J.; Georgiou, T.; Rode, J.

1994-01-01

Changes in the basement membrane are present in various neoplastic conditions such as neurofibrosarcoma, cervical carcinoma, colorectal cancers and hepatoblastoma. This study examines the expression of type IV collagen in the basement membrane, using an immunohistochemical method, in the normal pancreas (n = 10), chronic pancreatitis (n = 15) and pancreatic adenocarcinoma (n = 30). The formalin fixed, paraffin embedded tissue was sectioned and pretreated with protease prior to immunostaining for type IV collagen. There was a statistically significant difference in type IV collagen expression between pancreatic carcinoma and chronic pancreatitis (P = 0.0001; chi 2 test with continuity correction). In pancreatic adenocarcinoma, type IV collagen distribution in the basement membrane was discontinuous and irregular or absent around individual or groups of neoplastic cells (n = 30). Most cases of chronic pancreatitis showed continuous pattern of basement membrane type IV collagen around residual ducts (n = 10). In the normal pancreas, only one of the ten cases showed discontinuous basement membrane around pancreatic ducts, while in the rest of the cases, the pattern was continuous. This study suggests that there is abnormal distribution of type IV collagen in the basement membrane in pancreatic carcinoma, which may be related to either abnormal deposition or degradation of the collagen. Immunostaining for type IV collagen may be of some diagnostic use for distinguishing pancreatic adenocarcinoma from problematic cases of chronic pancreatitis. Images Figure 1 Figure 2 Figure 3 PMID:8199008

Interrogation of Multidrug Resistance (MDR1) P-glycoprotein (Pgp, ABCB1) Expression in Human Pancreatic Carcinoma Cells: Correlation of 99mTc-Sestamibi Uptake with Western Blot Analysis

PubMed Central

Harpstrite, Scott E.; Gu, Hannah; Natarajan, Radhika; Sharma, Vijay

2014-01-01

Objective Histopathological studies indicate approximately 63% of pancreatic tumors express MDR1 Pgp and its polymorphic variants. However, Pgp expression detected at the messenger RNA or protein level does not always correlate with functional transport activity. Because Pgp transport activity is affected by specific mutations as well as the phosphorylation state of the protein, altered or less active forms of Pgp may also be detected by PCR or immunohistochemistry, which do not accurately reflect the status of tumor cell resistance. To interrogate status of functional expression of MDR1 Pgp in MiaPaCa-2 and PANC-1 cells, cellular transport studies using 99mTc-Sestamibi were performed and correlated with western blot analysis. Methods Biochemical transport assays in human pancreatic carcinoma MiaPaCa-2 and PANC-1 cells, human epidermal carcinoma drug sensitive KB-3-1 cells and human breast carcinoma MCF-7 cells (negative controls), and human epidermal carcinoma drug resistant KB-8-5 cells, human breast carcinoma stably transfected with Pgp MCF-7/MDR1Pgp cells, and liver carcinoma HepG2 cells (positive controls) were performed. Protein levels were determined using a monoclonal antibody C219. Results 99mTc-Sestamibi demonstrates accumulation in human pancreatic carcinoma MiaPaCa-2 and PANC-1 cells. Uptake profiles are not affected by treatment with LY335979, a Pgp-inhibitor, and correlate to Western blot analysis. Conclusions These cellular transport studies indicate an absence of Pgp at a functional level in MiaPaCa-2 and PANC-1 cells. Because major pancreatic tumors originate from pancreatic duct and 99mTc-Sestamibi undergoes a dominant hepatobiliary mode of excretion, it would not be a sensitive probe for imaging pancreatic adenocarcinomas. Following interrogation of the functional status of Pgp in other pancreatic carcinoma cells, chemotherapeutic drugs that are also MDR1 substrates could offer alternative therapeutics for treating pancreatic adenocarcinomas

Irreversible electroporation therapy in the management of locally advanced pancreatic adenocarcinoma.

PubMed

Martin, Robert C G; McFarland, Kelli; Ellis, Susan; Velanovich, Vic

2012-09-01

Locally advanced pancreatic cancer patients have limited options for disease control. Local ablation technologies based on thermal damage have been used but are associated with major complications in this region of the pancreas. Irreversible electroporation (IRE) is a nonthermal ablation technology that we have shown is safe near vital vascular and ductal structures. The aim of this study was to evaluate the safety and efficacy of IRE as a therapy in the treatment of locally advanced pancreatic cancer. We performed a prospective multi-institutional pilot evaluation of patients undergoing IRE for locally advanced pancreatic cancer from December 2009 to March 2011. These patients were evaluated for 90-day morbidity, mortality, and local disease control. Twenty-seven patients (13 women and 14 men) underwent IRE, with median age of 61 years (range 45 to 80 years). Eight patients underwent margin accentuation with IRE in combination with left-sided resection (n = 4) or pancreatic head resection (n = 4). Nineteen patients had in situ IRE. All patients underwent successful IRE, with intraoperative imaging confirming effective delivery of therapy. All 27 patients demonstrated nonclinically relevant elevation of their amylase and lipase, which peaked at 48 hours and returned to normal at 72 hour postprocedure. There has been one 90-day mortality. No patient has shown evidence of clinical pancreatitis or fistula formation. After all patients have completed 90-day follow-up, there has been 100% ablation success. IRE ablation of locally advanced pancreatic cancer tumors is a safe and feasible primary local treatment in unresectable, locally advanced disease. Confirming these early results must occur in a planned phase II investigational device exemption (IDE) study to be initiated in 2012. Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Decoy receptor 3 (DcR3) overexpression predicts the prognosis and pN2 in pancreatic head carcinoma.

PubMed

Zhou, Jian; Song, Shiduo; Li, Dechun; He, Songbing; Zhang, Bing; Wang, Zhenxin; Zhu, Xinguo

2014-03-05

This study was carried out to examine decoy receptor 3 (DcR3) expression and investigate its clinical and prognostic significance in patients with pancreatic head carcinoma. Tissue samples were obtained from 50 patients with pancreatic head carcinoma. DcR3 protein expression in tissues and sera was assessed by immunohistochemistry and ELISA. Correlations between DcR3 and clinicopathologic features and prognoses were analyzed statistically. Serum DcR3 levels were significantly elevated in patients with pancreatic head carcinoma compared with patients with cystadenoma and healthy individuals (P < 0.01 and P < 0.01, respectively). DcR3 overexpression correlated with lymph node metastases and TNM stages (P < 0.05 and P < 0.05, respectively). Median overall survival for the high DcR3 group was 16.3 months, compared to 21.6 months for the low DcR3 group (P < 0.05). In the low DcR3 group, no significant difference was found in the overall survival between patients who underwent standard pancreatoduodenectomy (SPD) and those who had radical pancreatoduodenectomy (RPD) (P > 0.05). In the high DcR3 group, the median overall survival rates were 16.8 months in the RPD group and 13.5 months in the SPD group (P < 0.05). We found that DcR3 was overexpressed in pancreatic head carcinoma. The patients with high DcR3 levels had higher pN2 stages than those with low DcR3 levels. Detecting serum DcR3 level preoperatively might be an additional approach for evaluating pN2 stage and guiding the range of lymphadenectomy.

VX15/2503 and Immunotherapy in Resectable Pancreatic and Colorectal Cancer

ClinicalTrials.gov

2017-12-26

Colon Carcinoma Metastatic in the Liver; Colorectal Adenocarcinoma; Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma; Stage I Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Colorectal Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

Fractionated Radioimmunotherapy With 90Y-Clivatuzumab Tetraxetan and Low-Dose Gemcitabine Is Active in Advanced Pancreatic Cancer

PubMed Central

Ocean, Allyson J.; Pennington, Kenneth L.; Guarino, Michael J.; Sheikh, Arif; Bekaii-Saab, Tanios; Serafini, Aldo N.; Lee, Daniel; Sung, Max W.; Gulec, Seza A.; Goldsmith, Stanley J.; Manzone, Timothy; Holt, Michael; O’Neil, Bert H.; Hall, Nathan; Montero, Alberto J.; Kauh, John; Gold, David V.; Horne, Heather; Wegener, William A.; Goldenberg, David M.

2014-01-01

BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at

Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma

PubMed Central

Liu, Xu-Jie; Li, Liang; Liu, Xiu-Jun; Li, Yi; Zhao, Chun-Yan; Wang, Rui-Qi; Zhen, Yong-Su

2017-01-01

Previous studies have shown that mithramycin A (MIT) is a promising candidate for the treatment of pancreatic carcinoma through inhibiting transcription factor Sp1. However, systemic toxicities may limit its clinical application. Here, we report a rationally designed formulation of MIT-loaded nanoparticles (MIT-NPs) with a small size and sustained release for improved passive targeting and enhanced therapeutic efficacy. Nearly spherical MIT-NPs with a mean particle size of 25.0±4.6 nm were prepared by encapsulating MIT into methoxy poly(ethylene glycol)-block-poly(d,l-lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (NPs) with drug loading of 2.11%±0.51%. The in vitro release of the MIT-NPs lasted for >48 h with a sustained-release pattern. The cytotoxicity of MIT-NPs to human pancreatic cancer BxPC-3 and MIA Paca-2 cells was comparable to that of free MIT. Determined by flow cytometry and confocal microscopy, the NPs internalized into the cells quickly and efficiently, reaching the peak level at 1–2 h. In vivo fluorescence imaging showed that the prepared NPs were gradually accumulated in BxPC-3 and MIA Paca-2 xenografts and retained for 168 h. The fluorescence intensity in both BxPC-3 and MIA Paca-2 tumors was much stronger than that of various tested organs. Therapeutic efficacy was evaluated with the poorly permeable BxPC-3 pancreatic carcinoma xenograft model. At a well-tolerated dose of 2 mg/kg, MIT-NPs suppressed BxPC-3 tumor growth by 96%. Compared at an equivalent dose, MIT-NPs exerted significantly higher therapeutic effect than free MIT (86% versus 51%, P<0.01). Moreover, the treatment of MIT and MIT-NPs reduced the expression level of oncogene c-Myc regulated by Sp1, and notably, both of them decreased the protein level of CD47. In summary, the novel formulation of MIT-NPs shows highly therapeutic efficacy against pancreatic carcinoma xenograft. In addition, MIT-NPs can downregulate CD47 expression, implying that it might play a positive role in

[Pancreatic acinar neoplasms : Comparative molecular characterization].

PubMed

Bergmann, F

2016-11-01

Pancreatic acinar cell carcinomas are biologically aggressive neoplasms for which treatment options are very limited. The molecular mechanisms of tumor initiation and progression are largely not understood and precursor lesions have not yet been identified. In this study, pancreatic acinar cell carcinomas were cytogenetically characterized as well as by molecular and immunohistochemical analyses. Corresponding investigations were carried out on pancreatic ductal adenocarcinomas and pancreatic neuroendocrine neoplasms augmented by functional analyses. We show that pancreatic acinar cell carcinomas display a microsatellite stable, chromosomal unstable genotype, characterized by recurrent chromosomal imbalances that clearly discriminate them from pancreatic ductal adenocarcinomas and neuroendocrine neoplasms. Based on findings obtained from comparative genomic hybridization, candidate genes could be identified, such as deleted in colorectal cancer (DCC) and c-MYC. Furthermore, several therapeutic targets were identified in acinar cell carcinomas and other pancreatic neoplasms, including epidermal growth factor receptor (EGFR), L1 cell adhesion molecule (L1CAM) and heat shock protein 90 (HSP90). Moreover, L1CAM was shown to play a significant role in the tumorigenesis of pancreatic ductal adenocarcinoma. Functional analyses in cell lines derived from pancreatic neuroendocrine neoplasms revealed promising anti-tumorigenic effects using EGFR and HSP90 inhibitors affecting the cell cycle and in the case of HSP90, regulating several other oncogenes. Finally, based on mutational analyses of mitochondrial DNA, molecular evidence is provided that acinar cell cystadenomas (or better cystic acinar transformation) represent non-clonal lesions, suggesting an inflammatory reactive non-neoplastic nature.

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shinoto, Makoto, E-mail: shinoto@saga-himat.jp; Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m{sup 2} under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions undermore » the fixed recommended gemcitabine dose determined. Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m{sup 2}. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m{sup 2}) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.« less

Molecular biology of pancreatic cancer.

PubMed

Zavoral, Miroslav; Minarikova, Petra; Zavada, Filip; Salek, Cyril; Minarik, Marek

2011-06-28

In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors

ClinicalTrials.gov

2018-06-08

Advanced Malignant Solid Neoplasm; KRAS Gene Mutation; Metastatic Malignant Solid Neoplasm; NRAS Gene Mutation; Recurrent Colorectal Carcinoma; Recurrent Lung Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Pancreatic Carcinoma; Stage III Colorectal Cancer AJCC v7; Stage III Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Unresectable Malignant Neoplasm

Characterization of low active ghrelin ratio in patients with advanced pancreatic cancer.

PubMed

Miura, Tomofumi; Mitsunaga, Shuichi; Ikeda, Masafumi; Ohno, Izumi; Takahashi, Hideaki; Suzuki, Hidetaka; Irisawa, Ai; Kuwata, Takeshi; Ochiai, Atsushi

2018-05-18

Acyl ghrelin is an orexigenic peptide. Active ghrelin ratio, the ratio of acyl ghrelin to total ghrelin, has an important role in physiological functions and gastrointestinal symptoms. However, low active ghrelin ratio-related characteristics, gastrointestinal symptoms, and chemotherapy-induced gastrointestinal toxicity in patients with advanced pancreatic cancer have not been previously evaluated. The goal of this study was to identify low active ghrelin ratio-related factors in treatment-naïve advanced pancreatic cancer patients. Patients with treatment-naïve advanced pancreatic cancer were eligible for inclusion in this study. Active ghrelin ratio and clinical parameters of patients were prospectively recorded. Factors correlated with low active ghrelin ratio and survival were analyzed. In total, 92 patients were analyzed. Low active ghrelin ratio-related factors were advanced age (P < 0.01), severe appetite loss (P < 0.01), and decreased cholinesterase (P < 0.01). The adverse events of grade 2 or higher anorexia tended to increase in patients with low active ghrelin ratio. However, no differences were found in survival and body composition between low and high active ghrelin ratio groups. Low active ghrelin ratio was related to lack of appetite and low cholinesterase and tended to be related to anorexia grade 2 or higher in patients with treatment-naïve advanced pancreatic cancer.

Advances in counselling and surveillance of patients at risk for pancreatic cancer

PubMed Central

Brand, Randall E; Lerch, Markus M; Rubinstein, Wendy S; Neoptolemos, John P; Whitcomb, David C; Hruban, Ralph H; Brentnall, Teresa A; Lynch, Henry T; Canto, Marcia I

2007-01-01

Even with significant advances in imaging and our understanding of pancreatic cancer genetics, the survival rates for pancreatic cancer remain quite dismal. Although still at an early stage, there are efforts in place to develop surveillance and prevention strategies for people at high risk for pancreatic cancer. This comprehensive review article summarises the predispositions that put people at a high risk of developing pancreatic cancer and the current status in the counselling and surveillance of these people using not only available medical literature, but also incorporating international expert opinion. PMID:17872573

Study of Efficacy and Safety of PDR001 in Patients With Advanced or Metastatic, Well-differentiated, Non-functional Neuroendocrine Tumors of Pancreatic, Gastrointestinal (GI), or Thoracic Origin or Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC)

ClinicalTrials.gov

2017-11-15

Well-differentiated Non-functional NET of Thoracic Origin; Well-differentiated Non-functional NET of Gastrointestinal Origin; Well-differentiated Non-functional NET of Pancreatic Origin; Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma

Management of advanced pancreatic cancer in daily clinical practice.

PubMed

Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

2016-01-01

The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

Technical Advances in Endoscopic Ultrasound (EUS)-Guided Tissue Acquisition for Pancreatic Cancers: How Can We Get the Best Results with EUS-Guided Fine Needle Aspiration?

PubMed Central

Kedia, Prashant; Gaidhane, Monica

2013-01-01

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is one of the least invasive and most effective modality in diagnosing pancreatic adenocarcinoma in solid pancreatic lesions, with a higher diagnostic accuracy than cystic tumors. EUS-FNA has been shown to detect tumors less than 3 mm, due to high spatial resolution allowing the detection of very small lesions and vascular invasion, particularly in the pancreatic head and neck, which may not be detected on transverse computed tomography. Furthermore, this minimally invasive procedure is often ideal in the endoscopic procurement of tissue in patients with unresectable tumors. While EUS-FNA has been increasingly used as a diagnostic tool, most studies have collectively looked at all primary pancreatic solid lesions, including lymphomas and pancreatic neuroendocrine neoplasms, whereas very few studies have examined the diagnostic utility of EUS-FNA of pancreatic ductal carcinoma only. As with any novel and advanced endoscopic procedure that may incorporate several practices and approaches, endoscopists have adopted diverse techniques to improve the tissue procurement practice and increase diagnostic accuracy. In this article, we present a review of literature to date and discuss currently practiced EUS-FNA technique, including indications, technical details, equipment, patient selection, and diagnostic accuracy. PMID:24143320

Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer

ClinicalTrials.gov

2018-04-11

Adenocarcinoma of the Gastroesophageal Junction; Colorectal Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Non-Resectable Hepatocellular Carcinoma; Recurrent Cholangiocarcinoma; Recurrent Colorectal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Small Intestinal Carcinoma; Small Intestinal Adenocarcinoma; Stage III Colorectal Cancer; Stage III Gastric Cancer; Stage III Hepatocellular Carcinoma; Stage III Pancreatic Cancer; Stage III Small Intestinal Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Hepatocellular Carcinoma; Stage IIIA Small Intestinal Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Hepatocellular Carcinoma; Stage IIIB Small Intestinal Cancer; Stage IIIC Gastric Cancer; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Hepatocellular Carcinoma; Stage IV Pancreatic Cancer; Stage IV Small Intestinal Cancer; Stage IVA Colorectal Cancer; Stage IVA Hepatocellular Carcinoma; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Hepatocellular Carcinoma; Stage IVB Pancreatic Cancer; Unresectable Pancreatic Carcinoma; Unresectable Small Intestinal Carcinoma

Acinar cell carcinoma of the pancreas presenting as diffuse pancreatic enlargement: Two case reports and literature review.

PubMed

Luo, Yaping; Hu, Guilan; Ma, Yanru; Guo, Ning; Li, Fang

2017-09-01

Pancreatic acinar cell carcinoma (ACC) is a rare malignant tumor of exocrine pancreas. It is typically a well-marginated large solid mass arising in a certain aspect of the pancreas. Diffuse involvement of ACC in the pancreas is very rare, and may simulate pancreatitis in radiological findings. We report 2 cases of ACC presenting as diffuse enlargement of the pancreas due to tumor involvement without formation of a distinct mass. The patients consisted of a 41-year-old man with weight loss and a 77-year-old man who was asymptomatic. Computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed diffuse enlargement of the pancreas forming a sausage-like shape with homogenously increased FDG activity. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy of the pancreatic lesion was performed. Histopathology results from the pancreas confirmed the diagnosis of pancreatic ACC. Because diffuse enlargement of the pancreas is a common imaging feature of pancreatitis, recognition of this rare morphologic pattern of ACC is important for radiological diagnosis of this tumor.

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Cervical Carcinoma; Colon Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Glioma; Head and Neck Carcinoma; Kidney Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Lung Carcinoma; Lymphoma; Malignant Uterine Neoplasm; Melanoma; Ovarian Carcinoma; Pancreatic Carcinoma; Plasma Cell Myeloma; Prostate Carcinoma; Rectal Carcinoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Colon Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Glioma; Recurrent Head and Neck Carcinoma; Recurrent Liver Carcinoma; Recurrent Lung Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Plasma Cell Myeloma; Recurrent Prostate Carcinoma; Recurrent Rectal Carcinoma; Recurrent Skin Carcinoma; Recurrent Thyroid Gland Carcinoma; Recurrent Uterine Corpus Carcinoma; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma; Skin Carcinoma; Thyroid Gland Carcinoma; Uterine Corpus Cancer

Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

PubMed Central

Bournet, Barbara; Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome; Buscail, Louis; Cordelier, Pierre

2011-01-01

Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer. PMID:24212643

Optimization for the blockade of epidermal growth factor receptor signaling for therapy of human pancreatic carcinoma.

PubMed

Solorzano, C C; Baker, C H; Tsan, R; Traxler, P; Cohen, P; Buchdunger, E; Killion, J J; Fidler, I J

2001-08-01

We determined the optimal administration schedule of a novel epidermal growth factor receptor (EGFR) protein tyrosine kinase inhibitor (PKI), PKI 166 (4-(R)-phenethylamino-6-(hydroxyl)phenyl-7H-pyrrolo[2.3-d]-pyrimidine), alone or in combination with gemcitabine (administered i.p.) for therapy of L3.6pl human pancreatic carcinoma growing in the pancreas of nude mice. Seven days after orthotopic implantation of L3.6pl cells, the mice received daily oral doses of PKI 166. PKI 166 therapy significantly inhibited phosphorylation of the EGFR without affecting EGFR expression. EGFR phosphorylation was restored 72 h after cessation of therapy. Seven days after orthotopic injection of L3.6pl cells, groups of mice received daily or thrice weekly oral doses of PKI 166 alone or in combination with gemcitabine. Treatment with PKI 166 (daily), PKI 166 (3 times/week), or gemcitabine alone produced a 72%, 69%, or 70% reduction in the volume of pancreatic tumors in mice, respectively. Daily oral PKI 166 or thrice weekly oral PKI 166 in combination with injected gemcitabine produced 97% and 95% decreases in volume of pancreatic cancers and significant inhibition of lymph node and liver metastasis. Daily oral PKI 166 produced a 20% decrease in body weight, whereas treatment 3 times/week did not. Decreased microvessel density, decreased proliferating cell nuclear antigen staining, and increased tumor cell and endothelial cell apoptosis correlated with therapeutic success. Collectively, our results demonstrate that three weekly oral administrations of an EGFR tyrosine kinase inhibitor in combination with gemcitabine are sufficient to significantly inhibit primary and metastatic human pancreatic carcinoma.

[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. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

ClinicalTrials.gov

2013-01-24

Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

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.

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

PubMed Central

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

Autoimmune Pancreatitis Can Transform Into Chronic Features Similar to Advanced Chronic Pancreatitis With Functional Insufficiency Following Severe Calcification.

PubMed

Kanai, Keita; Maruyama, Masahiro; Kameko, Fumiko; Kawasaki, Kenji; Asano, Junpei; Oguchi, Takaya; Watanabe, Takayuki; Ito, Tetsuya; Muraki, Takashi; Hamano, Hideaki; Matsumoto, Akihiro; Arakura, Norikazu; Kawa, Shigeyuki

2016-09-01

Because several studies for autoimmune pancreatitis (AIP) have revealed pancreatic calcification resembling that in chronic pancreatitis (CP), we sought to clarify whether AIP could transform into chronic features similar to advanced CP with severe pancreatic dysfunction. Pancreatic functions of 92 AIP patients, 47 definite CP patients, and 30 healthy controls were assessed by fecal elastase-1 concentration (FEC), fasting immunoreactive insulin (IRI), and homeostatic model assessment (HOMA)-R. The 92 AIP patients included 17 (18%) with severe calcification (SC) and 75 without. The FEC levels in AIP and CP patients were significantly lower than that in controls. Exocrine insufficiency defined as FEC less than 200 μg/g was 39% in AIP without SC, 56% in AIP with SC, and 74% in CP. Fasting IRI and C-peptide reactivity values in CP were significantly lower than those in AIP, with no significant differences between AIP subgroups. The prevalence of endocrine insufficiency according to fasting IRI less than 5.0 μU/mL was 26% in AIP without SC, 31% in AIP with SC, and 59% in CP, respectively. HOMA-R values were significantly higher in all AIP groups than in CP. Autoimmune pancreatitis can transform into a state of pancreatic insufficiency after calcification that is less severe than that in definite CP.

Impact of preoperative levels of hemoglobin and albumin on the survival of pancreatic carcinoma.

PubMed

Ruiz-Tovar, J; Martín-Pérez, E; Fernández-Contreras, M E; Reguero-Callejas, M E; Gamallo-Amat, C

2010-11-01

Pancreatic cancer presents the worst survival rates of all neoplasms. Surgical resection is the only potentially curative treatment, but is associated with high complication rates and outcome is bad even in those resected cases. Therefore, candidates amenable for resection must be carefully selected. Identification of prognostic factors preoperatively may help to improve the treatment of these patients, focusing on individually management based on the expected response. We perform a retrospective study of 59 patients with histological diagnosis of pancreatic carcinoma between 1999 and 2003, looking for possible prognostic factors. We analyze 59 patients, 32 males and 27 females with a mean age of 63.8 years. All the patients were operated, performing palliative surgery in 32% and tumoral resection in 68%, including pancreaticoduodenectomies in 51% and distal pancreatectomy in 17%. Median global survival was 14 months (Range 1-110).We observed that preoperative levels of hemoglobin under 12 g/dl (p = 0.0006) and serum albumina under 2.8 g/dl (p = 0.021) are associated with worse survival. Preoperative levels of hemoglobin and serum albumina may be prognostic indicators in pancreatic cancer.

Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy.

PubMed

Tran, T C K; van 't Hof, G; Kazemier, G; Hop, W C; Pek, C; van Toorenenbergen, A W; van Dekken, H; van Eijck, C H J

2008-01-01

Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 microg/g (p < 0.0001), reflecting severe exocrine pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p < 0.0001). Neither pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright 2008 S. Karger AG, Basel.

Irreversible electroporation as treatment of locally advanced and as margin accentuation in borderline resectable pancreatic adenocarcinoma.

PubMed

Marsanic, P; Mellano, A; Sottile, A; De Simone, M

2017-07-01

In recent years, many local ablation technologies based on thermal damage have been used in the treatment of locally advanced pancreatic carcinoma (LAPC) and borderline resectable pancreatic carcinoma (BLRPC). However, they are associated with major complications because of possible vascular and ductal damage. Irreversible electroporation (IRE) is a nonthermal ablation technology that seems safe near vital vascular and ductal structures. IRE could be used as exclusive treatment of LAPC (en situ to IRE) after induction chemotherapy In BLRPC, surgery is not really radical in 6% of patients (microscopic residual) and local recurrences occur in 11-42% of apparent radical resections. IRE could be used as margin accentuation to increase posterior margin during radical surgery in BLRPC. Our outcomes are safety, time to progression. Secondary outcomes are overall survival, pain control and quality of life. We are performing a prospective evaluation of patients undergoing IRE for LAPC or BLRPC since July 2014. We have included patients with non-metastatic LAPC with maximum size ≤4 cm (en situ to IRE) and patients with BLRPC (complementary IRE). We have performed induction chemotherapy in both groups. After treatment, patients were evaluated on days 1, 2, 4, 7, 14, 21, 30, 60 and 90 with amylase and lipase serum and abdominal drainage test. Based on Ethics Committee's request, follow-up imaging was performed at the 10th day for safety evaluation, at 30, 60 and 90 days for response evaluation and then every 3 months. Seven patients (two women and five men) underwent IRE. Two patients had LAPC and received en situ to IRE. In five patients affected by BLRPC we performed IRE and pancreatic head resection. In all patients, intraoperative imaging confirmed that the treatment of the whole tumor volume was complete. All seven patients demonstrated nonclinically relevant elevation of their amylase and lipase, which returned normal at 5 days postprocedure. No patient showed

[The clinical impact of artery-first approach combined with vascular resection and reconstruction in the treatment of pancreatic head carcinoma].

PubMed

Huang, J L; Li, W G; Chen, F Z; Su, Z J; Li, F M; Liu, B

2017-03-23

Objective: To evaluate the application of artery first, combined vascular resection and reconstruction in the treatment of pancreatic head carcinoma. Methods: The clinical data of 13 patients with pancreatic head cancer were retrospectively analyzed from February 2014 to March 2016 in the Affiliated Hospital of Xiamen University. Preoperative computed tomography of high resolution layer or magnetic resonance imaging examination demonstrated pancreatic head carcinoma, as well as close adhesion, stenosis, compression or displacement of superior mesenteric vein or portal vein wall. In the operation, the artery first approach was used and the whole arterial blood supply in the head of the pancreas was fully exposed and interdicted. Finally, en block resection and vascular resection and reconstruction was adopted. Results: 12 of 13 patients had pancreatoduodenectomy synchronously with vascular resection and reconstruction; the other patient had these two surgery sequentially. Four patients received blood vessel wedge resection, five had segmental resection combined with end to end suture, and four had segmental resection combined with artificial vascular graft reconstruction. Operation time was (327.2±65.5) minutes, and the amount of blood loss was (472.6±226.4) millilitres. One patient suffered from delayed gastric emptying, and two patients had pancreatic fistula. All patients recovered from postoperative complications by conservative treatment. No patients developed biliary fistula, gastrointestinal fistula, abdominal infection, pulmonary infection, diarrhea, hypoglycemia or other complications, and none died in perioperative period. Postoperative pathological findings confirmed the diagnosis of pancreatic ductal adenocarcinoma. Mean tumor diameter was (4.2±1.5)cm, and (3.8±1.5) metastasis were found in (13.6±2.5) resected lymph nodes. In 11 cases, the tumor cells were found in the outer membrane of blood vessels, 2 cases were found to have tumor invasion in the

Neoadjuvant Chemotherapy Followed by Radiation Therapy and Gemcitabine/Sorafenib/Vorinostat in Pancreatic Cancer

ClinicalTrials.gov

2017-11-29

Pancreatic Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Recurrent Pancreatic Carcinoma

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

New therapeutic directions for advanced pancreatic cancer: cell cycle inhibitors, stromal modifiers and conjugated therapies.

PubMed

Matera, Robert; Saif, Muhammad Wasif

2017-09-01

Pancreatic adenocarcinoma is a devastating malignancy with an extremely poor prognosis. These tumors progress rapidly and somewhat silently with few specific symptoms and are relatively resistant to chemotherapeutic agents. Many agents, including cell cycle inhibitors, are under development for the treatment of this cancer for which there are disappointingly few treatment options. Areas covered: Here we outline the existing approved treatments for advanced pancreatic disease and discuss a range of novel therapies currently under development including cell cycle inhibitors, stromal modifiers and conjugated therapies. We also describe the current state of the pancreatic cancer therapeutics market both past and future. Expert opinion: Despite the recent explosion of novel therapies with an array of unique targets, the core treatment of pancreatic cancer still with traditional cytotoxic agents with a few exceptions. However, as these novel treatments move through the pipeline, we are hopeful that there will soon be a number of effective options for patients with advanced pancreatic cancer.

Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hurt, Christopher N., E-mail: hurtcn@cardiff.ac.uk; Mukherjee, Somnath; Bridgewater, John

Purpose: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. Methods and Materials: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-basedmore » CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). Results: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. Conclusions: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.« less

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

PubMed

Zhang, Xueying; Cao, Junxia; Pei, Yujun; Zhang, Jiyan; Wang, Qingyang

2016-05-01

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.

Fast neutron irradiation for locally advanced pancreatic cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, F.P.; Schein, P.S.; MacDonald, J.S.

1981-11-01

Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore,more » caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials.« less

Contemporary strategies to improve the outcome in locally advanced pancreatic cancer.

PubMed

Schneider, Rick; Späth, Christoph; Nitsche, Ulrich; Erkan, Mert; Kleeff, Jörg

2017-10-01

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of less than 7%. After many years of basic and clinical research efforts, pancreatic cancer patients presenting with locally advanced, unresectable tumors remain a therapeutic challenge. Despite the lack of high quality randomized controlled trials, perioperative/neoadjuvant treatment strategies seem to be beneficial in these patients. At present the FOLFIRINOX regimen, which was established in the palliative setting, is increasingly recognized as the backbone of neoadjuvant therapy for locally advanced PDAC. Surgical resection follows the same principles and guidelines as upfront surgery specifically regarding the extent of resection including lymphadenectomy, vascular resections and multivisceral resections. Because of the limited diagnostic accuracy of restaging after neoadjuvant treatment, an adjusted intraoperative strategy is necessary to minimize the risk of debulking procedures and maximize the chance of a potential curative resection. Locally advanced PDAC requires a multidisciplinary and individualized treatment approach, and further research efforts for novel and innovative therapies. This article provides an updated overview on strategies to improve the outcome in locally advanced PDAC.

Prospective assessment of the influence of pancreatic cancer resection on exocrine pancreatic function.

PubMed

Sikkens, E C M; Cahen, D L; de Wit, J; Looman, C W N; van Eijck, C; Bruno, M J

2014-01-01

Exocrine insufficiency frequently develops in patients with pancreatic cancer owing to tumour ingrowth and pancreatic duct obstruction. Surgery might restore this function by removing the primary disease and restoring duct patency, but it may also have the opposite effect, as a result of resection of functional parenchyma and anatomical changes. This study evaluated the course of pancreatic function, before and after pancreatic resection. This prospective cohort study included patients with tumours in the pancreatic region requiring pancreatic resection in a tertiary referral centre between March 2010 and August 2012. Starting before surgery, exocrine function was determined monthly by measuring faecal elastase 1 levels (normal value over 0.200 µg per g faeces). Endocrine function, steatorrhoea-related symptoms and bodyweight were also evaluated before and after surgery. Subjects were followed from diagnosis until 6 months after surgery, or until death. Twenty-nine patients were included, 12 with pancreatic cancer, 14 with ampullary carcinoma and three with bile duct carcinoma (median tumour size 2.6 cm). Twenty-six patients underwent pancreaticoduodenectomy and three distal pancreatectomy. Thirteen patients had exocrine insufficiency at preoperative diagnosis. After a median follow-up of 6 months, this had increased to 24 patients. Diabetes was present in seven patients at diagnosis, and developed in one additional patient within 1 month after surgery. Most patients with tumours in the pancreatic region requiring pancreatic resection either had exocrine insufficiency at diagnosis or became exocrine-insufficient soon after surgical resection. © 2013 BJS Society Ltd. Published by John Wiley & Sons Ltd.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

The Value of Routine Biochemical Tests in Discriminating Between Malignant and Benign Pancreatic Tumours

PubMed Central

Blind, P-J; Eriksson, S.

1991-01-01

The probability that routine hematological laboratory tests of liver and pancreatic function can discriminate between malignant and benign pancreatic tumours, incidentally detected during operation, was investigated. The records of 53 patients with a verified diagnosis of pancreatic carcinoma and 19 patients with chronic pancreatitis were reviewed with regard to preoperative total bilirubin, direct reacting bilirubin, alkaline phosphatase, glutamyltranspeptidase, aminotransferases, lactic dehydrogenase and amylase. Multivariate and discriminant analysis were performed to calculate the predictive value for cancer, using SYSTAT statistical package in a Macintosh II computer. Total and direct reacting bilirubin and glutamyltranspeptidase were significantly higher in patients with pancreatic carcinoma. However, only considerably increased levels of direct reating bilirubin were predictive of pancreatic carcinoma. PMID:1931781

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

PubMed

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

2013-10-01

The rat parvovirus H-1PV has oncolytic and tumour-suppressive properties potentially exploitable in cancer therapy. This possibility is being explored and results are encouraging, but it is necessary to improve the oncotoxicity of the virus. Here we show that this can be achieved by co-treating cancer cells with H-1PV and histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA). We demonstrate that these agents act synergistically to kill a range of human cervical carcinoma and pancreatic carcinoma cell lines by inducing oxidative stress, DNA damage and apoptosis. Strikingly, in rat and mouse xenograft models, H-1PV/VPA co-treatment strongly inhibits tumour growth promoting complete tumour remission in all co-treated animals. At the molecular level, we found acetylation of the parvovirus nonstructural protein NS1 at residues K85 and K257 to modulate NS1-mediated transcription and cytotoxicity, both of which are enhanced by VPA treatment. These results warrant clinical evaluation of H-1PV/VPA co-treatment against cervical and pancreatic ductal carcinomas. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

Metastatic Pancreatic Carcinoma and Experience with FOLFIRINOX - a Cross Sectional Analysis From a Developing Country.

PubMed

Zahir, Muhammad Nauman; Jabbar, Adnan Abdul

2015-01-01

Pancreatic cancer is the fourth leading cause of cancer related death with median survival ranging from 3 to 6 months for metastatic disease. Palliative chemotherapy has been the backbone of treatment in advanced stage and has evolved over time. Data pertaining to the disease are scarce from our part of the world where treatment poses a significant challenge due to lack of resources. A retrospective chart review was performed for all patients presenting with stage IV pancreatic carcinoma at a tertiary care hospital in Karachi, Pakistan between January 2008 and December 2012. Data were collected using a pre-designed, coded questionnaire looking at patient characteristics, treatment given and outcome. 101 patients were found to be eligible. Mean age was 56.7 ± 12.8 years, the male to female ratio was 2:1 and most patients had a good performance status. More than half of the tumors were located in the head (57%, n=58) and almost all were adenocarcinomas (95%, n=96). Some 58% (n=59) received first line chemotherapy of which 49% (n=29) received gemcitabine-based regimens and 39% (n=23) received FOLFIRINOX. The median progression free survival for gemcitabine based treatment was 2.9 months (IQR=1.6-5.6) as opposed to 7.3 months (IQR=4.5-9.2) for FOLFIRINOX (P=0.02). Median overall survival was 4.9 months (IQR=2.3-9.5) for first line gemcitabine based treatment and 10.5 months (IQR=7.0-13.2) for first line FOLFIRINOX therapy (P=0.002). Patients on FOLFIRINOX had better survival across all subgroups. Inpatient admissions and dose reductions were more frequent with FOLFIRINOX but the difference between the two regimens was not statistically significant. FOLFIRINOX could be successfully administered as outpatient therapy to a number of patients. FOLFIRINOX remains a suitable first line option in patients with metastatic pancreatic cancer with good performance status even in a resource-poor country where diagnostic and supportive care facilities may be less than optimal and

Image-Guided Intensity-Modulated Radiotherapy for Pancreatic Carcinoma

PubMed Central

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

2007-01-01

Purpose To present the techniques and preliminary outcomes of ultrasound-based image-guided intensity-modulated radiotherapy (IG-IMRT) for pancreatic cancer. Materials and Methods Retrospective analysis of 41 patients treated between November 2000 and March 2005 with IG-IMRT to mean total doses of 55 Gy (range, 45–64 Gy). We analyzed the clinical feasibility of IG-IMRT, dosimetric parameters, and outcomes, including acute gastrointestinal toxicity (RTOG grading). Survival was assessed for adenocarcinoma (n = 35) and other histologies. Results Mean daily image-guidance corrective shifts were 4.8 ± 4.3 mm, 7.5 ± 7.2 mm, and 4.6 ± 5.9 mm along the x-, y-, and z-axes, respectively (mean 3D correction vector, 11.7 ± 8.4 mm). Acute upper gastrointestinal toxicity was grade 0–1 in 22 patients (53.7%), grade 2 in 16 patients (39%), and grade 3 in 3 patients (7.3%). Lower gastrointestinal toxicity was grade 0–1 in 32 patients (78%), grade 2 in 7 patients (17.1%), and grade 4 in 2 patients (4.9%). Treatment was stopped early in 4 patients following administration of 30 to 54 Gy. Median survival for adenocarcinoma histology was 10.3 months (18.6 months in patients alive at analysis; n = 8) with actuarial 1- and 2-year survivals of 38% and 25%, respectively. Conclusion Daily image-guidance during delivery of IMRT for pancreatic carcinoma is clinically feasible. The data presented support the conclusion that safety margin reduction and moderate dose escalation afforded by implementation of these new radiotherapy technologies yields preliminary outcomes at least comparable with published survival data. PMID:19262697

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

PubMed

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

2005-06-15

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

High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers.

