CT diagnosis of pancreatic carcinoma and chronic pancreatitis

International Nuclear Information System (INIS)

Luan Baoqing; Jin Erhu; Zhang Lizhen; Jiang Haibin

1997-01-01

To improve the diagnostic accuracy of pancreatic carcinoma and chronic pancreatitis. The CT findings of 154 cases with pancreatic carcinoma, chronic pancreatitis and mis-diagnosed other pancreatic diseases proven clinically and pathologically were analysed. Slice thickness of 8 mm and slice interval of 8 mm were used and thin-section scan and enhancement study were performed in some cases. The main signs in degassing and differential diagnosis between pancreatic carcinoma and chronic pancreatitis included: (1) focal or diffuse enlargement and density abnormality of pancreas; (2) dilated common bile duct was suddenly obstructed, peripancreatic blood vessels were invaded and cancerous thrombus was revealed, enlargement of abdominal lymph nodes and metastasis in the liver were discovered; (3) calcium deposit in the pancreatic duct area and dilated pancreatic duct which passed through the lesion or not; (4) presence and location of pancreatic cyst and its relationship to pancreatic contour. CT is the imaging modality of choice in the diagnosis of pancreatic carcinoma and chronic pancreatitis at present. The diagnostic accuracy of CT was over 90% in this series

Differential diagnosis of pancreas cancer and chronic pancreatitis in computed tomography

International Nuclear Information System (INIS)

Fujita, Nobuyuki; Saitou, Hiroya; Hiromura, Tadao; Takahashi, Hiromichi; Shinohara, Masahiro; Morita, Yutaka; Irie, Goro

1987-01-01

Differential diagnosis of pancreas cancer and chronic pancreatitis in Computed Tomography. CT pictures of 46 cases of pancreas cancer and 16 cases of chronic pancreatitis were reviewed to clarify a way of differential diagnosis of these two disorders. The conclusion obtained in this study is as below. 1) Well-defined cystic central low density is a sign of chronic pancreatitis, and in the other hand, the solid central low density is a sign of pancreas cancer. 2) Effect of contrast enhancement was greater in chronic pancreatitis than in pancreas cancer. 3) Possibility of pancreas cancer is high in a case which has a sign of vascular involvement but no definite sign of tumor. 4) Sensitivity, specificity, total accuracy is 76.7 %, 87.5 %, 75.8 % respectively. (author)

Dual phase helical CT: diagnosis value for early pancreatic carcinoma

International Nuclear Information System (INIS)

Shen Bingqi; Zhang Ling; Zheng Keguo; Xu Dasheng

2006-01-01

Objective: To study dual-phase helical CT for the evaluation of early pancreatic cacinoma. Methods: Dual-phase helical CT was performed on 21 patients with early pancreatic carcinoma. In the enhanced imaging the contrast material was intravenously injected in a dose of 1.5 ml/kg at a rate of 3 ml/s. The image acquisition of the lesion in pancreatic phase (PP) and portal venous phase (PVP) were started at 35 seconds and 65 seconds after the start of the injection respectively. The enhancement of normal pancreas and tumor during the two phases was observed and compared. All data were statistically analyzed. Results: Tumor-pancreas contrast was significantly greater in PP (45.16±113.23) HU than in PVP (23.15±12.44) HU (t=2.13, P<0.01). Conclusion: Dual-phase helical CT scan for pancreas, including the imaging of the pancreatic and portal , venous phase, can be applied as an optimal selection. It can delineate early pancreatic carcinoma clearly and provide more information for the diagnosis of the lesion. The tumor-pancreas contrast was much higher' in PP than in PVP. (authors)

Utility of core biopsy with concurrent ROSE FNA in the diagnosis of pancreatic tumor-does the biopsy add any diagnostic benefit?

Science.gov (United States)

Yan, Lei; Ikemura, Kenji; Park, Ji-Weon

2018-02-01

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided core-needle biopsy (EUS-CNB) are widely used for diagnosis of pancreatic tumors. The aim of our study was to compare the diagnostic performance of ROSE EUS-FNA and EUS-CNB for diagnosis of pancreatic malignancy during the same EUS. Patients who underwent both FNA and CNB during the same EUS for pancreatic solid lesion were reviewed retrospectively. Sample adequacy, diagnostic yield (defined as percentage of definitive diagnosis), sensitivity and specificity for malignancy were compared between FNA and CNB. A total of 48 patients with solid pancreatic lesions were evaluated. The proportions of adequate samples were 48/48 (100%) for FNA and 45/48 (93.7%) for core biopsy (P = .24). The diagnostic yield was 42/48 (87.5%) and 33/48 (68.7%) for FNA and CNB respectively (P = .046). The incremental increase in diagnostic yield by combining both methods was 2/48 (4%). The diagnostic yield for malignancy was 30/32 (93.7%) for FNA and 23/32 (71.8%) for CNB (P = .043). The sensitivity for the diagnosis of malignancy for FNA and CNB were 90.6% and 69%, respectively (P = .045). The specificity was 100% for both methods. The sensitivity for diagnosing malignancy increased to 93.8% when the two methods were combined. The difference in diagnostic yield was not associated with lesion size or location. EUS-guided FNA is a superior method of assessing solid pancreatic lesion and pancreatic malignancy with better diagnostic yield and higher sensitivity than EUS-CNB. © 2017 Wiley Periodicals, Inc.

Imaging of pancreatic tumors

International Nuclear Information System (INIS)

Brambs, Hans-Juergen; Juchems, Markus

2010-01-01

Ductal adenocarcinoma is the most frequent solid tumor of the pancreas. This tumor has distinct features including early obstruction of the pancreatic duct, diminished enhancement after administration of contrast material due to desmoplastic growth, high propensity to infiltrate adjacent structures and to metastasize into the liver and the peritoneum. Hormone active endocrine tumors cause specific clinical symptoms. Imaging is aimed at localization of these hypervascular tumors. Non hormone active tumors are most frequently malignant and demonstrate very varying features. Cystic pancreatic tumors are increasingly detected by means of cross sectional imaging. Exact classification can be achieved with knowledge of the macropathology and considering clinical presentation as well as age and gender of the patients. (orig.)