PubMed

Muggia, F M; Brown, T D; Goodman, P J; Macdonald, J S; Hersh, E M; Fleming, T R; Leichman, L

1992-06-01

This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studies with enzymes less than two times beyond the normal range. Twenty nine patients with gastric cancer and 26 with pancreatic cancer were entered from various institutions in the Southwest Oncology Group with 27 and 22, respectively, meeting eligibility criteria. Drug treatment consisted of rTNF (Genentech) given at a dose of 150 micrograms intravenously for five consecutive days every 3 weeks; 50% dose reduction was made for acute intolerance such as hypotension or severe fever and chills. Although eight patients with gastric cancer and five patients with pancreatic cancer received four or more courses of treatment, no objective antitumor responses were recorded. As in other trials common toxicities of rTNF included nausea and vomiting, chills and fever, hypotension, headache, myalgias, fatigue and malaise. However, in this trial, other toxicities became prominent: four episodes of symptomatic disseminated intravascular clotting occurred among patients with pancreatic cancer. Eleven with this disease and five with gastric cancer manifested laboratory findings of abnormal amounts of fibrin split products, and/or hypofibrinogenemia, and/or thrombocytopenia after treatment began. Other laboratory abnormalities that were commonly encountered included hyperglycemia, hypertriglyceridemia, anemia, neutropenia and an elevation in liver enzymes. We conclude that rTNF does not demonstrate antitumor efficacy against adenocarcinomas of the stomach and the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

PubMed Central

Kaufman, Howard L; Kim-Schulze, Seunghee; Manson, Kelledy; DeRaffele, Gail; Mitcham, Josephine; Seo, Kang Seok; Kim, Dae Won; Marshall, John

2007-01-01

Purpose An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival. Patients and methods Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM) (PANVAC-V) and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F). Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis. Results The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%). Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; P = .002). Conclusion Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer. PMID:18039393

Pancreatic cancer

PubMed Central

Vincent, Audrey; Herman, Joseph; Schulick, Rich; Hruban, Ralph H; Goggins, Michael

2011-01-01

Substantial progress has been made in our understanding of the biology of pancreatic cancer, and advances in patients’ management have also taken place. Evidence is beginning to show that screening first-degree relatives of individuals with several family members affected by pancreatic cancer can identify non-invasive precursors of this malignant disease. The incidence of and number of deaths caused by pancreatic tumours have been gradually rising, even as incidence and mortality of other common cancers have been declining. Despite developments in detection and management of pancreatic cancer, only about 4% of patients will live 5 years after diagnosis. Survival is better for those with malignant disease localised to the pancreas, because surgical resection at present offers the only chance of cure. Unfortunately, 80–85% of patients present with advanced unresectable disease. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. Hence, we need to understand the biological mechanisms that contribute to development and progression of pancreatic tumours. In this Seminar we will discuss the most common and deadly form of pancreatic cancer, pancreatic ductal adenocarcinoma. PMID:21620466

Hepatocellular carcinoma: Advances in diagnostic imaging.

PubMed

Sun, Haoran; Song, Tianqiang

2015-10-01

Thanks to the growing knowledge on biological behaviors of hepatocellular carcinomas (HCC), as well as continuous improvement in imaging techniques and experienced interpretation of imaging features of the nodules in cirrhotic liver, the detection and characterization of HCC has improved in the past decade. A number of practice guidelines for imaging diagnosis have been developed to reduce interpretation variability and standardize management of HCC, and they are constantly updated with advances in imaging techniques and evidence based data from clinical series. In this article, we strive to review the imaging techniques and the characteristic features of hepatocellular carcinoma associated with cirrhotic liver, with emphasis on the diagnostic value of advanced magnetic resonance imaging (MRI) techniques and utilization of hepatocyte-specific MRI contrast agents. We also briefly describe the concept of liver imaging reporting and data systems and discuss the consensus and controversy of major practice guidelines.

Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

ClinicalTrials.gov

2017-09-26

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

Glucose Homeostasis, Pancreatic Endocrine Function, and Outcomes in Advanced Heart Failure.

PubMed

Melenovsky, Vojtech; Benes, Jan; Franekova, Janka; Kovar, Jan; Borlaug, Barry A; Segetova, Marketa; Tura, Andrea; Pelikanova, Tereza

2017-08-07

The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucose-regulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome ( P =0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L -1 , 68-101 mg·dL -1 ) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L -1 , 108-142 mg·dL -1 ; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P =0.002). Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia. © 2017 The Authors. Published on behalf of the American Heart Association, Inc

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

PubMed

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

1999-07-01

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

Progress in the study of pancreatic cancer and its pathology.

PubMed

Yanagisawa, A

1998-01-01

Recent advances in diagnostic techniques allow detection of relatively small ductal cancers and mucinous cystic neoplasms of the human pancreas. The histopathological characteristics of a series of such small pancreatic carcinomas encountered in our hospital were: 1) all were invasive ductal carcinomas accompanied by fibrosis, 2) four of seven carcinomas were thought to originate in the branch ducts, 3) no precancerous lesions were found, and 4) lymph node metastasis was detected in only one patient. Mucinous cystic neoplasms were of two types: megacystic and ductectatic. The megacystic type is the classical mucinous cystic neoplasm. The ductectatic type is characterized by the presence of multilocular cysts (reminiscent of bronchiectasia of the lung), and papillary proliferation of the lining epithelium-differing from typical ductal carcinomas as well as from megacystic lesions in terms of morphological features, intrapancreatic location, patient age, and sex. The ductectatic type occurs exclusively in the head and body of the pancreas, and is found predominantly in aging males.

Hexon modification to improve the activity of oncolytic adenovirus vectors against neoplastic and stromal cells in pancreatic cancer.

PubMed

Lucas, Tanja; Benihoud, Karim; Vigant, Frédéric; Schmidt, Christoph Q; Schmidt, Christoph Q Andreas; Wortmann, Andreas; Bachem, Max G; 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.

Silencing of decoy receptor 3 (DcR3) expression by siRNA in pancreatic carcinoma cells induces Fas ligand-mediated apoptosis in vitro and in vivo.

PubMed

Zhou, Jian; Song, Shiduo; He, Songbin; Wang, Zhenxin; Zhang, Bing; Li, Dechun; Zhu, Dongming

2013-09-01

Decoy receptor 3 (DcR3) is abundantly expressed in human tumors and protects cells from a wide range of apoptotic stimuli. In this study, we demonstrate that DcR3 is overexpressed in pancreatic carcinoma cells, and that the pancreatic carcinoma cell lines, Panc-1 and SW1990, are resistant to Fas ligand (FasL)-mediated apoptosis. To further define the function of DcR3 in cell growth and apoptosis, we used small interfering RNA (siRNA) to knockdown the expression of the DcR3 gene in Panc-1 and SW1990 cells. Our results revealed that the silencing of DcR3 expression enhanced the inhibitory effects of FasL and reduced the capabiltiy of the cells for proliferation and colony formation in vitro. In addition, the downregulation of DcR3 modulated the cell apoptotic regulators, Fas-associated death domain (FADD), caspase‑3 and caspase‑8, thus triggering cell apoptosis. Furthermore, the knockdown of DcR3 inhibited the growth of Panc-1 tumor xenografts. Taken together, our findings indicate that DcR3 is important in cancer progression and may be a used as a potential therapeutic target for the gene therapy of pancreatic carcinoma.

Pancreatic cancer ascites xenograft–an expeditious model mirroring advanced therapeutic resistant disease

PubMed Central

Schvimer, Michael; Atias, Dikla; Halperin, Sharon; Buzhor, Ella; Raitses-Gurevich, Maria; Cohen, Keren; Pri-Chen, Sara; Wilson, Julie; Denroche, Robert E.; Lungu, Ilinca; Bartlett, John M.S.; Mbabaali, Faridah; Yarden, Yosef; Nataraj, Nishanth Belugali; Gallinger, Steven; Berger, Raanan

2017-01-01

Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up to 20–30% of patients with pancreatic cancer; this milieu represents a highly cellular research resource of metastatic peritoneal spread. In this study, we utilized pancreatic ascites/pleural effusion cancer cells to establish patient derived xenografts. Ascites/pleural effusion-patient derived xenografts were established from twelve independent cases. Xenografts were serially passed in nude mice and tissue bio-specimen banking has been established. Histopathology of emergent tumors demonstrates poorly to moderately differentiated, glandular and mucin producing tumors, mirroring morphology of primary pancreatic cancer tumors. Whole genome sequencing of six patient derived xenografts samples demonstrates common mutations and structural variations similar to those reported in primary pancreatic cancer. Xenograft tumors were dissociated to single-cells and in-vitro drug sensitivity screen assays demonstrated chemo-resistance, correlating with patient clinical scenarios, thus serving as a platform for clinically relevant translational research. Therefore, establishment of this novel ascites/pleural effusion patient derived xenograft model, with extensive histopathology and genomic characterization, opens an opportunity for the study of advanced aggressive pancreatic cancer. Characterization of metastatic disease and mechanisms of resistance to therapeutics may lead to the development of novel drug combinations. PMID:28489577

Apatinib treatment in extensive metastatic advanced thymic carcinoma.

PubMed

He, Y; Liu, S; E, M; Wang, C; Shi, M; Liu, G; Abiyasi, N

2018-01-01

Apatinib is a novel oral, anti-tumor, angiogenic-targeting drug that can selectively target vascular endothelial growth factor receptor-2 (VEGFR-2). In clinical trials, this new tyrosine kinase inhibitor (TKI) has been shown to be an effective and safe treatment for a variety of malignancies. Currently, there is a lack of studies of patients with thymic carcinoma; therefore, we present a case of advanced thymic carcinoma treated with apatinib after chemotherapy failure with multiple lung metastases. This patient has been taking a dose of 500 mg of apatinib per day, and his efficacy has achieved partial response (PR), according to the RECIST 1.1 standard, and progression-free survival (PFS) is 6.3 months at this point. Apatinib will continue as his maintenance treatment. During the treatment, drug-related toxicity and side effects were tolerable. Thus, apatinib may be a meaningful option for the treatment of advanced metastatic thymic carcinoma after chemotherapy failure.

Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

PubMed

Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

2014-01-10

The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

Single incision laparoscopic pancreas resection for pancreatic metastasis of renal cell carcinoma.

PubMed

Barbaros, Umut; Sümer, Aziz; Demirel, Tugrul; Karakullukçu, Nazlı; Batman, Burçin; Içscan, Yalın; Sarıçam, Gülay; Serin, Kürçsat; Loh, Wei-Liang; Dinççağ, Ahmet; Mercan, Selçuk

2010-01-01

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. A 59-year-old female who had metastatic lesions on her pancreas underwent laparoscopic subtotal pancreatectomy through a 2-cm umbilical incision. 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. 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.

Clinicopathologic assessment of pancreatic ductal carcinoma located at the head of the pancreas, in relation to embryonic development.

PubMed

Okamura, Yukiyasu; Fujii, Tsutomu; Kanzaki, Akiyuki; Yamada, Suguru; Sugimoto, Hiroyuki; Nomoto, Shuji; Takeda, Shin; Nakao, Akimasa

2012-05-01

Pancreaticoduodenectomy is performed for pancreatic head cancer that originated from the dorsal or ventral primordium. Although the extent of lymph node (LN) dissection is the same irrespective of the origin, the lymphatic continuities may differ between the 2 primordia. Between March 2003 and September 2010, 152 patients underwent pancreaticoduodenectomy for pancreatic cancer. One hundred six patients were assigned into 2 groups according to tumor location on preoperative computed tomography, and their clinical and pathological features were retrospectively analyzed in view of the embryonic development of the pancreas. Sixty of 106 patients were classified with tumors that were derived from the dorsal pancreas (D group) and 46 from the ventral pancreas (V group). The frequency of LN involvement around the middle colic artery (LN 15) in the D group was higher than in the V group (P = 0.008). The rate of additional resection of the pancreas tended to be higher in the D group (P = 0.067). The present study showed the detailed pattern of spread of pancreatic ductal carcinoma to the LNs and provided important information for determining the optimal surgical strategy.

Clinicopathological Features of Intraductal Pancreatic Neuroendocrine Tumors.

PubMed

Chang, Xiao-Yan; Jia, Cong-Wei; Meng, Yun-Xiao; Chen, Jie

2016-10-10

Objective To evaluate the clinical and pathologic characteristics of intraductal pancreatic neuroendocrine tumors (PanNETs). Methods Four cases of intraductal PanNETs were studied by light microscopy and immunohistochemistry with the analysis of morphologic features and review of relevant literatures. Results Two female patients and two male patients aged 41- 58 years were enrolled in this study. The chief complaint was abdominal pain in two patients,vomiting in one patient,and jaundice in the last patient. Imaging examination showed intraductal neoplasm with diagnosis as intraductal papillary mucinous neoplasm (IPMN) in case 1; space-occupying lesions were found in the head of pancreas in the other three cases with pancreatic ductal ectasia and distal pancreatic atrophy. Grossly the masses were located in pancreatic main duct and invaded into surrounding pancreatic parachyma. Microscopically the tumors arranged with solid pattern,with some trabecular structures in the last two cases. Small duct and ductules were seen in intraductal PanNETs. The immunohistochemical expression showed that SYN and CgA were positive in neoplastic cells and negative in small duct and ductules.Conclusions Intraductal PanNETs are rare conditions. The clinical symptoms and imaging findings are similar to IPMN or pancreatic carcinoma. The tumors are located within pancreatic duct partly and can invade the pancreatic parenchyma. Microscopically the neuroendocrine tumors mix with small duct and forms ductulo-insular structure,which should be differentiated with mixed ductal endocrine carcinoma. The grade and prognosis are similar to those of classical neuroendocrine tumors.

Differential expression of heat shock protein (HSP) 70-2 gene polymorphism in benign and malignant pancreatic disorders and its relationship with disease severity and complications.

PubMed

Srivastava, Puja; Shafiq, Nusrat; Bhasin, Deepak Kumar; Rana, Surinder Singh; Pandhi, Promila; Behera, Arunanshu; Kapoor, Rakesh; Malhotra, Samir; Gupta, Rajesh

2012-07-10

The role of heat shock protein (HSP) 70-2 gene polymorphism (at position 1267, A to G transition) in patients with pancreatic disorders is not clear. To evaluate HSP 70-2 gene polymorphism (at position 1267, A to G transition) in patients with acute and chronic pancreatitis as well as pancreatic carcinoma, and to find any association of this polymorphism with disease complications and severity. One-hundred and fifty patients (50 each of acute, chronic pancreatitis, and pancreatic carcinoma) and 50 healthy blood donors as controls were prospectively studied. Three alleles (AA, AG and GG) of HSP 70-2 gene determined by PstI restriction fragment length polymorphism. There was a statistically significant difference in the distribution pattern of HSP 70-2 gene polymorphism in patients with acute pancreatitis (P=0.001) and pancreatic carcinoma (P<0.001) as compared to controls. The frequency of mutant allele (G allele) was significantly higher in diseased group as compared to control group (19% in control group, 40% in acute pancreatitis, 33% in chronic pancreatitis and 45% in pancreatic carcinoma). No association of this polymorphism was found with disease severity in patients with acute and chronic pancreatitis or pancreatic carcinoma. In our patient sample the frequency of mutant allele (G allele) of HSP 70-2 gene is significantly higher in patients with acute pancreatitis and pancreatic carcinoma compared to controls (50 healthy blood donors). However, this polymorphism was not associated with disease severity and complications.

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

PubMed

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

2015-02-01

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

Surgical Management of Chronic Pancreatitis.

PubMed

Parekh, Dilip; Natarajan, Sathima

2015-10-01

Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.

Advanced pancreatic adenocarcinoma outcomes with transition from devolved to centralised care in a regional Cancer Centre.

PubMed

Faluyi, Olusola O; Connor, Joanna L; Chatterjee, Madhuchanda; Ikin, Carl; Wong, Helen; Palmer, Daniel H

2017-02-14

Previous observations suggest suboptimal 'real world' survival outcomes for advanced pancreatic adenocarcinoma. We hypothesized that centralisation of advanced pancreatic adenocarcinoma management would improve chemotherapy treatment and survival from the disease. The data was prospectively collected on all cases of advanced pancreatic adenocarcinoma reviewed through Clatterbridge Cancer Centre according to two groups; 1 October 2009-31st Dec 2010 (devolved care) or 1 January 2013-31 March 2014 (centralised care). Analysis included treatment received, 30-day chemotherapy mortality rate and overall survival (OS). More patients received chemotherapy with central care (67.0% (n=115) vs 43.0% (n=121); P=2.2 × 10 -4 ) with no difference in 30-day mortality (20.8% vs 25%; P=0.573) but reduced time to commencement of chemotherapy (18 vs 28 days, P=1.0 × 10 -3 ). More patients received second-line chemotherapy with central care (23.4% vs 1.9%, P=1.4 × 10 -4 ), while OS was significantly increased with central care (median: Five vs three months, HR 0.785, P=0.045). Exploratory analysis suggested that it was those with a poorer performance status, elderly or with metastatic disease who benefited the most from transition to central care. A centralised clinic model for advanced pancreatic cancer management resulted in prompt, safe and higher use of chemotherapy compared with devolved care. This was associated with a modest survival benefit. Prospective studies are required to validate the findings reported and the basis for improved survival with centralised care.

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

ClinicalTrials.gov

2018-03-29

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

A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer.

PubMed

Cohen, Steven J; Zalupski, Mark M; Modiano, Manuel R; Conkling, Paul; Patt, Yehuda Z; Davis, Peg; Dorr, Robert T; Boytim, Michelle L; Hersh, Evan M

2010-07-01

Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m(2) intravenously (IV) over 30 min days 1-5, 15-19 and gemcitabine 800 or 1,000 mg/m(2) IV over 30 min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m(2) IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m(2) IV over 30 min on days 1, 8, and 15 every 28 days). One hundred five patients received 340 treatment cycles (median 2, range 1-16). median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half life 69 min at the MTD and no alteration of gemcitabine pharmacokinetics. The recommended phase II dose of imexon is 875 mg/m(2) with gemcitabine 1,000 mg/m(2). DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swartz, Michael J.; Hsu, Charles C.; Pawlik, Timothy 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 presentmore » 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.« less

Autoimmune pancreatitis can develop into chronic pancreatitis

PubMed Central

2014-01-01

Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

Autoimmune pancreatitis can develop into chronic pancreatitis.

PubMed

Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Kawa, Shigeyuki

2014-05-21

Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct.

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

"Puestow modified procedure in the era of advanced endoscopic interventions for the management of chronic lithiasic pancreatitis. A two cases report".

PubMed

Fragulidis, Georgios P; Vezakis, Αntonios; Dellaportas, Dionissios; Sotirova, Ira; Koutoulidis, Vassilis; Kontis, Elliseos; Polydorou, Andreas

2015-01-01

Pancreatic duct calculi in chronic pancreatitis (CP) patients are the main cause of intractable pain which is their main symptom. Decompression options of for the main pancreatic duct are both surgical and advanced endoscopic procedures. A 64-year-old male with known CP due to alcohol consumption and a 36-year-old female with known idiopathic CP and pancreatic duct calculi were managed recently in our hospital where endoscopic procedures were unsuccessful. A surgical therapy was considered and a longitudinal pancreaticojejunostomy (modified Puestow procedure) in both patients was performed with excellent results. Over the last 30 years, endoscopic procedures are developed to manage pancreatic duct strictures and calculi of the main pancreatic duct in CP patients. In both of our cases endoscopic therapy was first attempted but failed to extract the pancreatic duct stones, due to their size and speculations. Modified Puestow procedure was performed for both and it was successful for long term pain relief. Despite advancement in endoscopic interventions and less invasive therapies for the management of chronic lithiasic pancreatitis we consider that classic surgical management can be appropriate in certain cases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Preferential expression of cystein-rich secretory protein-3 (CRISP-3) in chronic pancreatitis.

PubMed

Liao, Q; Kleeff, J; Xiao, Y; Guweidhi, A; Schambony, A; Töpfer-Petersen, E; Zimmermann, A; Büchler, M W; Friess, H

2003-04-01

Chronic pancreatitis (CP) is a progressive inflammatory process resulting in exocrine and endocrine pancreatic insufficiency in advanced stages. Cysteine-rich secretory protein (CRISP-3) has been identified as a defense-associated molecule with predominant expression in the salivary gland, pancreas and prostate. In this study, we investigated CRISP-3 expression in normal pancreatic tissues, chronic pancreatitis tissues, pancreatic cancer tissues and pancreatic cancer cell lines, as well as in other gastrointestinal organs. 15 normal pancreatic tissues, 14 chronic pancreatitis tissues and 14 pancreatic cancer tissues as well as three pancreatic cancer cell lines were analyzed. Moreover, hepatocellular carcinoma and esophageal, stomach and colon cancers were also analyzed together with the corresponding normal controls. CRISP-3 was expressed at moderate to high levels in chronic pancreatitis tissues and at moderate levels in pancreatic cancer tissues but at low levels in normal pancreatic tissues, and was absent in three pancreatic cancer cell lines. CRISP-3 expression was below the level of detection in all cancerous gastrointestinal tissues and in all normal tissues except 2 of 16 colon tissue samples. CRISP-3 mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells and in small proliferating ductal cells in CP tissues and CP-like lesions in pancreatic cancer tissues. In contrast, CRISP-3 expression was weak to absent in the cytoplasm of cancer cells as well as in acinar cells and ductal cells in pancreatic cancer tissues and normal pancreatic tissues. These results reveal that the distribution of CRISP-3 in gastrointestinal tissues is predominantly in the pancreas. High levels of CRISP-3 in acinar cells dedifferentiating into small proliferating ductal cells in CP and CP-like lesions in pancreatic cancer suggests a role of this molecule in the pathophysiology of CP.

Chronic pancreatitis.

PubMed

DiMagno, Matthew J; DiMagno, Eugene P

2012-09-01

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

Apatinib concurrent gemcitabine for controlling malignant ascites in advanced pancreatic cancer patient

PubMed Central

Liang, Lijun; Wang, Lei; Zhu, Panrong; Xia, Youyou; Qiao, Yun; Hui, Kaiyuan; Hu, Chenxi; Ren, Yan; Jiang, Xiaodong

2017-01-01

Abstract Rationale: Malignant ascites (MA) is one of the poor prognostic factors for advanced pancreatic cancer and can bring about serious symptoms. The improvement of quality of life for patients is priority. However, there is no standard method for the treatment for pancreatic cancer-mediated MA. Apatinib is a novel and highly selective tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. There are no reports of concurrent apatinib with gemcitabine in patients with pancreatic cancer-mediated MA. Patient concerns: Herein, we presented a 64-year-old man patient who visited hospital due to abdominal pain for 1 month. Diagnoses: He was initially diagnosed with pancreatic cancer and his first symptom was MA. Interventions: After failing in tube drainage and gemcitabine therapy, the patient received gemcitabine combined apatinib orally and after administrated 1 month, the MA was evaluated as nearly clear response according to the RECIST 1.1 standard, and without further need of paracentesis. The CEA and CA199 reached the lowest level after administrating for 2.5 months during the treatment process. Outcomes: 10.5 months following apatinib administration, the patient achieved a progression-free survival for more than 11 months. Hypertension (grade IV), hand-foot syndrome (grade I) and proteinuria (grade II) were observed. Lessons: It indicated that apatinib concurrent gemcitabine may be a superior choice for pancreatic cancer-mediated MA. Further clinical trials required to confirm its efficacy and safety. PMID:29381963

Selective drainage for pancreatic, biliary, and duodenal obstruction secondary to chronic fibrosing pancreatitis.

PubMed Central

Sugerman, H J; Barnhart, G R; Newsome, H H

1986-01-01

Twenty-eight patients underwent surgery for intractable pain, duodenal or extrahepatic biliary obstruction secondary to chronic pancreatitis. Eleven had pancreatic duct obstruction alone, six biliary obstruction alone, seven combined pancreatic and biliary, two combined biliary and duodenal, one combined pancreatic and duodenal, and one simultaneous pancreatic, biliary, and duodenal obstruction. Pancreatitis was secondary to alcohol in all but one case. The following operations were performed: longitudinal pancreatojejunostomy (20), choledochoduodenostomy (8), choledochojejunostomy (7), cholecystojejunostomy (1), and gastrojejunostomy (4). Of the 20 patients with pancreatic duct drainage, pain relief was complete in 11 and partial in six. Initial incomplete relief of pain, or recurrence, stimulated further diagnostic procedures, leading to improvement or correction of the problem in five patients. A significant (p less than 0.01) fall in alkaline phosphatase (935 +/- 228 to 219 +/- 61 U/L) occurred following surgery. One patient was subsequently found to have pancreatic carcinoma. Two patients were lost to follow-up and four patients died (one perioperative and three late). In conclusion, the possibility of pancreatic, biliary, and duodenal obstruction must be considered in symptomatic patients with chronic pancreatitis. Surgery must be individualized. Drainage procedures, either alone or in combination, are associated with a low morbidity and improved clinical condition and may be preferable to resection in the surgical management of these patients. Images FIG. 1. FIG. 2. FIG. 4. PMID:3707234

Acute pancreatitis: recent advances through randomised trials.

PubMed

van Dijk, Sven M; Hallensleben, Nora D L; van Santvoort, Hjalmar C; Fockens, Paul; van Goor, Harry; Bruno, Marco J; Besselink, Marc G

2017-11-01

Acute pancreatitis is one of the most common GI conditions requiring acute hospitalisation and has a rising incidence. In recent years, important insights on the management of acute pancreatitis have been obtained through numerous randomised controlled trials. Based on this evidence, the treatment of acute pancreatitis has gradually developed towards a tailored, multidisciplinary effort, with distinctive roles for gastroenterologists, radiologists and surgeons. This review summarises how to diagnose, classify and manage patients with acute pancreatitis, emphasising the evidence obtained through randomised controlled trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Advances in therapeutic vaccines for pancreatic cancer.

PubMed

Plate, Janet M D

2012-08-01

Pancreatic cancer is one of the most difficult-to-treat cancers. Despite surgical resection, radiation and/or chemotherapy, greater than 94% of people with pancreatic cancer do not survive beyond 5 years. In fact, median survival after diagnosis of metastatic pancreatic cancer is 4.5 months. The majority of patients are diagnosed with nonresectable, metastatic disease, and chemotherapy only extends their median survival by less than 2 months with only 18% of those treated surviving beyond 1 year. Despite the severity of their disease, most patients exhibit tumor specific cellular immunity to their pancreatic cancer antigens. Obviously their immunity is ineffective in preventing tumor growth. Recent studies have demonstrated that the tumor microenvironment may hold the key to determining the nature of the tumors' ability to escape from immune attack. Preliminary clinical trials have suggested that blocking these escape mechanisms may result in survival benefit to the patients, and phase I and II clinical trials with tumor vaccines have led to some survival benefits. Perhaps combining therapies directed against immune escape mechanisms with tumor vaccines will result in even greater survival benefit for patients with pancreatic cancer. While therapeutic vaccines for pancreatic cancers have been reviewed previously (Plate, 2011), updates on recent preliminary reports of two clinical vaccine trials are worthy of our attention.

Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors

ClinicalTrials.gov

2017-07-15

Head and Neck Squamous Cell Carcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Pancreatic Adenocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Gallbladder Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pancreatic Cancer; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Cancer

Inhibitory effects of epigallocatechin-3-gallate on cell proliferation and the expression of HIF-1α and P-gp in the human pancreatic carcinoma cell line PANC-1.

PubMed

Zhu, Zhenni; Wang, Yu; Liu, Zhiqing; Wang, Fan; Zhao, Qiu

2012-05-01

The aim of this study was to verify the inhibitory effects of epigallocatechin-3-gallate (EGCG) on cell proliferation and the expression of hypoxia-inducible factor 1 (HIF-1α) and multidrug resistance protein 1 (MDR1/P-gp) in the human pancreatic carcinoma cell line PANC-1, thereby, reversing drug resistance of pancreatic carcinoma and improving its sensitivity to cancer chemotherapy. The human pancreatic carcinoma cell line PANC-1 was incubated under hypoxic conditions with different concentrations of epigallocatechin-3-gallate (EGCG) for indicated hours. The effects of EGCG on the mRNA or protein expression of HIF-1α and MDR1 were determined by RT-PCR or western blotting. Cellular proliferation and viability assays were measured using Cell Counting Kit-8. Western blotting revealed that EGCG inhibits the expression of the HIF-1α protein in a dose-dependent manner, while RT-PCR showed that it does not have any effects on HIF-1α mRNA. In addition, EGCG attenuated the mRNA and protein levels of P-gp in a dose-dependent manner, reaching a peak at the highest concentration. Furthermore, EGCG inhibited the proliferation of PANC-1 cells in a concentration- and time-dependent manner. The attenuation of HIF-1α and the consequently reduced P-gp could contribute to the inhibitory effects of EGCG on the proliferation of PANC-1 cells.

The Symptom Experience of Patients With Advanced Pancreatic Cancer: An Integrative Review.

PubMed

Tang, Chia-Chun; Von Ah, Diane; Fulton, Janet S

Pancreatic cancer is a devastating disease with limited treatment options. More than 80% of pancreatic cancers are diagnosed in advanced stages and often have debilitating symptoms, making symptom management paramount, yet the symptom experience of patients with advanced pancreatic cancer (APC) is not well understood. The purpose of this integrative review is to synthesize the current evidence regarding the symptom experience of patients with APC. An integrative literature review was conducted to identify the patient symptom experience in studies published from 2005 to 2015. Sixteen studies met the inclusion criteria. All studies used a quantitative approach; 44% were quasi-experimental, 31% were descriptive, and 25% were correlational. Physical symptoms, especially pain, were the primary focus in most studies. Fatigue, loss of appetite, and impaired sense of well-being were prevalent and reported by patients to be of high intensity. Few studies examined psychological symptoms in patients with APC, although anxiety and depression were noted. Findings suggest that physical and psychological symptoms are prevalent, some with high intensity. Preselection of symptom inventories limits our ability to fully understand the symptom experience of patients with APC. Future qualitative work is needed to provide a more in-depth understanding of symptoms, especially symptom quality and distress level, from patients' perspectives. More studies are needed to explore psychological symptoms and the interaction of physical and psychological symptoms. Findings help healthcare givers to better understand the symptom experience of their APC patients.

“Puestow modified procedure in the era of advanced endoscopic interventions for the management of chronic lithiasic pancreatitis. A two cases report”

PubMed Central

Fragulidis, Georgios P.; Vezakis, Αntonios; Dellaportas, Dionissios; Sotirova, Ira; Koutoulidis, Vassilis; Kontis, Elliseos; Polydorou, Andreas

2015-01-01

Introduction Pancreatic duct calculi in chronic pancreatitis (CP) patients are the main cause of intractable pain which is their main symptom. Decompression options of for the main pancreatic duct are both surgical and advanced endoscopic procedures. Presentation of cases A 64-year-old male with known CP due to alcohol consumption and a 36-year-old female with known idiopathic CP and pancreatic duct calculi were managed recently in our hospital where endoscopic procedures were unsuccessful. A surgical therapy was considered and a longitudinal pancreaticojejunostomy (modified Puestow procedure) in both patients was performed with excellent results. Discussion Over the last 30 years, endoscopic procedures are developed to manage pancreatic duct strictures and calculi of the main pancreatic duct in CP patients. In both of our cases endoscopic therapy was first attempted but failed to extract the pancreatic duct stones, due to their size and speculations. Modified Puestow procedure was performed for both and it was successful for long term pain relief. Conclusion Despite advancement in endoscopic interventions and less invasive therapies for the management of chronic lithiasic pancreatitis we consider that classic surgical management can be appropriate in certain cases. PMID:26318135

A Continuation Study Using Sunitinib Malate For Patients Leaving Treatment On A Previous Sunitinib Study.

ClinicalTrials.gov

2015-10-07

Metastatic Breast Cancer [F]; Advanced Breast Cancer; Metastatic Castration Resistant Prostate Cancer; Metastatic Renal Cell Cancer; Non-Small Cell Lung Cancer; Thyroid Cancer; Advanced/Metastatic Non-Small Cell Lung Cancer; Advanced Gastric Cancer; Gastrointestinal Stromal Tumor; Hepatocellular Carcinoma; Pancreatic Islet Cell Carcinoma; Pancreatic Neuroendocrine Tumor

Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances

PubMed Central

Dhanasekaran, Renumathy; Bandoh, Salome; Roberts, Lewis R.

2016-01-01

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and has an increasing incidence worldwide. HCC can be induced by multiple etiologies, is influenced by many risk factors, and has a complex pathogenesis. Furthermore, HCCs exhibit substantial heterogeneity, which compounds the difficulties in developing effective therapies against this highly lethal cancer. With advances in cancer biology and molecular and genetic profiling, a number of different mechanisms involved in the development and progression of HCC have been identified. Despite the advances in this area, the molecular pathogenesis of hepatocellular carcinoma is still not completely understood. This review aims to elaborate our current understanding of the most relevant genetic alterations and molecular pathways involved in the development and progression of HCC, and anticipate the potential impact of future advances on therapeutic drug development. PMID:27239288

PARP Inhibitors Synergize With Loss of Checkpoint Control to Kill Mammary Carcinoma Cells

DTIC Science & Technology

2011-06-01

from three studies S.E.M. B, MCF7 breast cancer and PANC -1 and MiaPaca2 pancreatic cancer cells were plated in triplicate and treated with vehicle...inhibitors to kill pancreatic carcinoma cells PANC -1 (pancreatic) and MiaPaca2 (pancreatic) carcinoma cells were plated as single cells (250–2000 cells...231 and PANC -1. Simian virus 40 large T antigen-transformed fibroblasts that are not tu- morigenic in mice were also sensitive to the drug schedule

Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-h gemcitabine infusion, in locally advanced pancreatic cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maurel, Joan; Martin-Richard, Marta; Conill, Carlos

Purpose: Pancreatic cancers are resistant to radiotherapy (RT) and current chemotherapy agents. Epidermal growth factor receptor is overexpressed in pancreatic cancer, and in vitro studies have shown that epidermal growth factor receptor inhibitors can overcome radio- and chemoresistance. The aim of the study was to determine whether the addition of gefitinib to RT and gemcitabine for patients with locally advanced pancreatic carcinoma (LAPC) was feasible and safe. Methods and Materials: Eighteen patients with pathologically proven LAPC, based on major vascular invasion based on helical computed tomography (CT) and endoscopic ultrasound, were entered into the study. The targeted irradiated volume includedmore » the tumor and 2-cm margin. Prophylactic irradiation of regional nodes was not allowed. Patients with >500 cm{sup 3} of planning tumor volume were excluded. An initial cohort of 6 patients was treated with RT (45 Gy/25 fractions/5 weeks) plus concomitant gefitinib (250 mg/day). Successive cohorts of patients received 100, 150, and 200 mg/m{sup 2}/day of gemcitabine in a 2-h infusion over Weeks 1, 2, 3, 4, and 5 with gefitinib (250 mg/day) and RT. Gefitinib was continued after RT until progression. A pharmacodynamic study of angiogenic markers was also performed to evaluate a possible antiangiogenic effect. Results: There were no dose-limiting toxicities. Common toxicities were mild neutropenia, asthenia, diarrhea, cutaneous rash and nausea/vomiting. The median (95% confidence interval [CI]) progression-free survival was 3.7 (95% CI = 1.9-5.5) months, and the median overall survival was 7.5 (95% CI 5.2-9.9) months. No significant reduction of vascular endothelial growth factor and interleukin-8 was observed after treatment. Conclusion: Our results support that the combination of gefitinib, RT, and gemcitabine has an acceptable toxicity but with modest activity in LAPC.« less

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.

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

PubMed Central

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

2017-01-01

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

Recent advances in genomic profiling of adenosquamous carcinoma of the pancreas.

PubMed

Marcus, Rebecca; Maitra, Anirban; Roszik, Jason

2017-11-01

Adenosquamous carcinoma of the pancreas (ASCP) is a mixed tumor type which contains squamous cell carcinoma and also ductal adenocarcinoma components. Due to the rarity of this malignancy, only very limited genomic profiling has been performed. A recent paper by Fang et al. published in The Journal of Pathology contributed to our knowledge of genomic alterations by performing whole-genome and -exome sequencing of 17 ASCP tumors. They found major genomic similarities to pancreatic ductal adenocarcinoma; however, the p53 pathway was altered in a greater proportion of cases, while a high frequency of 3p loss was a distinct copy number alteration pattern observed in ASCP. Laser capture microdissection revealed that adenocarcinoma and squamous carcinoma components of ASCP harbor similar genomic variations, indicating that the origin of tumor components is the same or similar. Although the study published by Fang et al. increases our knowledge of this rare mixed tumor type, further investigation, including RNA sequencing, will be needed to fully characterize this malignancy and to aid the development of novel treatment approaches. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Pancreatic Cancer—Patient Version

Cancer.gov

Pancreatic cancer can form in exocrine cells and neuroendocrine cells. The exocrine type is more common and is usually found at an advanced stage. Pancreatic neuroendocrine tumors are less common but have a better prognosis. Start here to find information on pancreatic cancer treatment, research, and statistics.

Laparoscopic common hepatic artery ligation and staging followed by distal pancreatectomy with en bloc resection of celiac artery for advanced pancreatic cancer.

PubMed

Raut, V; Takaori, K; Kawaguchi, Y; Mizumoto, M; Kawaguchi, M; Koizumi, M; Kodama, S; Kida, A; Uemoto, S

2011-11-01

Adeno-carcinomas of pancreatic body are usually asymptomatic and progress to advanced stage with involvement of major arteries. Resection of advanced cancer along with en bloc resection of a common hepatic artery and celiac trunk enables a "curative" resections and only possible treatment. However, the celiac axis resection always has a risk of compromising blood supply to liver, resulting in the hepatic insufficiency. We evaluated practicability of a two-stage procedure for the advanced pancreases body cancer, laparoscopic clamping of a common hepatic artery followed by open distal pancreatectomy with en bloc celiac arterial resection to prevent the hepatic insufficiency. Seventy-five-year-old woman diagnosed with a 50-mm pancreatic body mass, invading splenic artery, common hepatic artery, splenic vein, and portal vein at the confluence. STAGE-1: At laparoscopy, after confirming absence of the peritoneal, superficial liver metastases and negative peritoneal cytology; we approached the common hepatic artery through the lesser sac and ligated. STAGE-2: Her liver function tests were normal after 2 weeks, and CT angiography showed complete blockage of the common hepatic artery with sufficient collateral circulation to the liver through inferior pancreatico-duodenal artery and gastro-duodenal artery. We performed an open distal pancreatectomy with en bloc resection of celiac artery. Histopathology examination confirmed R0 resection. The celiac axis resection with distal pancreatectomy improves the chance of R0 resection and potentially, survival of the patient. Preoperative laparoscopic ligation of the common hepatic artery is a safe, effective, and in-expensive technique to prevent postoperative hepatic insufficiency and improves the safety of en bloc celiac artery resection with a distal pancreatectomy. Also these patients have high risk of peritoneal dissemination. Diagnostic laparoscopy is useful to detect occult metastasis, which are missed by per-operative CT

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.

American Gastroenterological Association guidelines are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic study of 225 patients with supporting molecular data.

PubMed

Singhi, Aatur D; Zeh, Herbert J; Brand, Randall E; Nikiforova, Marina N; Chennat, Jennifer S; Fasanella, Kenneth E; Khalid, Asif; Papachristou, Georgios I; Slivka, Adam; Hogg, Melissa; Lee, Kenneth K; Tsung, Allan; Zureikat, Amer H; McGrath, Kevin

2016-06-01

The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts. The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN. Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value. The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI

Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer.

PubMed

Strunk, H M; Henseler, J; Rauch, M; Mücke, M; Kukuk, G; Cuhls, H; Radbruch, L; Zhang, L; Schild, H H; Marinova, M

2016-07-01

Evaluation of ultrasound-guided high-intensity focused ultrasound (HIFU) used for the first time in Germany in patients with inoperable pancreatic cancer for reduction of tumor volume and relief of tumor-associated pain. 15 patients with locally advanced inoperable pancreatic cancer and tumor-related pain symptoms were treated by HIFU (n = 6 UICC stage III, n = 9 UICC stage IV). 13 patients underwent simultaneous standard chemotherapy. Ablation was performed using the JC HIFU system (Chongqing, China HAIFU Company) with an ultrasonic device for real-time imaging. Imaging follow-up (US, CT, MRI) and clinical assessment using validated questionnaires (NRS, BPI) was performed before and up to 15 months after HIFU. Despite biliary or duodenal stents (4/15) and encasement of visceral vessels (15/15), HIFU treatment was performed successfully in all patients. Treatment time and sonication time were 111 min and 1103 s, respectively. The applied total energy was 386 768 J. After HIFU ablation, contrast-enhanced imaging showed devascularization of treated tumor regions with a significant average volume reduction of 63.8 % after 3 months. Considerable pain relief was achieved in 12 patients after HIFU (complete or partial pain reduction in 6 patients). US-guided HIFU with a suitable acoustic pathway can be used for local tumor control and relief of tumor-associated pain in patients with locally advanced pancreatic cancer. • US-guided HIFU allows an additive treatment of unresectable pancreatic cancer.• HIFU can be used for tumor volume reduction.• Using HIFU, a significant reduction of cancer-related pain was achieved.• HIFU provides clinical benefit in patients with pancreatic cancer. Citation Format: • Strunk HM, Henseler J, Rauch M et al. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. Fortschr Röntgenstr 2016; 188: 662 - 670. © Georg Thieme Verlag KG

A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors

ClinicalTrials.gov

2018-06-04

Estrogen Receptor Negative; HER2/Neu Negative; Metastatic Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Progesterone Receptor Negative; Stage III Breast Cancer AJCC v7; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage III Small Cell Lung Carcinoma AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Small Cell Lung Carcinoma AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Small Cell Lung Carcinoma AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IV Small Cell Lung Carcinoma AJCC v7; Triple-Negative Breast Carcinoma; Unresectable Pancreatic Carcinoma

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

PubMed

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

2005-04-14

To study the effects of chromic-P32 phosphate (32P colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism. Ninety-eight tumor bearing nude mice were killed at different time points after the injection of 32P colloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32P colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Bax-related gene expression were observed too. The half-life of effective medication is 13 d after injection of 32P colloids to the tumor stroma, in 1-6 groups, the tumor cell necrosis rates were 20%, 45%, 65%, 70%, 95% and 4%, respectively (F = 4.14-105.36, P<0.01). MVD were 38.5+/-4.0, 28.0+/-2.9, 17.0+/-2.9, 8.8+/-1.5, 5.7+/-2.3 and 65.0+/-5.2 (t = 11.9-26.1, P<0.01), respectively. Under TEM fairly differentiated Pc-3 cells were found. Thirty days after medication, tumors were shrunk and dried with scabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM in animals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiation-induced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. 32P

Chronic pancreatitis.