Potential Applications of Nanotechnology for the Diagnosis and Treatment of Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Joshua eMcCarroll

2014-01-01

Full Text Available Despite improvements in our understanding of pancreatic cancer and the emerging concept of personalized medicine for the treatment of this disease, it is still the fourth most common cause of cancer death in the western world. It is established that pancreatic cancer is a highly heterogeneous disease with a complex tumor microenvironment. Indeed the extensive stroma surrounding the cancer cells has been shown to be important in promoting tumor growth and metastases, as well as sequestering chemotherapeutic agents consequently decreasing delivery to the tumor cells. Nanotechnology has come to the forefront in the areas of medical diagnostics, imaging, and therapeutic drug delivery. This review will focus on the potential applications of nanotechnology for diagnosis, imaging, and delivery of therapeutic agents for the treatment of pancreatic cancer.

Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report.

LENUS (Irish Health Repository)

Duffy, M J

2012-02-01

Pancreatic ductal adenocarcinoma is one of the most difficult malignancies to diagnose and treat. The aim of this article is to review how tumor markers can aid the diagnosis and management of patients with this malignancy. The most widely used and best validated marker for pancreatic cancer is CA 19-9. Inadequate sensitivity and specificity limit the use of CA 19-9 in the early diagnosis of pancreatic cancer. In non-jaundiced patients, however, CA 19-9 may complement other diagnostic procedures. In patients with resectable pancreatic cancer, presurgical and postresection CA 19-9 levels correlate with overall survival. In advanced disease, elevated pretreatment levels of CA 19-9 are associated with adverse patient outcome and thus may be combined with other factors for risk stratification. Most, but not all, reports indicate that serial levels of CA 19-9 correlate with response to systemic therapy. Use of CA 19-9 kinetics in conjunction with imaging is therefore recommended in monitoring therapy. Although several potential serum and tissue markers for pancreatic cancer are currently undergoing evaluation, none are sufficiently validated for routine clinical use. CA 19-9 thus remains the serum pancreatic cancer marker against which new markers for this malignancy should be judged.

SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

International Nuclear Information System (INIS)

Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den

2014-01-01

Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

Energy Technology Data Exchange (ETDEWEB)

Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den [UMC Utrecht, Utrecht, Utrecht (Netherlands)

2014-06-01

Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

Role of respiratory-gated PET/CT for pancreatic tumors: A preliminary result

International Nuclear Information System (INIS)

Kasuya, Takeo; Tateishi, Ukihide; Suzuki, Kazufumi; Daisaki, Hiromitsu; Nishiyama, Yuji; Hata, Masaharu; Inoue, Tomio

2013-01-01

Purpose: The aim of this study is to ascertain role of respiratory-gated PET/CT for accurate diagnosis of pancreatic tumors. Materials and methods: Prior to clinical study, the phantom study was performed to evaluate the impact of respiratory motion on lesion quantification. Twenty-two patients (mean age 65 years) with pancreatic tumors were enrolled. Pathological diagnoses by surgical specimens consisted of pancreatic cancer (n = 15) and benign intraductal papillary mucinous neoplasm (IPMN, n = 7). Whole-body scan of non-respiratory-gated PET/CT was performed at first, and subsequent respiratory-gated PET/CT for one bed position was performed. All PET/CT studies were performed prior to surgery. The SUV max obtained by non-respiratory-gated PET/CT and respiratory-gated PET/CT, and percent difference in SUVmax (%SUVmax) were compared. Results: The profile curve of 5 respiratory bin image was most similar to that of static image. The third bin of 5 respiratory bin image showed highest FWHM (24.0 mm) and FWTM (32.7 mm). The mean SUVmax of pancreatic cancer was similar to that of benign IPMN on non-respiratory-gated PET/CT (p = 0.05), whereas significant difference was found between two groups on respiratory-gated PET/CT (p = 0.016). The mean %SUV of pancreatic cancer was greater than that of benign IPMN (p < 0.0001). Identification of the primary tumor in pancreatic head (n = 13, 59%) was improved by using respiratory-gated PET/CT because of minimal affection of physiological accumulation in duodenum. Conclusion: Respiratory-gated PET/CT is a feasible technique for evaluation of pancreatic tumors and allows more accurate identification of pancreatic tumors compared with non-respiratory-gated PET/CT

Imaging of pancreatic tumors with PET

International Nuclear Information System (INIS)

Zanzi, I.; Robeson, W.; Vinciquerra, V.; Chaly, T.; Kroop, S.; Dahl, R.; Schulman, P.; Goldman, S.; Margouleff, D.

1990-01-01

This paper identifies pancreatic tumors with positron emission tomography (PET) using F-18 2-fluorodeoxyglucose (FDG). PET studies were performed in 13 patients with pancreatic tumors (11 adenocarcinomas; two islet cell tumors) using FDG. Data were acquired for 1 hour and in 14 contiguous 7-mm sections after attenuation correction. Suspicious areas were evaluated using quantitative techniques. In seven of 11 patients with adenocarcinomas, focal increase in FDG uptake correlated with pancreatic tumor shown on CT scans or MR images. Of the remaining four, one had a previous Whipple procedure, another had completed chemotherapy, and in two the tumor was out of the limited region imaged; in these four patients, liver metastases were identified in three

Indications for surgical resection of benign pancreatic tumors

International Nuclear Information System (INIS)

Isenmann, R.; Henne-Bruns, D.