PubMed

Yang, Dennis; Forsmark, Chris E

2017-09-01

Summarize key clinical advances in chronic pancreatitis reported in 2016. Early diagnosis of chronic pancreatitis remains elusive. Recent studies suggest that endoscopic ultrasound may be less accurate than previously thought and new MRI techniques may be helpful. Genetic predisposition may independently affect the clinical course of chronic pancreatitis and the risk for pancreatic cancer. Cigarette smoking may have a greater negative impact on chronic pancreatitis than previously thought and moderate alcohol consumption may be protective. A multidisciplinary approach is necessary for the treatment of type 3 diabetes and nutritional deficiencies in chronic pancreatitis. Although endoscopic therapy remains a reasonable first-line option in treating chronic pancreatitis and its complications, early surgical intervention may be indicated for pain in select patients. Newer endoscopic ultrasound and MRI techniques are being evaluated to help with the early diagnosis of chronic pancreatitis. Both genetic predisposition and cigarette smoking are increasingly recognized as having a major impact in the course of the disease and the risk for pancreatic cancer. Endoscopic therapy is well tolerated and effective for the treatment of chronic pancreatitis and its complications although an early surgical approach for pain may be associated with improved clinical outcomes.

Cost-effectiveness of modern radiotherapy techniques in locally advanced pancreatic cancer.

PubMed

Murphy, James D; Chang, Daniel T; Abelson, Jon; Daly, Megan E; Yeung, Heidi N; Nelson, Lorene M; Koong, Albert C

2012-02-15

Radiotherapy may improve the outcome of patients with pancreatic cancer but at an increased cost. In this study, the authors evaluated the cost-effectiveness of modern radiotherapy techniques in the treatment of locally advanced pancreatic cancer. A Markov decision-analytic model was constructed to compare the cost-effectiveness of 4 treatment regimens: gemcitabine alone, gemcitabine plus conventional radiotherapy, gemcitabine plus intensity-modulated radiotherapy (IMRT); and gemcitabine with stereotactic body radiotherapy (SBRT). Patients transitioned between the following 5 health states: stable disease, local progression, distant failure, local and distant failure, and death. Health utility tolls were assessed for radiotherapy and chemotherapy treatments and for radiation toxicity. SBRT increased life expectancy by 0.20 quality-adjusted life years (QALY) at an increased cost of $13,700 compared with gemcitabine alone (incremental cost-effectiveness ratio [ICER] = $69,500 per QALY). SBRT was more effective and less costly than conventional radiotherapy and IMRT. An analysis that excluded SBRT demonstrated that conventional radiotherapy had an ICER of $126,800 per QALY compared with gemcitabine alone, and IMRT had an ICER of $1,584,100 per QALY compared with conventional radiotherapy. A probabilistic sensitivity analysis demonstrated that the probability of cost-effectiveness at a willingness to pay of $50,000 per QALY was 78% for gemcitabine alone, 21% for SBRT, 1.4% for conventional radiotherapy, and 0.01% for IMRT. At a willingness to pay of $200,000 per QALY, the probability of cost-effectiveness was 73% for SBRT, 20% for conventional radiotherapy, 7% for gemcitabine alone, and 0.7% for IMRT. The current results indicated that IMRT in locally advanced pancreatic cancer exceeds what society considers cost-effective. In contrast, combining gemcitabine with SBRT increased clinical effectiveness beyond that of gemcitabine alone at a cost potentially acceptable by

Influence of high intensity focused ultrasound (HIFU) treatment to the pancreatic function in pancreatic cancer patients.

PubMed

Shi, Yulan; Ying, Xiao; Hu, Xiaoye; Zhao, Jing; Fang, Xuefeng; Wu, Minghui; Chen, Tian Zhou; Shen, Hong

2015-05-01

Present study was designed to investigate the pancreatic endocrine and exocrine function damage after High Intensity Focused Ultrasound (HIFU) therapy in patients with advanced pancreatic cancer. It was a retrospective analysis of blood glucose and amylase changes in 59 advanced pancreatic cancer patients treated with HIFU from 2010 February to 2014 January. The mean glucose and amylase before HIFU treatment were 6.02mmol/L and 59.17 U/L respectively. After HIFU treatment, it was shown that the mean glucose and amylase levels were 5.66mmol/L and 57.86/L respectively. There was no statistical significance between them. No acute pancreatitis was observed. The endocrine and exocrine function of pancreatic cancer patients was not damaged by HIFU treatment. HIFU treatment for the pancreatic cancer patients seems to be safe.

New clinical trial explores precision treatment for advanced pancreatic cancer | Center for Cancer Research

Cancer.gov

A new phase II clinical trial to assess the safety and efficacy of a drug called selumetinib for treating patients with advanced pancreatic cancer whose tumors harbor a specific genetic marker has opened at the Center for Cancer Research and is currently recruiting participants. Read more...

Modified fully covered self-expandable metal stents with antimigration features for benign pancreatic-duct strictures in advanced chronic pancreatitis, with a focus on the safety profile and reducing migration.

PubMed

Moon, Sung-Hoon; Kim, Myung-Hwan; Park, Do Hyun; Song, Tae Joon; Eum, Junbum; Lee, Sang Soo; Seo, Dong Wan; Lee, Sung Koo

2010-07-01

Fully covered self-expandable metal stent (FCSEMS) placement has recently been tried in the management of refractory pancreatic-duct strictures associated with advanced chronic pancreatitis. The major limitation of FCSEMSs was frequent migration. To assess the safety, migration rate, and removability of modified FCSEMSs with antimigration features used for the treatment of benign pancreatic-duct strictures. Prospective study. Tertiary academic center. Thirty-two patients with chronic painful pancreatitis and dominant ductal stricture. Transpapillary endoscopic placement of FCSEMSs in the pancreatic duct with removal after 3 months. Technical and functional success and adverse events associated with the placement of metal stents. FCSEMSs were successfully placed in all patients through the major (n = 27) or minor (n = 5) duodenal papilla. All patients achieved pain relief from stent placement. There was no occurrence of stent-induced pancreatitis or pancreatic sepsis. No stent migrated, and all stents were easily removed. Follow-up ERCP 3 months after stent placement showed resolution of duct strictures in all patients. Pancreatograms obtained at FCSEMS removal displayed de novo focal pancreatic duct strictures in 5 patients, but all were asymptomatic. No long-term follow-up. Temporary 3-month placement of FCSEMSs was effective in resolving pancreatic-duct strictures in chronic pancreatitis, with an acceptable morbidity profile. Modified FCSEMSs can prevent stent migration, but may be associated with de novo duct strictures. Further trials are needed to assess long-term safety and efficacy. Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

The interaction of long non-coding RNA MIAT and miR-133 play a role in the proliferation and metastasis of pancreatic carcinoma.

PubMed

Li, Ting-Fu; Liu, Jian; Fu, Shi-Jie

2018-05-14

Pancreatic cancer (PC) is one of the most aggressive malignancies in humans. Despite advances in early detection and treatment of PC, the prognosis is still limited. LncRNA myocardial infarction-associated transcript (MIAT) is found abnormally expressed in a variety of cancers. However, the role of MIAT in PC is still unknown. This study aimed to explore whether MIAT was related to the progression of PC and the underlying mechanism. Bioinformatics analysis and luciferase reporter assay validated that miR-133 may target MIAT 3'-UTR. MIAT expression was found remarkably increased and miR-133 expression was significantly decreased in PC tissues and PC cell lines (PATU-8988, BxPC-3, PANC-1, SW1990 and AsPC-1 cells). PC patients with high MIAT level had poor prognosis than that with low MITA level. Besides that, PATU-8988 cells transfected with siMIAT and/or miR-133 inhibitor. The results exhibited that the inhibition of miR-133 expression reversed the inhibition effect of MIAT down-regulation in the growth, migration and invasion of PC cells. Moreover, tumor growth was tremendously suppressed in nude rats received injection of PATU-8988 cells transfected with siMIAT. Taken together, our results suggest that the interaction of MIAT and miR-133 play a role in the proliferation and metastasis of pancreatic carcinoma. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Radiofrequency ablation for unresectable locally advanced pancreatic cancer: a systematic review

PubMed Central

Fegrachi, Samira; Besselink, Marc G; van Santvoort, Hjalmar C; van Hillegersberg, Richard; Molenaar, Izaak Quintus

2014-01-01

Background: Median survival in patients with unresectable locally advanced pancreatic cancer lies in the range of 9–15 months. Radiofrequency ablation (RFA) may prolong survival, but data on its safety and efficacy are scarce. Methods: A systematic literature search was performed in PubMed, EMBASE and the Cochrane Library with the syntax ‘(radiofrequency OR RFA) AND (pancreas OR pancreatic)’ for studies published until 1 January 2012. In addition, a search of the proceedings of conferences on pancreatic disease that took place during 2009–2011 was performed. Studies with fewer than five patients were excluded as they were considered to be case reports. The primary endpoint was survival. Secondary endpoints included morbidity and mortality. Results: Five studies involving a total of 158 patients with pancreatic cancer treated with RFA fulfilled the eligibility criteria. These studies reported median survival after RFA of 3–33 months, morbidity related to RFA of 4–37%, mortality of 0–19% and overall morbidity of 10–43%. Pooling of data was not appropriate as the study populations and reported outcomes were heterogeneous. Crucial safety aspects included ensuring a maximum RFA tip temperature of < 90 °C and ensuring minimum distances between the RFA probe and surrounding structures. Conclusions: Radiofrequency ablation seems to be feasible and safe when it is used with the correct temperature and at an appropriate distance from vital structures. It appears to have a positive impact on survival. Multicentre randomized trials are necessary to determine the true effect size of RFA and to minimize the impacts of selection and publication biases. PMID:23600801

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

The anti-tumor effects of the recombinant toxin protein rLj-RGD3 from Lampetra japonica on pancreatic carcinoma Panc-1 cells in nude mice.

PubMed

Wang, Yue; Zheng, Yuanyuan; Tu, Zuoyu; Dai, Yongguo; Xu, Hong; Lv, Li; Wang, Jihong

2017-02-01

Recombinant Lampetra japonica RGD peptide (rLj-RGD3) is a soluble toxin protein with three RGD (Arg-Gly-Asp) motifs and a molecular weight of 13.5kDa. The aim of this study was to investigate the effects and mechanisms of rLj-RGD3 on tumor growth and survival in pancreatic carcinoma Panc-1 cell-bearing mice. A Panc-1 human pancreatic carcinoma-bearing nude mouse model was successfully generated, and the animals were treated with different doses of rLj-RGD3 for 3 weeks. The volume and weight of the subcutaneous tumors, the survival of the nude mice, histopathological changes, the intratumoral MVD, the number of apoptotic Panc-1 cells, and apoptosis-related proteins and gene expressions were determined. rLj-RGD3 significantly decreased the tumor volumes and weights, and the maximum tumor volume and weight IR values were 53.2% (p<0.001) and 55.9% (p<0.001), respectively. The life expectancy of Panc-1-bearing nude mice treated with rLj-RGD3 was increased by 56.3% (p<0.001). Meanwhile, rLj-RGD3 promoted the expression of Bax, caspase-3, and caspase-9 and inhibited Bcl-2 and VEGF expression. In addition, rLj-RGD3 did not change FAK, PI3K and Akt expression, but p-FAK, p-PI3K and p-Akt, levels were down-regulated. These results show that rLj-RGD3 induced potent anti-tumor activity in vivo and suppressed the growth of transplanted Panc-1 cells in a nude mouse model, implying that rLj-RGD3 may serve as a potent clinical therapeutic agent for human pancreatic carcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

The specific localization of advanced glycation end-products (AGEs) in rat pancreatic islets.

PubMed

Morioka, Yuta; Teshigawara, Kiyoshi; Tomono, Yasuko; Wang, Dengli; Izushi, Yasuhisa; Wake, Hidenori; Liu, Keyue; Takahashi, Hideo Kohka; Mori, Shuji; Nishibori, Masahiro

2017-08-01

Advanced glycation end-products (AGEs) are produced by non-enzymatic glycation between protein and reducing sugar such as glucose. Although glyceraldehyde-derived AGEs (Glycer-AGEs), one of the AGEs subspecies, have been reported to be involved in the pathogenesis of various age-relating diseases such as diabetes mellitus or arteriosclerosis, little is known about the pathological and physiological mechanism of AGEs in vivo. In present study, we produced 4 kinds of polyclonal antibodies against AGEs subspecies and investigated the localization of AGEs-modified proteins in rat peripheral tissues, making use of these antibodies. We found that Glycer-AGEs and methylglyoxal-derived AGEs (MGO-AGEs) were present in pancreatic islets of healthy rats, distinguished clearly into the pancreatic α and β cells, respectively. Although streptozotocin-induced diabetic rats suffered from remarkable impairment of pancreatic islets, the localization and deposit levels of the Glycer- and MGO-AGEs were not altered in the remaining α and β cells. Remarkably, the MGO-AGEs in pancreatic β cells were localized into the insulin-secretory granules. These results suggest that the cell-specific localization of AGEs-modified proteins are presence generally in healthy peripheral tissues, involved in physiological intracellular roles, such as a post-translational modulator contributing to the secretory and/or maturational functions of insulin. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Pancreatic Calculus Causing Biliary Obstruction: Endoscopic Therapy for a Rare Initial Presentation of Chronic Pancreatitis.

PubMed

Shetty, Anurag J; Pai, C Ganesh; Shetty, Shiran; Balaraju, Girisha

2015-09-01

Biliary obstruction in chronic calcific pancreatitis (CCP) is often caused by inflammatory or fibrotic strictures of the bile duct, carcinoma of head of pancreas or less commonly by compression from pseudocysts. Pancreatic calculi causing ampullary obstruction and leading to obstructive jaundice is extremely rare. The medical records of all patients with CCP or biliary obstruction who underwent endoscopic retrograde cholangiopancreatography (ERCP) over 4 years between 2010-2014 at Kasturba Medical College, Manipal were analyzed. Five patients of CCP with impacted pancreatic calculi at the ampulla demonstrated during ERCP were identified. All 5 presented with biliary obstruction and were incidentally detected to have CCP when evaluated for the same; 3 patients had features of cholangitis. All the patients were managed successfully by endoscopic papillotomy and extraction of pancreatic calculi from the ampulla with resolution of biliary obstruction. Pancreatic calculus causing ampullary obstruction, though very rare, should be considered as a possibility in patients with CCP complicated by biliary obstruction. Endoscopic therapy is affective in the resolution of biliary obstruction in such patients.

Phase II Study of Oral S-1 and Concurrent Radiotherapy in Patients With Unresectable Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sudo, Kentaro, E-mail: kentarosudo9@yahoo.co.j; Yamaguchi, Taketo; Ishihara, Takeshi

2011-05-01

Purpose: S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer. The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day at a dose of 80 mg/m{sup 2}/day from day 1 to 14 and 22 to 35. Two weeksmore » after the completion of chemoradiotherapy, maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression. Results: Thirty-four patients were enrolled in this study. The most common Grade 3 toxicities during chemoradiotherapy were anorexia (24%) and nausea (12%). The overall response rate was 41% (95% confidence interval, 25%-58%) and overall disease control rate (partial response plus stable disease) was 97%. More than 50% decrease in serum CA 19-9 was seen in 27 of 29 evaluable patients (93%). The median progression-free survival was 8.7 months. The median overall survival and 1-year survival rate were 16.8 months and 70.6%, respectively. Conclusions: Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer. This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion.« less

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

ClinicalTrials.gov

2017-10-25

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

A Pilot Trial of Early Specialty Palliative Care for Patients with Advanced Pancreatic Cancer: Challenges Encountered and Lessons Learned.

PubMed

Schenker, Yael; Bahary, Nathan; Claxton, Rene; Childers, Julie; Chu, Edward; Kavalieratos, Dio; King, Linda; Lembersky, Barry; Tiver, Greer; Arnold, Robert M

2018-01-01

Patients with advanced pancreatic cancer suffer from high morbidity and mortality. Specialty palliative care may improve quality of life. Assess the feasibility, acceptability, and perceived effectiveness of early specialty physician-led palliative care for patients with advanced pancreatic cancer and their caregivers. A mixed-methods pilot randomized controlled trial in which patient-caregiver pairs were randomized (2:1) to receive specialty palliative care, in addition to standard oncology care versus standard oncology care alone. At a National Cancer Institute-designated comprehensive cancer center in Western Pennsylvania, 30 patients with advanced pancreatic adenocarcinoma and their caregivers (N = 30), oncologists (N = 4), and palliative care physicians (N = 3) participated. Feasibility (enrollment, three-month outcome-assessment, and intervention completion rates), acceptability, and perceived effectiveness (process interviews with patients, caregivers, and physicians). Consent:approach rate was 49%, randomized:consent rate 55%, and three-month outcome assessment rate 75%. Two patients and three caregivers withdrew early. The three-month mortality rate was 13%. Patients attended a mean of 1.3 (standard deviation 1.1) palliative care visits during the three-month period. Positive experiences with palliative care included receiving emotional support and symptom management. Negative experiences included inconvenience, long travel times, spending too much time at the cancer center, and no perceived palliative care needs. Physicians suggested embedding palliative care within oncology clinics, tailoring services to patient needs, and facilitating face-to-face communication between oncologists and palliative physicians. A randomized trial of early palliative care for advanced pancreatic cancer did not achieve feasibility goals. Integrating palliative care within oncology clinics may increase acceptability and perceived effectiveness.

[A Case of Pancreatic Head Cancer Treated with Pancreaticoduodenectomy Combined with Hepatic Artery Resection Following Neoadjuvant Chemotherapy].

PubMed

Maeda, Shintaro; Takano, Shigetsugu; Shimizu, Hiroaki; Ohtsuka, Masayuki; Kato, Atsushi; Yoshitomi, Hideyuki; Furukawa, Katsunori; Takayashiki, Tsukasa; Kuboki, Satoshi; Suzuki, Daisuke; Sakai, Nozomu; Kagawa, Shingo; Miyazaki, Masaru

2015-11-01

A 70-year-old woman was diagnosed with pancreatic head cancer with hepatic artery invasion by multi-detector computed tomography (MD-CT). After 3 courses of gemcitabine plus S-1 neoadjuvant therapy, the tumor size was not diminished; however, the tumor marker CA19-9 level was decreased to less than 90% of its initial level. Pancreaticoduodenectomy combined with hepatic artery resection was performed, and an end-to-end anastomosis was made between the common and proper hepatic artery to reconstruct the hepatic artery. The pathological examination indicated adenosquamous carcinoma, no vascular invasion, and negative margin status, and the efficacy of chemotherapy was classified as GradeⅡb using Evans' classification. Usually, pancreatic head cancer with hepatic artery invasion is considered unresectable due to its high morbidity/mortality and poor prognosis. However, with the recently developed surgical strategy and appropriate therapeutic interventions, such as a combination of neoadjuvant chemotherapy and resection/reconstruction of the hepatic artery, a curative operation can be feasible for locally advanced pancreatic head cancer.

Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis.

PubMed

Kudo, Yujin; Kamisawa, Terumi; Anjiki, Hajime; Takuma, Kensuke; Egawa, Naoto

2011-01-01

Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. This study aimed to identify risk factors for developing pancreatic cancer associated with chronic pancreatitis. The incidence of pancreatic cancer developing in 218 patients with chronic pancreatitis and clinical features of the chronic pancreatitis patients who developed pancreatic cancer were studied. Nine patients developed pancreatic cancer. Average period from the diagnosis of chronic pancreatitis to the diagnosis of pancreatic cancer was 9.6 years. All pancreatic cancers were diagnosed at an advanced stage. Only 2 patients had been followed-up periodically. There were no significant differences between chronic pancreatitis patients who developed pancreatic cancer and those who did not in male/female ratio (3.5 vs. 8), average age on diagnosis (65.0 vs. 56.5), alcoholic/non-alcoholic chronic pancreatitis (1.6 vs. 2.6), smoking habits (62.5% vs. 70.7%), diabetes mellitus (77.8% vs. 54.4%), and continued alcohol drinking (37.5% vs. 53.1%). Over the period examined, 4% of chronic pancreatitis patients developed pancreatic cancer. Sex ratio, onset age, etiology, smoking habits, diabetes mellitus, and continued alcohol drinking were not significant risk factors for developing pancreatic cancer in chronic pancreatitis patients. Periodic follow-up due to the possibility of pancreatic cancer is necessary in chronic pancreatitis patients.

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

Supportive and palliative care of pancreatic cancer.

PubMed

Fazal, Salman; Saif, Muhammad Wasif

2007-03-10

Pancreatic cancer is one of the most lethal malignancies. An estimated 32,300 patients will die of pancreatic cancer in year 2006. It is the tenth most common malignancy in the United States. Despite recent advances in pathology, molecular basis and treatment, the overall survival rate remains 4% for all stages and races. Palliative care represents an important aspect of care in patient with pancreatic malignancy. Identifying and treating disease related symptomology are priorities. As a physician taking care of these patients it is essential to know these symptoms and treatment modalities. This review discusses symptom management and supportive care strategies. Common problems include pain, intestinal obstruction, biliary obstruction, pancreatic insufficiency, anorexia-cachexia and depression. Success is needed in managing these symptoms to palliate patients with advanced pancreatic cancer. Pancreatic cancer is a model illness to learn the palliative and supportive management in cancer patient. It is important for oncologists to recognize the importance of control measures and supportive measures that can minimize the symptoms of advanced disease and side effects of cancer treatment.

Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

PubMed

Thigpen, T; Brady, M F; Homesley, H D; Soper, J T; Bell, J

2001-01-15

In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents.

Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

ClinicalTrials.gov

2018-03-08

Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer

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. © 2015 Zambirinis et al.

Advances in the endoscopic management of pancreatic collections.

PubMed

Ruiz-Clavijo, David; de la Higuera, Belen González; Vila, Juan J

2015-04-16

Treatment of pancreatic collections has experienced great progress in recent years with the emergence of alternative minimally invasive techniques comparing to the classic surgical treatment. Such techniques have been shown to improve outcomes of morbidity vs surgical treatment. The recent emergence of endoscopic drainage is noteworthy. The advent of endoscopic ultrasonography has been crucial for treatment of these specific lesions. They can be characterized, their relationships with neighboring structures can be evaluated and the drainage guided by this technique has been clearly improved compared with the conventional endoscopic drainage. Computed tomography is the technique of choice to characterize the recently published new classification of pancreatic collections. For this reason, the radiologist's role establishing and classifying in a rigorously manner the collections according to the new nomenclature is essential to making therapeutic decisions. Ideal scenario for comprehensive treatment of these collections would be those centers with endoscopic ultrasound and interventional radiology expertise together with hepatobiliopancreatic surgery. This review describes the different types of pancreatic collections: acute peripancreatic fluid collection, pancreatic pseudocysts, acute necrotic collection and walled-off necrosis; the indications and the contraindications for endoscopic drainage, the drainage technique and their outcomes. The integrated management of pancreatic collections according to their type and evolution time is discussed.

Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium

PubMed Central

Wroblewski, Kristen; Wallace, James A.; Hall, Michael J.; Locker, Gershon; Nattam, Sreenivasa; Agamah, Edem; Stadler, Walter M.; Vokes, Everett E.

2015-01-01

Summary Background Sorafenib, an inhibitor of B-raf, VEGFR2, and PDGFR-β, has activity against pancreatic cancer in preclinical models. In a phase I trial of gemcitabine plus sorafenib, 57% of pancreatic cancer patients achieved stable disease. Patients and methods We conducted a multi-center phase II trial of sorafenib plus gemcitabine in chemo-naïve patients with histologicallyconfirmed, advanced pancreatic cancer. Patients received sorafenib 400 mg twice daily and gemcitabine 1,000 mg/m2 on days 1, 8 and 15 of a 28 day cycle. Results Seventeen patients enrolled at 4 centers; 13 were evaluable for response. There were no objective responses; 18% had stable disease. Median overall survival was 4.0 months (95% CI: 3.4, 5.9); median progression-free survival was 3.2 months (95% CI: 1.6, 3.6). Grade 3/4 toxicities included thrombosis in 18% of patients, dehydration or hand-foot syndrome in 12%, and hypertension or gastrointestinal bleeding in 6%. Conclusion Gemcitabine plus sorafenib is inactive in advanced pancreatic cancer. PMID:20803052

Culturing primary mouse pancreatic ductal cells.

PubMed

Reichert, Maximilian; Rhim, Andrew D; Rustgi, Anil K

2015-06-01

The most common subtype of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). PDAC resembles ductal cells morphologically. To study pancreatic ductal cell (PDC) and pancreatic intraepithelial neoplasia (PanIN)/PDAC biology, it is essential to have reliable in vitro culture conditions. Here we describe a methodology to isolate, culture, and passage PDCs and duct-like cells from the mouse pancreas. It can be used to isolate cells from genetically engineered mouse models (GEMMs), providing a valuable tool to study disease models in vitro to complement in vivo findings. The culture conditions allow epithelial cells to outgrow fibroblast and other "contaminating" cell types within a few passages. However, the resulting cultures, although mostly epithelial, are not completely devoid of fibroblasts. Regardless, this protocol provides guidelines for a robust in vitro culture system to isolate, maintain, and expand primary pancreatic ductal epithelial cells. It can be applied to virtually all GEMMs of pancreatic disease and other diseases and cancers that arise from ductal structures. Because most carcinomas resemble ductal structures, this protocol has utility in the study of other cancers in addition to PDAC, such as breast and prostate cancers. © 2015 Cold Spring Harbor Laboratory Press.

Challenges of advanced hepatocellular carcinoma

PubMed Central

Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

2016-01-01

Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

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

New Insights into the Pathogenesis of Pancreatitis

PubMed Central

Sah, Raghuwansh P.; Dawra, Rajinder K.; Saluja, Ashok K.

2014-01-01

Purpose of review In this article, we review important advances in our understanding of the mechanisms of pancreatitis. Recent Findings The relative contribution of intra-pancreatic trypsinogen activation and NFκB activation, the two major early independent cellular events in the etiology of pancreatitis, have been investigated using novel genetic models. Trypsinogen activation has traditionally held the spotlight for many decades as it is believed to be the central pathogenic event of pancreatitis However, recent experimental evidence points to the role of trypsin activation in early acinar cell damage but not in the inflammatory response of acute pancreatitis through NFκB activation. Further, chronic pancreatitis in the caerulein model develops independently of typsinogen activation. Sustained activation of the NFκB pathway, but not persistent intra-acinar expression of active trypsin, was shown to result in chronic pancreatitis. Calcineurin-NFAT signaling was shown to mediate downstream effects of pathologic rise in intracellular calcium. IL-6 was identified as a key cytokine mediating pancreatitis-associated lung injury. Summary Recent advances challenge the long-believed trypsin-centered understanding of pancreatitis. It is becoming increasingly clear that activation of intense inflammatory signaling mechanisms in acinar cells is crucial to the pathogenesis of pancreatitis, which may explain the strong systemic inflammatory response in pancreatitis. PMID:23892538

Treatment outcomes in locally advanced colorectal carcinoma

PubMed Central

Harish, K; Narayanaswamy, YV; Nirmala, S

2004-01-01

Background Locally advanced colorectal cancers form a distinct subgroup where contiguous organs could be involved without distant metastases and so may be amenable to curative surgical resection. It was our objective to report our experience in treating six such patients with operable locally advanced colorectal carcinomas. Methods We retrospectively reviewed the case notes of 47 patients who were diagnosed with colorectal cancers at M S Ramaiah Medical Teaching Hospital between the years 1996 – 2001. Six patients were identified with T4 lesions, adjacent organ involvement and with no nodal involvement. The treatments and outcomes for these patients were then reviewed. Results Two of three patients with rectal malignancies who underwent pelvic exenteration succumbed to disease recurrence within the first 18 months. One of the three patients with colonic cancers died of non malignant causes. The other two are disease free till date. Conclusions Aggressive multivisceral resections for locally advanced colonic cancers might be appropriate. Rectal cancers when locally advanced may be considered for pelvic exenteration, but a more guarded prognosis may apply. PMID:15527504

Apatinib concurrent gemcitabine for controlling malignant ascites in advanced pancreatic cancer patient: A case report.

PubMed

Liang, Lijun; Wang, Lei; Zhu, Panrong; Xia, Youyou; Qiao, Yun; Hui, Kaiyuan; Hu, Chenxi; Ren, Yan; Jiang, Xiaodong

2017-11-01

Malignant ascites (MA) is one of the poor prognostic factors for advanced pancreatic cancer and can bring about serious symptoms. The improvement of quality of life for patients is priority. However, there is no standard method for the treatment for pancreatic cancer-mediated MA. Apatinib is a novel and highly selective tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. There are no reports of concurrent apatinib with gemcitabine in patients with pancreatic cancer-mediated MA. Herein, we presented a 64-year-old man patient who visited hospital due to abdominal pain for 1 month. He was initially diagnosed with pancreatic cancer and his first symptom was MA. After failing in tube drainage and gemcitabine therapy, the patient received gemcitabine combined apatinib orally and after administrated 1 month, the MA was evaluated as nearly clear response according to the RECIST 1.1 standard, and without further need of paracentesis. The CEA and CA199 reached the lowest level after administrating for 2.5 months during the treatment process. 10.5 months following apatinib administration, the patient achieved a progression-free survival for more than 11 months. Hypertension (grade IV), hand-foot syndrome (grade I) and proteinuria (grade II) were observed. It indicated that apatinib concurrent gemcitabine may be a superior choice for pancreatic cancer-mediated MA. Further clinical trials required to confirm its efficacy and safety. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

English language version of the S3-consensus guidelines on chronic pancreatitis: Definition, aetiology, diagnostic examinations, medical, endoscopic and surgical management of chronic pancreatitis.

PubMed

Hoffmeister, A; Mayerle, J; Beglinger, C; Büchler, M W; Bufler, P; Dathe, K; Fölsch, U R; Friess, H; Izbicki, J; Kahl, S; Klar, E; Keller, J; Knoefel, W T; Layer, P; Loehr, M; Meier, R; Riemann, J F; Rünzi, M; Schmid, R M; Schreyer, A; Tribl, B; Werner, J; Witt, H; Mössner, J; Lerch, M M

2015-12-01

Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy. © Georg Thieme Verlag KG Stuttgart · New York.

Screening for Pancreatic Cancer

PubMed Central

Brand, Randall E.

2007-01-01

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

Management of acute pancreatitis in children.

PubMed

Abu-El-Haija, Maisam; Lin, Tom K; Nathan, Jaimie D

2017-10-01

Pediatric acute pancreatitis has been on the rise in the last decades, with an incidence close to adult pancreatitis. In the majority of cases acute pancreatitis resolves spontaneously, but in a subset of children the disease progresses to severe acute pancreatitis with attendant morbidity and mortality. Pediatric acute pancreatitis in this era is recognized as a separate entity from adult acute pancreatitis given that the causes and disease outcomes are different. There are slow but important advances made in understanding the best management for acute pancreatitis in children from medical, interventional, and surgical aspects. Supportive care with fluids, pain medications, and nutrition remain the mainstay for acute pancreatitis management. For complicated or severe pancreatitis, specialized interventions may be required with endoscopic or drainage procedures. Surgery has an important but limited role in pediatric acute pancreatitis.

TAS102 in Combination With NAL-IRI in Advanced GI Cancers

ClinicalTrials.gov

2018-03-29

Colorectal Adenocarcinoma; Gastric Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer; Unresectable Pancreatic Carcinoma

Response to apatinib in chemotherapy-failed advanced spindle cell breast carcinoma.

PubMed

Zhou, Na; Liu, Congmin; Hou, Helei; Zhang, Chuantao; Liu, Dong; Wang, Guanqun; Liu, Kewei; Zhu, Jingjuan; Lv, Hongying; Li, Tianjun; Zhang, Xiaochun

2016-11-01

Spindle cell carcinoma of the breast is a rare subtype of metaplastic carcinoma, and no effective chemotherapy special for metaplastic carcinoma exists until now. As spindle cell carcinomas of the breast are typically "Triple Negative", endocrine therapy and molecular therapy targeted to Her2 might not be favorable, resulting in poor prognosis. Apatinib is currently being tested in patients with breast or lung cancers. Here we report a successful case using Apatinib to treat spindle cell carcinoma of breast.A 52- year- old woman presented with a gradually enlarged lump in left breast, which was revealed to be a triple-negative spindle cell carcinoma, underwent a modified radical mastectomy. After the first line chemotherapy with Cyclophosphamide and Epirubicin, multiple metastases in bilateral lung and left anterior thoracic wall appeared. After disease progressed with therapy of Bevacizumab combined with Albumin-bound Paclitaxel and Cisplatin, we treated the patient with Apatinib according to her VEGFR expression, which showed nearly complete response and controllable and tolerated side effects. Next-generation sequencing analysis of the tumor specimen and real time ctDNA was performed to observe the mutated gene numbers matched with therapeutic effect. The present case can help to provide a new and effective therapy strategy to treat advanced spindle cell carcinoma.

Response to apatinib in chemotherapy-failed advanced spindle cell breast carcinoma

PubMed Central

Zhou, Na; Liu, Congmin; Hou, Helei; Zhang, Chuantao; Liu, Dong; Wang, Guanqun; Liu, Kewei; Zhu, Jingjuan; Lv, Hongying; Li, Tianjun; Zhang, Xiaochun

2016-01-01

Spindle cell carcinoma of the breast is a rare subtype of metaplastic carcinoma, and no effective chemotherapy special for metaplastic carcinoma exists until now. As spindle cell carcinomas of the breast are typically “Triple Negative”, endocrine therapy and molecular therapy targeted to Her2 might not be favorable, resulting in poor prognosis. Apatinib is currently being tested in patients with breast or lung cancers. Here we report a successful case using Apatinib to treat spindle cell carcinoma of breast. A 52- year- old woman presented with a gradually enlarged lump in left breast, which was revealed to be a triple-negative spindle cell carcinoma, underwent a modified radical mastectomy. After the first line chemotherapy with Cyclophosphamide and Epirubicin, multiple metastases in bilateral lung and left anterior thoracic wall appeared. After disease progressed with therapy of Bevacizumab combined with Albumin-bound Paclitaxel and Cisplatin, we treated the patient with Apatinib according to her VEGFR expression, which showed nearly complete response and controllable and tolerated side effects. Next-generation sequencing analysis of the tumor specimen and real time ctDNA was performed to observe the mutated gene numbers matched with therapeutic effect. The present case can help to provide a new and effective therapy strategy to treat advanced spindle cell carcinoma. PMID:27738308

Pancreatic sarcoidosis discovered during Whipple procedure.

PubMed

Cook, Jonathan; Spees, Tanner; Telefus, Phillip; Ranaudo, Jeffrey M; Carryl, Stephen; Xiao, Philip

2013-04-04

Pancreatic sarcoidosis is a rare variant of systemic sarcoidosis, with cases described in literature as recently as January 2010. We present here a case of pancreatic involvement with non-caseating granulomas discovered on laparotomy in a patient with a preoperative diagnosis of pancreatic carcinoma. Computer tomography scan without contrast revealed a well-marginated smooth-shaped tumor in the head of the pancreas morphologically consistent with malignancy. During Whipple procedure, the mass was found to be a large lymph node that contained numerous non-caseating granulomas. Radiologically and clinically, non-caseating granulomas of the pancreas are often misdiagnosed as malignant tumor. Special attention given to this differential diagnosis by surgeons, pathologists and clinicians can avoid misdiagnosis and unnecessary treatment. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2013.

Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions.

PubMed

Beger, Hans G; Schwarz, Michael; Poch, Bertram

2012-11-01

Cystic neoplasms of the pancreas are diagnosed frequently due to early use of abdominal imaging techniques. Intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and serous pseudopapillary neoplasia are considered pre-cancerous lesions because of frequent transformation to cancer. Complete surgical resection of the benign lesion is a pancreatic cancer preventive treatment. The application for a limited surgical resection for the benign lesions is increasingly used to reduce the surgical trauma with a short- and long-term benefit compared to major surgical procedures. Duodenum-preserving total pancreatic head resection introduced for inflammatory tumors in the pancreatic head transfers to the patient with a benign cystic lesion located in the pancreatic head, the advantages of a minimalized surgical treatment. Based on the experience of 17 patients treated for cystic neoplastic lesions with duodenum-preserving total pancreatic head resection, the surgical technique of total pancreatic head resection for adenoma, borderline tumors, and carcinoma in situ of cystic neoplasm is presented. A segmental resection of the peripapillary duodenum is recommended in case of suspected tissue ischemia of the peripapillary duodenum. In 305 patients, collected from the literature by PubMed search, in about 40% of the patients a segmental resection of the duodenum and 60% a duodenum and common bile duct-preserving total pancreatic head resection has been performed. Hospital mortality of the 17 patients was 0%. In 305 patients collected, the hospital mortality was 0.65%, 13.2% experienced a delay of gastric emptying and a pancreatic fistula in 18.2%. Recurrence of the disease was 1.5%. Thirty-two of 175 patients had carcinoma in situ. Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions is a safe surgical procedure with low post-operative morbidity and mortality.

The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis.

PubMed

Tong, Hongxuan; Fan, Zhu; Liu, Biyuan; Lu, Tao

2018-06-06

FOLFIRINOX has been one of the first-line options for advanced pancreatic cancer, even though it induces significant adverse effects. Several institutions have begun using modified FOLFIRINOX to decrease its side effects and increase its tolerability. We systematically investigated the outcome from patients who initially received modified FOLFIRINOX as a chemotherapy regimen for advanced pancreatic cancer. We used the random-model generic inverse variance method to analyse the binary data with 95% confidence intervals (CIs). Eleven studies were included in the meta-analysis with 563 total patients. The 6-month and 1-year overall survival (OS) rates of locally advanced pancreatic cancer (LAPC) were 90.9% and 76.2%. The 6-month and 1-year progression-free survival (PFS) rates of LAPC were 81.5% and 48.5%. The 6-month and 1-year OS rates of metastatic pancreatic cancer (MPC) were 79.7% and 47.6%. The 6-month and 1-year PFS rates of MPC were 56.3% and 20.6%. The following rates were also calculated: complete response rate (CR): 2.9%; partial response rate (PR): 35.9%; stable disease rate (SD): 41.2%; overall response rate (OR): 34.6%; disease control rate (DCR): 76.7%; progressive disease: 23.1%; and grade III/IV adverse events (AEs): neutropenia 23.1%, febrile neutropenia 4.8%, thrombocytopenia 4.8%, anaemia 5.7%, fatigue 11.5%, nausea 9.1%, diarrhoea 10.1%, vomiting 5.7%, neuropathy 3.8%, and increased ALT 5.7%. In conclusion, modified FOLFIRINOX could provide comparative survival benefits with fewer adverse events compared to the conventional dosage.

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

PubMed

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

2017-02-14

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

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

PubMed

Meesiri, Somchai

2012-02-21

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

Chronic pancreatitis: diagnosis, classification, and new genetic developments.

PubMed

Etemad, B; Whitcomb, D C

2001-02-01

The utilization of recent advances in molecular and genomic technologies and progress in pancreatic imaging techniques provided remarkable insight into genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis. Translation of these advances into clinical practice demands a reassessment of current approaches to diagnosis, classification, and staging. We conclude that an adequate pancreatic biopsy must be the gold standard against which all diagnostic approaches are judged. Although computed tomography remains the initial test of choice for the diagnosis of chronic pancreatitis, the roles of endoscopic retrograde pancreatography, endoscopic ultrasonography, and magnetic resonance imaging are considered. Once chronic pancreatitis is diagnosed, proper classification becomes important. Major predisposing risk factors to chronic pancreatitis may be categorized as either (1) toxic-metabolic, (2) idiopathic, (3) genetic, (4) autoimmune, (5) recurrent and severe acute pancreatitis, or (6) obstructive (TIGAR-O system). After classification, staging of pancreatic function, injury, and fibrosis becomes the next major concern. Further research is needed to determine the clinical and natural history of chronic pancreatitis developing in the context of various risk factors. New methods are needed for early diagnosis of chronic pancreatitis, and new therapies are needed to determine whether interventions will delay or prevent the progression of the irreversible damage characterizing end-stage chronic pancreatitis.

Effective multimodality treatment for advanced epidermoid carcinoma of the female genital tract

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalra, J.; Cortes, E.; Chen, S.

1985-07-01

Fifteen patients with advanced or recurrent squamous-cell carcinoma of the cervix, vulva, vagina, and urethra were treated with simultaneous combination chemotherapy (5-fluorouracil infusion and mitomycin C) and radiotherapy (3,000 rad for a period of three weeks). Three to four weeks after completion of radiotherapy, 13 of 15 patients achieved partial or complete tumor shrinkage. Nine of 15 patients are alive, eight of whom (at a median follow-up time of 24 months) have no evidence of disease. The longest survival time was 45 + months. There was minimal toxicity associated with this therapy. The results of this pilot study suggest thatmore » the simultaneous administration of radiation and chemotherapy is an effective method of treatment of advanced female genital tract carcinoma.« less

State-of-the-art magnetic resonance imaging of pancreatic cancer.

PubMed

Schima, Wolfgang; Ba-Ssalamah, Ahmed; Goetzinger, Peter; Scharitzer, Martina; Koelblinger, Claus

2007-12-01

Technical advances of magnetic resonance imaging (MRI), including ultrahigh-field magnetic resonance at 3.0 T, parallel imaging techniques, and multichannel receive coils of the abdomen, have promoted MRI of the pancreas. For adenocarcinoma, which is the most common malignant pancreatic tumor, helical CT has been most often used for detection and staging, but it has limitations in the detection of small cancers 2 cm in diameter or less (sensitivity, 63%). Moreover, it is not very accurate in determining nonresectability, because small liver metastases, peritoneal carcinomatosis, and subtle signs of vascular infiltration may be missed. At ultrahigh field at 3.0 T, gadolinium-enhanced MRI using volume-interpolated 3-dimensional gradient-recalled echo pulse sequences with near-isotropic voxels are very useful for detection of subtle abnormalities. Mangafodipir-enhanced MRI reveals a very high tumor-pancreas contrast, which helps to diagnose small cancers. Contrast-enhanced MRI is a problem-solving tool in case of equivocal CT: it helps to differentiate between cancer and focal pancreatitis. Neuroendocrine carcinoma may present with a spectrum of appearances at MRI, but the primary tumor and liver metastases are hypervascular in approximately 70%. In this article, pancreas imaging protocols for 1.5 and 3.0 T are explained. We present the imaging features of pancreatic cancer and the important questions in staging, which should be addressed by the radiologist.

Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sudo, Kentaro; Yamaguchi, Taketo; Ishihara, Takeshi

Purpose: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m{sup 2}/day. Results: Sixteen patients were enrolled in this study. Three patients received S-1more » at 60 mg/m{sup 2}/day, 3 at 70 mg/m{sup 2}/day, and 10 at 80 mg/m{sup 2}/day. Though 1 patient at the final dose level (80 mg/m{sup 2}/day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. Conclusions: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m{sup 2}/day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated.« less

The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth of colon carcinoma in the liver.

PubMed

Meijer, Joost; Zeelenberg, Ingrid S; Sipos, Bence; Roos, Ed

2006-10-01

The chemokine receptor CXCR5 is expressed by B cells and certain T cells and controls their migration into and within lymph nodes. Its ligand BCA-1/CXCL13 is present in lymph nodes and spleen and also in the liver. Surprisingly, we detected CXCR5 in several mouse and human carcinoma cell lines. CXCR5 was particularly prominent in pancreatic carcinoma cell lines and was also detected by immunohistochemistry in 7 of 18 human pancreatic carcinoma tissues. Expression in CT26 colon carcinoma was low in vitro, up-regulated in vivo, and rapidly lost when cells were explanted in vitro. CXCL13 strongly promoted proliferation of CXCR5-transfected CT26 cells in vitro. In the liver, after intrasplenic injection, these CXCR5 transfectants initially grew faster than controls, but the growth rate of control tumors accelerated later to become similar to the transfectants, likely due to the up-regulation of CXCR5. Inhibition of CXCR5 function, by trapping CXCR5 in the endoplasmic reticulum using a CXCL13-KDEL "intrakine," had no effect on initial growth of liver foci but later caused a prolonged growth arrest. In contrast, s.c. and lung tumors of CXCR5- and intrakine-transfected cells grew at similar rates as controls. We conclude that expression of CXCR5 on tumor cells promotes the growth of tumor cells in the liver and, at least for CT26 cells, seems to be required for outgrowth to large liver tumors. Given the limited expression on normal cells, CXCR5 may constitute an attractive target for therapy, particularly for pancreatic carcinoma.

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

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

PubMed

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

2014-12-11

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

Recent advances in 3D computed tomography techniques for simulation and navigation in hepatobiliary pancreatic surgery.

PubMed

Uchida, Masafumi

2014-04-01

A few years ago it could take several hours to complete a 3D image using a 3D workstation. Thanks to advances in computer science, obtaining results of interest now requires only a few minutes. Many recent 3D workstations or multimedia computers are equipped with onboard 3D virtual patient modeling software, which enables patient-specific preoperative assessment and virtual planning, navigation, and tool positioning. Although medical 3D imaging can now be conducted using various modalities, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasonography (US) among others, the highest quality images are obtained using CT data, and CT images are now the most commonly used source of data for 3D simulation and navigation image. If the 2D source image is bad, no amount of 3D image manipulation in software will provide a quality 3D image. In this exhibition, the recent advances in CT imaging technique and 3D visualization of the hepatobiliary and pancreatic abnormalities are featured, including scan and image reconstruction technique, contrast-enhanced techniques, new application of advanced CT scan techniques, and new virtual reality simulation and navigation imaging. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Association between protein C levels and mortality in patients with advanced prostate, lung and pancreatic cancer.

PubMed

Wilts, I T; Hutten, B A; Meijers, J C M; Spek, C A; Büller, H R; Kamphuisen, P W

2017-06-01

Procoagulant factors promote cancer progression and metastasis. Protein C is involved in hemostasis, inflammation and signal transduction, and has a protective effect on the endothelial barrier. In mice, administration of activated protein C reduced experimental metastasis. We assessed the association between protein C and mortality in patients with three types of cancer. The study population consisted of patients with advanced prostate, non-small cell lung or pancreatic cancer, who participated in the INPACT trial (NCT00312013). The trial evaluated the addition of nadroparin to chemotherapy in patients with advanced malignancy. Patients were divided into tertiles based on protein C at baseline. The association between protein C levels and mortality was evaluated with Cox proportional hazard models. We analysed 477 patients (protein C tertiles: <97, 97-121 and ≥121%). Mean age was 65±9years; 390 (82%) were male; 191 patients (40%) had prostate cancer, 161 (34%) had lung cancer, and 125 (26%) pancreatic cancer. During a median follow-up of 10.4months, 291 patients (61%) died. Median protein C level was 107% (IQR 92-129). In the lowest tertile, 75 patients per 100 patient-years died, as compared to 60 and 54 in the middle and high tertile, respectively. Lower levels of protein C were associated with increased mortality (in tertiles: HR for trend 1.18, 95%CI 1.02-1.36, adjusted for age, sex and nadroparin use; as a continuous variable: HR 1.004, 95%CI 1.00-1.008, p=0.07). Protein C seems inversely associated with mortality in patients with advanced prostate, lung and pancreatic cancer. Further research should validate protein C as a biomarker for mortality, and explore the effects of protein C on progression of cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, P.-I.; National Yang-Ming University School of Medicine, Taipei, Taiwan; Chao, Yee

Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m{sup 2}/wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m{sup 2}) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- andmore » 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p < 0.001). The responders had a better Karnofsky performance status (KPS) (86 {+-} 2 vs. 77 {+-} 2, p = 0.002) and had received a greater GEM dose intensity (347 {+-} 13 mg/m{sup 2}/wk vs. 296 {+-} 15 mg/m{sup 2}/wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP.« less

Radioembolization in Advanced Hepatocellular Carcinoma.

PubMed

Riaz, Ahsun; Lewandowski, Robert; Salem, Riad

2018-05-02

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 68-year-old man with a remote history of alcohol abuse presented with vague abdominal pain. A review of systems suggested the patient had an Eastern Cooperative Oncology Group performance status 1 (restriction of strenuous physical activity). There were no physical examination findings of note. Laboratory studies disclosed Child-Pugh A liver status (no ascites; no encephalopathy; total bilirubin, 1 mg/dL; albumin, 3.5 g/dL; and international normalized rato, 1.2). The alpha-fetoprotein was mildly elevated (19.5 ng/mL). Magnetic resonance imaging with contrast disclosed an infiltrative mass with extensive malignant right and left portal vein thrombosis ( Fig 1A ) with cavernous transformation of the portal vein. The infiltrative mass ( Fig 2A ) was biopsied, revealing hepatocellular carcinoma. No distant metastases were found on a bone scintigraphy or computerized tomography scan. Given these features, this patient was classified as Barcelona Clinic for Liver Cancer stage C. The patient was referred for management of advanced hepatocellular carcinoma.

Middle-preserving pancreatectomy for advanced transverse colon cancer invading the duodenun and non-functioning endocrine tumor in the pancreatic tail.

PubMed

Noda, Hiroshi; Kato, Takaharu; Kamiyama, Hidenori; Toyama, Nobuyuki; Konishi, Fumio

2011-02-01

A 73-year-old female was referred to our hospital with a diagnosis of advanced transverse colon cancer with severe anemia and body weight loss. Preoperative evaluations, including colonoscopy, gastroduodenoscopy, and computed tomography, revealed not only a transverse colon cancer massively invading the duodenum, but also a non-functioning endocrine tumor in the pancreatic tail. We performed middle-preserving pancreatectomy (MPP) with right hemicolectomy for these tumors with a curative intent. After the resection, about 6 cm of the body of the pancreas was preserved, and signs of diabetes mellitus have not appeared. The postoperative course was complicated by a grade B pancreatic fistula, but this was successfully treated with conservative management. After a 33-day hospital stay, the patient returned to daily life without signs of pancreatic exocrine insufficiency. Although the long-term follow-up of the patient is indispensable, in this case, MPP might be able to lead to the curative resection of transverse colon cancer massively invading the duodenum and non-functioning endocrine tumor in the pancreatic tail with preservation of pancreatic function.

Chemical strategies for pancreatic β cell differentiation, reprogramming, and regeneration.

PubMed

Ma, Xiaojie; Zhu, Saiyong

2017-04-01

Generation of unlimited functional pancreatic β cells is critical for the study of pancreatic biology and treatment of diabetes mellitus. Recent advances have suggested several promising directions, including directed differentiation of pancreatic β cells from pluripotent stem cells, reprogramming of pancreatic β cells from other types of somatic cells, and stimulated proliferation and enhanced functions of existing pancreatic β cells. Small molecules are useful in generating unlimited numbers of functional pancreatic cells in vitro and could be further developed as drugs to stimulate endogenous pancreatic regeneration. Here, we provide an updated summary of recent major achievements in pancreatic β cell differentiation, reprogramming, proliferation, and function. These studies will eventually lead to significant advances in the field of pancreatic biology and regeneration. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Durvalumab and Tremelimumab in Combination With First-Line Chemotherapy in Advanced Solid Tumors

ClinicalTrials.gov

2018-05-16

Small Cell Lung Carcinoma; Carcinoma, Squamous Cell of Head and Neck; Stomach Neoplasms; Triple Negative Breast Neoplasms; Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Esophagogastric Junction Neoplasms; Carcinoma, Pancreatic Ductal; Esophageal Squamous Cell Carcinoma

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

PubMed Central

Meesiri, Somchai

2012-01-01

Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or pseudocysts. Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass. The patient was diagnosed with pancreatic TB and acquired immunodeficiency syndrome, and was treated with antituberculous drugs and percutaneous catheter drainage without a laparotomy. The clinical presentation, radiographic investigation and management of pancreatic TB are summarized in this paper to emphasize the importance of considering this rare disease in the differential diagnosis of pancreatic masses concomitant with human immunodeficiency virus infection. I also emphasize the need for both histopathological and microbiological diagnosis via fine-needle aspiration. PMID:22363146

Advances of high intensity focused ultrasound (HIFU) for pancreatic cancer.

PubMed

Xiaoping, Li; Leizhen, Zheng

2013-11-01

High intensity focused ultrasound (HIFU) is a novel therapeutic modality. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumours, including pancreatic cancer. Preliminary studies suggest that HIFU may be useful for the palliative therapy of cancer-related pain in patients with unresectable pancreatic cancer. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 weremore » 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.« less

Wilms tumor gene (WT1) peptide-based cancer vaccine combined with gemcitabine for patients with advanced pancreatic cancer.

PubMed

Nishida, Sumiyuki; Koido, Shigeo; Takeda, Yutaka; Homma, Sadamu; Komita, Hideo; Takahara, Akitaka; Morita, Satoshi; Ito, Toshinori; Morimoto, Soyoko; Hara, Kazuma; Tsuboi, Akihiro; Oka, Yoshihiro; Yanagisawa, Satoru; Toyama, Yoichi; Ikegami, Masahiro; Kitagawa, Toru; Eguchi, Hidetoshi; Wada, Hiroshi; Nagano, Hiroaki; Nakata, Jun; Nakae, Yoshiki; Hosen, Naoki; Oji, Yusuke; Tanaka, Toshio; Kawase, Ichiro; Kumanogoh, Atsushi; Sakamoto, Junichi; Doki, Yuichiro; Mori, Masaki; Ohkusa, Toshifumi; Tajiri, Hisao; Sugiyama, Haruo

2014-01-01

Wilms tumor gene (WT1) protein is an attractive target for cancer immunotherapy. We aimed to investigate the feasibility of a combination therapy consisting of gemcitabine and WT1 peptide-based vaccine for patients with advanced pancreatic cancer and to make initial assessments of its clinical efficacy and immunologic response. Thirty-two HLA-A*24:02 patients with advanced pancreatic cancer were enrolled. Patients received HLA-A*24:02-restricted, modified 9-mer WT1 peptide (3 mg/body) emulsified with Montanide ISA51 adjuvant (WT1 vaccine) intradermally biweekly and gemcitabine (1000 mg/m) on days 1, 8, and 15 of a 28-day cycle. This combination therapy was well tolerated. The frequencies of grade 3-4 adverse events for this combination therapy were similar to those for gemcitabine alone. Objective response rate was 20.0% (6/30 evaluable patients). Median survival time and 1-year survival rate were 8.1 months and 29%, respectively. The association between longer survival and positive delayed-type hypersensitivity to WT1 peptide was statistically significant, and longer survivors featured a higher frequency of memory-phenotype WT1-specific cytotoxic T lymphocytes both before and after treatment. WT1 vaccine in combination with gemcitabine was well tolerated for patients with advanced pancreatic cancer. Delayed-type hypersensitivity-positivity to WT1 peptide and a higher frequency of memory-phenotype WT1-specific cytotoxic T lymphocytes could be useful prognostic markers for survival in the combination therapy with gemcitabine and WT1 vaccine. Further clinical investigation is warranted to determine the effectiveness of this combination therapy.

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.

Radiofrequency assisted pancreaticoduodenectomy for palliative surgical resection of locally advanced pancreatic adenocarcinoma.

PubMed

Kumar, Jayant; Reccia, Isabella; Sodergren, Mikael H; Kusano, Tomokazu; Zanellato, Artur; Pai, Madhava; Spalding, Duncan; Zacharoulis, Dimitris; Habib, Nagy

2018-03-20

Despite careful patient selection and preoperative investigations curative resection rate (R0) in pancreaticoduodenectomy ranges from 15% to 87%. Here we describe a new palliative approach for pancreaticoduodenectomy using a radiofrequency energy device to ablate tumor in situ in patients undergoing R1/R2 resections for locally advanced pancreatic ductal adenocarcinoma where vascular reconstruction was not feasible. There was neither postoperative mortality nor significant morbidity. Each time the ablation lasted less than 15 minutes. Following radiofrequency ablation it was observed that the tumor remnant attached to the vessel had shrunk significantly. In four patients this allowed easier separation and dissection of the ablated tumor from the adherent vessel leading to R1 resection. In the other two patients, the ablated tumor did not separate from vessel due to true tumor invasion and patients had an R2 resection. The ablated remnant part of the tumor was left in situ. Whenever pancreaticoduodenectomy with R0 resection cannot be achieved, this new palliative procedure could be considered in order to facilitate resection and enable maximum destruction in remnant tumors. Six patients with suspected tumor infiltration and where vascular reconstruction was not warranted underwent radiofrequency-assisted pancreaticoduodenectomy for locally advanced pancreatic ductal adenocarcinoma. Radiofrequency was applied across the tumor vertically 5-10 mm from the edge of the mesenteric and portal veins. Following ablation, the duodenum and the head of pancreas were removed after knife excision along the ablated line. The remaining ablated tissue was left in situ attached to the vessel.

Changing the course of pancreatic cancer--Focus on recent translational advances.

PubMed

Javle, Milind; Golan, Talia; Maitra, Anirban

2016-03-01

In the past decade, insightful preclinical research has led to important breakthroughs in our understanding of pancreatic cancer. Even though the vast majority of pancreatic cancers are KRAS mutated, not all pancreatic cancer tumors are "KRAS equal"; there seems to be varying dependencies on the KRAS pathway. While KRAS-targeting therapies have been disappointing in the clinic, 'synthetic lethal' approaches hold promise in this setting. The pancreatic cancer stromal microenvironment appears to have contradictory roles. While there is evidence to suggest that stromal barrier prevents drug delivery, in other circumstances, stroma can play a protective role and its disruption enhances tumor dissemination. Clinical trials aimed at manipulating the various stromal components are in progress. BRCA mutation-related pancreatic tumors illustrate a unique subtype with enhanced susceptibility to DNA damaging agents and PARP-inhibition. DNA repair defects in cancer extend beyond germ line BRCA mutation and may extend the indications for DNA repair-targeting agents. Immune strategies are an area of active investigation in pancreatic cancer. Although the initial trials of single-agent checkpoint inhibitors have been negative, combinational approaches using immune-modifying agents and vaccines appear promising and goal is to identify an 'immune-therapy responsive' profile in pancreatic cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2013-12-01

Chronic pancreatitis is progressive and irreversible, leading to digestive and absorptive disorders by destruction of the exocrine pancreas and to diabetes mellitus by destruction of the endocrine pancreas. When complications such as pancreatolithiasis and pseudocyst occur, elevated pancreatic ductal pressure exacerbates pain and induces other complications, worsening the patient's general condition. Combined treatment with extracorporeal shock-wave lithotripsy and endoscopic lithotripsy is a useful, minimally invasive, first-line treatment approach that can preserve pancreatic exocrine function. Pancreatic duct stenosis elevates intraductal pressure and favor both pancreatolithiasis and pseudocyst formation, making effective treatment vitally important. Endoscopic treatment of benign pancreatic duct stenosis stenting frequently decreases pain in chronic pancreatitis. Importantly, stenosis of the main pancreatic duct increases risk of stone recurrence after treatment of pancreatolithiasis. Recently, good results were reported in treating pancreatic duct stricture with a fully covered self-expandable metallic stent, which shows promise for preventing stone recurrence after lithotripsy in patients with pancreatic stricture. Chronic pancreatitis has many complications including pancreatic carcinoma, pancreatic atrophy, and loss of exocrine and endocrine function, as well as frequent recurrence of stones after treatment of pancreatolithiasis. As early treatment of chronic pancreatitis is essential, the new concept of early chronic pancreatitis, including characteristics findings in endoscopic ultrasonograms, is presented. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Itraconazole therapy in a pancreatic adenocarcinoma patient: A case report.

PubMed

Lockhart, Nicholas R; Waddell, James Aubrey; Schrock, Nathan Eric

2016-06-01

To report the case of a patient receiving itraconazole for the treatment of histoplasmosis and his subsequent reduction in pancreatic tumor size. A 64-year-old male was diagnosed with Stage III locally advanced unresectable pancreatic adenocarcinoma. The patient was administered radiation plus chemotherapy, which included cisplatin and capecitabine. Upon restaging, the patient's tumor was again determined to be unresectable; therefore, palliative chemotherapy treatments were initiated, which included gemcitabine and erlotinib. After two gemcitabine cycles, he was admitted to the hospital because of loss of motor function due to spinal cord hemisection. After the surgery, the patient became neutropenic because of previous chemotherapy cycle and developed disseminated histoplasmosis. After he received his nine-month course of itraconazole, the pancreatic cancer was readdressed and he was then deemed to be resectable and had a Whipple procedure. Over the next several years, he showed no evidence of pancreatic metastases or relapse. Itraconazole has been shown to have many mechanisms by which it could potentially suppress tumor cell growth, which includes inhibition of the Hedgehog pathway, vascular endothelial growth factor receptor-2, and P-glycoprotein efflux pump. This azole antifungal has been studied in small patient populations with various types of cancers. Studies of basal cell carcinoma, nonsmall cell lung cancer, ovarian cancer, and malignant pleural mesothelioma have shown favorable results suggesting that more study of itraconazole is warranted to decide its clinical utility. There would need to be much more research performed to determine if this agent had a role as a chemotherapy agent; however, health care professionals should be aware of itraconazole's potential antineoplastic mechanisms. © The Author(s) 2015.

Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications.

PubMed

Reid, Michelle D; Saka, Burcu; Balci, Serdar; Goldblum, Andrew S; Adsay, N Volkan

2014-02-01

To summarize the most clinically and biologically relevant advances in molecular/genetic characteristics of various pancreatic neoplasms, with morphologic correlation. Whole-exome sequencing of numerous benign and malignant pancreatic tumors, along with the plethora of highly sensitive molecular studies now available for analyzing these tumors, provide mounting evidence to support the long-held belief that cancer is essentially a genetic disease. These genetic discoveries have not only helped to confirm the age-old, morphology-based classifications of pancreatic neoplasia but have shed new light on their mechanisms. Many of these molecular discoveries are currently being used in preoperative diagnosis. Mutations in KRAS, P16/CDKN2A, TP53, and SMAD4/DPC4 are commonly seen in ductal neoplasia but not in nonductal tumors; ductal adenocarcinomas with SMAD4/DPC4 loss are associated with widespread metastasis and poor prognosis. GNAS and RNF43 mutations have been discovered in most intraductal pancreatic mucinous neoplasms, providing critical molecular fingerprints for their diagnosis. Mutation in DAXX/ATRX is only seen in pancreatic neuroendocrine tumors, making it a useful potential marker in distinguishing these tumors from mimics. When combined with morphologic observations, molecular studies will increase our understanding of the pathogenesis and morphomolecular signatures associated with specific neoplasms and provide new horizons for precision medicine and targeted therapies.

Superior therapeutic efficacy of nab-paclitaxel over cremophor-based paclitaxel in locally advanced and metastatic models of human pancreatic cancer.

PubMed

Rajeshkumar, N V; Yabuuchi, Shinichi; Pai, Shweta G; Tong, Zeen; Hou, Shihe; Bateman, Scott; Pierce, Daniel W; Heise, Carla; Von Hoff, Daniel D; Maitra, Anirban; Hidalgo, Manuel

2016-08-09

Albumin-bound paclitaxel (nab-paclitaxel, nab-PTX) plus gemcitabine (GEM) combination has demonstrated efficient antitumour activity and statistically significant overall survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) compared with GEM monotherapy. This regimen is currently approved as a standard of care treatment option for patients with metastatic PDAC. It is unclear whether cremophor-based PTX combined with GEM provide a similar level of therapeutic efficacy in PDAC. We comprehensively explored the antitumour efficacy, effect on metastatic dissemination, tumour stroma and survival advantage following GEM, PTX and nab-PTX as monotherapy or in combination with GEM in a locally advanced, and a highly metastatic orthotopic model of human PDAC. Nab-PTX treatment resulted in significantly higher paclitaxel tumour plasma ratio (1.98-fold), robust stromal depletion, antitumour efficacy (3.79-fold) and survival benefit compared with PTX treatment. PTX plus GEM treatment showed no survival gain over GEM monotherapy. However, nab-PTX in combination with GEM decreased primary tumour burden, metastatic dissemination and significantly increased median survival of animals compared with either agents alone. These therapeutic effects were accompanied by depletion of dense fibrotic tumour stroma and decreased proliferation of carcinoma cells. Notably, nab-PTX monotherapy was equivalent to nab-PTX plus GEM in providing survival advantage to mice in a highly aggressive metastatic PDAC model, indicating that nab-PTX could potentially stop the progression of late-stage pancreatic cancer. Our data confirmed that therapeutic efficacy of PTX and nab-PTX vary widely, and the contention that these agents elicit similar antitumour response was not supported. The addition of PTX to GEM showed no survival advantage, concluding that a clinical combination of PTX and GEM may unlikely to provide significant survival advantage over GEM monotherapy and may not be a

A pilot study of the experience of family caregivers of patients with advanced pancreatic cancer using a mixed methods approach.

PubMed

Sherman, Deborah W; McGuire, Deborah B; Free, David; Cheon, Joo Young

2014-09-01

Pancreatic cancer presents a wide spectrum of significant symptomatology. The high symptom burden, coupled with a rapidly fatal diagnosis, limits preparation or time for adjustment for both patients and their family caregivers. From the initial diagnosis and throughout the illness experience, the physical and emotional demands of caregiving can predispose caregivers themselves to illness and a greater risk of mortality. Understanding the negative and positive aspects of caregiving for patients with advanced pancreatic cancer will inform interventions that promote positive caregiver outcomes and support caregivers in their role. To provide feasibility data for a larger, mixed methods, longitudinal study focused on the experience of family caregivers of patients with advanced pancreatic cancer and preliminary qualitative data to substantiate the significance of studying this caregiver population. This was a mixed methods study guided by the Stress Process Model. Eight family caregivers of patients with advanced pancreatic cancer from oncology practices of a university-affiliated medical center were surveyed. The pilot results supported the ability to recruit and retain participants and informed recruitment and data collection procedures. The qualitative results provided preliminary insights into caregiver experiences during the diagnosis and treatment phases. Key findings that substantiated the significance of studying these caregivers included the caregiving context of the history of sentinel symptoms, the crisis of diagnosis, the violation of assumptions about life and health, recognition of the circle of association, and contextual factors, as well as primary and secondary stressors, coping strategies, resources, discoveries, gains and growth, associated changes/transitions, and unmet caregiver needs. Findings indicated caregivers' willingness to participate in research, highlighted the negative and positive aspects of the caregiver experience, and reinforced the

[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%. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Genes and Proteins Differentially Expressed during In Vitro Malignant Transformation of Bovine Pancreatic Duct Cells1

PubMed Central

Jesnowski, R; Zubakov, Dmitri; Faissner, Ralf; Ringel, Jörg; Hoheisel, Jörg D; Lösel, Ralf; Schnölzer, Martina; Löhr, Matthias

2007-01-01

Abstract Pancreatic carcinoma has an extremely bad prognosis due to lack of early diagnostic markers and lack of effective therapeutic strategies. Recently, we have established an in vitro model recapitulating the first steps in the carcinogenesis of the pancreas. SV40 large T antigen-immortalized bovine pancreatic duct cells formed intrapancreatic adenocarcinoma tumors on k-rasmut transfection after orthotopic injection in the nude mouse pancreas. Here we identified genes and proteins differentially expressed in the course of malignant transformation using reciprocal suppression subtractive hybridization and 2D gel electrophoresis and mass spectrometry, respectively. We identified 34 differentially expressed genes, expressed sequence tags, and 15 unique proteins. Differential expression was verified for some of the genes or proteins in samples from pancreatic carcinoma. Among these genes and proteins, the majority had already been described either to be influenced by a mutated ras or to be differentially expressed in pancreatic adenocarcinoma, thus proving the feasibility of our model. Other genes and proteins (e.g., BBC1, GLTSCR2, and rhoGDIα), up to now, have not been implicated in pancreatic tumor development. Thus, we were able to establish an in vitro model of pancreatic carcinogenesis, which enabled us to identify genes and proteins differentially expressed during the early steps of malignant transformation. PMID:17356710

State-of-the-art pancreatic MRI.

PubMed

Sandrasegaran, Kumaresan; Lin, Chen; Akisik, Fatih M; Tann, Mark

2010-07-01

The purpose of this article is to discuss the most current techniques used for pancreatic imaging, highlighting the advantages and disadvantages of state-of-the-art and emerging pulse sequences and their application to pancreatic disease. Given the technologic advances of the past decade, pancreatic MRI protocols have evolved. Most sequences can now be performed in one or a few breath-holds; 3D sequences with thin, contiguous slices offer improved spatial resolution; and better fat and motion suppression allow improved contrast resolution and image quality. The diagnostic potential of MRCP is now almost as good as ERCP, with pancreatic MRI as the main imaging technique to investigate biliopancreatic pain, chronic pancreatitis, and cystic pancreatic tumors at many institutions. In addition, functional information is provided with secretin-enhanced MRCP.

Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma

PubMed Central

Rohloff, J; Zinke, J; Schoppmeyer, K; Tannapfel, A; Witzigmann, H; Mössner, J; Wittekind, C; Caca, K

2002-01-01

Pancreatic ductal adenocarcinoma has a median survival of less than 6 months from diagnosis. This is due to the difficulty in early diagnosis, the aggressive biological behaviour of the tumour and a lack of effective therapies for advanced disease. Mammalian heparanase is a heparan-sulphate proteoglycan cleaving enzyme. It helps to degrade the extracellular matrix and basement membranes and is involved in angiogenesis. Degradation of extracellular matrix and basement membranes as well as angiogenesis are key conditions for tumour cell spreading. Therefore, we have analysed the expression of heparanase in human pancreatic cancer tissue and cell lines. Heparanase is expressed in cell lines derived from primary tumours as well as from metastatic sites. By immunohistochemical analysis, it is preferentially expressed at the invading edge of a tumour at both metastatic and primary tumour sites. There is a trend towards heparanase expression in metastasising tumours as compared to locally growing tumours. Postoperative survival correlates inversely with heparanase expression of the tumour reflected by a median survival of 34 and 17 month for heparanase negative and positive tumours, respectively. Our results suggest, that heparanase promotes cancer cell invasion in pancreatic carcinoma and could be used as a prognostic indicator for postoperative survival of patients. British Journal of Cancer (2002) 86, 1270–1275. DOI: 10.1038/sj/bjc/6600232 www.bjcancer.com © 2002 Cancer Research UK PMID:11953884

Proximal migration of transanastomotic pancreatic stent following pancreaticoduodenectomy and pancreaticojejunostomy.

PubMed

Ammori, B J; White, C M

1999-06-01

The use of catheters to stent the pancreaticojejunal anastomosis following pancreaticoduodenectomy is practiced by some surgeons. Their long-term effects in this setting, however, remain unknown. A 60-yr-old woman underwent a potentially curative pylorus preserving pancreaticoduodenectomy for Stage I ampullary carcinoma. Roux-en-Y pancreaticojejunostomy was constructed over a short stent. She presented 4 yr later with abdominal pain, steatorrhea, and weight loss. Computed tomography revealed a stent within the proximal pancreatic duct, with gross upstream ductal dilatation and parenchymal features of chronic pancreatitis. Laparotomy revealed no disease recurrence. The stent, removed through a jejunotomy, was occluded. On-table pancreatogram demonstrated a 3-cm proximal duct stricture. Drainage was achieved with a lateral pancreaticojejunostomy (modified Puestow procedure). Recovery was uneventful, with clinical recovery of pancreatic exocrine function at 6 mo follow-up. Proximal migration of transanastomotic pancreatic stent with subsequent development of chronic pancreatitis is a potential complication following pancreaticoduodenectomy. It can be managed effectively with stent removal and a lateral pancreaticojejunostomy.

Polyarthritis and bone lesions complicating traumatic pancreatitis in two children.

PubMed Central

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

1978-01-01

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

Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

PubMed

Di, Baoshan; Pan, Bei; Ge, Long; Ma, Jichun; Wu, Yiting; Guo, Tiankang

2018-03-01

Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

New insights into pancreatic cancer biology.

PubMed

Hidalgo, M

2012-09-01

Pancreatic cancer remains a devastating disease. Over the last few years, there have been important advances in the molecular and biological understanding of pancreatic cancer. This included understanding of the genomic complexity of the disease, the role of pancreatic cancer stem cells, the relevance of the tumor microenvironment, and the unique metabolic adaptation of pancreas cancer cells to obtain nutrients under hypoxic environment. In this paper, we review the most salient developments in these few areas.

Sarcomatoid renal cell carcinoma: Biology and treatment advances.

PubMed

Mouallem, Nemer El; Smith, Steven C; Paul, Asit K

2018-06-01

Sarcomatoid transformation in renal cell carcinoma, so called sacromatoid RCC (sRCC), is associated with an aggressive behavior and a poor prognosis. Current therapeutic approaches are largely ineffective. Recent studies looking into the genomic and molecular characterization of sRCCs have provided insights into the biology and pathogenesis of this entity. These advances in molecular signatures may help development of effective treatment strategies. We herein present a review of recent developments in the pathology, biology, and treatment modalities in sRCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Overexpression of α3, β3 and γ2 chains of laminin-332 is associated with poor prognosis in pancreatic ductal adenocarcinoma

PubMed Central

Chen, Jun; Zhang, Hao; Luo, Jiansheng; Wu, Xiaokang; Li, Xueming; Zhao, Xinyi; Zhou, Dongkai; Yu, Shian

2018-01-01

Pancreatic ductal adenocarcinoma (PDA) is a worldwide health problem. Early diagnosis and assessment may enhance the quality of life and survival of patients. The present study investigated the potential correlations between the gene and protein expression of laminin-332 (LM-332 or laminin-5) and clinicopathological factors as well as evaluating its influence on the survival of patients with PDA. The expression of LM-332 subunit mRNAs in pancreatic carcinoma specimens from 37 patients was investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Using immunohistochemical methods, the protein expressions of the three chains of LM-322 (LNα3, LNβ3 and LNγ2) were determined in 96 pancreatic carcinoma specimens, for association analysis with clinicopathological characteristics from patient data. The results of the prognosis analysis of three mRNAs expression datasets were validated in The Cancer Genome Atlas datasets. RT-qPCR results indicated that the overall relative values of LNα3 and LNγ2 mRNAs were increased in pancreatic carcinoma compared with the control. In immunostaining analyses LNα3 and LNγ2 expression was observed in all tumor tissues from the 96 patient samples. The expression levels of LNα3, LNβ3 and LNγ2 were associated with each other. LNα3 and LNγ2 positivity was significantly associated with differentiation, depth of invasion and advanced stage (P<0.05). The samples were classified into three groups: Basement membrane (B) type, cytoplasmic (C) type and mixed (M) type, according to their LNγ2 immunohistochemical expression patterns. The B type correlated significantly with differentiation (P=0.010) and the M type was significantly associated with hepatic metastasis (P=0.031). Patients with B-type LNγ2 demonstrated significantly better outcomes than patients with the C or M type (P=0.012 and P=0.003, respectively). Overexpression of the α3, β3 and γ2 chains of LM-332 may serve an important role in

Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project

PubMed Central

Iacobuzio-Donahue, Christine A

2012-01-01

Pancreatic cancer is a disease caused by the accumulation of genetic alterations in specific genes. Elucidation of the human genome sequence, in conjunction with technical advances in the ability to perform whole exome sequencing, have provided new insight into the mutational spectra characteristic of this lethal tumour type. Most recently, exomic sequencing has been used to clarify the clonal evolution of pancreatic cancer as well as provide time estimates of pancreatic carcinogenesis, indicating that a long window of opportunity may exist for early detection of this disease while in the curative stage. Moving forward, these mutational analyses indicate potential targets for personalised diagnostic and therapeutic intervention as well as the optimal timing for intervention based on the natural history of pancreatic carcinogenesis and progression. PMID:21749982

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp; Ioka, Tatsuya; Ito, Yoshinori

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 amore » 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.« less

Dose effects of raw soybean flour on pancreatic growth.

PubMed

Morgan, R G; Crass, R A; Oates, P S

1986-01-01

Raw soya flour (RSF) feeding to rats produces pancreatic hypertrophy and hyperplasia, and, if sufficiently prolonged, the spontaneous development of pancreatic neoplasms and the potentiation of pancreatic carcinogens. With continuous exposure to RSF the threshold dose for pancreatic growth is approximately 20% RSF, but the threshold for the other effects has not been defined. If 100% RSF is fed for less than 24 weeks continuously the effects on the pancreas are completely reversible, but feeding for longer than this leads to irreversible progression to pancreatic adenoma and carcinoma over the next 50-70 weeks. Repeated alternation of the diet between 100% RSF and rat chow for prolonged periods leads to effects on the pancreas at least as marked as those seen with continuous RSF feeding. This occurs with RSF feeding for periods as short as 2 days out of 7. The effects seen in the rat must be applied to human nutrition with caution, but it is suggested that infants fed soya based milk substitutes and fad dieters who frequently radically alter dietary composition may be more susceptible to spontaneous or carcinogen-induced pancreatic neoplasms.

Pain affecting procedures in non-resectable pancreatic carcinoma.

PubMed

Plachkov, I; Chernopolski, P; Bozhkov, V; Madjov, R

2013-01-01

Pancreatic cancer is third most common cancer of the gastrointestinal tract in Bulgaria, accouting for 11, 6% in 2008. The leading symptom in patients with pancreatic cancer is the pain. The pain can be related with neoplasms and their metastasis. We should use all kind of resourses for pain relief: conventional drugs (according to the three steps strategy of WHO), interventional or surgical procedures. To present the interventional and surgical techniques in our practice and to share our experience for pain control in patients with nonresectable pancreatic cancer to improve their quality of life. In a seven year period (2004-2011) we performed 59 thoracoscopic splanhnicectomies/30--bilateral/ 4 intraoperative resections of celiac ganglion, 25 CT--control celiac plexus neurolysis and 90 cases pain relief with epidural analgesia. Concerning the quality of life we applied a questionnaire of a spannish medical center " City of Hope" adapted for patients with cancer and the level of pain with visual analogue scale VAS. The long-term duration of the pain relief technique depends on applied technic, of cancer invasion and of the technic itself. The technique with the longest effect are the intraoperative celiac ganglion removal and the bilateral thoracoscopic splanhnicectomy. On the other hand the shortest effect we report the celiac plexus neurolysis, and the epudural analgesia. These data are in correlation with the reduction of the pain shown using VAS thus improving the quality of life. The surgical and interventional methods for control of cancer pain have their own collocation improving the quality of life of these patients. New strategies for the pain control are need in the future.

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

Dietary consumption of advanced glycation end products and pancreatic cancer in the prospective NIH-AARP Diet and Health Study.

PubMed

Jiao, Li; Stolzenberg-Solomon, Rachael; Zimmerman, Thea Palmer; Duan, Zhigang; Chen, Liang; Kahle, Lisa; Risch, Adam; Subar, Amy F; Cross, Amanda J; Hollenbeck, Albert; Vlassara, Helen; Striker, Gary; Sinha, Rashmi

2015-01-01

Advanced glycation end products (AGEs) are a heterogeneous group of compounds present in uncooked foods as well as in foods cooked at high temperatures. AGEs have been associated with insulin resistance, oxidative stress, and chronic inflammation in patients with diabetes. Dietary AGEs are an important contributor to the AGE pool in the body. N(ϵ)-(carboxymethyl)lysine (CML) AGE is one of the major biologically and chemically well-characterized AGE markers. The consumption of red meat, which is CML-AGE rich, has been positively associated with pancreatic cancer in men. With the use of a published food CML-AGE database, we estimated the consumption of CML AGE in the prospective NIH-AARP Diet and Health Study and evaluated the association between CML-AGE consumption and pancreatic cancer and the mediating effect of CML AGE on the association between red meat consumption and pancreatic cancer. Multivariate Cox proportional hazard regression models were used to estimate HRs and 95% CIs for pancreatic cancer. During an average of 10.5 y of follow-up, we identified 2193 pancreatic cancer cases (1407 men and 786 women) from 528,251 subjects. With the comparison of subjects in the fifth and the first quintiles of CML-AGE consumption, we observed increased pancreatic cancer risk in men (HR: 1.43; 95% CI: 1.06, 1.93, P-trend = 0.003) but not women (HR: 1.14; 95% CI: 0.76, 1.72, P-trend = 0.42). Men in the highest quintile of red meat consumption had higher risk of pancreatic cancer (HR: 1.35; 95% CI: 1.07, 1.70), which attenuated after adjustment for CML-AGE consumption (HR: 1.20; 95% CI: 0.95, 1.53). Dietary CML-AGE consumption was associated with modestly increased risk of pancreatic cancer in men and may partially explain the positive association between red meat and pancreatic cancer. © 2015 American Society for Nutrition.

Merkel cell carcinoma - recent advances in the biology, diagnostics and treatment.

PubMed

Czapiewski, Piotr; Biernat, Wojciech

2014-08-01

Merkel cell carcinoma (MCC) is an uncommon primary cutaneous carcinoma with neuroendocrine differentiation. Since recent discovery of MCCs strong association with Merkel cell polyomavirus (MCPyV), there has been a rapid increase in the understanding of the carcinomas genetics, molecular biology and pathogenesis. In our study, we reviewed recent advances and controversies concerning MCC histogenesis, epidemiology, diagnostic and prognostic markers. We analyzed the association of MCPyV with MCC and the possible new targets for therapy. We also examined English-based literature regarding MCC pathogenesis published between 2008 and 2013, which lead to a deeper understanding of the topic. Our study showed that the association of MCPyV strongly influences the course of MCC. Additionally, it has been shown that a immunological response to MCPyV may in the future give hope to identify new therapeutic strategies in treatment of this fatal malignancy. This article is part of a Directed Issue entitled: Rare Cancers. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plastic biliary stent patency in patients with locally advanced pancreatic adenocarcinoma receiving downstaging chemotherapy.