2008-01-01

Benign pancreatic tumors should undergo surgical resection when they are symptomatic or - in the case of incidental discovery - bear malignant potential. This is the case for the majority of benign pancreatic tumors, especially for intraductal papillary mucinous neoplasms or mucinous cystic adenomas. In addition, resection is indicated for all tumors where preoperative diagnostic fails to provide an exact classification. Several different operative techniques are available. The treatment of choice depends on the localization of the tumor, its size and on whether there is evidence of malignant transformation. Partial duodenopancreatectomy is the oncological treatment of choice for tumors of the pancreatic head whereas for tumors of the pancreatic tail a left-sided pancreatectomy is appropriate. Middle pancreatectomy or duodenum-preserving resection of the pancreatic head is not a radical oncologic procedure. They should only be performed in cases of tumors without malignant potential. (orig.) [de

Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

Science.gov (United States)

Ferri, María José; Saez, Marc; Figueras, Joan; Fort, Esther; Sabat, Miriam; López-Ben, Santiago; de Llorens, Rafael; Aleixandre, Rosa Núria; Peracaula, Rosa

2016-01-01

There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.

Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

Directory of Open Access Journals (Sweden)

María José Ferri

Full Text Available There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9 is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies.CA 19-9, carcinoembryonic antigen (CEA, C-reactive protein, albumin, insulin growth factor-1 (IGF-1 and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls.The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients.Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.

Two-photon excited fluorescence imaging of the pancreatic solid pseudopapillary tumor without hematoxylin and eosin stains.

Science.gov (United States)

Xu, Yahao; Liao, Chenxi; Chen, Jing; Chen, Youting; Zhu, Xiaoqin; Chen, Jianxin

2016-05-01

Solid pseudopapillary tumor (SPT) of the pancreas is an epithelial tumor with low-grade malignant potential and present more common in females. At present, the gold standard for accurate diagnosis of pancreatic tumor was mostly depending on the pathological and/or cytological evaluation. In this work, TPEF microscopy was applied to obtain the images of human normal pancreas and SPT of the pancreas without hematoxylin and eosin (H&E) staining, for the purpose of identifying the organization structural, cell morphological, and cytoplasm changing, which were then compared to their corresponding H&E stained histopathological results. Our results showed that high-resolution TPEF imaging of the pancreatic SPT can clearly distinguish the pathological features from normal pancreas in unstained histological sections, and the results are consistent with the histological results. Moreover, we measured the nuclear-cytoplasmic ratios of the pancreatic SPT and normal pancreas to characterize their difference in the cytomorphological feature. It indicated that this technique can achieve the consistent information of pathological diagnosis, and has the potential to substantially improve the optical diagnosis and treatment of the pancreatic SPT without H&E staining in the future. SCANNING 38:245-250, 2016. © 2015 Wiley Periodicals, Inc. © Wiley Periodicals, Inc.

CA19-9: A promising tumor marker for pancreatic carcinoma

International Nuclear Information System (INIS)

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

1984-01-01

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

CT diagnosis of pancreatitis and carcinoma of the pancreas

International Nuclear Information System (INIS)

Sager, W.D.; Nedden, D. zur; Lepuschuetz, H.; Zalaudek, G.; Bodner, E.; Fotter, R.; Lammer, J.; Innsbruck Univ.; Graz Univ.; Innsbruck Univ.

1981-01-01

The article reports on 78 CT scans of surgically diseases of the pancreas, 30 cases of chronic pancreatitis, 12 cases of haemorrhagic-necrotizing pancreatitis, and 36 cases of carcinoma of the pancreas. 12 of these cases were operable, whereas 234 were inoperable. The operable carcinomas were so small that proper diagnosis was effected in 50% only, whereas the inoperable carcinomas eluded CT identification in 17% of the cases only. The most important signs of an operable carcinoma of the pancreas are a well-defined enlargement and inhomogeneity of the parenchyma with reduced contrast, especially on bolus injection, as well as dilatation of the bile duct system. The most essential criteria for inoperability are absence of boundaries, especially towards the dorsal side, with infiltration of the retroperitoneal fatty tissue, and lack of delineation of the large vessels. According to the present state of the art, CT does not supply definite criteria for differentiating between an operable carcinoma of the pancreas and chronic fibrotic pancreatitis. Overstepping of the marginal contours is a reliably distinctive feature between carcinoma and pancreatitis, but it also points to the inoperable nature of the disease. Haemorrhagic-necrotizing pancreatitis is characterized by definite CT criteria, so that diagnosis is easy. Computerised tomography is a valuable diagnostic tool in diseases of the pancreas and can supply conclusive pointers towards the operability of a tumor. (orig.) [de

Differential diagnosis of focal pancreatitis and pancreatic cancer

NARCIS (Netherlands)

van Gulik, T. M.; Moojen, T. M.; van Geenen, R.; Rauws, E. A.; Obertop, H.; Gouma, D. J.

1999-01-01

The differentiation of focal, chronic pancreatitis (CP) and pancreatic cancer (PAC) poses a diagnostic dilemma. Both conditions may present with the same symptoms and signs. The complexity of differential diagnosis is enhanced because PAC is frequently associated with secondary inflammatory changes

The role of tumor cell-derived connective tissue growth factor (CTGF/CCN2) in pancreatic tumor growth.

Science.gov (United States)

Bennewith, Kevin L; Huang, Xin; Ham, Christine M; Graves, Edward E; Erler, Janine T; Kambham, Neeraja; Feazell, Jonathan; Yang, George P; Koong, Albert; Giaccia, Amato J

2009-02-01

Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA-expressing clones showed dramatically reduced growth in soft agar and when implanted s.c. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by positron emission tomography imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed colocalization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell-derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer.

Long-term follow-up of nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children.

Science.gov (United States)

Sugito, Kiminobu; Furuya, Takeshi; Kaneda, Hide; Masuko, Takayuki; Ohashi, Kensuke; Inoue, Mikiya; Ikeda, Taro; Koshinaga, Tsugumichi; Tomita, Ryouichi; Maebayashi, Toshiya

2012-05-01

The objectives of the present study were to determine nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children. The nutritional status was evaluated by the patterns of growth. Pancreatic function was evaluated by using a questionnaire, the Bristol stool form chart, the serum levels of fasting blood glucose, and hemoglobin A1c (HbA1c). Morphological changes of the pancreatic remnant were evaluated by computed tomography, magnetic resonance image, or magnetic resonance cholangiopancreatography. The present study consisted of 6 patients with pancreatic tumor (5 solid pseudopapillary tumors of the pancreas and 1 pancreatoblastoma) who underwent the following operations: tumor enucleation (3), distal pancreatectomy with splenectomy (1), and pylorus-preserving pancreatoduodenectomy (PPPD [2]). The serum levels of HbA1c have been gradually elevated in 2 patients with PPPD. A significant decrease in pancreatic parenchymal thickness and dilatation of the main pancreatic duct were observed in 2 patients with PPPD. Endocrine pancreatic insufficiency after PPPD may be explainable by obstructive pancreatitis after operation. Taking together the results of pancreatic endocrine function and morphological changes of pancreatic remnant after PPPD, tumor enucleation should be considered as surgical approach in children with pancreas head tumor whenever possible.

Duct-ectatic type of mucin producing tumor of the pancreas--new concept of pancreatic neoplasia.

Science.gov (United States)

Kimura, W; Sasahira, N; Yoshikawa, T; Muto, T; Makuuchi, M

1996-01-01

Although there have been recent reports of mucin-producing tumor of the pancreas, there has been no thorough clinicopathological analysis of a large number of cases. Two hundred forty four cases of mucin-producing tumor of the pancreas from Japanese, European and American reports, together with 15 cases of our own, were analyzed clinicopathologically. Mucin-producing tumor of the pancreas was found in 177 males and 82 females (M:F = 2.2:1). The mean age was 65.5 years. Jaundice, diabetes mellitus and a past history of pancreatitis were found in 15%-19% of the cases. The tumor was most frequently (62%) found in the head of the pancreas. Pathologically, hyperplasia or adenoma was found in 58 cases, and adenocarcinoma in 160 cases. Five-year-survival rate by the Kaplan-Meier method was 82.6% in all of the cases and postoperative survival curve was much better in cases with this type of carcinoma than in cases with ordinary pancreatic duct cell carcinoma (5-year-survival rate: 82.6% vs 17.3%). Serum tumor markers such as CEA or CA 19-9 were not effective in differentiating between benign and malignant, or in determining the degree of cancerous spread, while cytology of the pancreatic juice and biopsy of the tumor could contribute to the diagnosis. Mucin-producing tumor has unique clinicopathological characteristics, such as the dilated main pancreatic duct or branches, dilatation of the orifice of the papilla of Vater, or good prognosis. Since a diagnosis for benign or malignant is very difficult in some cases, methods for distinguishing benign from malignant lesions or for determining cancerous spread, such as molecular biological techniques, should be established.

Diagnosis and treatment of pancreatic cancer. Oncology overview

International Nuclear Information System (INIS)

1982-09-01

Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Radiological diagnosis of pancreatic cancer; Biopsy and cytology in the diagnosis of pancreatic cancer; Pathology and morphology of pancreatic cancer; Staging and prognosis of pancreatic cancer; Biological and immunological markers in the diagnosis of pancreatic cancer; Surgical treatment of pancreatic cancer; Drug therapy of pancreatic cancer; Radiation therapy of pancreatic cancer; Selected studies on the epidemiology of pancreatic cancer; Clinical correlates and syndromes associated with pancreatic neoplasia

Gene expression patterns in pancreatic tumors, cells and tissues.

Directory of Open Access Journals (Sweden)

Anson W Lowe

2007-03-01

Full Text Available Cancers of the pancreas originate from both the endocrine and exocrine elements of the organ, and represent a major cause of cancer-related death. This study provides a comprehensive assessment of gene expression for pancreatic tumors, the normal pancreas, and nonneoplastic pancreatic disease.DNA microarrays were used to assess the gene expression for surgically derived pancreatic adenocarcinomas, islet cell tumors, and mesenchymal tumors. The addition of normal pancreata, isolated islets, isolated pancreatic ducts, and pancreatic adenocarcinoma cell lines enhanced subsequent analysis by increasing the diversity in gene expression profiles obtained. Exocrine, endocrine, and mesenchymal tumors displayed unique gene expression profiles. Similarities in gene expression support the pancreatic duct as the origin of adenocarcinomas. In addition, genes highly expressed in other cancers and associated with specific signal transduction pathways were also found in pancreatic tumors.The scope of the present work was enhanced by the inclusion of publicly available datasets that encompass a wide spectrum of human tissues and enabled the identification of candidate genes that may serve diagnostic and therapeutic goals.

Contrast-Enhanced Endoscopic Ultrasonography for Pancreatic Tumors

Directory of Open Access Journals (Sweden)

Yasunobu Yamashita

2015-01-01

Full Text Available Objectives. To investigate the usefulness of contrast-enhanced endoscopic ultrasonography (CE-EUS for histological differentiation of pancreatic tumors. Methods. CE-EUS was performed for consecutive patients having a pancreatic solid lesion, and tumors were classified into three vascular patterns (hypervascular, isovascular, and hypovascular at two time phases (early-phase and late-phase. Correlation between vascular patterns and histopathology of resected pancreatic cancer (PC tissues was ascertained. Results. The final diagnoses of 147 examined tumors were PC (n=109, inflammatory mass (n=11, autoimmune pancreatitis (n=9, neuroendocrine tumor (n=8, and others (n=10. In late-phase images, 104 of 109 PCs had the hypovascular pattern, for a diagnostic sensitivity and specificity of 94% and 71%, respectively. Of 28 resected PCs, 10 had isovascular, and 18 hypovascular, patterns on the early-phase image. Early-phase isovascular PCs were more likely to be differentiated than were early-phase hypovascular PCs (6 well and 4 moderately differentiated versus 3 well, 14 moderately, and 1 poorly differentiated, P=0.028. Immunostaining revealed that hypovascular areas of early-phase images reflected heterogeneous tumor cells with fibrous tissue, necrosis, and few vessels. Conclusion. CE-EUS could be useful for distinguishing PC from other solid pancreatic lesions and for histological differentiation of PCs.