PubMed

Ge, Phillip S; Hamerski, Christopher M; Watson, Rabindra R; Komanduri, Srinadh; Cinnor, Birtukan B; Bidari, Kiran; Klapman, Jason B; Lin, Cui L; Shah, Janak N; Wani, Sachin; Donahue, Timothy R; Muthusamy, V Raman

2015-02-01

Plastic stents in patients with biliary obstruction caused by pancreatic adenocarcinoma are typically exchanged at 3-month intervals. Plastic stents may have reduced durability in patients receiving chemotherapy. To determine the duration of plastic biliary stent patency in patients undergoing chemotherapy for pancreatic adenocarcinoma. Retrospective, multicenter cohort study. Three tertiary academic referral centers. A total of 173 patients receiving downstaging chemotherapy for locally advanced or borderline resectable pancreatic adenocarcinoma from 1996 to 2013. Placement of 10F or larger plastic biliary stents. Primary outcome was overall duration of stent patency. Secondary outcomes included the incidence of premature stent exchange (because of cholangitis or jaundice) and hospitalization rates. A total of 233 plastic stents were placed, and the overall median duration of stent patency was 53 days (interquartile range [IQR] 25-99 days). Eighty-seven stents were removed at the time of surgical resection, and 63 stents were exchanged routinely per protocol. The remaining 83 stent exchanges were performed for worsening liver function test results, jaundice, or cholangitis, representing a 35.6% rate of premature stent exchange. The median stent patency duration in the premature stent exchange group was 49 days (IQR 25-91 days) with a 44.6% hospitalization rate. The overall rate of cholangitis was 15.0% of stent exchanges, occurring a median of 56 days after stent placement (IQR 26-89 days). Retrospective study. Plastic biliary stents placed during chemotherapy/chemoradiation for pancreatic adenocarcinoma have a shorter-than-expected patency duration, and a substantial number of patients will require premature stent exchange. Consideration should be given to shortening the interval for plastic biliary stent exchange. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Effects of CPG ODN on biological behavior of PANC-1 and expression of TLR9 in pancreatic cancer.

PubMed

Wu, Han-Qing; Wang, Bo; Zhu, Shi-Kai; Tian, Yuan; Zhang, Jing-Hui; Wu, He-Shui

2011-02-28

To determine the expression of toll-like receptor 9 (TLR9) in pancreatic tumor and the effects of cytosine phosphate-guanosine oligodeoxynucleotides 2216 (CPG ODN2216) on biological behavior of pancreatic carcinoma cell line PANC-1 and explore their clinical significance. The immunohistochemistry and Western blot were used to determine the expression of TLR9 protein in pancreatic cancer tissues, and immunofluorescence staining was performed to detect the TLR9 protein expression in pancreatic carcinoma cell line PANC-1. To assess the effects of CPG ODN2216 on the invasive property of Panc-1 cells, in vitro cell adhesion, wound-healing scrape, and invasion and cell colony formation were evaluated. TLR9 was highly expressed in pancreatic cancer tissues and PANC-1 cells. The percentage of positive cells expressing TLR9 protein in human pancreatic tissues, paracancerous tissues and normal tissues were 73.3%, 33.3% and 20.0%, respectively, and the protein expression level of TLR9 was gradually descending (P < 0.05). In vitro tests in wound-healing scrape, cell adhesion, colony formation and matrigel invasion showed that the adhesion and motility of PANC-1 cells in CPG ODN 2216 treatment group were significantly lower than in the control group (P < 0.05). The cell growth assay showed that the proliferative ability of PANC-1 cells in treatment group was significantly decreased and CPG ODN2216 had an inhibitive effect in the growth of Panc-1 cells in a dose and time-dependent manner (P < 0.05). The gene of TLR9 is correlated with the invasive and metastatic potential of human pancreatic carcinoma, and CPG ODN2216 induces the inhibition of migration and invasion of Panc-1 cells.

Phase 1 Study of Erlotinib Plus Radiation Therapy in Patients With Advanced Cutaneous Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heath, C. Hope; Deep, Nicholas L.; Nabell, Lisle

Purpose: To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Methods and Materials: This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. Results: The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%).more » Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Conclusions: Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls.« less

Gamma-Secretase Inhibitor RO4929097 and Cediranib Maleate in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2014-12-22

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Solid Neoplasm; Male Breast Carcinoma; Recurrent Adult Brain Neoplasm; Recurrent Breast Carcinoma; Recurrent Colon Carcinoma; Recurrent Melanoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Carcinoma; Recurrent Rectal Carcinoma; Recurrent Renal Cell Carcinoma; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Breast Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Breast Cancer; Stage IIIC Colon Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

[A case of mucinous noncystic carcinoma of the pancreas].

PubMed

Jung, Jun Young; Song, Moon Hee; Park, Young Sook; Jo, Yun Ju; Kim, Seong Hwan; Jun, Dae-Won; Kim, Dong Hee; Lee, Won Mi

2008-03-01

Mucinous (colloid) carcinoma is defined as pools of stromal extracellular mucin containing scanty, floating carcinoma cells. It is a well-defined entity in breast or large bowel. However, mucinous noncystic carcinoma of the pancreas (MNCC) is uncommon, comprising between 1% and 3% of all carcinomas of the pancreas. In the past, MNCC generally had been categorized together with ordinary ductal adenocarcinoma or misdiagnosed as mucinous cystadenocarcinoma or signet-ring cell carcinoma. The new WHO classification lists MNCC as a variant of ductal adenocarcinoma. Herein, we report a 32-year-old woman with incidentally found pancreatic body mass who underwent subtotal pancreatectomy. She was diagnosed as MNCC histologically.

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

Important technical remarks on distal pancreatectomy with en-bloc celiac axis resection for locally advanced pancreatic body cancer (with video).

PubMed

Tanaka, Eiichi; Hirano, Satoshi; Tsuchikawa, Takahiro; Kato, Kentaro; Matsumoto, Joe; Shichinohe, Toshiaki

2012-03-01

We have already reported the feasibility, safety, and excellent long-term results of distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) for locally advanced pancreatic body cancer. An international standard for the surgical technique of DP-CAR has yet to be established. DP-CAR was carefully performed in 42 patients in Hokkaido University Hospital from 1998 to July 2007. Arterial blood flow alteration and collateral flow development toward the liver and stomach was obtained following preoperative routine transcatheter arterial embolization of the common hepatic artery. The right-sided approach to the superior mesenteric artery and celiac artery, and the preservation of the inferior pancreatoduodenal artery during the dissection of the plexus around the pancreatic head, are the key techniques in DP-CAR. The operative morbidity and mortality were 43 and 4.8%, respectively. R0 resection could be done in 39 (93%) patients. Median operation time and intraoperative blood loss were 478 min and 1030 ml, respectively. Ischemic gastropathy was complicated in 5 (12%) patients, but liver abscess was found in only one patient and no liver failure was encountered. We emphasize again the feasibility and safety of DP-CAR; it should be a treatment of choice for locally advanced pancreatic body cancer.

Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma.

PubMed

Dugnani, Erica; Balzano, Gianpaolo; Pasquale, Valentina; Scavini, Marina; Aleotti, Francesca; Liberati, Daniela; Di Terlizzi, Gaetano; Gandolfi, Alessandra; Petrella, Giovanna; Reni, Michele; Doglioni, Claudio; Bosi, Emanuele; Falconi, Massimo; Piemonti, Lorenzo

2016-12-01

To study whether insulin resistance accelerates the development and/or the progression of pancreatic adenocarcinoma (PDAC), we hypothesized that patients with insulin resistance, compared with those without insulin resistance, show: (1) a younger age and more advanced PDAC stage at diagnosis and (2) a shorter disease-free and overall survival after PDAC diagnosis. Prospective observational study of patients admitted to a referral center for pancreatic disease. Insulin resistance was defined as a HOMA-IR value greater than the 66th percentile value of the patients included in this study. Survival was estimated according to Kaplan-Meier and by Cox regression. Of 296 patients with PDAC, 99 (33 %) met criteria for being classified as insulin resistant at diagnosis. Median follow-up time after diagnosis was 5.27 ± 0.23 years. Patients with insulin resistance received a diagnosis of PDAC at a similar age compared to patients without insulin resistance (67.1 ± 9 vs. 66.8 ± 10 years, p = 0.68), but were more likely to have a cancer stage ≥3 (23.2 vs. 14.2 %, p = 0.053) and a residual disease after surgery (R1 56.4 vs. 38 %; p = 0.007). The median overall survival was 1.3 ± 0.14 and 1.79 ± 0.11 years for the patients with and without insulin resistance, respectively (p = 0.016). Results did not change when patients with diabetes at PDAC diagnosis were excluded from the analysis. Multivariate analysis showed that insulin resistance was independently associated with overall survival. Insulin resistance is associated with the aggressiveness of PDAC.

The role of pancreatic islets in experimental pancreatic carcinogenicity.

PubMed Central

Ishikawa, O.; Ohigashi, H.; Imaoka, S.; Nakai, I.; Mitsuo, M.; Weide, L.; Pour, P. M.

1995-01-01

Our previous studies have suggested that the presence of intact islets is essential for the induction of pancreatic exocrine tumors in the Syrian hamster model. To validate this, we investigated the effect of the carcinogen, N-nitrosobis(2-oxo-propyl)amine (BOP) in hamsters, in which homologous isolated intact islets were transplanted into the submandibular gland (SMG). Freshly isolated pure islets from hamster donors were transplanted into the left SMG of 20 female host hamsters. Ten of these hamsters (group 1) received BOP (40 mg/kg) weekly for 3 weeks. Another 10 hamsters (group 2) were kept untreated. In groups 3 and 4 (10 hamsters each) the salt solution or isolated pancreatic ductal cells, respectively, was injected into the gland. In other groups (10 hamsters each) islets were transplanted into the peri-SMG connective tissue (group 5) or into the renal subcapsular space (group 6). Hamsters of group 1 (40 mg/kg, weekly for 3 weeks) as were group 7 hamsters, which served as BOP-treated controls. All BOP-treated hamsters developed pancreatic lesions. Similar hyperplastic and atypical ductal/ductular proliferation and in situ carcinoma were found in the SMG of many group 1 hamsters. No such lesions were found in the SMG, peri-SMG, or renal subcapsular space of the other groups. Islets appear to be involved in carcinogenicity of BOP. The mechanism is obscure. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7485408

Metastatic pancreatic cancer presenting as linitis plastica of the stomach.

PubMed

Garg, Shivani; Mulki, Ramzi; Sher, Daniel

2016-03-08

Metastatic disease from pancreatic carcinoma involving the stomach is an unusual event, and the pattern of spread in the form of linitis plastica, to our knowledge, has not been reported previously. Local recurrence after curative resection for pancreatic cancer is the most common pattern of disease. We report a case of metastatic pancreatic adenocarcinoma presenting as linitis plastica of the stomach 4 years after curative resection. A 52-year-old man presented with epigastric pain and melaena 4 years after undergoing a Whipple's procedure for a poorly-differentiated pancreatic adenocarcinoma, stage IB; T2N0M0. CT imaging of the abdomen revealed thickening of the gastric wall, and subsequent oesophagogastroduodenoscopy (OGD) revealed diffuse friable erythaematous tissue. The biopsy specimen obtained during the OGD revealed a poorly differentiated adenocarcinoma, with similar appearance to the prior specimen obtained from the pancreas. 2016 BMJ Publishing Group Ltd.

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

PKD signaling and pancreatitis

PubMed Central

Yuan, Jingzhen; Pandol, Stephen J.

2016-01-01

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

Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial.

PubMed

Basset-Seguin, Nicole; Hauschild, Axel; Grob, Jean-Jacques; Kunstfeld, Rainer; Dréno, Brigitte; Mortier, Laurent; Ascierto, Paolo A; Licitra, Lisa; Dutriaux, Caroline; Thomas, Luc; Jouary, Thomas; Meyer, Nicolas; Guillot, Bernard; Dummer, Reinhard; Fife, Kate; Ernst, D Scott; Williams, Sarah; Fittipaldo, Alberto; Xynos, Ioannis; Hansson, Johan

2015-06-01

The Hedgehog pathway inhibitor vismodegib has shown clinical benefit in patients with advanced basal cell carcinoma and is approved for treatment of patients with advanced basal cell carcinoma for whom surgery is inappropriate. STEVIE was designed to assess the safety of vismodegib in a situation similar to routine practice, with a long follow-up. In this multicentre, open-label trial, adult patients with histologically confirmed locally advanced basal cell carcinoma or metastatic basal cell carcinoma were recruited from regional referral centres or specialist clinics. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and adequate organ function. Patients with locally advanced basal cell carcinoma had to have been deemed ineligible for surgery. All patients received 150 mg oral vismodegib capsules once a day on a continuous basis in 28-day cycles. The primary objective was safety (incidence of adverse events until disease progression or unacceptable toxic effects), with assessments on day 1 of each treatment cycle (28 days) by principal investigator and coinvestigators at the site. Efficacy variables were assessed as secondary endpoints. The safety evaluable population included all patients who received at least one dose of study drug. Patients with histologically confirmed basal cell carcinoma who received at least one dose of study drug were included in the efficacy analysis. An interim analysis was pre-planned after 500 patients achieved 1 year of follow-up. This trial is registered with ClinicalTrials.gov, number NCT01367665. The study is still ongoing. Between June 30, 2011, and Nov 6, 2014, we enrolled 1227 patients. At clinical cutoff (Nov 6, 2013), 499 patients (468 with locally advanced basal cell carcinoma and 31 with metastatic basal cell carcinoma) had received study drug and had the potential to be followed up for 12 months or longer. Treatment was discontinued in 400 (80

Translating Discovery in Zebrafish Pancreatic Development to Human Pancreatic Cancer: Biomarkers, Targets, Pathogenesis, and Therapeutics

PubMed Central

Kazi, Abid A.; Yee, Rosemary K.

2013-01-01

Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer. PMID:23682805

Translating discovery in zebrafish pancreatic development to human pancreatic cancer: biomarkers, targets, pathogenesis, and therapeutics.

PubMed

Yee, Nelson S; Kazi, Abid A; Yee, Rosemary K

2013-06-01

Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

[Latest advances in acute pancreatitis].

PubMed

de-Madaria, Enrique

2013-10-01

The present article analyzes the main presentations on acute pancreatitis (AP) in Digestive Disease Week 2013. Perfusion computed tomography allows early diagnosis of pancreatic necrosis. Neutrophil gelatinase-associated lipocalin predicts the development of acute renal failure, severe AP and death. Factors associated with greater fluid sequestration in AP are alcoholic etiology, an elevated hematocrit, and the presence of criteria of systemic inflammatory response syndrome; fluid sequestration is associated with a worse outcome. True pseudocysts (fluid collections without necrosis for more than 4 weeks) are a highly infrequent complication in AP. Patients with necrotic collections have a poor prognosis, especially if associated with infection. A meta-analysis on fluid therapy suggests that early aggressive fluid administration is associated with higher mortality and more frequent respiratory complications. According to a meta-analysis, enteral nutrition initiated within 24 hours of admission improves the outcome of AP compared with later initiation of enteral nutrition. Pentoxifylline could be a promising alternative in AP; a double-blind randomized study showed that this drug reduced the length of hospital and intensive care unit stay, as well as the need for intensive care unit admission. The association of octreotide and celecoxib seems to reduce the frequency of organ damage compared with octreotide alone. Mild AP can be managed in the ambulatory setting through hospital-at-home units after a short, 24-hour admission. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Gut microbial profile analysis by MiSeq sequencing of pancreatic carcinoma patients in China

PubMed Central

Xie, Haiyang; Li, Ang; Lu, Haifeng; Xu, Shaoyan; Zhou, Lin; Zhang, Hua; Cui, Guangying; Chen, Xinhua; Liu, Yuanxing; Wu, Liming; Qin, Nan; Sun, Ranran; Wang, Wei; Li, Lanjuan; Wang, Weilin; Zheng, Shusen

2017-01-01

Pancreatic carcinoma (PC) is a lethal cancer. Gut microbiota is associated with some risk factors of PC, e.g. obesity and types II diabetes. However, the specific gut microbial profile in clinical PC in China has never been reported. This prospective study collected 85 PC and 57 matched healthy controls (HC) to analyze microbial characteristics by MiSeq sequencing. The results showed that gut microbial diversity was decreased in PC with an unique microbial profile, which partly attributed to its decrease of alpha diversity. Microbial alterations in PC featured by the increase of certain pathogens and lipopolysaccharides-producing bacteria, and the decrease of probiotics and butyrate-producing bacteria. Microbial community in obstruction cases was separated from the un-obstructed cases. Streptococcus was associated with the bile. Furthermore, 23 microbial functions e.g. Leucine and LPS biosynthesis were enriched, while 13 functions were reduced in PC. Importantly, based on 40 genera associated with PC, microbial markers achieves a high classification power with AUC of 0.842. In conclusion, gut microbial profile was unique in PC, providing a microbial marker for non-invasive PC diagnosis. PMID:29221120

Sapanisertib and Ziv-Aflibercept in Treating Patients With Recurrent Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-03-07

Advanced Malignant Solid Neoplasm; Fibrolamellar Carcinoma; Metastatic Malignant Solid Neoplasm; Ovarian Carcinoma; Pancreatic Neuroendocrine Tumor; Recurrent Malignant Solid Neoplasm; Refractory Malignant Solid Neoplasm; Unresectable Solid Neoplasm

Safety and Immune Response to a Multi-component Immune Based Therapy (MKC1106-PP) for Patients With Advanced Cancer.

ClinicalTrials.gov

2010-08-02

Ovarian; Melanoma; Renal; Prostate; Colorectal; Endometrial Carcinoma; Cervical Carcinoma; Testicular Cancer; Thyroid Cancer; Small Cell Lung Carcinoma; Mesothelioma; Breast Carcinoma; Esophageal Carcinoma; Gastric Cancer; Pancreatic Carcinoma; Neuroendocrine Cancer; Liver Cancer; Gallbladder Cancer; Biliary Tract Cancer; Anal Carcinoma; Bone Sarcomas; Soft Tissue Sarcomas; Carcinoma of Unknown Origin, Primary

Overcoming Drug Resistance in Pancreatic Cancer

PubMed Central

Long, Jiang; Zhang, Yuqing; Yu, Xianjun; Yang, Jingxuan; LeBrun, Drake; Chen, Changyi; Yao, Qizhi; Li, Min

2011-01-01

Introduction Pancreatic cancer has the worst survival rate of all cancers. The current standard care for metastatic pancreatic cancer is gemcitabine, however, the success of this treatment is poor and overall survival has not improved for decades. Drug resistance (both intrinsic and acquired) is thought to be a major reason for the limited benefit of most pancreatic cancer therapies. Areas covered Previous studies have indicated various mechanisms of drug resistance in pancreatic cancer, including changes in individual genes or signaling pathways, the influence of the tumor microenvironment, and the presence of highly resistant stem cells. This review summarizes recent advances in the mechanisms of drug resistance in pancreatic cancer, and potential strategies to overcome this. Expert Opinion Increasing drug delivery efficiency and decreasing drug resistance is the current aim in pancreatic cancer treatment, and will also benefit the treatment of other cancers. Understanding the molecular and cellular basis of drug resistance in pancreatic cancer will lead to the development of novel therapeutic strategies with the potential to sensitize pancreatic cancer to chemotherapy, and to increase the efficacy of current treatments in a wide variety of human cancers. PMID:21391891

Animal models for investigating chronic pancreatitis

PubMed Central

2011-01-01

Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

Therapeutic options in locally advanced thyroid carcinoma. Our experience.

PubMed

Avenia, Nicola; Monacelli, Massimo; Sanguinetti, Alessandro; Santoprete, Stefano; Pecoriello, Roberta; Ragusa, Mark; Puma, Francesco

2012-01-01

Thyroid cancer is the most common endocrine malignancy with an incidence equal to 1% of all malignant tumors. Prognostic factors affecting survival are manifold, including in several classifications (AMES, AGES, CORN and TNM). In this sense, the invasion of adjacent structures is one of the most important variables. The authors describe the experience of a single center in surgical treatment of advanced thyroid cancer. Between 1986 and 2010 , 1565 patients were undergoing surgery with thyroid cancer. In particular, 1403 interventions were made for differentiated cancer, 97 for medullary carcinoma, 25 for insular carcinoma, 29 for anaplastic carcinoma, 2 for plasmacytoma, and 7 for lymphoma and 2 for angiosarcoma. Among these 896 showed invasion of adjacent structures and / or distant metastases. There were no perioperative deaths or major complications. Surgical procedures consisted of: 13 loboistmectomy, 519 total thyroidectomy (TT), 325 TT with lymphadenectomy of the central compartment, 7 TT with radical lymphectomy, 621 TT with functional lymphectomy, 6 TT with breast lumpectomy, 5 TT with with video-assisted lung metastasectomy, 16-TT with resection and tracheal anastomosis, 6 TT with laryngotracheal resection, 3 TT with laryngectomy, 4 TT with trachetomy, 28 TT with respiratory stent placement, 12 tracheotomy. At present, 1328 patients were free of disease, while 104 showed recurrence. Total of 133 deaths were recorded, all linked to disease relapse. The role of surgery in the treatment of advanced thyroid cancer is still undeniable. In the presence of extracapsular trespassing, in fact, the adoption of interventions demolition permits long-term survival, given the lack of aggressiveness of the tumor differentiated representing the majority of cases. The aim of surgical radicalization addition, even in the presence of distant metastases, it is justified by the possibilities offered by the therapeutic radioiodine treatment, which is not feasible in the

Gemcitabine Chemotherapy and Single-Fraction Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schellenberg, Devin; Goodman, Karyn A.; Lee, Florence

2008-11-01

Purpose: Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control. This prospective trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered between Cycle 1 and 2 of gemcitabine chemotherapy. Methods and Materials: A total of 16 patients with locally advanced, nonmetastatic, pancreatic adenocarcinoma received gemcitabine with SBRT delivered 2 weeks after completion of the first cycle. Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity. The gross tumor volume, with a 2-3-mm margin, was treated in a single 25-Gy fraction by Cyberknife.more » Patients were evaluated at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All 16 patients completed SBRT. A median of four cycles (range one to nine) of chemotherapy was delivered. Three patients (19%) developed local disease progression at 14, 16, and 21 months after SBRT. The median survival was 11.4 months, with 50% of patients alive at 1 year. Patients with normal carbohydrate antigen (CA)19-9 levels either at diagnosis or after Cyberknife SBRT had longer survival (p <0.01). Acute gastrointestinal toxicity was mild, with 2 cases of Grade 2 (13%) and 1 of Grade 3 (6%) toxicity. Late gastrointestinal toxicity was more common, with five ulcers (Grade 2), one duodenal stenosis (Grade 3), and one duodenal perforation (Grade 4). A trend toward increased duodenal volumes radiated was observed in those experiencing late effects (p = 0.13). Conclusion: SBRT with gemcitabine resulted in comparable survival to conventional chemoradiotherapy and good local control. However, the rate of duodenal ulcer development was significant.« less

Icotinib plus gemcitabine for metastatic pancreatic cancer: A case report

PubMed Central

Zhao, Jing; Shen, Hong; Hu, Han-Guang; Huang, Jian-Jin

2015-01-01

A large majority of patients diagnosed with pancreatic cancer have advanced metastatic disease with unresectable malignancies. Despite treatment advances, the survival benefit from chemotherapeutic regimens and targeted drugs is limited. Moreover, their application is limited in China because of high toxicity and cost. Recently, inhibitors of epidermal growth factor receptor activity have shown promise for the treatment of solid cancers when used in combination with standard therapy. However, these drugs have not been evaluated extensively for the treatment of pancreatic cancer. Here, we report the treatment of a 64-year-old male with metastatic pancreatic cancer using a novel regimen of icotinib with gemcitabine. Marked shrinkage of the mass was observed after two treatment cycles, and partial remission was achieved. The abdominal pain was relieved. The adverse effects were tolerable and treatment cost was acceptable. This is the first reported case for the treatment of advanced pancreatic cancer with icotinib plus gemcitabine and demonstrates a promising therapeutic alternative. PMID:25805958

Icotinib plus gemcitabine for metastatic pancreatic cancer: a case report.

PubMed

Zhao, Jing; Shen, Hong; Hu, Han-Guang; Huang, Jian-Jin

2015-03-21

A large majority of patients diagnosed with pancreatic cancer have advanced metastatic disease with unresectable malignancies. Despite treatment advances, the survival benefit from chemotherapeutic regimens and targeted drugs is limited. Moreover, their application is limited in China because of high toxicity and cost. Recently, inhibitors of epidermal growth factor receptor activity have shown promise for the treatment of solid cancers when used in combination with standard therapy. However, these drugs have not been evaluated extensively for the treatment of pancreatic cancer. Here, we report the treatment of a 64-year-old male with metastatic pancreatic cancer using a novel regimen of icotinib with gemcitabine. Marked shrinkage of the mass was observed after two treatment cycles, and partial remission was achieved. The abdominal pain was relieved. The adverse effects were tolerable and treatment cost was acceptable. This is the first reported case for the treatment of advanced pancreatic cancer with icotinib plus gemcitabine and demonstrates a promising therapeutic alternative.

Inaugural Meeting of North American Pancreatic Cancer Organizations: Advancing Collaboration and Communication.

PubMed

Kenner, Barbara J; Fleshman, Julie M; Goldberg, Ann E; Rothschild, Laura J

2015-11-01

A meeting of North American Pancreatic Cancer Organizations planned by Kenner Family Research Fund and Pancreatic Cancer Action Network was held on July 15-16, 2015, in New York City. The meeting was attended by 32 individuals from 20 nonprofit groups from the United States and Canada. The objectives of this inaugural convening were to share mission goals and initiatives, engage as leaders, cultivate potential partnerships, and increase participation in World Pancreatic Cancer Day. The program was designed to provide opportunities for informal conversations, as well as facilitated discussions to meet the stated objectives. At the conclusion of the meeting, the group agreed that enhancing collaboration and communication will result in a more unified approach within the field and will benefit individuals diagnosed with pancreatic cancer. As a first step, the group will actively collaborate to participate in World Pancreatic Cancer Day, which is planned for November 13, 2015, and seeks to raise the level of visibility about the disease globally.

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

PubMed

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

2016-03-01

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

Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

PubMed

Anderson, Mark J; Kwong, Christina A; Atieh, Mohammed; Pappas, Sam G

2016-06-02

Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies. 2016 BMJ Publishing Group Ltd.

The side effects and complications of percutaneous iodine-125 seeds implantation under CT-guide for patients with advanced pancreatic cancer.

PubMed

Lv, Wei-Fu; Lu, Dong; Xiao, Jing-Kun; Mukhiya, Gauri; Tan, Zhong-Xiao; Cheng, De-Lei; Zhou, Chun-Ze; Zhang, Xing-Min; Zhang, Zheng-Feng; Hou, Chang-Long

2017-12-01

The present study investigates the side effects and complications of computed tomography (CT)-guided percutaneous iodine-125 (I-125) seeds implantation for advanced pancreatic cancer. The clinical data were retrospectively analyzed for patients treated with implantation of I-125 seeds under CT-guide in our hospital from May 2010 to April 2015. The side effects and complications were collected and their possible reasons were analyzed. A total of 78 patients were enrolled. The side effects were categorized as fever in 29 cases (37.18%), abdominal pain in 26 cases (33.33%), nausea and vomiting in 9 cases (11.54%), diarrhea in 5 cases (6.41%), and constipation in 4 cases (5.13%). Complications were composed of pancreatitis in 9 cases (11.54%), infection in 5 cases (6.41%), seed migration in 2 cases (2.56%), intestinal perforation in 1 case (1.28%), and intestinal obstruction in 1 case. The incidence of complication was 23.08% (18/78). The difference in incidence of complication was statistically significant between patients implanted with ≤27 seeds and those with >27 seeds (P = .032). The side effects and complications frequently occur in implantation of I-125 seeds for patients with advanced pancreatic cancer. More concern should be given to the patients treated by this technique. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

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

PubMed

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

2016-03-01

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.

Secretin-stimulated MRI characterization of pancreatic morphology and function in patients with chronic pancreatitis.

PubMed

Madzak, Adnan; Olesen, Søren Schou; Haldorsen, Ingfrid Salvesen; Drewes, Asbjørn Mohr; Frøkjær, Jens Brøndum

Chronic pancreatitis (CP) is characterized by abnormal pancreatic morphology and impaired endocrine and exocrine function. However, little is known about the relationship between pancreatic morphology and function, and also the association with the etiology and clinical manifestations of CP. The aim was to explore pancreatic morphology and function with advanced MRI in patients with CP and healthy controls (HC) METHODS: Eighty-two patients with CP and 22 HC were enrolled in the study. Morphological imaging parameters included pancreatic main duct diameter, gland volume, fat signal fraction and apparent diffusion coefficient (ADC) values. Functional secretin-stimulated MRI (s-MRI) parameters included pancreatic secretion (bowel fluid volume) and changes in pancreatic ADC value before and after secretin stimulation. Patients were classified according to the modified Cambridge and M-ANNHEIM classification system and fecal elastase was collected. All imaging parameters differentiated CP patients from HC; however, correlations between morphological and functional parameters in CP were weak. Patients with alcoholic and non-alcoholic etiology had comparable s-MRI findings. Fecal elastase was positively correlated to pancreatic gland volume (r = 0.68, P = 0.0016) and negatively correlated to Cambridge classification (r = -0.35, P < 0.001). Additionally, gland volume was negatively correlated to the duration of CP (r = -0.39, P < 0.001) and baseline ADC (r = -0.35, P = 0.027). When stratified by clinical stage (M-ANNHEIM), the pancreatic gland volume was significantly decreased in the severe stages of CP (P = 0.001). S-MRI provides detailed information about pancreatic morphology and function and represents a promising non-invasive imaging method to characterize pancreatic pathophysiology and may enable monitoring of disease progression in patients with CP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

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.

Advances in Merkel cell carcinoma from a pathologist's perspective.

PubMed

Barksdale, Sarah Kay

2017-10-01

Merkel cell carcinoma (MCC) is a rarely made but potentially devastating diagnosis. While local disease might be cured by surgery and radiotherapy, advanced disease is usually rapidly progressive and fatal. Until very recently, the only approach to metastatic MCC was cytotoxic chemotherapy with results so disappointing that current treatment guidelines discourage its use and recommend clinical trial as a more viable treatment option. Fortunately, recent advances in the understanding of the molecular pathogenesis of this tumour have produced a wide variety of experimental treatments for MCC, some of which are quite promising. The most current information regarding the diagnosis, staging, management of this tumour is briefly presented as well as new insights into the molecular basis of MCC and therapeutic approaches to MCC. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials.

PubMed

Zahra, Amir; Fath, Melissa A; Opat, Emyleigh; Mapuskar, Kranti A; Bhatia, Sudershan K; Ma, Daniel C; Rodman, Samuel N; Snyders, Travis P; Chenard, Catherine A; Eichenberger-Gilmore, Julie M; Bodeker, Kellie L; Ahmann, Logan; Smith, Brian J; Vollstedt, Sandy A; Brown, Heather A; Hejleh, Taher Abu; Clamon, Gerald H; Berg, Daniel J; Szweda, Luke I; Spitz, Douglas R; Buatti, John M; Allen, Bryan G

2017-06-01

Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes. Mice bearing MIA PaCa-2 pancreatic cancer xenografts were fed either a ketogenic diet or standard rodent chow, treated with conventionally fractionated radiation (2 Gy/fraction), and tumor growth rates were assessed daily. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modfied proteins as a marker of oxidative stress. Based on this and another previously published preclinical study, phase 1 clinical trials in locally advanced NSCLC and pancreatic cancer were initiated, combining standard radiation and chemotherapy with a ketogenic diet for six weeks (NSCLC) or five weeks (pancreatic cancer). The xenograft experiments demonstrated prolonged survival and increased 4HNE-modfied proteins in animals consuming a ketogenic diet combined with radiation compared to radiation alone. In the phase 1 clinical trial, over a period of three years, seven NSCLC patients enrolled in the study. Of these, four were unable to comply with the diet and withdrew, two completed the study and one was withdrawn due to a dose-limiting toxicity. Over the same time period, two pancreatic cancer patients enrolled in the trial. Of these, one completed the study and the other was withdrawn due to a dose-limiting toxicity. The preclinical experiments demonstrate that a ketogenic diet increases radiation sensitivity

Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma.

PubMed

Ito, Yasuhiro; Onoda, Naoyoshi; Ito, Ken-Ichi; Sugitani, Iwao; Takahashi, Shunji; Yamaguchi, Iku; Kabu, Koki; Tsukada, Katsuya

2017-09-01

Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent. A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7-5.6], and median OS was 5.0 months [confidence interval 0.7-5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%. The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and

Mechanisms of inhibition of growth of human pancreatic carcinoma implanted in nude mice by somatostatin receptor subtype 2.

PubMed

Kumar, Manoj; Liu, Zheng-Ren; Thapa, Laxmi; Wang, Da-Yu; Tian, Rui; Qin, Ren-Yi

2004-08-01

significant differences were observed between the vector control and mock control (P > 0.05). Re-expression of the SSTR2 gene, the expression of which is frequently lost in human pancreatic adenocarcinoma, induces apoptosis, which may be mediated via down-regulation of Bcl-2 and up-regulation of Bax (alteration of Bcl-2/Bax ratio) and inhibits tumor angiogenesis in pancreatic carcinoma, resulting in inhibition of tumor growth.

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

2018-06-22

Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary-Mucinous Neoplasm; Stage I Pancreatic Cancer AJCC v6 and v7; Stage IA Pancreatic Cancer AJCC v6 and v7; Stage IB Pancreatic Cancer AJCC v6 and v7; Stage II Pancreatic Cancer AJCC v6 and v7; Stage IIA Pancreatic Cancer AJCC v6 and v7; Stage IIB Pancreatic Cancer AJCC v6 and v7

Identification and characterization of poorly differentiated invasive carcinomas in a mouse model of pancreatic neuroendocrine tumorigenesis.

PubMed

Hunter, Karen E; Quick, Marsha L; Sadanandam, Anguraj; Hanahan, Douglas; Joyce, Johanna A

2013-01-01

Pancreatic neuroendocrine tumors (PanNETs) are a relatively rare but clinically challenging tumor type. In particular, high grade, poorly-differentiated PanNETs have the worst patient prognosis, and the underlying mechanisms of disease are poorly understood. In this study we have identified and characterized a previously undescribed class of poorly differentiated PanNETs in the RIP1-Tag2 mouse model. We found that while the majority of tumors in the RIP1-Tag2 model are well-differentiated insulinomas, a subset of tumors had lost multiple markers of beta-cell differentiation and were highly invasive, leading us to term them poorly differentiated invasive carcinomas (PDICs). In addition, we found that these tumors exhibited a high mitotic index, resembling poorly differentiated (PD)-PanNETs in human patients. Interestingly, we identified expression of Id1, an inhibitor of DNA binding gene, and a regulator of differentiation, specifically in PDIC tumor cells by histological analysis. The identification of PDICs in this mouse model provides a unique opportunity to study the pathology and molecular characteristics of PD-PanNETs.

The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer

PubMed Central

Martínez-Bosch, Neus; Guerrero, Pedro Enrique; Moreno, Mireia; José, Anabel; Iglesias, Mar; Munné-Collado, Jessica; Anta, Héctor; Gibert, Joan; Orozco, Carlos Alberto; Vinaixa, Judith; Fillat, Cristina; Viñals, Francesc; Navarro, Pilar

2016-01-01

Current treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in pancreatic cancer using the Ela-myc transgenic mouse model. We showed that Ela-myc pancreatic tumors express PDGFR and VEGFR in blood vessels and epithelial cells, rendering these tumors sensitive to sunitinib by more than only its anti-angiogenic activity. However, sunitinib treatment of Ela-myc mice with either early or advanced tumor progression had no impact on either survival or tumor burden. Further histopathological characterization of these tumors did not reveal differences in necrosis, cell differentiation, angiogenesis, apoptosis or proliferation. In stark contrast, in vitro sunitinib treatment of Ela-myc– derived cell lines showed high sensitivity to the drug, with increased apoptosis and reduced proliferation. Correspondingly, subcutaneous tumors generated from these cell lines completely regressed in vivo after sunitinib treatments. These data point at the pancreatic tumor microenvironment as the most likely barrier preventing sunitinib treatment efficiency in vivo. Combined treatments with drugs that disrupt tumor fibrosis may enhance sunitinib therapeutic effectiveness in pancreatic cancer treatment. PMID:27374084

Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2018-01-12

Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

PubMed Central

Kang, Tae Wook; Rhim, Hyunchul

2015-01-01

Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

Biological effects of low-dose-rate irradiation of pancreatic carcinoma cells in vitro using 125I seeds

PubMed Central

Wang, Zhong-Min; Lu, Jian; Zhang, Li-Yun; Lin, Xiao-Zhu; Chen, Ke-Min; Chen, Zhi-Jin; Liu, Fen-Ju; Yan, Fu-Hua; Teng, Gao-Jun; Mao, Ai-Wu

2015-01-01

AIM: To determine the mechanism of the radiation-induced biological effects of 125I seeds on pancreatic carcinoma cells in vitro. METHODS: SW1990 and PANC-1 pancreatic cancer cell lines were cultured in DMEM in a suitable environment. Gray’s model of iodine-125 (125I) seed irradiation was used. In vitro, exponential phase SW1990, and PANC-1 cells were exposed to 0, 2, 4, 6, and 8 Gy using 125I radioactive seeds, with an initial dose rate of 12.13 cGy/h. A clonogenic survival experiment was performed to observe the ability of the cells to maintain their clonogenic capacity and to form colonies. Cell-cycle and apoptosis analyses were conducted to detect the apoptosis percentage in the SW1990 and PANC-1 cells. DNA synthesis was measured via a tritiated thymidine (3H-TdR) incorporation experiment. After continuous low-dose-rate irradiation with 125I radioactive seeds, the survival fractions at 2 Gy (SF2), percentage apoptosis, and cell cycle phases of the SW1990 and PANC-1 pancreatic cancer cell lines were calculated and compared. RESULTS: The survival fractions of the PANC-1 and SW1990 cells irradiated with 125I seeds decreased exponentially as the dose increased. No significant difference in SF2 was observed between SW1990 and PANC-1 cells (0.766 ± 0.063 vs 0.729 ± 0.045, P < 0.05). The 125I seeds induced a higher percentage of apoptosis than that observed in the control in both the SW1990 and PANC-1 cells. The rate of apoptosis increased with increasing radiation dosage. The percentage of apoptosis was slightly higher in the SW1990 cells than in the PANC-1 cells. Dose-dependent G2/M cell-cycle arrest was observed after 125I seed irradiation, with a peak value at 6 Gy. As the dose increased, the percentage of G2/M cell cycle arrest increased in both cell lines, whereas the rate of DNA incorporation decreased. In the 3H-TdR incorporation experiment, the dosimetry results of both the SW1990 and PANC-1 cells decreased as the radiation dose increased, with a minimum

Endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma: Is it a significant prognostic factor?

PubMed

Shin, Hae Jin; Moon, Hee Seok; Kang, Sun Hyung; Sung, Jae Kyu; Jeong, Hyun Yong; Kim, Seok Hyun; Lee, Byung Seok; Kim, Ju Seok; Yun, Gee Young

2017-12-01

The purpose of this study was to evaluate the prognostic impact of endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma.This retrospective study was based on medical records from a single tertiary medical center. The records of 317 patients with esophageal squamous cell carcinoma treated with surgery or definitive chemoradiotherapy (CRT) between January 2009 and March 2016 were reviewed. Finally, we retrieved the data on 168 consecutive patients. These 168 patients were divided into 2 groups based on their endoscopic traversability findings: Group A (the endoscope traversable group), and Group B (the endoscope non-traversable group). We then retrospectively compared the clinical characteristics of these 2 groups.The endoscope non-traversable group (Group B) revealed an advanced clinical stage, a poor Eastern Cooperative Oncology Group (ECOG) score, a lower serum albumin level, a higher rate of requirement for esophageal stent insertion and definitive CRT as initial treatment than the endoscope traversable group (Group A). Patients with endoscope traversable cancer showed a significantly higher 3-year overall survival and 3-year relapse-free survival than patients who were endoscope non-traversable (53.8% vs 17.3%, P < .001 and 71.1% vs 45.3%, P = .003, respectively). Upon multivariate analysis of patients with locally advanced esophageal squamous cell carcinoma treated with definitive CRT, the serum albumin level <3.5 g/dL and endoscopic non-traversability were significant negative factors of survival.Endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma treated with definitive CRT is a significant prognostic factor. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system.