Diagnosis of pancreatic ductal adenocarcinoma and chronic pancreatitis by measurement of microRNA abundance in blood and tissue.

Directory of Open Access Journals (Sweden)

Andrea S Bauer

Full Text Available A solid process for diagnosis could have a substantial impact on the successful treatment of pancreatic cancer, for which currently mortality is nearly identical to incidence. Variations in the abundance of all microRNA molecules from peripheral blood cells and pancreas tissues were analyzed on microarrays and in part validated by real-time PCR assays. In total, 245 samples from two clinical centers were studied that were obtained from patients with pancreatic ductal adenocarcinoma or chronic pancreatitis and from healthy donors. Utilizing the minimally invasive blood test, receiver operating characteristic (ROC curves and the corresponding area under the curve (AUC analysis demonstrated very high sensitivity and specificity of a distinction between healthy people and patients with either cancer or chronic pancreatitis; respective AUC values of 0.973 and 0.950 were obtained. Confirmative and partly even more discriminative diagnosis could be performed on tissue samples with AUC values of 1.0 and 0.937, respectively. In addition, discrimination between cancer and chronic pancreatitis was achieved (AUC = 0.875. Also, several miRNAs were identified that exhibited abundance variations in both tissue and blood samples. The results could have an immediate diagnostic value for the evaluation of tumor reoccurrence in patients, who have undergone curative surgical resection, and for people with a familial risk of pancreatic cancer.

Imaging in the diagnosis of chronic pancreatitis

Directory of Open Access Journals (Sweden)

Vasile D. Balaban

2014-12-01

Full Text Available Chronic pancreatitis is characterised by progressive and irreversible damage of the pancreatic parenchyma and ductal system, which leads to chronic pain, loss of endocrine and exocrine functions. Clinically, pancreatic exocrine insufficiency becomes apparent only after 90% of the parenchima has been lost. Despite the simple definition, diagnosing chronic pancreatitis remains a challenge, especially for early stage disease. Because pancreatic function tests can be normal until late stages and have significant limitations, there is an incresing interest in the role of imaging techniques for the diagnosis of chronic pancreatitis. In this article we review the utility and accuracy of different imaging methods in the diagnosis of chronic pancreatitis, focusing on the role of advanced imaging (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound.

Diagnosis and treatment of pancreatic pseudocysts and cystic tumors based on own material and quoted literature

Directory of Open Access Journals (Sweden)

Grzegorz Ćwik

2013-09-01

Full Text Available Pseudocysts constitute the most basic cystic lesions of the pancreas. Symptomatic cysts may be treated by means of both minimally invasive methods and surgery. Currently, it is believed that approximately 5% of cystic lesions in the pancreas may in fact, be neoplastic cystic tumors. Their presence is manifested by generally irregular multilocular structures, solid nodules inside the cyst or in the pancreatic duct, frequently vascularized, as well as fragmentary thickening of the cystic wall or septation. Aim: The aim of this paper was to present current management, both diagnostic and therapeutic, in patients with pancreatic pseudocysts and cystic tumors. The article has been written based on the material collected and prepared in the author’s Department as well as on the basis of current reports found in the quoted literature. Material and methods, results: In 2000–2012, the Second Department of General, Gastrointestinal and Oncological Surgery of the Alimentary Tract treated 179 patients with cystic lesions in the region of the pancreas. This group comprised 12 cases of cystic tumors and 167 pseudocysts. Twenty-three patients (13.8% were monitored only and 144 received procedural treatment. Out of the latter group, 75 patients underwent drainage procedures and 48 were qualified to endoscopic cystogastrostomy or cystoduodenostomy. The endoscopic procedure was unsuccessful in 11 cases (23%. In a group of patients with a pancreatic cystic tumor (12 patients, 6 of them (50% underwent therapeutic resection of the tumor with adequate fragment of the gland. Conclusions: Endoscopic drainage is an effective and safe method of minimally invasive treatment of pancreatic cysts. The patients who do not qualify to endoscopic procedures require surgical treatment. The differentiation of a neoplasm from a typical cyst is of fundamental significance for the selection of the treatment method.

Acute Pancreatitis: Etiology, Pathology, Diagnosis, and Treatment.

Science.gov (United States)

Majidi, Shirin; Golembioski, Adam; Wilson, Stephen L; Thompson, Errington C

2017-11-01

Acute pancreatitis is a fascinating disease. In the United States, the two most common etiologies of acute pancreatitis are gallstones and excessive alcohol consumption. The diagnosis of acute pancreatitis is made with a combination of history, physical examination, computed tomography scan, and laboratory evaluation. Differentiating patients who will have a benign course of their pancreatitis from patients who will have severe pancreatitis is challenging to the clinician. C-reactive protein, pro-calcitonin, and the Bedside Index for Severity of Acute Pancreatitis appeared to be the best tools for the early and accurate diagnosis of severe pancreatitis. Early laparoscopic cholecystectomy is indicated for patients with mild gallstone pancreatitis. For patients who are going to have a prolonged hospitalization, enteral nutrition is preferred. Total parenteral nutrition should be reserved for patients who cannot tolerate enteral nutrition. Prophylactic antibiotics are not indicated for patients with pancreatic necrosis. Surgical intervention for infected pancreatic necrosis should be delayed as long as possible to improve patient outcomes.

Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions : A pooled analysis

NARCIS (Netherlands)

van der Waaij, LA; van Dullemen, HM; Porte, RJ

Background: Pancreatic cystic tumors commonly include serous cystadenoma (SCA), mucinous cystadenoma (MCA), and mucinous cystadenocarcinoma (MCAC). A differential diagnosis with pseudocysts (PC) can be difficult. Radiologic criteria are not reliable. The objective of the study is to investigate the

EUS – Fine- Needle Aspiration Biopsy (FNAB in the Diagnosis of Pancreatic Adenocarcinoma: A Review

Directory of Open Access Journals (Sweden)

Kalogeraki Alexandra

2016-03-01

Full Text Available Solid masses of the pancreas represent a variety of benign and malignant neoplasms of the exocrine and endocrine tissues of the pancreas. A tissue diagnosis is often required to direct therapy in the face of uncertain diagnosis or if the patient is not a surgical candidate either due to advanced disease or comorbidities. Endoscopic ultrasound (EUS is a relatively new technology that employs endoscopy and high-frequency ultrasound (US. EUS involves imaging of the pancreatic head and the uncinate from the duodenum and imaging of the body and tail from the stomach. It has been shown to be a highly sensitive method for the detection of pancreatic masses. It is superior to extracorporeal US and computed tomographic (CT scans, especially when the pancreatic tumor is smaller than 2-3 cm. Although EUS is highly sensitive in detecting pancreatic solid masses, its ability to differentiate between inflammatory masses and malignant disease is limited. Endoscopic retrograde cholangiopancreatography (ERCP brushing, CT-guided biopsies, and transabdominal ultrasound (US have been the standard nonsurgical methods for obtaining a tissue diagnosis of pancreatic lesions, but a substantial false-negative rate has been reported. Transabdominal US-guided fine-needle aspiration biopsy (US-FNAB has been used for tissue diagnosis in patients with suspected pancreatic carcinoma. It has been shown to be highly specific, with no false-positive diagnoses. With the advent of curvilinear echoendoscopes, transgastric and transduodenal EUS-FNAB of the pancreas have become a reality EUS with FNAB has revolutionized the ability to diagnose and stage cancers of the gastrointestinal tract and assess the pancreas. Gastrointestinal cancers can be looked at with EUS and their depth of penetration into the intestinal wall can be determined. Any suspicious appearing lymph nodes can be biopsied using EUS/FNAB. The pancreas is another organ that is well visualized with EUS. Abnormalities

Rare presentation of pancreatic schwannoma: a case report

Directory of Open Access Journals (Sweden)

Tofigh Arash

2008-08-01

Full Text Available Abstract Introduction Schwannoma is a rare tumor among pancreatic neoplasms. Schwannomas vary in size, and most of them are cystic, mimicking pancreatic cystic lesions. Generally, a definitive diagnosis is made at the time of histological analysis. The mainstay treatment is surgical resection. Case presentation We report an unusual presentation of pancreatic schwannoma with abdominal pain and several episodes of cholangitis in a 54-year-old Caucasian (Iranian man. The condition was not diagnosed pre-operatively and Whipple's procedure was performed. Conclusion Pancreatic schwannoma is an important clinical entity to include in the differential diagnosis of pancreatic lesions. Pre-operative diagnosis is difficult but computed tomographic findings may be helpful. The tumor may also have atypical and rare presentations, such as cholangitis and weight loss. For benign tumors, simple enucleation is usually adequate, whereas malignant tumors require standard oncological resection.

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

Science.gov (United States)

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.

A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor.

Science.gov (United States)

Sikkens, Edmée C M; Cahen, Djuna L; de Wit, Jill; Looman, Caspar W N; van Eijck, Casper; Bruno, Marco J

2014-01-01

In cancer of the pancreatic head region, exocrine insufficiency is a well-known complication, leading to steatorrhea, weight loss, and malnutrition. Its presence is frequently overlooked, however, because the primary attention is focused on cancer treatment. To date, the risk of developing exocrine insufficiency is unspecified. Therefore, we assessed this function in patients with tumors of the pancreatic head, distal common bile duct, or ampulla of Vater. Between March 2010 and August 2012, we prospectively included patients diagnosed with cancer of the pancreatic head region at our tertiary center. To preclude the effect of a resection, we excluded operated patients. Each month, the exocrine function was determined with a fecal elastase test. Furthermore, endocrine function, steatorrhea-related symptoms, and body weight were evaluated. Patients were followed for 6 months, or until death. Thirty-two patients were included. The tumor was located in the pancreas in 75%, in the bile duct in 16%, and in the ampullary region in 9%, with a median size of 2.5 cm. At diagnosis, the prevalence of exocrine insufficiency was 66%, which increased to 92% after a median follow-up of 2 months (interquartile range, 1 to 4 mo). Most patients with cancer of the pancreatic head region were already exocrine insufficient at diagnosis, and within several months, this function was impaired in almost all cases. Given this high prevalence, physicians should be focused on diagnosing and treating exocrine insufficiency, to optimize the nutritional status and physical condition, especially for those patients undergoing palliative chemotherapy and/or radiotherapy.

Comparison of F-18-FDG PET/CT findings between pancreatic solid pseudopapillary tumor and pancreatic ductal adenocarcinoma

International Nuclear Information System (INIS)

Kim, Yong-il; Kim, Seok-ki; Paeng, Jin Chul; Lee, Ho-Young

2014-01-01

Objective: Pancreatic solid pseudopapillary tumor (SPT) is a rare benign tumor. Little data are available on positron emission tomographic/computed tomographic (PET/CT) characteristics of this tumor. Therefore, we analyzed the metabolic characteristics of SPT using F-18-FDG PET/CT and compared the results with those of pancreatic ductal adenocarcinoma. Methods: We retrospectively reviewed the records of 11 SPT patients and 46 patients with ductal adenocarcinoma. Ten SPT patients had primary tumors and 1 patient had metastatic SPT. Maximum standardized uptake value (max SUV), mean SUV, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-background ratio (TBR) were evaluated. Mann–Whitney U test between pancreatic SPT and ductal adenocarcinoma was performed. In addition, age, gender and tumor size-adjusted analysis of covariance (ANCOVA) was done between pancreatic SPT and ductal adenocarcinoma. Results: Compared with pancreatic ductal adenocarcinomas, SPTs had significantly higher tumor size-adjusted MTV and TLG. MTV and TLG values were significantly correlated with T-stage of the SPTs. In 1 SPT patient, metastases in the liver and mesentery were revealed by intense uptake of FDG on F-18-FDG PET/CT, and after PET/CT had suggested the presence of pancreatic SPT. Conclusion: We recommend that SPT be considered when a solid pancreatic mass with increased FDG metabolism is encountered on PET/CT. F-18-FDG PET/CT may be useful in detecting subtle metastases of SPT

Diagnosis and management of pancreatic exocrine insufficiency.