PubMed

Yamaguchi, Tomohiro; Machida, Nozomu; Morizane, Chigusa; Kasuga, Akiyoshi; Takahashi, Hideaki; Sudo, Kentaro; Nishina, Tomohiro; Tobimatsu, Kazutoshi; Ishido, Kenji; Furuse, Junji; Boku, Narikazu; Okusaka, Takuji

2014-09-01

This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato-biliary-pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n = 85), stomach (n = 70), small bowel (n = 6), colorectum (n = 31), hepato-biliary system (n = 31) and pancreas (n = 31). Median overall survival (OS) was 13.4 months the esophagus, 13.3 months for the stomach, 29.7 months for the small bowel, 7.6 months for the colorectum, 7.9 months for the hepato-biliary system and 8.5 months for the pancreas. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI-NEC and HBP-NEC. For patients treated with IP/EP (n = 160/46), the response rate was 50/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs HBP; hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.97) and baseline serum lactate dehydrogenase levels (not elevated vs elevated; HR 0.65, 95% CI 0.46-0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48-1.33; P = 0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated lactate dehydrogenase levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Advances in surgical treatment of chronic pancreatitis.

PubMed

Ni, Qingqiang; Yun, Lin; Roy, Manish; Shang, Dong

2015-02-08

The incidence of chronic pancreatitis (CP) is between 2 and 200 per 100,000 persons and shows an increasing trend year by year. India has the highest incidence of CP in the world at approximately 114 to 200 per 100,000 persons. The incidence of CP in China is approximately 13 per 100,000 persons. The aim of this review is to assist surgeons in managing patients with CP in surgical treatment. We conducted a PubMed search for "chronic pancreatitis" and "surgical treatment" and reviewed relevant articles. On the basis of our review of the literature, we found that CP cannot be completely cured. The purpose of surgical therapy for CP is to relieve symptoms, especially pain; to improve the patient's quality of life; and to treat complications. Decompression (drainage), resection, neuroablation and decompression combined with resection are commonly used methods for the surgical treatment of CP. Before developing a surgical regimen, surgeons should comprehensively evaluate the patient's clinical manifestations, auxiliary examination results and medical history to develop an individualized surgical treatment regimen.

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

Pancreatic Cancer: Multicenter Prospective Data Collection and Analysis by the Hungarian Pancreatic Study Group.

PubMed

Lakatos, Gábor; Balázs, Anita; Kui, Balázs; Gódi, Szilárd; Szücs, Ákos; Szentesi, Andrea; Szentkereszty, Zsolt; Szmola, Richárd; Kelemen, Dezső; Papp, Róbert; Vincze, Áron; Czimmer, József; Pár, Gabriella; Bajor, Judit; Szabó, Imre; Izbéki, Ferenc; Halász, Adrienn; Leindler, László; Farkas, Gyula; Takács, Tamás; Czakó, László; Szepes, Zoltán; Hegyi, Péter; Kahán, Zsuzsanna

2016-06-01

Pancreatic cancer is a devastating disease with poor prognosis. There is very limited information available regarding the epidemiology and treatment strategies of pancreatic cancer in Central Europe. The purpose of the study was to prospectively collect and analyze data of pancreatic cancer in the Hungarian population. The Hungarian Pancreatic Study Group (HPSG) organized prospective, uniform data collection. Altogether 354 patients were enrolled from 14 Hungarian centers. Chronic pancreatitis was present in 3.7% of the cases, while 33.7% of the patients had diabetes. Family history for pancreatic cancer was positive in 4.8%. The most frequent presenting symptoms included pain (63.8%), weight loss (63%) and jaundice (52.5%). The reported frequency of smoking and alcohol consumption was lower than expected (28.5% and 27.4%, respectively). The majority of patients (75.6%) were diagnosed with advanced disease. Most patients (83.6%) had a primary tumor located in the pancreatic head. The histological diagnosis was ductal adenocarcinoma in 90.7% of the cases, while neuroendocrine tumor was present in 5.3%. Biliary stent implantation was performed in 166 patients, 59.2% of them received metal stents. Primary tumor resection was performed in 60 (16.9%) patients. Enteral or biliary bypass was done in 35 and 49 patients, respectively. In a multivariate Cox-regression model, smoking status and presence of gemcitabine-based chemotherapy were identified as independent predictors for overall survival. We report the first data from a large cohort of Hungarian pancreatic cancer patients. We identified smoking status and chemotherapy as independent predictors in this cohort.

Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis.

PubMed

Cahen, Djuna L; Gouma, Dirk J; Laramée, Philippe; Nio, Yung; Rauws, Erik A J; Boermeester, Marja A; Busch, Olivier R; Fockens, Paul; Kuipers, Ernst J; Pereira, Stephen P; Wonderling, David; Dijkgraaf, Marcel G W; Bruno, Marco J

2011-11-01

A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

High immunosuppressive burden in advanced hepatocellular carcinoma patients: Can effector functions be restored?

PubMed

Lugade, Amit A; Kalathil, Suresh; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

2013-07-01

The accumulation of immunosuppressive cells and exhausted effector T cells highlight an important immune dysfunction in advanced stage hepatocellular carcinoma (HCC) patients. These cells significantly hamper the efficacy immunotherapies and facilitate HCC progression. We have recently demonstrated that the multipronged depletion of immunosuppressive cells potentially restores effector T-cell function in HCC.

Cost-effectiveness analysis of gemcitabine, S-1 and gemcitabine plus S-1 for treatment of advanced pancreatic cancer based on GEST study.

PubMed

Zhou, Jing; Zhao, Rongce; Wen, Feng; Zhang, Pengfei; Tang, Ruilei; Du, Zedong; He, Xiaofeng; Zhang, Jian; Li, Qiu

2015-04-01

Gemcitabine (GEM) alone, S-1 alone and gemcitabine plus S-1 (GS) have shown a marginal clinical benefit for the treatment of advanced pancreatic cancer. However, there is no clearly defined optimal cost-effectiveness treatment. The objective of this study was to assess the cost-effectiveness of GEM alone, S-1 alone and GS for the treatment of advanced pancreatic cancer based on GEST study for public payers. A decision model compared GEM alone, S-1 alone and GS. Primary base case data were identified using the GEST study and the literatures. Costs were estimated from West China Hospital, Sichuan University, China, and incremental cost-effectiveness ratios (ICERs) were calculated. Survival benefits were reported in quality-adjusted life-months (QALMs). Sensitive analyses were performed by varying potentially modifiable parameters of the model. The base case analysis showed that the GEM cost $21,912 and yielded survival of 6.93 QALMs, S-1 cost $19,371 and yielded survival of 7.90 QALMs and GS cost $22,943 and yielded survival of 7.46 QALMs in the entire treatment. The one-way sensitivity analyses showed that the ICER of S-1 was driven mostly by the S-1 group utility score of stable state compared with GEM, and the GEM group utility score of progressed state played a key role on the ICER of GS compared with GEM. S-1 represents an attractive cost-effective treatment for advanced pancreatic cancer, given the favorable cost per QALM and improvement in clinical efficacy, especially the limited available treatment options.

Percutaneous ablation of pancreatic cancer

PubMed Central

D’Onofrio, Mirko; Ciaravino, Valentina; De Robertis, Riccardo; Barbi, Emilio; Salvia, Roberto; Girelli, Roberto; Paiella, Salvatore; Gasparini, Camilla; Cardobi, Nicolò; Bassi, Claudio

2016-01-01

Pancreatic ductal adenocarcinoma is a highly aggressive tumor with an overall 5-year survival rate of less than 5%. Prognosis and treatment depend on whether the tumor is resectable or not, which mostly depends on how quickly the diagnosis is made. Chemotherapy and radiotherapy can be both used in cases of non-resectable pancreatic cancer. In cases of pancreatic neoplasm that is locally advanced, non-resectable, but non-metastatic, it is possible to apply percutaneous treatments that are able to induce tumor cytoreduction. The aim of this article will be to describe the multiple currently available treatment techniques (radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation), their results, and their possible complications, with the aid of a literature review. PMID:27956791

Novel therapies in advanced renal cell carcinoma: management of adverse events from sorafenib and sunitinib.

PubMed

Ivanyi, Philipp; Winkler, Thomas; Ganser, Arnold; Reuter, Christoph; Grünwald, Viktor

2008-03-01

Sorafenib and Sunitinib are the first tyrosine kinase inhibitors licensed for the treatment of advanced renal cell carcinoma. In contrast to conventional chemotherapy, targeted therapies have distinct and specific side effects. Selective review in Medline and the data base of the American Society of Clinical Oncology on the treatment and side effects of tyrosine kinase inhibitors in renal cell carcinoma, drawing on the authors' own experience. Tyrosine kinase inhibitors are characterized by a variety of uncommon side effects, such as lassitude, mucosal inflammation and skin changes. The detection and treatment of adverse events are critical for interdisciplinary cancer treatment in order to ensure patients' safety. This article offers an overview of the unwanted effects of drug therapy in the management of renal cell carcinoma.

Thyroid gland invasion in advanced squamous cell carcinoma of the larynx and hypopharynx.

PubMed

Mangussi-Gomes, João; Danelon-Leonhardt, Fernando; Moussalem, Guilherme Figner; Ahumada, Nicolas Galat; Oliveira, Cleydson Lucena; Hojaij, Flávio Carneiro

Squamous cell carcinoma of the larynx and hypopharynx has the potential to invade the thyroid gland. Despite this risk, the proposition of either partial or total thyroidectomy as part of the surgical treatment of all such cases remains controversial. To evaluate the frequency of invasion of the thyroid gland in patients with advanced laryngeal or hypopharyngeal squamous cell carcinoma submitted to total laryngectomy or pharyngolaryngectomy and thyroidectomy; to determine whether clinic-pathological characteristics can predict glandular involvement. A retrospective case series with chart review, from January 1998 to July 2013, was undertaken in a tertiary care university medical center. An inception cohort of 83 patients with larynx/hypopharynx squamous cell carcinoma was considered. All patients had advanced stage disease (clinically T3-T4) and underwent total laryngectomy or total pharyngolaryngectomy in association with thyroidectomy. Adjuvant therapy was indicated when tumor or neck conditions required. Frequency of thyroid cartilage invasion was calculated; univariate and multivariate analysis of demographic, clinical and pathological characteristics associated with cartilage invasion were performed. The overall frequency of invasion of the thyroid gland was 18.1%. Glandular involvement was associated with invasion of the following structures: anterior commissure (odds ratio=5.13; 95% confidence interval 1.07-24.5), subglottis (odds ratio=12.44; 95% confidence interval 1.55-100.00) and cricoid cartilage (odds ratio=15.95; 95% confidence interval 4.23-60.11). Invasion of the thyroid gland is uncommon in the context of laryngopharyngeal squamous cell carcinoma. Clinical and pathological features such as invasion of the anterior commissure, subglottis and cricoid cartilage are more associated with glandular invasion. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights

First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer.

PubMed

Vaccaro, Vanja; Bria, Emilio; Sperduti, Isabella; Gelibter, Alain; Moscetti, Luca; Mansueto, Giovanni; Ruggeri, Enzo Maria; Gamucci, Teresa; Cognetti, Francesco; Milella, Michele

2013-07-28

To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m(2), infused at 10 mg/m(2) per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA

First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

PubMed Central

Vaccaro, Vanja; Bria, Emilio; Sperduti, Isabella; Gelibter, Alain; Moscetti, Luca; Mansueto, Giovanni; Ruggeri, Enzo Maria; Gamucci, Teresa; Cognetti, Francesco; Milella, Michele

2013-01-01

AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS: We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m2, infused at 10 mg/m2 per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of

Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome

PubMed Central

Serracant Barrera, Anna; Serra Pla, Sheila; Blázquez Maña, Carmen María; Salas, Rubén Carrera; García Monforte, Neus; Bejarano González, Natalia; Romaguera Monzonis, Andreu; Andreu Navarro, Francisco Javier; Bella Cueto, Maria Rosa

2017-01-01

Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and sebomatricoma. With the exception of one P-NET, all these conditions were associated with LS, as confirmed by immunohistochemistry (IHC) and polymerase chain reaction (PCR). LS is caused by a mutation of a mismatch repair (MMR) gene which leads to a loss of expression of its protein. CRC is the most common tumor, followed by EC. Pancreatic tumors have also been associated with LS. Diagnosis of LS is based on clinical criteria (Amsterdam II and Bethesda) and genetic study (MMR gene mutation). The association between LS and our patient’s tumors was confirmed by IHC (loss of expression of proteins MLH1 and its dimer PMS2) and the detection of microsatellite instability (MSI) using PCR. PMID:29184699

[In vitro interaction of human pancreatic cancer cells and rat dorsal root ganglia: a co-culture model].

PubMed

Liu, Zhi-sheng; Wang, Ye; Li, Qiang; Zhang, Sheng-lin; Shi, Yu-rong

2012-04-01

dorsal root ganglion and human pancreatic cancer cell line is successfully established in this study. This MIA PaCa-2/DRG co-culture system demonstrates that the neural-pancreatic carcinoma cell interaction is a mutually beneficial process for the growth of neurites and pancreatic carcinoma cells. The pancreatic cancer cells show a trend of migrating to the DRG along the neurite outgrowth.

Stereotactic Body Radiation Therapy for Locally Advanced and Borderline Resectable Pancreatic Cancer Is Effective and Well Tolerated

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuong, Michael D.; Springett, Gregory M.; Freilich, Jessica M.

Purpose: Stereotactic body radiation therapy (SBRT) provides high rates of local control (LC) and margin-negative (R0) resections for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), respectively, with minimal toxicity. Methods and Materials: A single-institution retrospective review was performed for patients with nonmetastatic pancreatic cancer treated with induction chemotherapy followed by SBRT. SBRT was delivered over 5 consecutive fractions using a dose painting technique including 7-10 Gy/fraction to the region of vessel abutment or encasement and 5-6 Gy/fraction to the remainder of the tumor. Restaging scans were performed at 4 weeks, and resectable patients were considered formore » resection. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: Seventy-three patients were evaluated, with a median follow-up time of 10.5 months. Median doses of 35 Gy and 25 Gy were delivered to the region of vessel involvement and the remainder of the tumor, respectively. Thirty-two BRPC patients (56.1%) underwent surgery, with 31 undergoing an R0 resection (96.9%). The median OS, 1-year OS, median PFS, and 1-year PFS for BRPC versus LAPC patients was 16.4 months versus 15 months, 72.2% versus 68.1%, 9.7 versus 9.8 months, and 42.8% versus 41%, respectively (all P>.10). BRPC patients who underwent R0 resection had improved median OS (19.3 vs 12.3 months; P=.03), 1-year OS (84.2% vs 58.3%; P=.03), and 1-year PFS (56.5% vs 25.0%; P<.0001), respectively, compared with all nonsurgical patients. The 1-year LC in nonsurgical patients was 81%. We did not observe acute grade ≥3 toxicity, and late grade ≥3 toxicity was minimal (5.3%). Conclusions: SBRT safely facilitates margin-negative resection in patients with BRPC pancreatic cancer while maintaining a high rate of LC in unresectable patients. These data support the expanded implementation of SBRT for pancreatic cancer.« less

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiofrequency ablation for locally advanced pancreatic cancer: SMAD4 analysis segregates a responsive subgroup of patients.

PubMed

Paiella, Salvatore; Malleo, Giuseppe; Cataldo, Ivana; Gasparini, Clizia; De Pastena, Matteo; De Marchi, Giulia; Marchegiani, Giovanni; Rusev, Borislav; Scarpa, Aldo; Girelli, Roberto; Giardino, Alessandro; Frigerio, Isabella; D'Onofrio, Mirko; Secchettin, Erica; Bassi, Claudio; Salvia, Roberto

2018-03-01

SMAD4 mutational status correlates with pancreatic ductal adenocarcinoma (PDAC) failure pattern. We investigated in a subset of locally advanced patients submitted to radiofrequency ablation (RFA) whether the assessment of SMAD4 status is a useful way to select the patients. Clinical, radiological, and follow-up details of patients submitted to RFA for locally advanced pancreatic cancer (LAPC), in whom cytohistological material was available at our institution, were retrospectively retrieved. SMAD4 expression was evaluated by immunohistochemistry (IHC) and considered "negative" or "positive." The survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models. The study population consisted of 30 patients. Thirteen patients (43.3%) received RFA upfront, whereas 17 (56.7%) after induction treatments. SMAD4 was mutant in 18 out of 30 patients (60%). The overall estimated post-RFA disease-specific survival (DSS) was 15 months (95% CI 11.64-18.35). The estimated post-RFA DSS of patients with wild-type and mutant SMAD4 was 22 and 12 months, respectively (log-rank p < 0.05). At the multivariate analysis, SMAD4 was the only independent predictor of survival (p = 0.05). The pattern of failure was not associated with SMAD4 status (p = 0.4). Within patients undergoing RFA for LAPC, SMAD4 analysis could segregate a subgroup of subjects with improved survival, who likely benefited from tumor ablation.

Altered expression of extracellular matrix molecules and their receptors in chronic pancreatitis and pancreatic adenocarcinoma in comparison with normal pancreas.

PubMed

Shimoyama, S; Gansauge, F; Gansauge, S; Oohara, T; Beger, H G

1995-12-01

The aim of this study was to elucidate the expression and distribution patterns of both integrins and extracellular matrix (ECM) molecules in chronic pancreatitis (CP) and pancreatic adenocarcinoma (PC) compared with normal pancreas (NP). Expression of nine alpha-subunits (alpha 2-alpha 6, alpha V, alpha L, alpha M, and alpha X), four beta-subunits (beta 1, beta 3-beta 5), and four ECM molecules (type IV collagen, laminin, fibronectin, and vitronectin) was investigated immunohistochemically. In CP, all integrins except alpha V showed nearly the same staining patterns compared with NP. Some acinar cells in CP expressed alpha V. Whereas alpha 2, alpha 3, and alpha 6 expression was stronger and diffuse, no alpha 5 expression was seen in PC. Basement membrane (BM) showed continuous staining in CP, whereas it showed discontinuous/absent staining in PC with antitype IV collagen, laminin, and vitronectin antibodies. Some carcinoma cells showed reverse correlation between alpha 2, alpha 3, and alpha 6 expression and type IV collagen and laminin expression. Fibronectin showed diffuse stromal expression in CP and PC. Some acinar cells or duct cells in CP carcinoma cells in PC showed intracellular VN expression. These results suggest that these integrins and ECM molecules are involved in inflammatory and malignant processes in pancreas.

Does the pancreatic volume reduction rate using serial computed tomographic volumetry predict new onset diabetes after pancreaticoduodenectomy?

PubMed Central

Yun, Sung Pil; Seo, Hyung-Il; Kim, Suk; Kim, Dong Uk; Baek, Dong Hoon

2017-01-01

Abstract Volume reduction of the pancreatic tissues following a pancreatectomy can lead to the deterioration of glucose homeostasis. This is defined as pancreatogenic diabetes mellitus (DM). The objective of this study was to investigate the occurrence of new-onset DM (NODM) and evaluate the risk factors, including the pancreas volume reduction rate in patients undergoing pancreaticoduodenectomy (PD). Sixty-six patients without preoperative DM underwent PD for periampullary tumors between August 2007 and December 2012 and were included in this analysis. These patients underwent follow-up tests and abdominal computed tomography (CT) scan 7 days, 6 months, 12 months, 24 months, and 36 months after the operation. The pancreas volume reduction rate was calculated by CT volumetry. The patients were divided into 2 groups according to the postoperative development of DM. After PD, newly diagnosed DM occurred in 16 patients (24.2%). The incidence of DM was highest among patients with carcinomas with an advanced T stage. The pancreatic volume reduction rate after 6 and 12 months in the NODM group was significantly higher than the normal glucose group in the univariate analysis. In the multivariate analysis, the pancreatic volume reduction rate 6 months after PD was the only significant predictive factor for the development of NODM (P = 0.002). This study suggests that the pancreatic volume reduction rate 6 months after PD was the only significant predictive factor for the development of NODM. CT volumetry of the pancreas may be useful as a predictor of NODM after PD. PMID:28353594

MRI assessed pancreatic morphology and exocrine function are associated with disease burden in chronic pancreatitis.

PubMed

Madzak, Adnan; Olesen, Søren Schou; Lykke Poulsen, Jakob; Bolvig Mark, Esben; Mohr Drewes, Asbjørn; Frøkjær, Jens Brøndum

2017-11-01

The aim of this study was to explore the association between morphological and functional secretin-stimulated MRI parameters with hospitalization, quality of life (QOL), and pain in patients with chronic pancreatitis (CP). This prospective cohort study included 82 patients with CP. Data were obtained from clinical information, QOL, and pain as assessed by questionnaires (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and modified Brief Pain Inventory short form). Secretin-stimulated MRI morphological parameters included pancreatic gland volume, main pancreatic duct diameter, the modified Cambridge Classification of Duct Abnormality, apparent diffusion coefficient, fat signal fraction, and the pancreatic secretion volume as a functional parameter. The primary outcomes were time to first hospitalization related to the CP, as well as annual hospitalization frequency and duration. The secondary outcomes were pain severity, QOL, and pain interference scores. A main pancreatic duct diameter below 5 mm was associated with reduced time to first hospitalization (hazard ratio=2.06; 95% confidence interval: 1.02-4.17; P=0.043). Pancreatic secretion volume was correlated with QOL (r=0.31; P=0.0072) and pain interference score (r=-0.27; P=0.032), and fecal elastase was also correlated with QOL (r=0.28; P=0.017). However, functional and morphological findings were not related to pain intensity. Advanced pancreatic imaging techniques may be a highly sensitive tool for prognostication and monitoring of disease activity and its consequences.

Stent selection for both biliary and pancreatic strictures caused by chronic pancreatitis: multiple plastic stents or metallic stents?

PubMed

Gupta, Rajesh; Reddy, D Nageshwar

2011-09-01

Endoscopic stenting is an effective treatment option in the management of both benign biliary strictures and pancreatic ductal strictures. Plastic stents and self-expandable metal stents have been used with variable success for the management of both benign biliary strictures and pancreatic ductal strictures caused by chronic pancreatitis. Fully covered self-expandable metal stents of improved design represent a major technological advance which has added to the endoscopic armamentarium. Both multiple plastic stents and covered self-expandable metal stents have shown promising results. However, data to support the use of self-expandable metal stents over multiple plastic stents or vice versa are still lacking.

MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

ClinicalTrials.gov

2017-02-08

Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8.

PubMed

Karanjawala, Zarir E; Illei, Peter B; Ashfaq, Raheela; Infante, Jeffrey R; Murphy, Kathleen; Pandey, Akhilesh; Schulick, Richard; Winter, Jordan; Sharma, Rajni; Maitra, Anirban; Goggins, Michael; Hruban, Ralph H

2008-02-01

New markers to distinguish benign reactive glands from infiltrating ductal adenocarcinoma of the pancreas are needed. The gene expression patterns of 24 surgically resected primary infiltrating ductal adenocarcinomas of the pancreas were compared with 18 non-neoplastic samples using the Affymetrix U133 Plus 2.0 Arrays and the Gene Logic GeneExpress Software System. Gene fragments from 4 genes (annexin A8, claudin 18, CXCL5, and S100 A2) were selected from the fragments found to be highly expressed in infiltrating adenocarcinomas when compared with normal tissues. The protein expression of these genes was examined using immunohistochemical labeling of tissue microarrays. Claudin 18 labeled infiltrating carcinomas in a membranous pattern. When compared with normal and reactive ducts, claudin 18 was overexpressed, at least focally, in 159 of 166 evaluable carcinomas (96%). Strong and diffuse claudin 18 overexpression was most often seen in well-differentiated carcinomas (P=0.02). Claudin 18 was overexpressed in 51 of 52 cases (98%) of pancreatic intraepithelial neoplasia. Annexin A8 was at least focally overexpressed in 149 of 154 evaluable infiltrating carcinomas (97%). S100 A2 was at least focally overexpressed in 118 of 154 evaluable infiltrating carcinomas (77%). Non-neoplastic glands also frequently expressed S100 A2 diminishing its potential diagnostic utility. Immunolabeling with antibodies directed against CXCL5 did not reveal any significant differences in protein expression between infiltrating adenocarcinomas and normal pancreatic ducts. Claudin 18 and annexin A8 are frequently highly overexpressed in infiltrating ductal adenocarcinomas when compared with normal reactive ducts, suggesting a role for these molecules in pancreatic ductal adenocarcinomas. Furthermore, these may serve as diagnostic markers, as screening tests and as therapeutic targets.

Management of unresectable, locally advanced pancreatic adenocarcinoma.

PubMed

Salgado, M; Arévalo, S; Hernando, O; Martínez, A; Yaya, R; Hidalgo, M

2018-02-01

The diagnosis of unresectable locally advanced pancreatic adenocarcinoma (LAPC) requires confirmation, through imaging tests, of the unfeasibility of achieving a complete surgical resection, in the absence of metastatic spread. The increase in overall survival (OS), together with an appropriate symptom management is the therapeutic target in LAPC, maintaining an acceptable quality of life and, if possible, increasing the time until the appearance of metastasis. Chemoradiation (CRT) improves OS compared to best support treatment or radiotherapy (RT) but with greater toxicity. No significant increase in OS has been achieved with CRT when compared to chemotherapy (QT) alone in patients without disease progression after four months of treatment with QT. However, a significantly better local control, that is, a significant increase in the time to disease progression was associated with this approach. The greater effectiveness of the schemes FOLFIRINOX and gemcitabine (Gem) + Nab-paclitaxel compared to gemcitabine alone, has been extrapolated from metastatic disease to LAPC, representing a possible alternative for patients with good performance status (ECOG 0-1). In the absence of randomized clinical trials, Gem is the standard treatment in LAPC. If disease control is achieved after 4-6 cycles of QT, the use of CRT for consolidation can be considered an option vs QT treatment maintenance. Capecitabine has a better toxicity profile and effectiveness compared to gemcitabine as a radiosensitizer. After local progression, and without evidence of metastases, treatment with RT or CRT, in selected patients, can support to maintain the regional disease control.

Phase 2 study of ABT-510 in patients with previously untreated advanced renal cell carcinoma.

PubMed

Ebbinghaus, Scot; Hussain, Maha; Tannir, Nizar; Gordon, Michael; Desai, Apurva A; Knight, Raymond A; Humerickhouse, Rod A; Qian, Jiang; Gordon, Gary B; Figlin, Robert

2007-11-15

Angiogenesis is a characteristic of renal cell carcinoma. ABT-510 is an angiogenesis inhibitor that mimics the antiangiogenic properties of thrombospondin-1. This study was designed to assess the safety and efficacy of ABT-510 in patients with advanced renal cell carcinoma. Patients with previously untreated metastatic or unresectable renal cell carcinoma were randomized to treatment with one of two doses of ABT-510, self-administered s.c. twice daily in 28-day treatment periods without intervening rest periods. End points were progression-free survival (PFS), objective response rate, overall survival, and toxicity. The objective response rate was 4% in the 10 mg twice daily group, and there were two unconfirmed PRs in the 100 mg twice daily group. Respective median PFS was 4.2 and 3.3 months, with a 6-month PFS of 39% and 32%. Median overall survival was 27.8 months (10 mg twice daily) and 26.1 months (100 mg twice daily). The most frequent adverse events were injection site reactions (84%), fatigue (50%), headache (20%), and nausea (19%). The incidence of treatment-related, grade 3/4 adverse events was low and included three bleeding episodes (gastrointestinal hemorrhage, intracranial hemorrhage, and hemoptysis) and one thrombotic event (deep vein thrombosis). No deaths were attributed to ABT-510. There was little evidence of clinical activity for ABT-510, and further evaluation as a single agent for treating advanced renal cell carcinoma is not warranted. The evidence of a favorable safety profile may justify further evaluation in combination therapy.

Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

Cancer.gov

A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

Pancreatic stellate cell: physiologic role, role in fibrosis and cancer.

PubMed

Apte, Minote; Pirola, Romano C; Wilson, Jeremy S

2015-09-01

Ever since the first descriptions of methods to isolate pancreatic stellate cells (PSCs) from rodent and human pancreas 17 years ago, rapid advances have been made in our understanding of the biology of these cells and their functions in health and disease. This review updates recent literature in the field, which indicates an increasingly complex role for the cells in normal pancreas, pancreatitis and pancreatic cancer. Work reported over the past 12 months includes improved methods of PSC immortalization, a role for PSCs in islet fibrosis, novel factors causing PSC activation as well as those inducing quiescence, and translational research aimed at inhibiting the facilitatory effects of PSCs on disease progression in chronic pancreatitis as well as pancreatic cancer. Improved understanding of the role of PSCs in pancreatic pathophysiology has prompted a focus on translational studies aimed at developing novel approaches to modulate PSC function in a bid to improve clinical outcomes of two major fibrotic diseases of the pancreas: chronic pancreatitis and pancreatic cancer.

The Epidemiology of Pancreatitis and Pancreatic Cancer

PubMed Central

Yadav, Dhiraj; Lowenfels, Albert B.

2013-01-01

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

Neoadjuvant therapy in pancreatic cancer: an emerging strategy.

PubMed

Bittoni, Alessandro; Santoni, Matteo; Lanese, Andrea; Pellei, Chiara; Andrikou, Kalliopi; Stefano, Cascinu

2014-01-01

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths among men and women, being responsible for 6% of all cancer-related deaths. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. In recent years, increasing evidences support the use of neoadjuvant strategies in pancreatic cancer in patients with resectable pancreatic cancer as well as in patients with borderline resectable or locally advanced PDAC in order to allow early treatment of micrometastatic disease, tumour regression, and reduced risk of peritoneal tumour implantation during surgery. Furthermore, neoadjuvant treatment allows evaluation of tumour response and increases patient's compliance. However, most evidences in this setting come from retrospective analysis or small case series and in many studies chemotherapy or chemoradiation therapies used were suboptimal. Currently, prospective randomized trials using the most active chemotherapy regimens available are trying to define the real benefit of neoadjuvant strategies compared to conventional adjuvant strategies. In this review, the authors examined available data on neoadjuvant treatment in patients with resectable pancreatic cancer as well as in patients with borderline resectable or locally advanced PDAC and the future directions in this peculiar setting.

A prospective study of soluble receptor for advanced glycation end products and adipokines in association with pancreatic cancer in postmenopausal women.

PubMed

White, Donna L; Hoogeveen, Ron C; Chen, Liang; Richardson, Peter; Ravishankar, Milan; Shah, Preksha; Tinker, Lesley; Rohan, Thomas; Whitsel, Eric A; El-Serag, Hashem B; Jiao, Li

2018-05-01

Advanced glycation end products (AGEs) dysregulate adipokines and induce inflammation by binding to their adipocyte receptor (RAGE). Soluble RAGE (sRAGE) prevents AGEs/RAGE signaling. We performed a nested case-control study of the association between sRAGE, adipokines, and incident pancreatic cancer risk in the prospective Women's Health Initiative Study. We individually matched controls (n = 802) to cases (n = 472) on age, race, and blood draw date. We evaluated serum concentrations of sRAGE, adiponectin, leptin, monocyte chemotactic protein 1 (MCP1), and plasminogen activator inhibitor-1 (PAI1) using immunoassay. We used conditional logistic regression model to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for pancreatic cancer over biomarker quartiles (Q1-Q4). We used principal component analysis to create two composite biomarkers and performed a confirmatory factor analysis to examine the association between composite biomarker scores (CBS) and pancreatic cancer risk. Baseline serum sRAGE concentrations were inversely associated with pancreatic cancer risk (aOR Q4 vs. Q1  = 0.70, 95% CI: 0.50-0.99). High MCP1 (aOR Q4 vs. Q1  = 2.55, 95% CI: 1.41-4.61) and the higher CBS including MCP1, PAI1, and leptin (aOR Q4 vs. Q1  = 1.82, 95% CI = 1.04-3.18) were also associated with increased pancreatic cancer risk among women with BMI <25 kg/m 2 (P values for interaction <0.05). We found an inverse association between prediagnostic sRAGE concentrations and risk of incident pancreatic cancer in postmenopausal women. A proinflammatory CBS was associated with increased risk only in women with normal BMI. MCP1 was not modulated by sRAGE. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

ClinicalTrials.gov

2015-09-28

Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; 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 Small Intestine 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; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

[Management of localized, locally advanced and metastatic pancreatic adenocarcinoma].

PubMed

Delpero, Jean-Robert; Turrini, Olivier; Raoul, Jean-Luc

2015-03-01

Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy. The prognosis is extremely poor because PDAC is usually a systemic disease at diagnosis. All stages, the survival does not exceed 5% at 5 years. However 15% of PDAC can be resected and today a margin-negative resection followed by adjuvant chemotherapy remains the only potential for a prolonged survival. Postoperative mortality had significantly decreased and the benefit of postoperative adjuvant chemotherapy has been clearly shown. Substantial progress has been made in the field of palliative chemotherapy by introducing new chemotherapy regimens (FOLFIRINOX [folinic acid, 5-fluorouracil, irinotecan and oxaliplatin] and gemcitabine/nab-paclitaxel), when the patient's performance status allows the use of these drugs. The role of radiation therapy remains controversial.

Management strategies in pancreatic cancer.

PubMed

Campen, Christopher J; Dragovich, Tomislav; Baker, Amanda F

2011-04-01

Current first-line and adjuvant chemotherapeutic strategies for management of patients with pancreatic cancer are reviewed. Pancreatic adenocarcinoma is the 10th most prevalent cancer and the fourth most common cause of cancer deaths in the United States. More than 80% of patients with pancreatic cancer are diagnosed with locally advanced or metastatic disease and are not candidates for surgery; these patients often require multimodal treatment. The most widely used chemotherapy for such patients, as well as patients requiring adjuvant therapy after surgery, is gemcitabine or gemcitabine-based chemotherapy. All current chemotherapies for pancreatic cancer are associated with dose-limiting hematologic toxicity and other adverse effects that require ongoing monitoring and dosage adjustment to balance the benefits and risks of treatment. Pharmacists can play an important role in monitoring and providing drug information and guidance to patients and oncologists. Current investigational strategies include efforts to improve chemotherapy response rates and outcomes through modulation of cell signaling pathways and use of nanotechnology to improve drug delivery. Current management of pancreatic cancer is multifaceted, involving anticancer therapy, supportive care, and toxicity management. Standard systemic therapy with gemcitabine as a single agent or in combination with other cytotoxic agents provides modest benefits in terms of response and symptom control.

Preoperative radiotherapy followed by radical vulvectomy with inguinal lymphadenectomy for advanced vulvar carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rotmensch, J.; Rubin, S.J.; Sutton, H.G.

1990-02-01

A therapeutic alternative to exenteration for large locally advanced vulvar carcinoma involving the rectum, anus, or vagina is the use of preoperative radiation followed by radical surgery. Between 1980 and 1988, 13 patients with Stage III and 3 with Stage IV vulvar carcinoma involving the rectum/anus, urethra, or vagina were treated with 4000 rad to the vulva and 4500 rad to the inguinal and pelvic nodes followed by a radical vulvectomy and inguinal lymphadenectomy 4 weeks later. The overall 5 year cumulative survival was 45%. Twelve tumors regressed after radiation with 62.5% of the patients having visceral preservation while inmore » 4 patients there was no major response to radiation and urinary or fecal diversion was required. Of the 6 recurrences 4 were central and 2 distant. Three patients with central recurrences had tumor within 1 cm of the vulvectomy margin. Complications included wet desquamation, inguinal wound separation, lymphedema, and urethral strictures. There were no operative deaths. It is concluded that the use of preoperative radiation followed by radical vulvectomy may be an alternative to pelvic exenteration in selected patients with advanced vulvar lesions.« less

Utility of Diffusion Weighted Magnetic Resonance Imaging with Multiple B Values in Evaluation of Pancreatic Malignant and Benign Lesions and Pancreatitis.

PubMed

Karadeli, Elif; Erbay, Gurcan; Parlakgumus, Alper; Koc, Zafer

2018-02-01

To determine the feasibility of diffusion-weighted imaging in evaluation of pancreatic lesions and in differentiation of benign from malignant lesions. Descriptive study. Baskent University Adana Teaching and Research Center, Adana, Turkey, between September 2013 and May 2015. Forty-three lesions [pancreas adenocarcinoma (n=25)], pancreatitis (n=10), benign lesion (n=8)] were utilized with diffusion-weighted magnetic resonance imaging with multiple b-values. Different ADC maps of diffusion weighted images by using b-values were acquired. The median ADC at all b values for malignant lesions was significantly different from that for benign lesions (p<0.001). When ADCs at all b values were compared between benign lesions/normal parenchyma and malignant lesions/normal parenchyma, there was a significant statistical difference in all b values between benign and malignant lesions except at b 50 and b 200 (p<0.05). The lesion/normal parenchyma ADC ratio for b 600 value (AUC=0.804) was more effective than the lesion ADC for b 600 value (AUC=0.766) in differentiation of benign and malignant lesions. The specificity and sensitivity of the lesion/normal parenchyma ADC ratio were higher than those of ADC values of lesions. When the ADC was compared between benign lesions and pancreatitis, a significant difference was found at all b values (p<0.001). There was not a statistically significant difference between the ADC for pancreatitis and that for malignant lesions at any b value combinations (p>0.05). Diffusion-weighted magnetic resonance images can be helpful in differentiation of pancreatic carcinoma and benign lesions. Lesion ADC / normal parenchyma ADC ratios are more important than lesion ADC values in assessment of pancreatic lesions.

The epidemiology of pancreatitis and pancreatic cancer.

PubMed

Yadav, Dhiraj; Lowenfels, Albert B

2013-06-01

Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Safety and clinical efficacy of everolimus in the treatment of advanced renal cell carcinoma (RCC)

PubMed Central

Shahani, Rohan; Kwan, Kevin G; Kapoor, Anil

2010-01-01

Renal cell carcinoma (RCC) is one of the most lethal genitourinary malignancies. Recently, there has been a paradigm shift in the management of advanced RCC. New targeted therapies including vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors have been developed which have shown promising results in a patient population who otherwise had very few options for treatment. The first mTOR inhibitor, temsirolimus, an intravenous prodrug, has shown improved overall survival in poor prognosis patients. More recently, an oral mTOR inhibitor, everolimus (RAD 001), has been developed which has been shown to delay disease progression in patients with metastatic RCC who have progressed on other targeted therapies. Although a survival advantage in phase III trials is seen with everolimus, associated systemic toxicities, while generally well tolerated, are not insignificant. These include mucositis, hyperglycemia, hyperlipidemia, and pneumonitis. Despite the side effects, emerging evidence points to everolimus as the optimal second-line treatment for patients with advanced renal cell carcinoma. PMID:21701620

Anaplastic carcinoma occurring in association with a mucinous cystic neoplasm of the pancreas.

PubMed

Lane, R B; Sangüeza, O P

1997-05-01

Anaplastic carcinomas of the pancreas are considered variants of ductal adenocarcinoma. They typically occur in elderly men. They have rarely been reported to occur in association with mucinous cystic neoplasms of the pancreas. We report a case of anaplastic carcinoma occurring in association with a pancreatic mucinous cystic neoplasm, borderline-type, in a 25-year-old woman who presented with lymph node and hepatic metastases.

Establishment and characterization of a new human acinar cell carcinoma cell line, Faraz-ICR, from pancreas.

PubMed

Rezaei, Marzieh; Hosseini, Ahmad; Nikeghbalian, Saman; Ghaderi, Abbas

Basic research in the field of acinar cell carcinoma (ACC) as a rare neoplasm of the pancreas is dependent on the availability of pragmatic model such as new pancreatic cancer cell lines. Thus, establishment and characterization of new pancreatic cancer cell lines from ACC origin are deemed important. Faraz-ICR cell line was derived from a 58-years old woman with pancreatic acinar cell carcinoma by the collagenase digestion protocol. We characterized the cell line by examining its morphology and cytostructural and functional profile. Faraz-ICR has a doubling time of 35 hours and grows in soft agar with a colony-forming efficiency of 25%. The cell had nearly normal pattern of chromosomes in karyotype analysis and Comparative Genomic Hybridization (CGH) array analysis. Evaluation of cells by flowcytometry showed that Faraz-ICR is negative for EpCAM and mesenchymal markers in different passages, and has epithelial nature. Immunofluorescence staining revealed that cells were strongly positive for vimentin, desmin, ezrin, S100, nestin and they were negative for pan-cytokeratins, chromogranin and alpha smooth muscle actin. We were able to establish a new pancreatic carcinoma cell line with partial aspects of Epithelial-mesenchymal transition and aggressiveness. This cell line might be suitable for studying various anticancer drugs and protein profile aiming to see any possible tumor associated marker for ACC. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer

PubMed Central

Arnoletti, J. P.; Frolov, A.; Eloubeidi, M.; Keene, K.; Posey, J.; Wood, T.; Greeno, Edward; Jhala, N.; Varadarajulu, S.; Russo, S.; Christein, J.; Oster, R.; Buchsbaum, D. J.; Vickers, S. M.