Science.gov (United States)

Nikfarjam, Mehrdad; Wilson, Jeremy S; Smith, Ross C

2017-08-21

In 2015, the Australasian Pancreatic Club (APC) published the Australasian guidelines for the management of pancreatic exocrine insufficiency (http://pancreas.org.au/2016/01/pancreatic-exocrine-insufficiency-guidelines). Pancreatic exocrine insufficiency (PEI) occurs when normal digestion cannot be sustained due to insufficient pancreatic digestive enzyme activity. This may be related to a breakdown, at any point, in the pancreatic digestive chain: pancreatic stimulation; synthesis, release or transportation of pancreatic enzymes; or synchronisation of secretions to mix with ingested food. Main recommendations: The guidelines provide advice on diagnosis and management of PEI, noting the following: A high prevalence of PEI is seen in certain diseases and conditions, such as cystic fibrosis, acute and chronic pancreatitis, pancreatic cancer and pancreatic surgery. The main symptoms of PEI are steatorrhoea or diarrhoea, abdominal pain, bloating and weight loss. These symptoms are non-specific and often go undetected and untreated. PEI diagnosis is predominantly based on clinical findings and the presence of underlying disease. The likelihood of PEI in suspected patients has been categorised into three groups: definite, possible and unlikely. If left untreated, PEI may lead to complications related to fat malabsorption and malnutrition, and have an impact on quality of life. Pancreatic enzyme replacement therapy (PERT) remains the mainstay of PEI treatment with the recommended adult initial enzyme dose being 25 000-40 000 units of lipase per meal, titrating up to a maximum of 75 000-80 000 units of lipase per meal. Adjunct acid-suppressing therapy may be useful when patients still experience symptoms of PEI on high dose PERT. Nutritional management by an experienced dietitian is essential. Changes in management as a result of these guidelines: These are the first guidelines to classify PEI as being definite, possible or unlikely, and provide a diagnostic algorithm to

IgG4-related disease: with emphasis on the biopsy diagnosis of autoimmune pancreatitis and sclerosing cholangitis.

Science.gov (United States)

Detlefsen, Sönke; Klöppel, Günter

2018-04-01

In 2011, chronic fibroinflammatory processes occurring simultaneously or metachronously in various organs and associated with elevated IgG4 serum levels and/or tissue infiltration with IgG4-positive plasma cells have been recognized as manifestations of a systemic disorder called IgG4-related disease (IgG4-RD). The histologic key findings are lymphoplasmacytic infiltration rich in IgG4-positive plasma cells combined with storiform fibrosis and obliterative phlebitis. Among the organs mainly affected by IgG4-RD are the pancreas and the extrahepatic bile ducts. The pancreatic and biliary alterations have been described under the terms autoimmune pancreatitis (AIP) and sclerosing cholangitis, respectively. These diseases are currently more precisely called IgG4-related pancreatitis (or type 1 AIP to distinguish it from type 2 AIP that is unrelated to IgG4-RD) and IgG4-related sclerosing cholangitis (IgG4-related SC). Clinically and grossly, both diseases commonly imitate pancreatic and biliary adenocarcinoma, tumors that are well known for their dismal prognosis. As IgG4-RD responds to steroid treatment, making a resection of a suspected tumor unnecessary, a biopsy is often required to establish the preoperative diagnosis. This review discusses the morphologic spectrum of IgG4-related pancreatitis and IgG4-related SC and focuses on the biopsy relevant histologic features for the diagnosis and differential diagnosis of these diseases.

Groove Pancreatitis – A Mimic of Pancreatic and Periampullary Tumors

Directory of Open Access Journals (Sweden)

Sivakami R Pradheepkumar

2017-10-01

Full Text Available Groove Pancreatitis (GP is a rare form of focal chronic pancreatitis involving the pancreatico-duodenal groove (PDG. GP was first described by Becker in 1973. Though, GP has been described so many years ago, it is still unfamiliar among most physicians because of lack of sufficient case studies and clinical similarity of GP to conventional pancreatitis. Imaging based differentiation of GP from other lesions, like pancreatic and periampullary adenocarcinoma is also not possible in all the cases, unless there are typical findings favoring GP. Since, the line of treatment and outcome is totally different in these two conditions, appreciation of the fine differences between these two entities is very significant. Groove pancreatitis is symptomatically treated with medicines and only for patients with continuous and severe symptoms which are not amenable to medical treatment surgical management is considered. Radiological differentiation of GP from pancreatic and periampullary malignancies will help to avoid unnecessary surgery in the initial stages. We report two cases of GP, one of pure and other of segmental form where we found typical imaging features which pointed to the diagnosis of GP with a small discussion about the Computed tomography (CT and Magnetic Resonance Imaging (MRI appearance of this entity as well as its differential diagnosis.

Diagnostic Management of Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Dabizzi, Emanuele [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States); Assef, Mauricio Saab [Faculdade de Ciências Médicas da Santa Casa de São Paulo, Rua Dr. Cesário Motta Jr. #61 Cep: 01221-020, São Paulo (Brazil); Raimondo, Massimo, E-mail: raimondo.massimo@mayo.edu [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States)

2011-01-31

Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used.