2012-01-01

Purpose (1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial–mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti-EGFR treatment. Methods Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0–300 mg/m2/week) given concurrently with cetuximab (400 mg/m2 loading dose, 250 mg/m2 weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens. Results Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1–2 adverse events was 96%, and incidence of 3–4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients. Conclusions Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m2/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer. PMID:20589377

Molecular Targeted Intervention for Pancreatic Cancer

PubMed Central

Mohammed, Altaf; Janakiram, Naveena B.; Pant, Shubham; Rao, Chinthalapally V.

2015-01-01

Pancreatic cancer (PC) remains one of the worst cancers, with almost uniform lethality. PC risk is associated with westernized diet, tobacco, alcohol, obesity, chronic pancreatitis, and family history of pancreatic cancer. New targeted agents and the use of various therapeutic combinations have yet to provide adequate treatments for patients with advanced cancer. To design better preventive and/or treatment strategies against PC, knowledge of PC pathogenesis at the molecular level is vital. With the advent of genetically modified animals, significant advances have been made in understanding the molecular biology and pathogenesis of PC. Currently, several clinical trials and preclinical evaluations are underway to investigate novel agents that target signaling defects in PC. An important consideration in evaluating novel drugs is determining whether an agent can reach the target in concentrations effective to treat the disease. Recently, we have reported evidence for chemoprevention of PC. Here, we provide a comprehensive review of current updates on molecularly targeted interventions, as well as dietary, phytochemical, immunoregulatory, and microenvironment-based approaches for the development of novel therapeutic and preventive regimens. Special attention is given to prevention and treatment in preclinical genetically engineered mouse studies and human clinical studies. PMID:26266422

Apatinib-treated advanced medullary thyroid carcinoma: a case report.

PubMed

Chen, Kan; Gao, Yun; Shi, Fei; Cao, Guangqiang; Bao, Jiandong

2018-01-01

Medullary thyroid carcinoma (MTC) is a rare malignancy originating from calcitonin-producing parafollicular C cells of the thyroid. Neither radiotherapy nor chemotherapy has demonstrated durable objective responses in patients with advanced MTC. Vandetanib and cabozantinib are the 2 tyrosine kinase inhibitors recently approved by the US Food and Drug Administration, which are not affordable for most Chinese patients. Herein, we report a case of an MTC patient who responded to apatinib, a Chinese homemade tyrosine kinase inhibitor-targeted vascular endothelial growth factor receptor. The patient was treated with thyroid lobectomy but developed MTC with extensive metastasis. The levels of serum calcitonin and carcino-embryonic antigen were much higher than the normal range. Apatinib was given at a dose of 500 mg daily and adjusted according to tolerance. Sixteen weeks following apatinib administration, the patient achieved a partial response, which lasted more than 9 weeks. No severe toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib could be a new option for the treatment of advanced MTC.

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

PubMed Central

Watanapa, P.; Williamson, R. C.

1993-01-01

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

Molecular biology of pancreatic cancer: how useful is it in clinical practice?

PubMed

Sakorafas, George H; Smyrniotis, Vasileios

2012-07-10

During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years). Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active) etc. Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology in pancreatic cancer will expand in the future, improving the

Quantitative Proteomic Analysis of Serum Exosomes from Patients with Locally Advanced Pancreatic Cancer Undergoing Chemoradiotherapy.

PubMed

An, Mingrui; Lohse, Ines; Tan, Zhijing; Zhu, Jianhui; Wu, Jing; Kurapati, Himabindu; Morgan, Meredith A; Lawrence, Theodore S; Cuneo, Kyle C; Lubman, David M

2017-04-07

Pancreatic cancer is the third leading cause of cancer-related death in the USA. Despite extensive research, minimal improvements in patient outcomes have been achieved. Early identification of treatment response and metastasis would be valuable to determine the appropriate therapeutic course for patients. In this work, we isolated exosomes from the serum of 10 patients with locally advanced pancreatic cancer at serial time points over a course of therapy, and quantitative analysis was performed using the iTRAQ method. We detected approximately 700-800 exosomal proteins per sample, several of which have been implicated in metastasis and treatment resistance. We compared the exosomal proteome of patients at different time points during treatment to healthy controls and identified eight proteins that show global treatment-specific changes. We then tested the effect of patient-derived exosomes on the migration of tumor cells and found that patient-derived exosomes, but not healthy controls, induce cell migration, supporting their role in metastasis. Our data show that exosomes can be reliably extracted from patient serum and analyzed for protein content. The differential loading of exosomes during a course of therapy suggests that exosomes may provide novel insights into the development of treatment resistance and metastasis.

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 ...

The evolution of the surgical treatment of chronic pancreatitis.

PubMed

Andersen, Dana K; Frey, Charles F

2010-01-01

To establish the current status of surgical therapy for chronic pancreatitis, recent published reports are examined in the context of the historical advances in the field. The basis for decompression (drainage), denervation, and resection strategies for the treatment of pain caused by chronic pancreatitis is reviewed. These divergent approaches have finally coalesced as the head of the pancreas has become apparent as the nidus of chronic inflammation. The recent developments in surgical methods to treat the complications of chronic pancreatitis and the results of recent prospective randomized trials of operative approaches were reviewed to establish the current best practices. Local resection of the pancreatic head, with or without duct drainage, and duodenum-preserving pancreatic head resection offer outcomes as effective as pancreaticoduodenectomy, with lowered morbidity and mortality. Local resection or excavation of the pancreatic head offers the advantage of lowest cost and morbidity and early prevention of postoperative diabetes. The late incidences of recurrent pain, diabetes, and exocrine insufficiency are equivalent for all 3 surgical approaches. Local resection of the pancreatic head appears to offer best outcomes and lowest risk for the management of the pain of chronic pancreatitis.

Hedgehog Signaling in Pancreatic Fibrosis and Cancer

PubMed Central

Bai, Yongyu; Bai, Yongheng; Dong, Jiaojiao; Li, Qiang; Jin, Yuepeng; Chen, Bicheng; Zhou, Mengtao

2016-01-01

Abstract The hedgehog signaling pathway was first discovered in the 1980s. It is a stem cell-related pathway that plays a crucial role in embryonic development, tissue regeneration, and organogenesis. Aberrant activation of hedgehog signaling leads to pathological consequences, including a variety of human tumors such as pancreatic cancer. Multiple lines of evidence indicate that blockade of this pathway with several small-molecule inhibitors can inhibit the development of pancreatic neoplasm. In addition, activated hedgehog signaling has been reported to be involved in fibrogenesis in many tissues, including the pancreas. Therefore, new therapeutic targets based on hedgehog signaling have attracted a great deal of attention to alleviate pancreatic diseases. In this review, we briefly discuss the recent advances in hedgehog signaling in pancreatic fibrogenesis and carcinogenesis and highlight new insights on their potential relationship with respect to the development of novel targeted therapies. PMID:26962810

Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree.

PubMed

Gelibter, Alain; Malaguti, Paola; Di Cosimo, Serena; Bria, Emilio; Ruggeri, Enzo Maria; Carlini, Paolo; Carboni, Fabio; Ettorre, Giuseppe Maria; Pellicciotta, Mario; Giannarelli, Diana; Terzoli, Edmondo; Cognetti, Francesco; Milella, Michele

2005-09-15

Gemcitabine infusion at the fixed dose rate of 10 mg/m(2) per minute (FDR-gemcitabine) has pharmacokinetic advantages and may result in improved therapeutic efficacy. Between April 2002 and September 2003, 40 patients with advanced-stage pancreatic adenocarcinoma (PDAC; n = 27) or biliary tree carcinoma (BTC; n = 13) were treated with weekly FDR-gemcitabine (1000 mg/m(2)). The primary end point was the response rate. The secondary end points were progression-free and overall survival (PFS and OS), tumor marker response, and clinical benefit response (CBR). The overall response rate (ORR) on an intent-to-treat basis was 15% (95% confidence interval [95% CI], 4-26%). A positive CBR was obtained in 14 of 29 (48%) patients. Seventeen of 25 (68%) patients had a reduction in carbohydrate antigen 19-9 (CA 19-9) of > 25%. The median time to treatment failure and the median PFS were 17 weeks (95% CI, 13-22 weeks) and 19 weeks (95% CI, 15-23 weeks), respectively. The median OS was 40 weeks (95% CI, 36-45 weeks) and the 1-year actuarial survival rate was 25.8%. Multivariate analysis showed that a performance status score of 0-1 at study entry and locally advanced disease were the only independent predictors of longer PFS and OS, whereas a reduction in CA 19-9 serum levels > 75% was an independent predictor of longer PFS, but had no impact on OS. Toxicity was mild with Grade 3-4 neutropenia (according to the National Cancer Institute-Common Toxicity Criteria [version 2.0]) in 18 of 427 treatment weeks (4.2%), and Grade 3 anemia and thrombocytopenia in 6 of 427 treatment weeks (1.4%) and 9 of 427 treatment weeks (2.1%), respectively, and asymptomatic Grade 3-4 transaminase elevation in 21 of 427 treatment weeks (4.9%). FDR-gemcitabine at the weekly dose of 1000 mg/m(2) demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC. Copyright 2005 American Cancer Society.

Chronic Pancreatitis.

PubMed

Stram, Michelle; Liu, Shu; Singhi, Aatur D

2016-12-01

Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Combination Chemotherapy Plus Filgrastim in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2013-08-27

Bladder Cancer; Breast Cancer; Carcinoma of Unknown Primary; Esophageal Cancer; Gastric Cancer; Head and Neck Cancer; Lung Cancer; Melanoma (Skin); Ovarian Cancer; Pancreatic Cancer; Prostate Cancer; Sarcoma

Profile of vismodegib and its potential in the treatment of advanced basal cell carcinoma.

PubMed

Macha, Muzafar A; Batra, Surinder K; Ganti, Apar Kishor

2013-01-01

Basal cell carcinoma (BCC) is the most common human malignancy. Recent advances in our understanding of the critical biologic pathways implicated in the development and progression of BCC have led to the development of the first molecular targeted therapy for this disease. The hedgehog pathway is mutated in virtually all patients with BCC and recent trials with vismodegib, an inhibitor of this pathway, have shown significant responses. This review will discuss the importance of the hedgehog pathway in the pathogenesis of BCC and describe in detail the pharmacology of vismodegib in relation to its activity in advanced BCC.

Profile of vismodegib and its potential in the treatment of advanced basal cell carcinoma

PubMed Central

Macha, Muzafar A; Batra, Surinder K; Ganti, Apar Kishor

2013-01-01

Basal cell carcinoma (BCC) is the most common human malignancy. Recent advances in our understanding of the critical biologic pathways implicated in the development and progression of BCC have led to the development of the first molecular targeted therapy for this disease. The hedgehog pathway is mutated in virtually all patients with BCC and recent trials with vismodegib, an inhibitor of this pathway, have shown significant responses. This review will discuss the importance of the hedgehog pathway in the pathogenesis of BCC and describe in detail the pharmacology of vismodegib in relation to its activity in advanced BCC. PMID:23940421

Outcomes after extended pancreatectomy in patients with borderline resectable and locally advanced pancreatic cancer.

PubMed

Hartwig, W; Gluth, A; Hinz, U; Koliogiannis, D; Strobel, O; Hackert, T; Werner, J; Büchler, M W

2016-11-01

In the recent International Study Group of Pancreatic Surgery (ISGPS) consensus on extended pancreatectomy, several issues on perioperative outcome and long-term survival remained unclear. Robust data on outcomes are sparse. The present study aimed to assess the outcome of extended pancreatectomy for borderline resectable and locally advanced pancreatic cancer. A consecutive series of patients with primary pancreatic adenocarcinoma undergoing extended pancreatectomies, as defined by the new ISGPS consensus, were compared with patients who had a standard pancreatectomy. Univariable and multivariable analysis was performed to identify risk factors for perioperative mortality and characteristics associated with survival. Long-term outcome was assessed by means of Kaplan-Meier analysis. The 611 patients who had an extended pancreatectomy had significantly greater surgical morbidity than the 1217 patients who underwent a standard resection (42·7 versus 34·2 per cent respectively), and higher 30-day mortality (4·3 versus 1·8 per cent) and in-hospital mortality (7·5 versus 3·6 per cent) rates. Operating time of 300 min or more, extended total pancreatectomy, and ASA fitness grade of III or IV were associated with increased in-hospital mortality in multivariable analysis, whereas resections involving the colon, portal vein or arteries were not. Median survival and 5-year overall survival rate were reduced in patients having extended pancreatectomy compared with those undergoing a standard resection (16·1 versus 23·6 months, and 11·3 versus 20·6 per cent, respectively). Older age, G3/4 tumours, two or more positive lymph nodes, macroscopic positive resection margins, duration of surgery of 420 min or above, and blood loss of 1000 ml or more were independently associated with decreased overall survival. Extended resections are associated with increased perioperative morbidity and mortality, particularly when extended total pancreatectomy is performed. Favourable

Stimulation of islet cell proliferation enhances pancreatic ductal carcinogenesis in the hamster model.

PubMed Central

Pour, P. M.; Kazakoff, K.

1996-01-01

Previous studies have shown that some N-nitrosobis (2-oxopropyl)amine (BOP)-induced ductal/ductular pancreatic cancers in the hamster model develop within islets and that streptozotocin (SZ) pretreatment that caused islet degeneration and atrophy inhibits pancreatic cancer induction. Hence, it appears that in this model islets play a significant role in exocrine pancreatic carcinogenesis. To examine whether stimulation of islet cell proliferation (nesidioblastosis) enhances pancreatic exocrine cancer development, we tested the effect of the pancreatic carcinogen BOP in hamsters after induction of nesidioblastosis by cellophane wrapping. Before wrapping, hamsters were treated with SZ to inhibit pancreatic tumor induction in the unwrapped pancreatic tissues. Control groups with a wrapped pancreas did not receive SZ. Six weeks after SZ treatment, all hamsters were treated with BOP (10 mg/kg body weight) weekly for 10 weeks and the experiment was terminated 38 weeks after the last BOP treatment. Many animals recovered from their diabetes at the time when BOP was injected and many more after BOP treatment. Only nine hamsters remained diabetic until the end of the experiment. Both SZ-treated and control groups developed proliferative and malignant pancreatic ductal-type lesions primarily in the wrapped area (47%) but less frequently in the larger segments of the pancreas, including the splenic lobe (34%), gastric lobe (13%), and duodenal lobe (6%). Only a few lesions developed in the unwrapped pancreatic region of nine diabetic hamsters with atrophic islets, whereas seven of these hamsters had tumors in the wrapped area. Histologically, most tumors appeared to originate from islets, many invasive carcinomas had foci of islets, and some tumor cells showed reactivity with anti-insulin. The results show that, in the BOP hamster model, islets are the site of formation of the major fraction of exocrine pancreatic cancer and that induction of nesidioblastosis enhances

Early Detection of Sporadic Pancreatic Cancer

PubMed Central

Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

2015-01-01

Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

Pancreatic cancer surgery: past, present, and future

PubMed Central

Poruk, Katherine E.

2015-01-01

The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19th century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the post-operative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy (PD), was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20th century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections. PMID:26361403

Pancreatic cancer surgery: past, present, and future.

PubMed

Griffin, James F; Poruk, Katherine E; Wolfgang, Christopher L

2015-08-01

The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19(th) century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the post-operative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy (PD), was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20(th) century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections.

Predictors of malignancy in intraductal papillary mucinous neoplasm of the pancreas: analysis of 310 pancreatic resection patients at multiple high-volume centers.

PubMed

Shimizu, Yasuhiro; Yamaue, Hiroki; Maguchi, Hiroyuki; Yamao, Kenji; Hirono, Seiko; Osanai, Manabu; Hijioka, Susumu; Hosoda, Waki; Nakamura, Yasushi; Shinohara, Toshiya; Yanagisawa, Akio

2013-07-01

The present study was a retrospective investigation of predictors of malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The subjects were 310 patients who underwent pancreatic resection at 3 high-volume centers. Preoperative laboratory and imaging findings were analyzed in logistic regression analyses. Endoscopic ultrasonography measurements were essential for the size of mural nodules, and a central review was conducted for pathological diagnosis. Pathological diagnosis was benign IPMN in 150 cases and malignant in 160 (noninvasive carcinoma, n = 100; invasive, n = 60). In multivariate analysis, size of mural nodules, diameter of main pancreatic duct, and cyst size of branch pancreatic duct were independent predictors of malignancy, and areas under the receiver operating characteristic curve for these 3 factors were 0.798, 0.643, and 0.601, respectively. With 7 mm taken as the cutoff value for the size of mural nodules, the diagnosis of malignant IPMN had sensitivity of 74.3% and specificity of 72.7%. Carcinoma without nodules was present in 15 patients (15/160 [9.4%]). The size of mural nodules measured with endoscopic ultrasonography showed high predictive ability. However, about 10% of carcinoma patients did not have nodules, and the handling of the diagnosis in such cases is a problem for the future.

Circulating RNAs as new biomarkers for detecting pancreatic cancer

PubMed Central

Kishikawa, Takahiro; Otsuka, Motoyuki; Ohno, Motoko; Yoshikawa, Takeshi; Takata, Akemi; Koike, Kazuhiko

2015-01-01

Pancreatic cancer remains difficult to treat and has a high mortality rate. It is difficult to diagnose early, mainly due to the lack of screening imaging modalities and specific biomarkers. Consequently, it is important to develop biomarkers that enable the detection of early stage tumors. Emerging evidence is accumulating that tumor cells release substantial amounts of RNA into the bloodstream that strongly resist RNases in the blood and are present at sufficient levels for quantitative analyses. These circulating RNAs are upregulated in the serum and plasma of cancer patients, including those with pancreatic cancer, compared with healthy controls. The majority of RNA biomarker studies have assessed circulating microRNAs (miRs), which are often tissue-specific. There are few reports of the tumor-specific upregulation of other types of small non-coding RNAs (ncRNAs), such as small nucleolar RNAs and Piwi-interacting RNAs. Long ncRNAs (lncRNAs), such as HOTAIR and MALAT1, in the serum/plasma of pancreatic cancer patients have also been reported as diagnostic and prognostic markers. Among tissue-derived RNAs, some miRs show increased expression even in pre-cancerous tissues, and their expression profiles may allow for the discrimination between a chronic inflammatory state and carcinoma. Additionally, some miRs and lncRNAs have been reported with significant alterations in expression according to disease progression, and they may thus represent potential candidate diagnostic or prognostic biomarkers that may be used to evaluate patients once detection methods in peripheral blood are well established. Furthermore, recent innovations in high-throughput sequencing techniques have enabled the discovery of unannotated tumor-associated ncRNAs and tumor-specific alternative splicing as novel and specific biomarkers of cancers. Although much work is required to clarify the release mechanism, origin of tumor-specific circulating RNAs, and selectivity of carrier complexes

[Mediastinal Pancreatic Pseudocyst with Pancreatic Pleural Effusion].

PubMed

Sasajima, Motoko; Kawai, Hideki; Suzuki, Yohei; Saito, Yoshitaro; Eto, Takeshi

2017-06-01

A 72-year-old man with chronic alcohol related pancreatitis was admitted for dyspnea and pain at the upper body. Chest X-ray showed right massive pleural effusion. Chest and abdominal contrast enhanced thin slice computed tomography revealed the route from the pancreatic head reaching the right thoracic cavity via the esophagus hiatus and the communication between the cystic lesion and main pancreatic duct. We drained the pleural effusion that showed abnormally high amylase activity. We diagnosed his illness as mediastinal pancreatic pseudocyst with pancreatic pleural effusion. Endoscopic Nasopancreatic Drainage catheter was placed in the main pancreatic duct, and the pleural effusion disappeared.

FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive Advanced Urothelial Carcinoma after Platinum‐Containing Chemotherapy

PubMed Central

Suzman, Daniel; Maher, V. Ellen; Zhang, Lijun; Tang, Shenghui; Ricks, Tiffany; Palmby, Todd; Fu, Wentao; Liu, Qi; Goldberg, Kirsten B.; Kim, Geoffrey; Pazdur, Richard

2017-01-01

Abstract Until recently in the United States, no products were approved for second‐line treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum‐containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum‐containing chemotherapy. Atezolizumab is a programmed death‐ligand 1 (PD‐L1) blocking antibody and represents the first approved product directed against PD‐L1. This accelerated approval was based on results of a single‐arm trial in 310 patients with locally advanced or metastatic urothelial carcinoma who had disease progression after prior platinum‐containing chemotherapy. Patients received atezolizumab 1,200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity. Key efficacy measures were objective response rate (ORR), as assessed by Independent Review per RECIST 1.1, and duration of response (DoR). With a median follow‐up of 14.4 months, confirmed ORR was 14.8% (95% CI: 11.1, 19.3) in all treated patients. Median DoR was not reached and response durations ranged from 2.1+ to 13.8+ months. Of the 46 responders, 37 patients had an ongoing response for ≥ 6 months. The most common adverse reactions (≥20%) were fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation. Infection and immune‐related adverse events also occurred, including pneumonitis, hepatitis, colitis, endocrine disorders, and rashes. Overall, the benefit‐risk assessment was favorable to support accelerated approval. The observed clinical benefits need to be verified in confirmatory trial(s). Implications for Practice. This accelerated approval of atezolizumab for second‐line use in advanced urothelial carcinoma provides patients with an effective, novel treatment option for

FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive Advanced Urothelial Carcinoma after Platinum-Containing Chemotherapy.

PubMed

Ning, Yang-Min; Suzman, Daniel; Maher, V Ellen; Zhang, Lijun; Tang, Shenghui; Ricks, Tiffany; Palmby, Todd; Fu, Wentao; Liu, Qi; Goldberg, Kirsten B; Kim, Geoffrey; Pazdur, Richard

2017-06-01

Until recently in the United States, no products were approved for second-line treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Atezolizumab is a programmed death-ligand 1 (PD-L1) blocking antibody and represents the first approved product directed against PD-L1. This accelerated approval was based on results of a single-arm trial in 310 patients with locally advanced or metastatic urothelial carcinoma who had disease progression after prior platinum-containing chemotherapy. Patients received atezolizumab 1,200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity. Key efficacy measures were objective response rate (ORR), as assessed by Independent Review per RECIST 1.1, and duration of response (DoR). With a median follow-up of 14.4 months, confirmed ORR was 14.8% (95% CI: 11.1, 19.3) in all treated patients. Median DoR was not reached and response durations ranged from 2.1+ to 13.8+ months. Of the 46 responders, 37 patients had an ongoing response for ≥ 6 months. The most common adverse reactions (≥20%) were fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation. Infection and immune-related adverse events also occurred, including pneumonitis, hepatitis, colitis, endocrine disorders, and rashes. Overall, the benefit-risk assessment was favorable to support accelerated approval. The observed clinical benefits need to be verified in confirmatory trial(s). This accelerated approval of atezolizumab for second-line use in advanced urothelial carcinoma provides patients with an effective, novel treatment option for the management of their disease. This represents the first

Imaging modalities for characterising focal pancreatic lesions.

PubMed

Best, Lawrence Mj; Rawji, Vishal; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-17

or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or benign lesions provided no test in which meta-analysis was performed.There were no major alterations in the subgroup analysis of cystic pancreatic focal lesions (42 studies; 2086 participants). None of the included studies evaluated EUS elastography or sequential testing. We were unable to arrive at any firm conclusions because of the differences in the way that study authors classified focal pancreatic lesions into cancerous, precancerous, and benign lesions; the inclusion of few studies with wide confidence intervals for each comparison; poor methodological quality in the studies; and heterogeneity in the estimates within comparisons.

Double-modulation of 5-Fluorouracil by methotrexate and leucovorin in advanced colorectal-carcinoma.

PubMed

Leone, B; Romero, A; Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Paris, A; Lacava, J

1993-11-01

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and leucovorin (LV) as first line chemotherapy in advanced colorectal carcinoma. Between January 1990, and April 1992, 42 patients with metastatic or advanced recurrent (inoperable) colorectal cancer were entered into the study. Therapy consisted of a sequential combination of MTX, LV and 5-FU. MTX was administered at a dose of 150 mg/m2 over 20 minutes I.V. infusion at hour (h) 0, followed 19 h later by LV 50 mg/m2 over 2 h infusion. 5-FU 900 mg/m2 was given by I.V. push injection at h 20. Starting 24 h after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 h for six doses. Treatment was repeated every 15 days until progressive disease, severe toxicity, or death. Four patients were considered not evaluable for response. Objective regression (OR) was observed in 14 of 38 patients (37%, 95% confidence interval 23-53%). Two patients (5%) obtained complete response (CR) and 12 (32%) partial response (PR). Median time to treatment failure was 6 months (range 1-21). Median survival for the whole group of patients was 13 months (range 1-27). Toxicity was within acceptable limits but one therapy-related death due to severe leukopenia and sepsis was observed. Double modulation of 5-FU with MTX and low dose of LV is an active regimen against advanced colorectal carcinoma and represents a promising strategy that should be further explored.

A novel monoclonal antibody targeting carboxymethyllysine, an advanced glycation end product in atherosclerosis and pancreatic cancer.

PubMed

Wendel, Ulrika; Persson, Nina; Risinger, Christian; Bengtsson, Eva; Nodin, Björn; Danielsson, Lena; Welinder, Charlotte; Nordin Fredrikson, Gunilla; Jansson, Bo; Blixt, Ola

2018-01-01

Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers. Current methods for advanced glycation end product detection are though limited and solely measure total glycation. This study describes a new epitope-mapped single chain variable fragment, D1-B2, against carboxymethyllysine, produced from a phage library that was constructed from mouse immunizations. The phage library was selected against advanced glycation end product targets using a phage display platform. Characterization of its binding pattern was performed using large synthetic glycated peptide and protein libraries displayed on microarray slides. D1-B2 showed a preference for an aspartic acid, three positions N-terminally from a carboxymethyllysine residue and also bound to a broad collection of glycated proteins. Positive immunohistochemical staining of mouse atherosclerotic plaques and of a tissue microarray of human pancreatic tumors confirmed the usability of the new scFv for advanced glycation end product detection in tissues. This study demonstrates a promising methodology for high-throughput generation of epitope-mapped monoclonal antibodies against AGE.

A novel monoclonal antibody targeting carboxymethyllysine, an advanced glycation end product in atherosclerosis and pancreatic cancer

PubMed Central

Wendel, Ulrika; Persson, Nina; Risinger, Christian; Bengtsson, Eva; Nodin, Björn; Danielsson, Lena; Welinder, Charlotte; Nordin Fredrikson, Gunilla

2018-01-01

Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers. Current methods for advanced glycation end product detection are though limited and solely measure total glycation. This study describes a new epitope-mapped single chain variable fragment, D1-B2, against carboxymethyllysine, produced from a phage library that was constructed from mouse immunizations. The phage library was selected against advanced glycation end product targets using a phage display platform. Characterization of its binding pattern was performed using large synthetic glycated peptide and protein libraries displayed on microarray slides. D1-B2 showed a preference for an aspartic acid, three positions N-terminally from a carboxymethyllysine residue and also bound to a broad collection of glycated proteins. Positive immunohistochemical staining of mouse atherosclerotic plaques and of a tissue microarray of human pancreatic tumors confirmed the usability of the new scFv for advanced glycation end product detection in tissues. This study demonstrates a promising methodology for high-throughput generation of epitope-mapped monoclonal antibodies against AGE. PMID:29420566

The role of intraoperative radiation therapy in patients with pancreatic cancer.

PubMed

Palta, Manisha; Willett, Christopher; Czito, Brian

2014-04-01

Intraoperative radiation therapy (IORT) techniques allow for the delivery of high doses of radiation therapy while excluding part or all of the nearby dose-limiting sensitive structures. Therefore, the effective radiation dose is increased and local tumor control potentially improved. This is pertinent in the case of pancreatic cancer because local failure rates are as high as 50%-80% in patients with resected and locally advanced disease. Available data in patients receiving IORT after pancreaticoduodenectomy reveal an improvement in local control, though overall survival benefit is unclear. Series of patients with locally advanced pancreatic cancer also suggest pain relief, and in select studies, improved survival associated with the inclusion of IORT. At present, no phase III data clearly supports the use of IORT in the management of pancreatic cancer. © 2013 Published by Elsevier Inc.

Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update.

PubMed

Chen, Leon; Silapunt, Sirunya; Migden, Michael R

2016-09-01

The Hedgehog inhibitors are promising alternative for patients with advanced basal cell carcinoma that are not amenable to radiotherapy or surgery. Sonidegib, also known as LDE225, is an orally available SMO antagonist that was recently approved by the US FDA for the treatment of patients with locally advanced basal cell carcinoma. This article will provide an overview of the pharmacology and pharmacokinetics of sonidegib and in-depth analysis of the BOLT trial with additional data from the 12-month update. The present challenges associated with Hedgehog inhibitors will also be discussed.

A decrease in miR-150 regulates the malignancy of pancreatic cancer by targeting c-Myb and MUC4.

PubMed

Yang, Ke; He, Miaoxia; Cai, Zailong; Ni, Canrong; Deng, Jingjing; Ta, Na; Xu, Jingjing; Zheng, Jianming

2015-04-01

Pancreatic cancer is an aggressive cancer with high mortality. Conventional treatments have little impact on its progression. Limited research investigating the role of oncogene miR-150 specifically in pancreatic cancer has been published. The purpose of this study was to determine the tumorigenesis of miR-150 in pancreatic cancer. One hundred six pancreatic ductal adenocarcinomas were analyzed together with their adjacent benign pancreatic tissues. The associations of miR-150, c-Myb, and MUC4 expression with survival rates were determined. Functional studies on miR-150 in pancreatic cancer were used to assess its effect on proliferation and malignancy in several pancreatic cell lines. miR-150 expression was significantly down-regulated in pancreatic ductal adenocarcinoma tissues compared with adjacent benign pancreatic tissues. Patients with low miR-150 expression had significantly higher mortality rates than those with high miR-150 expression. The in vitro and in vivo assays of pancreatic cancer cells showed that miR-150 overexpression leads to reduced cell growth, clonogenicity, migration, invasion, modular cell cycles, and induced apoptosis. Moreover, miR-150 expression was inversely correlated with c-Myb and MUC4 activities in pancreatic tissue, cell lines, and nude mouse model. miR-150 is an important suppressor of pancreatic ductal carcinoma and acts as a regulator of c-Myb and MUC4 in aggressive progress.

The presence of advanced lesions and associating risk factors for advanced cervical carcinoma in patients with atypical sguamous cells of undetermined significance.

PubMed

Sun, L L; Chen, W; Fan, Y Y; Wang, M L; Wang, L N

2015-01-01

To characterize histopathological status, high-risk human papillomavirus (hr-HPV) infection status, and associated risk factors in patients with atypical squamous cells of undetermined significance (ASCUS). Cervical biopsies obtained from 130 ASCUS patients were subjected to histopathological examination and hr-HPV testing. Associations between advanced lesions and hr-HPV load or age were analyzed, and the confounding factors for high-grade cervical lesions were identified. Cervical biopsies from ASCUS patients had a wide range of pathological states, ranging from normal to invasive cervical carcinoma. High-risk HPV infection was significantly associated with advanced cervical lesions in ASCUS patients; hr-HPV infection and the number of gestations were risk factors for developing advanced cervical disease. A significant portion of ASCUS patients harbor advanced cervical lesions. The number of gestations and hr-HPV infection can increase the risk of developing advanced cervical lesions in ASCUS patients.

CFTR: A new horizon in the pathomechanism and treatment of pancreatitis

PubMed Central

Hegyi, Péter; Wilschanski, Michael; Muallem, Shmuel; Lukacs, Gergely; Sahin-Tóth, Miklós; Uc, Aliye; Gray, Michael A.; Rakonczay, Zoltán; Maléth, József

2017-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that conducts chloride and bicarbonate ions across epithelial cell membranes. Mutations in the CFTR gene diminish the ion channel function and lead to impaired epithelial fluid transport in multiple organs such as the lung and the pancreas resulting in cystic fibrosis. Heterozygous carriers of CFTR mutations do not develop cystic fibrosis but exhibit increased risk for pancreatitis and associated pancreatic damage characterized by elevated mucus levels, fibrosis and cyst formation. Importantly, recent studies demonstrated that pancreatitis causing insults, such as alcohol, smoking or bile acids strongly inhibit CFTR function. Furthermore, human studies showed reduced levels of CFTR expression and function in all forms of pancreatitis. These findings indicate that impairment of CFTR is critical in the development of pancreatitis; therefore, correcting CFTR function could be the first specific therapy in pancreatitis. In this review, we summarize recent advances in the field and discuss new possibilities for the treatment of pancreatitis. PMID:26856995

Adjuvant therapy for advanced renal cell carcinoma.

PubMed

Meissner, Matthew A; McCormick, Barrett Z; Karam, Jose A; Wood, Christopher G

2018-07-01

Locally advanced, non-metastatic renal cell carcinoma (RCC) is conventionally managed with surgery. However, patients are at a high risk of RCC recurrence and have poor survival outcomes. An effective adjuvant systemic treatment is needed to improve on these outcomes. Targeted molecular and immune-based therapies have been investigated, or are under investigation, but their role in this setting remains unclear. Areas covered: A comprehensive search of PubMed and ClinicalTrials.gov was performed for relevant literature. The following topics pertinent to adjuvant therapy in RCC were evaluated: strategies for patient selection, cytokine-based immunotherapy, vaccine therapy, VEGF and non-VEGF targeted molecular agents, and immune checkpoint inhibitors. Expert commentary: Strong evidence for the incorporation of adjuvant therapy in high-risk RCC is lacking. Multiple targeted molecular therapies have been examined with only one approved for use. Genetic and molecular-based prognostic models are needed to determine who may benefit from adjuvant therapy. Developing adjuvant therapy strategies in the future depends on the results of important ongoing trials with immunotherapy and targeted agents.

[Clinical efficacy of alternating chemo-radiotherapy for locally advanced nasopharyngeal carcinoma].

PubMed

You, Xi; Yang, Yucheng

2014-03-01

The purpose of this study is to investigate the effective of alternating Chemo-radiotherapy for locally Advanced Nasopharyngeal Carcinoma. Retrospective analysis 106 cases of patients with locally advanced nasopharyngeal carcinoma between November 2005 and March 2007. All patients received cisplatin-based chemotherapy but 15 patients received radiotherapy(RT) alone. Inducing chemotherapy (IC) + RT + adju-vant chemotherapy (AC) regimen in 36 patients, IC+RT regimen was delivered in 25 patients and AC + RT regimen in 30 patients. 61 patients received 1 to 2 cycles of inducing chemotherapy and 66 patients received 3 to 6 cycles of adjuvant chemotherapy after radiotherapy. Chemotherapy started on the first day after the end of the induction chemotherapy, adjuvant chemotherapy begun after radiotherapy for a week. All patients were treated by radiotherapy using 60 Co r-ray, the nasophyarynx primary site was given a total does of 68 -74 Gy. The lymph nodes of the neck was given 60 to 70 Gy. The prophylactic irradiation does of the neck was 48-50 Gy. RESCULT: The median follow up time was 51 months. A total of 58 patients died, the overall survival rate was 45% in whole groups. The 5-year overall survival rates were 33%, 63%, 60% and 50% in RT, IC + RT + AC, IC + RT and RT+AC group, respectively. The 5-year disease-free survival rates were 13%, 56%, 48% and 40% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year relapse-free survival rates were 13%, 53%, 48% and 50% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year metastasis-free survival rates were 6%, 50%, 44% and 47% in RT, IC + RT + AC, IC+ RT and RT + AC group, respectively. There was significant difference in all groups (P < 0.05). The median time to relapses were 22 months, 29 months, 28 months and 25 months in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The median time to first distant metastasis were 10 months, 19 months, 15 months and 12 months in RT, IC

Management of pancreatic cancer in the elderly.

PubMed

Higuera, Oliver; Ghanem, Ismael; Nasimi, Rula; Prieto, Isabel; Koren, Laura; Feliu, Jaime

2016-01-14

Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. The aging of the population will result in a rise in the incidence of pancreatic adenocarcinoma within the next years. Thus, the management of pancreatic cancer in the elderly population is gaining increasing relevance. Older cancer patients represent a heterogeneous group with different biological, functional and psychosocial characteristics that can modify the usual management of this disease, including pharmacokinetic and pharmacodynamic changes, polypharmacy, performance status, comorbidities and organ dysfunction. However, the biological age, not the chronological age, of the patient should be the limiting factor in determining the most appropriate treatment for these patients. Unfortunately, despite the increased incidence of this pathology in older patients, there is an underrepresentation of these patients in clinical trials, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients. In this review, the special characteristics of the elderly, the multidisciplinary management of localized and advanced ductal adenocarcinoma of the pancreas and the most recent advances in the management of this condition will be discussed, focusing on surgery, chemotherapy, radiation and palliative care.

Management of Inflammatory Fluid Collections and Walled-Off Pancreatic Necrosis.

PubMed

Shah, Apeksha; Denicola, Richard; Edirisuriya, Cynthia; Siddiqui, Ali A

2017-12-01

Pancreatic fluid collections are a frequent complication of acute pancreatitis. The revised Atlanta criterion classifies chronic fluid collections into pseudocysts and walled-off pancreatic necrosis (WON). Symptomatic PFCs require drainage options that include surgical, percutaneous, or endoscopic approaches. With the advent of newer and more advanced endoscopic tools and expertise, minimally invasive endoscopic drainage has now become the preferred approach. An endoscopic ultrasonography (EUS)-guided approach for pancreatic fluid collection drainage is now the preferred endoscopic approach. Both plastic stents and metal stents are efficacious and safe; however, metal stents may offer an advantage, especially in infected pseudocysts and in WON. Direct endoscopic necrosectomy is often required in WON. Lumen apposing metal stents allow for direct endoscopic necrosectomy and debridement through the stent lumen and are now preferred in these patients. Endoscopic retrograde cholangiopancreatography with pancreatic duct exploration should be performed concurrent to PFC drainage in patients with suspected PD disruption. PD disruption is associated with an increased severity of pancreatitis, an increased risk of recurrent attacks of pancreatitis and long-term complications, and a decreased rate of PFC resolution after drainage. Ideally, pancreatic ductal disruption should be bridged with endoscopic stenting.

Out-FOXing Pancreatic Cancer | Center for Cancer Research

Cancer.gov

Pancreatic cancer is one of the most lethal cancer types worldwide with increasing incidence and mortality rates in the United States. Consequently, it is projected to become the second leading cause of cancer death by 2020. Poor patient outcomes are due to a combination of diagnosis at an advanced stage and a lack of effective treatments. However, a better understanding of the molecular pathways at work in pancreatic cancers may lead to the identification of novel therapeutic targets.

Nutritional status of patients with locally advanced pancreatic cancer: a pilot study.

PubMed

Ferrucci, Leah M; Bell, Diana; Thornton, Jennifer; Black, Glenda; McCorkle, Ruth; Heimburger, Douglas C; Saif, Muhammad Wasif

2011-11-01

Nutritional status may influence quality of life and prognosis among pancreatic cancer patients, yet few studies describe measures of nutritional status during treatment. We evaluated the nutritional status of locally advanced pancreatic cancer (LAPC) patients undergoing chemoradiotherapy who received baseline nutritional assessment and counseling. Fourteen newly diagnosed LAPC patients enrolled in phase I/II trials of capecitabine with concomitant radiotherapy were assessed for baseline clinical nutrition measures (body mass index, albumin, weight loss, total energy, and protein intake). Participants completed the Anorexia/Cachexia Subscale (A/CS) questionnaire at baseline and during the 6 weeks of treatment. We evaluated associations between baseline characteristics and subsequent A/CS scores with linear regression and changes in A/CS were assessed with the paired t test. We observed a statistically significant increase in mean A/CS between baseline [24.9, standard deviation (SD) = 9.7] and end of treatment (29.9, SD = 6.2). Controlling for baseline A/CS score, only weight loss greater than 5% of body weight over 1 month was associated with A/CS scores at 6 weeks (β = 10.558, standard error = 3.307, p value = 0.009) and mean A/CS scores during the last 3 weeks of treatment (β = 12.739, standard error = 2.251, p value = 0.001). After 6 weeks of chemoradiotherapy, LAPC patients reported a statistically significant improvement in appetite and weight concerns. Increases in AC/S scores were associated with higher baseline A/CS scores and weight loss of 5% or more during 1 month. Further research is needed to determine the impact of nutritional support during treatment, as improvements in this domain may impact LAPC patients' overall quality of life.

Definition of fields margins for palliative radiotherapy of pancreatic carcinoma.

PubMed

Buwenge, Milly; Marinelli, Alfonso; Deodato, Francesco; Macchia, Gabriella; Wondemagegnhu, Tigeneh; Salah, Tareq; Cammelli, Silvia; Uddin, A F M Kamal; Sumon, Mostafa A; Donati, Constanza M; Cilla, Savino; Morganti, Alessio G

2018-06-01

The present study aimed to provide practical guidelines for palliative treatment of advanced carcinoma of the pancreas (CAP) with the 2D technique. Fifteen patients with locally advanced CAP consecutively treated with radiation therapy at the Radiation Oncology Center, Research and Care Foundation 'Giovanni Paolo II' (Campobasso, Italy) underwent computed tomography simulation in supine position. Definition of the clinical target volume (CTV) included the head and body of the pancreas, and the retropancreatic space. The planning target volume was defined by adding a margin of 14 mm to the CTV in the cranio-caudal direction and of 11 mm in radial direction. For each patient, 3 treatment plans were calculated using a cobalt source, 6 MV photons and 15 MV photons (box technique). Beams were drawn using the primary collimators without using multileaf collimators, and progressively optimized in order to respect the minimum dose (D min >90%) constraint. Once the final plan was achieved, distances of the fields edges from a set of reference points (bony or duodenal landmarks) were measured. Using this technique, 15 anterior-posterior and postero-anterior (AP-PA) beams and 15 pairs of lateral-lateral (LL) beams were defined for the different patients. Finally, the single minimal AP-PA and LL beams able to include the 15 sets of AP-PA and LL beams were defined. The results of this analysis are reported in tabular form. Guidelines are provided for treatment based on cobalt unit or Linear accelerator (both 6 and 15 MV photons). This study provides information regarding field size and position. A dosimetric study has been planned to identify the dose to be administered with this technique taking into account current dose-volume constraints.

Nedaplatin concurrent with three-dimensional conformal radiotherapy for treatment of locally advanced esophageal carcinoma.

PubMed

Shen, Ze-Tian; Wu, Xin-Hu; Li, Bing; Shen, Jun-Shu; Wang, Zhen; Li, Jing; Zhu, Xi-Xu

2013-12-28

To evaluate the efficacy and toxicity of nedaplatin (NDP) concurrent with radiotherapy in the treatment of locally advanced esophageal carcinoma. Sixty-eight patients with locally advanced esophageal carcinoma were randomized into either a NDP group (n = 34) or a cisplatin (DDP) group (n = 34). The NDP group received NDP 80-100 mg/m² iv on day 1 + leucovorin (CF) 100 mg/m² iv on days 1-5 + 5-fluorouracil (5-FU) 500 mg/m² iv on days 1-5. The DDP group received DDP 30 mg/m² iv on days 1-3 + CF 100 mg/m² on days 1-5 + 5-FU 500 mg/m² iv on days 1-5. The treatment was repeated every 4 wk in both groups. Concurrent radiotherapy [60-66 Gy/(30-33 f)/(6-7 wk)] was given during chemotherapy. There was no significant difference in the short-term response rate between the NDP group and DDP group (90.9% vs 81.3%, P = 0.528). Although the 1- and 2-year survival rates were higher in the NDP group than in the DDP group (75.8% vs 68.8%, 57.6% vs 50.0%), the difference in the overall survival rate was not statistically significant between the two groups (P = 0.540). The incidences of nausea, vomiting and nephrotoxicity were significantly lower in the NDP group than in the DDP group (17.6% vs 50.0%, P = 0.031; 11.8% vs 47.1%, P = 0.016; 8.8% vs 38.2%, P = 0.039). There was no significant difference in the incidence of myelosuppression, radiation-induced esophagitis or radiation-induced pneumonia between the two groups. NDP-based concurrent chemoradiotherapy is effective and well-tolerated in patients with locally advanced esophageal carcinoma. NDP-based regimen has comparable efficacy to DDP-based regimen but is associated with lower incidences of gastrointestinal and renal toxicity.

Splenic Abscess Caused by Streptococcus gallolyticus subsp. pasteurianus as Presentation of a Pancreatic Cancer

PubMed Central

Su, Yanli; Miao, Bin; Wang, Hong; Wang, Chao

2013-01-01

Splenic abscesses caused by Streptococcus bovis are rarely reported in the literature and are mainly seen in patients with endocarditis and associated colonic neoplasia/carcinoma. We report the first case of splenic abscess caused by Streptococcus gallolyticus subsp. pasteurianus (Streptococcus bovis biotype II/2) as presentation of a pancreatic cancer. PMID:24025909

A case report of mixed acinar-endocrine carcinoma of the pancreas treated with S-1 chemotherapy: Does it work or induce endocrine differentiation?

PubMed

Yokode, Masataka; Itai, Ryosuke; Yamashita, Yukimasa; Zen, Yoh

2017-11-01

Acinar cell carcinomas (ACCs) and mixed acinar-endocrine carcinomas (MAECs) of the pancreas are rare, accounting for only 1% of pancreatic tumors. Although both typically present at an advanced stage, chemotherapeutic regimes have not yet been standardized. A 65-year-old man presented with a large mass in the pancreatic tail with multiple liver metastases. He was initially treated with gemcitabine for suspected ductal carcinoma of the pancreas, but no response was observed. S-1, administered as second-line chemotherapy, showed an approximately 38% reduction in the size of the primary tumor and metastatic deposits with therapeutic effects being maintained for 12 months. When the tumor progressed again, he underwent a percutaneous liver biopsy, which led to the diagnosis of MAEC. Combination therapy with cisplatin and etoposide targeting the endocrine component was administered, and this was based on the endocrine component potentially being less sensitive to S-1 than the ACC element. However, therapy was stopped due to the development of neutropenia, and the patient is currently receiving best supportive care. Given the previous studies suggested that S-1 is more effective for ACCs than gemcitabine, MAECs may also respond to S-1 chemotherapy, similar to ACCs. Another potential interpretation is that S-1 was effective when the condition was ACC, and eventually showed decreased effectiveness when the condition shifted to MAEC. Future studies are needed to conclude whether S-1 chemotherapy truly works against MAECs or induces endocrine differentiation in ACCs as a part of the drug-resistance process.

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

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

The serum miR-21 level serves as a predictor for the chemosensitivity of advanced pancreatic cancer, and miR-21 expression confers chemoresistance by targeting FasL.

PubMed

Wang, Peng; Zhuang, Liping; Zhang, Juan; Fan, Jie; Luo, Jianmin; Chen, Hao; Wang, Kun; Liu, Luming; Chen, Zhen; Meng, Zhiqiang

2013-06-01

miR-21 expression in cancer tissue has been reported to be associated with the clinical outcome and activity of gemcitabine in pancreatic cancer. However, resection is possible in only a minority of patients due to the advanced stages often present at the time of diagnosis, and safely obtaining sufficient quantities of pancreatic tumor tissue for molecular analysis is difficult at the unresectable stages. In this study, we investigated whether the serum level of miR-21 could be used as a predictor of chemosensitivity. We tested the levels of serum miR-21 in a cohort of 177 cases of advanced pancreatic cancer who received gemcitabine-based palliative chemotherapy. We found that a high level of miR-21 in the serum was significantly correlated with a shortened time-to-progression (TTP) and a lower overall survival (OS). The serum miR-21 level was an independent prognostic factor for both the TTP and the OS (HR 1.920; 95% CI, 1.274-2.903, p = 0.002 for TTP and HR 1.705; 95% CI, 1.147-2.535, p = 0.008 for OS). The results from a functional study showed that gemcitabine exposure down-regulated miR-21 expression and up-regulated FasL expression. The increased FasL expression following gemcitabine treatment induced cancer cell apoptosis, whereas the ectopic expression of miR-21 partially protected the cancer cells from gemcitabine-induced apoptosis. Additionally, we confirmed that FasL was a direct target of miR-21. Therefore, the serum level of miR-21 may serve as a predictor of chemosensitivity in advanced pancreatic cancer. Additionally, we identified a new mechanism of chemoresistance mediated by the effects of miR-21 on the FasL/Fas pathway. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Circulating tumor DNA as a liquid biopsy target for detection of pancreatic cancer.

PubMed

Takai, Erina; Yachida, Shinichi

2016-10-14

Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The "liquid biopsy" addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA (ctDNA) could provide diagnostic information. In this review, we provide an overview of the current status of blood-based tests for diagnosis of pancreatic cancer and the potential utility of ctDNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ctDNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer.

Targeting Epidermal Growth Factor Receptor-Related Signaling Pathways in Pancreatic Cancer.

PubMed

Philip, Philip A; Lutz, Manfred P

2015-10-01

Pancreatic cancer is aggressive, chemoresistant, and characterized by complex and poorly understood molecular biology. The epidermal growth factor receptor (EGFR) pathway is frequently activated in pancreatic cancer; therefore, it is a rational target for new treatments. However, the EGFR tyrosine kinase inhibitor erlotinib is currently the only targeted therapy to demonstrate a very modest survival benefit when added to gemcitabine in the treatment of patients with advanced pancreatic cancer. There is no molecular biomarker to predict the outcome of erlotinib treatment, although rash may be predictive of improved survival; EGFR expression does not predict the biologic activity of anti-EGFR drugs in pancreatic cancer, and no EGFR mutations are identified as enabling the selection of patients likely to benefit from treatment. Here, we review clinical studies of EGFR-targeted therapies in combination with conventional cytotoxic regimens or multitargeted strategies in advanced pancreatic cancer, as well as research directed at molecules downstream of EGFR as alternatives or adjuncts to receptor targeting. Limitations of preclinical models, patient selection, and trial design, as well as the complex mechanisms underlying resistance to EGFR-targeted agents, are discussed. Future clinical trials must incorporate translational research end points to aid patient selection and circumvent resistance to EGFR inhibitors.

Quantification of CT images for the classification of high- and low-risk pancreatic cysts

NASA Astrophysics Data System (ADS)

Gazit, Lior; Chakraborty, Jayasree; Attiyeh, Marc; Langdon-Embry, Liana; Allen, Peter J.; Do, Richard K. G.; Simpson, Amber L.

2017-03-01

Pancreatic cancer is the most lethal cancer with an overall 5-year survival rate of 7%1 due to the late stage at diagnosis and the ineffectiveness of current therapeutic strategies. Given the poor prognosis, early detection at a pre-cancerous stage is the best tool for preventing this disease. Intraductal papillary mucinous neoplasms (IPMN), cystic tumors of the pancreas, represent the only radiographically identifiable precursor lesion of pancreatic cancer and are known to evolve stepwise from low-to-high-grade dysplasia before progressing into an invasive carcinoma. Observation is usually recommended for low-risk (low- and intermediate-grade dysplasia) patients, while high-risk (high-grade dysplasia and invasive carcinoma) patients undergo resection; hence, patient selection is critically important in the management of pancreatic cysts.2 Radiologists use standard criteria such as main pancreatic duct size, cyst size, or presence of a solid enhancing component in the cyst to optimally select patients for surgery.3 However, these findings are subject to a radiologist's interpretation and have been shown to be inconsistent with regards to the presence of a mural nodule or solid component.4 We propose objective classification of risk groups based on quantitative imaging features extracted from CT scans. We apply new features that represent the solid component (i.e. areas of high intensity) within the cyst and extract standard texture features. An adaptive boost classifier5 achieves the best performance with area under receiver operating characteristic curve (AUC) of 0.73 and accuracy of 77.3% for texture features. The random forest classifier achieves the best performance with AUC of 0.71 and accuracy of 70.8% with the solid component features.

Singapore Cancer Network (SCAN) Guidelines for Systemic Therapy of Pancreatic Adenocarcinoma.

PubMed

2015-10-01

The SCAN pancreatic cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated- those developed by the National Cancer Comprehensive Network (2014), the European Society of Medical Oncology (2012), Cancer Care Ontario (2013), the Japan Pancreas Society (2013) and the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, and the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (2005). Recommendations on the management of resected, borderline resectable, locally advanced and metastatic pancreatic adenocarcinoma were developed. These adapted guidelines form the SCAN Guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore.

PANCREATITIS AND CARCINOMA OF THE PANCREAS—Some Aspects of the Pathologic Physiology

PubMed Central

Edmondson, Hugh A.

1952-01-01

The physiological phenomena accompanying pancreatic disease in adults are related to the local and generalized reaction of the body to the blockage and/or leakage of the three enzymes—amylase, lipase and trypsin. The measurements of amylase and lipase in the serum are the most reliable criteria in the diagnosis of acute disease. Related changes may include hypocalcemia, hypopotassemia, hyperlipemia, hyperglycemia and decreased renal function. In chronic pancreatitis, there is less fluctuation in the amounts of the enzymes in the blood. The presence of diabetes mellitus, demonstration of calculi by x-ray, and examination of the stools for excess fat and meat fibers are more important diagnostic guides. In cancer of the pancreas, function tests using secretin stimulation of the gland followed by an examination of the external secretion or determination of the serum amylase have been used with some success. PMID:12988052

Pancreatitis and carcinoma of the pancreas; some aspects of the pathologic physiology.

PubMed

EDMONDSON, H A

1952-09-01

The physiological phenomena accompanying pancreatic disease in adults are related to the local and generalized reaction of the body to the blockage and/or leakage of the three enzymes-amylase, lipase and trypsin. The measurements of amylase and lipase in the serum are the most reliable criteria in the diagnosis of acute disease. Related changes may include hypocalcemia, hypopotassemia, hyperlipemia, hyperglycemia and decreased renal function. In chronic pancreatitis, there is less fluctuation in the amounts of the enzymes in the blood. The presence of diabetes mellitus, demonstration of calculi by x-ray, and examination of the stools for excess fat and meat fibers are more important diagnostic guides. In cancer of the pancreas, function tests using secretin stimulation of the gland followed by an examination of the external secretion or determination of the serum amylase have been used with some success.

New insights into the pathways initiating and driving pancreatitis

PubMed Central

Gukovskaya, Anna S.; Pandol, Stephen J.; Gukovsky, Ilya

2016-01-01

Purpose of review In this article, we discuss recent studies that advance our understanding of molecular and cellular factors initiating and driving pancreatitis, with the emphasis on the role of acinar cell organelle disorders. Recent findings The central physiologic function of the pancreatic acinar cell – to synthesize, store, and secrete digestive enzymes – critically relies on coordinated actions of the endoplasmic reticulum (ER), the endolysosomal system, mitochondria, and autophagy. Recent studies begin to unravel the roles of these organelles’ disordering in the mechanism of pancreatitis. Mice deficient in key autophagy mediators Atg5 or Atg7, or lysosome-associated membrane protein-2, exhibit dysregulation of multiple signaling and metabolic pathways in pancreatic acinar cells and develop spontaneous pancreatitis. Mitochondrial dysfunction caused by sustained opening of the permeability transition pore is shown to mediate pancreatitis in several clinically relevant experimental models, and its inhibition by pharmacologic or genetic means greatly reduces local and systemic pathologic responses. Experimental pancreatitis is also alleviated with inhibitors of ORAI1, a key component of the plasma membrane channel mediating pathologic rise in acinar cell cytosolic Ca2+. Pancreatitis-promoting mutations are increasingly associated with the ER stress. These findings suggest novel pathways and drug targets for pancreatitis treatment. In addition, the recent studies identify new mediators (e.g., neutrophil extracellular traps) of the inflammatory and other responses of pancreatitis. Summary The recent findings illuminate a critical role of organelles regulating the autophagic, endolysosomal, mitochondrial, and ER pathways in maintaining pancreatic acinar cell homeostasis and secretory function; provide compelling evidence that organelle disordering is a key pathogenic mechanism initiating and driving pancreatitis; and identify molecular and cellular factors

Molecular and genetic bases of pancreatic cancer.

PubMed

Vaccaro, Vanja; Gelibter, Alain; Bria, Emilio; Iapicca, Pierluigi; Cappello, Paola; Di Modugno, Francesca; Pino, Maria Simona; Nuzzo, Carmen; Cognetti, Francesco; Novelli, Francesco; Nistico, Paola; Milella, Michele

2012-06-01

Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

Oral bacteria in pancreatic cancer: mutagenesis of the p53 tumour suppressor gene

PubMed Central

Öğrendik, Mesut

2015-01-01

Carcinoma of exocrine pancreas is the fourth leading cause of cancer deaths, worldwide. The prevalence of this disease is very high in patients with chronic pancreatitis. Orodigestive cancers are frequently seen in patients with periodontitis. These findings suggest that this type of cancer may have some bacterial origins. This study hypothesizes that the peptidyl arginine deaminase (PAD) enzymes found in oral bacteria may be responsible for the p53 point mutations that occur in patients with pancreatic cancer. Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Treponema denticola possess the PAD enzyme, and p53 arginine mutations have been detected in patients with pancreatic cancer. Moreover, the Pro allele p53Arg72-Pro is a risk factor for the development of this cancer. Anti-P. gingivalis antibody titers have been found to be higher in patients with pancreatic cancer as compared to healthy controls. The hypothesis in question can be tested if the DNA of P. gingivalis or the antibodies against P. gingivalis can be detected in patients with the p53 arginine mutation.If this hypothesis is true, it could reveal the real cause of pancreatic cancer, which is a fatal disease. Further studies are necessary in order to confirm this hypothesis. PMID:26617937

Genetic and molecular alterations in pancreatic cancer: implications for personalized medicine.

PubMed

Fang, Yantian; Yao, Qizhi; Chen, Zongyou; Xiang, Jianbin; William, Fisher E; Gibbs, Richard A; Chen, Changyi

2013-10-31

Recent advances in human genomics and biotechnologies have profound impacts on medical research and clinical practice. Individual genomic information, including DNA sequences and gene expression profiles, can be used for prediction, prevention, diagnosis, and treatment for many complex diseases. Personalized medicine attempts to tailor medical care to individual patients by incorporating their genomic information. In a case of pancreatic cancer, the fourth leading cause of cancer death in the United States, alteration in many genes as well as molecular profiles in blood, pancreas tissue, and pancreas juice has recently been discovered to be closely associated with tumorigenesis or prognosis of the cancer. This review aims to summarize recent advances of important genes, proteins, and microRNAs that play a critical role in the pathogenesis of pancreatic cancer, and to provide implications for personalized medicine in pancreatic cancer.

Everolimus for the Treatment of Advanced Pancreatic Neuroendocrine Tumors: Overall Survival and Circulating Biomarkers From the Randomized, Phase III RADIANT-3 Study.

PubMed

Yao, James C; Pavel, Marianne; Lombard-Bohas, Catherine; Van Cutsem, Eric; Voi, Maurizio; Brandt, Ulrike; He, Wei; Chen, David; Capdevila, Jaume; de Vries, Elisabeth G E; Tomassetti, Paola; Hobday, Timothy; Pommier, Rodney; Öberg, Kjell

2016-11-10

Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low- or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to open-label everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intent-to-treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85%) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95% CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95% CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95% CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of

[Chronic pancreatitis diagnosed after the first attack of acute pancreatitis].

PubMed

Bojková, Martina; Dítě, Petr; Uvírová, Magdalena; Dvořáčková, Nina; Kianička, Bohuslav; Kupka, Tomáš; Svoboda, Pavel; Klvaňa, Pavel; Martínek, Arnošt

2016-02-01

One of the diseases involving a potential risk of developing chronic pancreatitis is acute pancreatitis. Of the overall number of 231 individuals followed with a diagnosis of chronic pancreatitis, 56 patients were initially treated for acute pancreatitis (24.2 %). Within an interval of 12- 24 months from the first attack of acute pancreatitis, their condition gradually progressed to reached the picture of chronic pancreatitis. The individuals included in the study abstained (from alcohol) following the first attack of acute pancreatitis and no relapse of acute pancreatitis was proven during the period of their monitoring. The etiology of acute pancreatitis identified alcohol as the predominant cause (55.3 %), biliary etiology was proven in 35.7 %. According to the revised Atlanta classification, severe pancreatitis was established in 69.6 % of the patients, the others met the criterion for intermediate form, those with the light form were not included. Significant risk factors present among the patients were smoking, obesity and 18 %, resp. 25.8 % had pancreatogenous diabetes mellitus identified. 88.1 % of the patients with acute pancreatitis were smokers. The majority of individuals with chronic pancreatitis following an attack of acute pancreatitis were of a productive age from 25 to 50 years. It is not only acute alcoholic pancreatitis which evolves into chronic pancreatitis, we have also identified this transition for pancreatitis of biliary etiology.

Ropidoxuridine in Treating Patients With Advanced Gastrointestinal Cancer Undergoing Radiation Therapy

ClinicalTrials.gov

2018-03-02

Advanced Bile Duct Carcinoma; Stage II Esophageal Cancer AJCC v7; Stage II Pancreatic Cancer AJCC v6 and v7; Stage IIA Esophageal Cancer AJCC v7; Stage IIA Pancreatic Cancer AJCC v6 and v7; Stage IIB Esophageal Cancer AJCC v7; Stage IIB Pancreatic Cancer AJCC v6 and v7; Stage III Colon Cancer AJCC v7; Stage III Esophageal Cancer AJCC v7; Stage III Gastric Cancer AJCC v7; Stage III Liver Cancer; Stage III Pancreatic Cancer AJCC v6 and v7; Stage III Rectal Cancer AJCC v7; Stage III Small Intestinal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Esophageal Cancer AJCC v7; Stage IIIA Gastric Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIA Small Intestinal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Esophageal Cancer AJCC v7; Stage IIIB Gastric Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIB Small Intestinal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Esophageal Cancer AJCC v7; Stage IIIC Gastric Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Esophageal Cancer AJCC v7; Stage IV Gastric Cancer AJCC v7; Stage IV Liver Cancer; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IV Rectal Cancer AJCC v7; Stage IV Small Intestinal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Liver Cancer; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Liver Cancer; Stage IVB Rectal Cancer AJCC v7

Biochemical modulation of 5-fluorouracil by methotrexate in patients with advanced gastric carcinoma.

PubMed

Pérez, J E; Lacava, J A; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Romero Acuña, L A; Langhi, M J; Romero Acuña, J M; Vallejo, C T; Leone, B A; Machiavelli, M R; Romero, A O

1998-10-01

A phase II trial was conducted to evaluate the efficacy and toxicity of a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV) rescue) as first-line chemotherapy in patients with locally advanced (inoperable) or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients with advanced gastric carcinoma received a regimen that consisted of: MTX 200 mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24 hours after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 hours for six doses. Cycles were repeated every 15 days. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved complete response and 14 (40%) achieved partial response. No change was recorded in 14 patients (40%) and progressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death resulting from severe leukopenia occurred. The dose-limiting toxicity was mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with advanced gastric cancer. Further investigation both in experimental and clinical fields is needed to clearly define its role and to design the best modulatory strategy.

Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose.

PubMed

Wilkowski, Ralf; Thoma, Martin; Weingandt, Helmut; Dühmke, Eckhart; Heinemann, Volker

2005-05-10

Review of the role of chemoradiotherapy in the treatment of locally advanced pancreatic cancer with a specific focus on the technical feasibility and the integration of chemoradiotherapy into multimodal treatment concepts. Combined chemoradiotherapy of pancreatic cancer is a safe treatment with an acceptable profile of side effects when applied with modern planning and radiation techniques as well as considering tissue tolerance. Conventionally fractionated radiation regimens with total doses of 45-50 Gy and small-volume boost radiation with 5.4 Gy have found the greatest acceptance. Locoregional lymphatic drainage should be included in the planning of target volumes because the risk of tumor involvement and local or loco-regional recurrence is high. Up to now, 5-fluorouracil has been considered the "standard" agent for concurrent chemoradiotherapy. The role of gemcitabine given concurrently with radiation has not yet been defined, since high local efficacy may also be accompanied by enhanced toxicities. In addition, no dose or administration form has been determined to be "standard" up to now. The focus of presently ongoing research is to define an effective and feasible regimen of concurrent chemoradiotherapy. While preliminary results indicate promising results using gemcitabine-based chemoradiotherapy, reliable data derived from mature phase III trials are greatly needed. Intensity-modulated radiotherapy has been developed to improve target-specific radiation and to reduce organ toxicity. Its clinical relevance still needs to be defined.

Robotic transgastric cystgastrostomy and pancreatic debridement in the management of pancreatic fluid collections following acute pancreatitis.

PubMed

Kirks, Russell C; Sola, Richard; Iannitti, David A; Martinie, John B; Vrochides, Dionisios

2016-01-01

Pancreatic and peripancreatic fluid collections may develop after severe acute pancreatitis. Organized fluid collections such as pancreatic pseudocyst and walled-off pancreatic necrosis (WOPN) that mature over time may require intervention to treat obstructive or constitutional symptoms related to the size and location of the collection as well as possible infection. Endoscopic, open surgical and minimally invasive techniques are described to treat post-inflammatory pancreatic fluid collections. Surgical intervention may be required to treat collections containing necrotic pancreatic parenchyma or in locations not immediately apposed to the stomach or duodenum. Comprising a blend of the surgical approach and the clinical benefits of minimally invasive surgery, the robot-assisted technique of pancreatic cystgastrostomy with pancreatic debridement is described.

A phase II trial of gemcitabine plus carboplatin in advanced transitional cell carcinoma of the urothelium.

PubMed

Xu, Nong; Zhang, Xiao Chen; Xiong, Jian Ping; Fang, Wei Jia; Yu, Lan Fang; Qian, Jiong; Zhang, Ling

2007-06-09

Recent studies have demonstrated the effectiveness of cisplatin-based combinations in patients with advanced transitional cell carcinoma(TCC) of the urothelium. Concern over cisplatin toxicity instigated a search for alternative regimens. The aim of the study was to evaluate the activity and tolerability of gemcitabine plus carboplatin combination as first-line treatment in patients with advanced transitional cell carcinoma of the urothelium. Patients with advanced TCC were treated with gemcitabine 1200 mg/m2 on days 1 and 8 and carboplatin area under the concentration-time curve(AUC) 5 on day 1 every 21 days. Out of 41 patients, thirty-nine were evaluable for efficacy and 41 for toxicity. A median of 5 cycles (range 1-6) was administered. Overall response rate was 46.2% (95% confidence interval: 32-65%) including 10.3% complete responses and 35.9% partial responses. The median time to progression and median overall survival were 7.5 months (95% confidence interval: 6.6-8.4 months) and 13.6 months (95% confidence interval: 10.2-17.0 months), respectively. Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 36.6%, 26.8, and 24.4% of patients, respectively. Non-hematological toxicity was generally mild. Grade 3 vomiting occurred in 1 (2.4%) patients. The gemcitabine plus carboplatin combination is active in advanced TCC with acceptable toxicity and needs to be evaluated further and compared with other non-cisplatin-containing regimens. ISRCTN88259320.

Circulating tumor DNA as a liquid biopsy target for detection of pancreatic cancer

PubMed Central

Takai, Erina; Yachida, Shinichi

2016-01-01

Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The “liquid biopsy” addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA (ctDNA) could provide diagnostic information. In this review, we provide an overview of the current status of blood-based tests for diagnosis of pancreatic cancer and the potential utility of ctDNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ctDNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer. PMID:27784960

Generation of glyceraldehyde-derived advanced glycation end-products in pancreatic cancer cells and the potential of tumor promotion

PubMed Central

Takata, Takanobu; Ueda, Tadashi; Sakasai-Sakai, Akiko; Takeuchi, Masayoshi

2017-01-01

AIM To determine the possibility that diabetes mellitus promotes pancreatic ductal adenocarcinoma via glyceraldehyde (GA)-derived advanced glycation-end products (GA-AGEs). METHODS PANC-1, a human pancreatic cancer cell line, was treated with 1-4 mmol/L GA for 24 h. The cell viability and intracellular GA-AGEs were measured by WST-8 assay and slot blotting. Moreover, immunostaining of PANC-1 cells with an anti-GA-AGE antibody was performed. Western blotting (WB) was used to analyze the molecular weight of GA-AGEs. Heat shock proteins 90α, 90β, 70, 27 and cleaved caspase-3 were analyzed by WB. In addition, PANC-1 cells were treated with GA-AGEs-bovine serum albumin (GA-AGEs-BSA), as a model of extracellular GA-AGEs, and proliferation of PANC-1 cells was measured. RESULTS In PANC-1 cells, GA induced the production of GA-AGEs and cell death in a dose-dependent manner. PANC-1 cell viability was approximately 40% with a 2 mmol/L GA treatment and decreased to almost 0% with a 4 mmol/L GA treatment (each significant difference was P < 0.01). Cells treated with 2 and 4 mmol/L GA produced 6.4 and 21.2 μg/mg protein of GA-AGEs, respectively (P < 0.05 and P < 0.01). The dose-dependent production of some high-molecular-weight (HMW) complexes of HSP90β, HSP70, and HSP27 was observed following administration of GA. We considered HMW complexes to be dimers and trimers with GA-AGEs-mediated aggregation. Cleaved caspase-3 could not be detected with WB. Furthermore, 10 and 20 μg/mL GA-AGEs-BSA was 27% and 34% greater than that of control cells, respectively (P < 0.05 and P < 0.01). CONCLUSION Although intracellular GA-AGEs induce pancreatic cancer cell death, their secretion and release may promote the proliferation of other pancreatic cancer cells. PMID:28785145

GLI1, a master regulator of the hallmark of pancreatic cancer.

PubMed

Kasai, Kenji

2016-12-01

Hedgehog signaling is highly conserved across species and governs proper embryonic development. Germline gene mutations that reduce this signaling activity cause a variety of developmental abnormalities such as holoprosencephaly, while those that enhance Hedgehog signaling activity induce a tumor-predisposition condition Nevoid basal cell carcinoma syndrome. Furthermore, dysregulated activation of Hedgehog signaling has been recognized in various sporadic malignancies, including pancreatic adenocarcinoma. Pancreatic adenocarcinoma develops through a multistep carcinogenesis starting with oncogenic mutation of the KRAS gene. During this process, precancerous or cancer cells secrete Hedgehog ligand proteins to promote characteristic desmoplastic stroma around the cells, which in turn activates the expression of the downstream transcription factor GLI1 inside the cells. The quantitative and spatiotemporal dysregulation of GLI1 subsequently leads to the expression of transcriptional target genes of GLI1 that govern the hallmark of malignant properties. Here, after a brief introductory outline, a perspective is offered of Hedgehog signaling with a special focus on the role of GLI1 in pancreatic carcinogenesis. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Advanced glycation end products impair glucose-induced insulin secretion from rat pancreatic β-cells.

PubMed

Hachiya, Hiroyuki; Miura, Yoshikazu; Inoue, Ken-Ichi; Park, Kyung Hwa; Takeuchi, Masayoshi; Kubota, Keiichi

2014-02-01

Advanced glycation end products (AGEs) are derivative compounds generated from non-enzymatic glycosylation and oxidation. In comparison with glucose-derived AGEs (Glu-AGEs), glyceraldehyde-derived AGEs (Glycer-AGEs) have stronger toxicity to living systems. In this study, we compared the effects of Glu-AGE and Glycer-AGE on insulin secretion. Rat pancreatic islets were isolated by collagenase digestion and primary-cultured in the presence of 0.1 mg/ml bovine serum albumin (BSA) or 0.1 mg/ml Glu-AGE or Glycer-AGE-albumin. After 48 h of culture, we performed an insulin secretion test and identified the defects by a battery of rescue experiments [corrected]. Also, mRNA expression of genes associated with insulin secretion was measured. Insulin secretion induced by a high glucose concentration was 164.1 ± 6.0, 124.4 ± 4.4 (P < 0.05) and 119.8 ± 7.1 (P < 0.05) μU/3 islets/h in the presence of BSA, Glu-AGE, and Glycer-AGE, respectively. Inhibition of insulin secretion by Glu-AGE or Glycer-AGE was rescued by a high extracellular potassium concentration, tolbutamide and α-ketoisocaproic acid, but not by glyceraldehyde, dihydroxacetone, methylpyruvate, glucagon-like peptide-1 and acetylcholine. Glu-AGE or Glycer-AGE reduced the expression of the malate dehydrogenase (Mdh1/2) gene, which plays a critical role in the nicotinamide adenine dinucleotide (NADH) shuttle. Despite its reported cytotoxicity, the effects of Glycer-AGE on insulin secretion are similar to those of Glu-AGE. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Neoadjuvant radiotherapeutic strategies in pancreatic cancer

PubMed Central

Roeder, Falk

2016-01-01

This review summarizes the current status of neoadjuvant radiation approaches in the treatment of pancreatic cancer, including a description of modern radiation techniques, and an overview on the literature regarding neoadjuvant radio- or radiochemotherapeutic strategies both for resectable and irresectable pancreatic cancer. Neoadjuvant chemoradiation for locally-advanced, primarily non- or borderline resectable pancreas cancer results in secondary resectability in a substantial proportion of patients with consecutively markedly improved overall prognosis and should be considered as possible alternative in pretreatment multidisciplinary evaluations. In resectable pancreatic cancer, outstanding results in terms of response, local control and overall survival have been observed with neoadjuvant radio- or radiochemotherapy in several phase I/II trials, which justify further evaluation of this strategy. Further investigation of neoadjuvant chemoradiation strategies should be performed preferentially in randomized trials in order to improve comparability of the current results with other treatment modalities. This should include the evaluation of optimal sequencing with newer and more potent systemic induction therapy approaches. Advances in patient selection based on new molecular markers might be of crucial interest in this context. Finally modern external beam radiation techniques (intensity-modulated radiation therapy, image-guided radiation therapy and stereotactic body radiation therapy), new radiation qualities (protons, heavy ions) or combinations with alternative boosting techniques widen the therapeutic window and contribute to the reduction of toxicity. PMID:26909133

Pancreatic trauma.

PubMed

Lahiri, R; Bhattacharya, S

2013-05-01

Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised. A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: 'pancreatic trauma', 'pancreatic duct injury', 'radiology AND pancreas injury', 'diagnosis of pancreatic trauma', and 'management AND surgery'. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors. Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon. The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important prognostic factor is pancreatic duct disruption and in these cases

Covered self-expandable metal stents with an anti-migration system improve patency duration without increased complications compared with uncovered stents for distal biliary obstruction caused by pancreatic carcinoma: a randomized multicenter trial.

PubMed

Kitano, Masayuki; Yamashita, Yukitaka; Tanaka, Kiyohito; Konishi, Hideyuki; Yazumi, Shujiro; Nakai, Yoshitaka; Nishiyama, Osamu; Uehara, Hiroyuki; Mitoro, Akira; Sanuki, Tsuyoshi; Takaoka, Makoto; Koshitani, Tatsuya; Arisaka, Yoshifumi; Shiba, Masatsugu; Hoki, Noriyuki; Sato, Hideki; Sasaki, Yuichi; Sato, Masako; Hasegawa, Kazunori; Kawabata, Hideaki; Okabe, Yoshihiro; Mukai, Hidekazu

2013-11-01

The requirements of biliary stents used in the palliation of malignant biliary obstruction are a long duration of patency and minimal adverse effects. Covered self-expandable metal stents (SEMSs) have been shown to prevent tumor ingrowth, which is the most frequent complication of uncovered SEMSs. However, because they are prone to migration, the superiority of covered SEMS has yet to be convincingly demonstrated. The aim of this study was to evaluate the superiority of covered over uncovered SEMSs in the palliation of distal biliary obstruction due to unresectable pancreatic carcinoma, using both stent types with relatively low axial force and uncovered flared ends to prevent their migration. From April 2009 to December 2010, 120 patients who were admitted to 22 tertiary-care centers because of distal biliary obstruction from unresectable pancreatic carcinomas were enrolled in this prospective randomized multicenter study. Patients were randomly assigned to receive a covered or uncovered SEMS deployed at the site of the biliary stricture during endoscopic retrograde cholangiopancreatography. Stent patency time, patient survival time, patient survival time without stent dysfunction (time to stent dysfunction or patient death), cause of stent dysfunction (ingrowth, overgrowth, migration, or sludge formation), and serious adverse events were compared between covered and uncovered SEMS groups. Patient survival time in the two groups did not significantly differ (median: 285 and 223 days, respectively; P=0.68). Patient survival time without stent dysfunction was significantly longer in the covered than in the uncovered SEMS group (median: 187 vs. 132 days; P=0.043). Stent patency was also significantly longer in the covered than in the uncovered SEMS group (mean±s.d.: 219.3±159.1 vs. 166.9±124.9 days; P=0.047). Reintervention for stent dysfunction was performed in 14 of 60 patients with covered SEMSs (23%) and in 22 of 60 patients with uncovered SEMSs (37%; P=0

Molecular Imaging of Pancreatic Cancer with Antibodies

PubMed Central

2015-01-01

Development of novel imaging probes for cancer diagnostics remains critical for early detection of disease, yet most imaging agents are hindered by suboptimal tumor accumulation. To overcome these limitations, researchers have adapted antibodies for imaging purposes. As cancerous malignancies express atypical patterns of cell surface proteins in comparison to noncancerous tissues, novel antibody-based imaging agents can be constructed to target individual cancer cells or surrounding vasculature. Using molecular imaging techniques, these agents may be utilized for detection of malignancies and monitoring of therapeutic response. Currently, there are several imaging modalities commonly employed for molecular imaging. These imaging modalities include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance (MR) imaging, optical imaging (fluorescence and bioluminescence), and photoacoustic (PA) imaging. While antibody-based imaging agents may be employed for a broad range of diseases, this review focuses on the molecular imaging of pancreatic cancer, as there are limited resources for imaging and treatment of pancreatic malignancies. Additionally, pancreatic cancer remains the most lethal cancer with an overall 5-year survival rate of approximately 7%, despite significant advances in the imaging and treatment of many other cancers. In this review, we discuss recent advances in molecular imaging of pancreatic cancer using antibody-based imaging agents. This task is accomplished by summarizing the current progress in each type of molecular imaging modality described above. Also, several considerations for designing and synthesizing novel antibody-based imaging agents are discussed. Lastly, the future directions of antibody-based imaging agents are discussed, emphasizing the potential applications for personalized medicine. PMID:26620581

Apatinib is effective for treatment of advanced hepatocellular carcinoma.

PubMed

Kong, Yinlong; Sun, Lin; Hou, Zhenyu; Zhang, Yongqiang; Chen, Ping; Cui, Yunlong; Zhu, Xiaolin; Song, Tianqiang; Li, Qiang; Li, Huikai; Zhang, Ti; Qin, Lunxiu

2017-12-01

As treatment options for hepatocellular carcinoma (HCC) are currently limited, we evaluated the efficacy and safety of oral apatinib, a VEGFR-2 inhibitor, on patients with advanced HCC. Twenty-two patients from Tianjin Medical University Cancer Institute and Hospital were enrolled for evaluation. Apatinib was administered at 500 mg/day or 250 mg/day continuously. Clinical endpoints were time to disease progression (TTP), overall survival (OS), and safety. The median TTP of treated patients was 10.4 months (95% CI 3.4 -17.5). At the last follow-up, 50% patients had survived longer than 11.4 months from the first dose. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) rates were 0%, 40.9%, 40.9%, and 18.2%, respectively. The most common apatinib-related adverse events were hand-foot skin reaction (HFSR) (81.8%) and diarrhea (77.3%). Hypertension (27.3%) and HFSR (13.6%) were the most frequent grade 3/4 adverse events. In summary, results of this small study indicate that apatinib is well tolerated and extremely effective for the treatment of advanced HCC. It is therefore imperative to design and carry out well-controlled clinical trials to confirm its efficacy.

Pancreatitis in Children.

PubMed

Sathiyasekaran, Malathi; Biradar, Vishnu; Ramaswamy, Ganesh; Srinivas, S; Ashish, B; Sumathi, B; Nirmala, D; Geetha, M

2016-11-01

Pancreatic disease in children has a wide clinical spectrum and may present as Acute pancreatitis (AP), Acute recurrent pancreatitis (ARP), Chronic pancreatitis (CP) and Pancreatic disease without pancreatitis. This article highlights the etiopathogenesis and management of pancreatitis in children along with clinical data from five tertiary care hospitals in south India [Chennai (3), Cochin and Pune].

Course of alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study.

PubMed

Ammann, R W; Heitz, P U; Klöppel, G

1996-07-01

The pathogenesis of alcoholic chronic pancreatitis and its relationship to alcoholic acute pancreatitis are debated. According to our recent clinical long-term study, alcoholic chronic pancreatitis seems to evolve from severe acute pancreatits. The aim of this study was to correlate clinical findings to the pancreatic histopathology at early and advanced stages of the disease. Morphological changes (pseudocysts, autodigestive necrosis, calcification, and perilobular and intralobular fibrosis) were recorded in 37 surgical and 46 postmortem pancreas specimens of 73 patients from our long-term series, who progressed from clinically acute to chronic pancreatitis (mean follow-up, 12 years). Pancreatic function was monitored at yearly intervals. Surgical interventions were performed at a mean of 4.1 years from onset. Histologically, focal necrosis (49%) and mild perilobular fibrosis (54%) predominated, Pseudocysts (n = 41, mostly postnecrotic) occurred in 88% within 6 years from onset. Autopsy specimens were obtained at a mean of 12 years. These pancreata often showed severe perilobular and intralobular fibrosis (85%) and calcifications (74%), but rarely necrosis (4%). Fibrosis correlated with progressive pancreatic dysfunction (P < 0.001), particularly in the 10 patients with two histological assessments (mean interval between biopsy and autopsy, 8 years). The data support an evolution from severe alcoholic acute pancreatitis to chronic pancreatitis.