Diagnostic Management of Pancreatic Cancer

International Nuclear Information System (INIS)

Dabizzi, Emanuele; Assef, Mauricio Saab; Raimondo, Massimo

2011-01-01

Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used

Diagnosis and treatment of traumatic pancreatic injury

International Nuclear Information System (INIS)

Hirakawa, Akihiko; Isayama, Kenji; Nakatani, Toshio

2011-01-01

The diagnosis of traumatic pancreatic injury in the acute stage is difficult to establish blood tests and abdominal findings alone. Moreover, to determine treatment strategies, it is important not only that a pancreatic injury is diagnosed but also whether a pancreatic ductal injury can be found. At our center, to diagnose isolated pancreatic injuries, we actively perform endoscopic retrograde pancreatography (ERP) in addition to abdominal CT at the time of admission. For cases with complications such as abdominal and other organ injuries, we perform a laparotomy to ascertain whether a pancreatic duct injury is present. In regard to treatment options, for grade III injuries to the pancreatic body and tail, we basically choose distal pancreatectomy, but we also consider the Bracy method depending on the case. As for grade III injuries to the pancreatic head, we primarily choose pancreaticoduodenectomy, but also apply drainage if the situation calls for it. However, pancreatic injuries are often complicated by injuries of other regions of the body. Thus, diagnosis and treatment of pancreatic injury should be based on a comprehensive decision regarding early prioritization of treatment, taking hemodynamics into consideration after admission, and how to minimize complications such as anastomotic leak and pancreatic fistulas. (author)

Targeting pancreatic expressed PAX genes for the treatment of diabetes mellitus and pancreatic neuroendocrine tumors.

Science.gov (United States)

Martin-Montalvo, Alejandro; Lorenzo, Petra I; López-Noriega, Livia; Gauthier, Benoit R

2017-01-01

Four members of the PAX family, PAX2, PAX4, PAX6 and PAX8 are known to be expressed in the pancreas. Accumulated evidences indicate that several pancreatic expressed PAX genes play a significant role in pancreatic development/functionality and alterations in these genes are involved in the pathogenesis of pancreatic diseases. Areas covered: In this review, we summarize the ongoing research related to pancreatic PAX genes in diabetes mellitus and pancreatic neuroendocrine tumors. We dissect the current knowledge at different levels; from mechanistic studies in cell lines performed to understand the molecular processes controlled by pancreatic PAX genes, to in vivo studies using rodent models that over-express or lack specific PAX genes. Finally, we describe human studies associating variants on pancreatic-expressed PAX genes with pancreatic diseases. Expert opinion: Based on the current literature, we propose that future interventions to treat pancreatic neuroendocrine tumors and diabetes mellitus could be developed via the modulation of PAX4 and/or PAX6 regulated pathways.

Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice

Directory of Open Access Journals (Sweden)

Liao Dezhong J

2008-01-01

Full Text Available Abstract Background Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Results Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT and liver metastatic lesions (LM compared to normal pancreas (NP. In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1 and Serine proteinase inhibitor A1 (Serpina1, and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. Conclusion We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.

Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice.

Science.gov (United States)

Thakur, Archana; Bollig, Aliccia; Wu, Jiusheng; Liao, Dezhong J

2008-01-24

Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT) and liver metastatic lesions (LM) compared to normal pancreas (NP). In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1) and Serine proteinase inhibitor A1 (Serpina1), and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.

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

Science.gov (United States)

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

2016-09-01

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

Accuracy of computed tomography in determining pancreatic cancer tumor size

International Nuclear Information System (INIS)

Aoki, Kazunori; Okada, Shuichi; Moriyama, Noriyuki

1994-01-01

We compared tumor sizes determined by computed tomography (CT) with those of the resected specimens in 26 patients with pancreatic cancer in order to clarify whether or not the size of a pancreatic tumor can be accurately determined by CT. From the precontrast, postcontrast and arterial dominant phases of dynamic CT, the arterial dominant phase was found to yield the highest correlation between CT measured tumor size and that of the resected specimens (p<0.01). The correlation coefficient was, however, not high (r=0.67). CT alone may therefore be insufficient to determine tumor size in pancreatic cancer accurately. (author)

Prospective evaluation of yield of endoscopic ultrasonography in the etiological diagnosis of "idiopathic" acute pancreatitis

Directory of Open Access Journals (Sweden)

Narendra S Choudhary

2016-01-01

Full Text Available Background: Etiology of acute pancreatitis (AP remains idiopathic in 30% of patients. Endoscopic ultrasound (EUS has been shown to increase the diagnostic yield in patients with idiopathic AP (IAP. Aim: The aim of this study was to evaluate the role of EUS in achieving etiological diagnosis in patients with IAP. Materials and Methods: Consecutive 192 patients with IAP were evaluated prospectively with EUS over a period of 2 years. Patients who had no etiological diagnosis for AP after detailed history, clinical examination, laboratory investigations, and magnetic resonance cholangiopancreatography were included in the study. Results: The mean age of patients was 34.6 ± 12 and male:female ratio was 2.1:1. Of these, 135 patients had gallbladder intact (Group A and 57 patients had undergone cholecystectomy (Group B. In Group A, EUS identified a possible cause in 79 (58.5% patients; microlithiasis (n = 48, chronic pancreatitis (CP (n = 23, common bile duct (CBD and gallbladder stone (n = 3, pancreatic divisum (n = 3, small pancreatic tumor (n = 1, and anomalous pancreaticobiliary junction (n = 1. In Group B, EUS yielded diagnosis in 28 (49.1% patients; CP (n = 22, ascariasis (n = 3, CBD stone (n = 2, and pancreatic divisum (n = 1. Overall EUS helped in achieving etiological diagnosis in 107 (55.1% of patients with IAP. The presence of intact gallbladder showed a tendency for increased diagnostic yield (P = 0.06. Conclusion: EUS is a useful modality to establish the diagnosis in IAP and this technique should be incorporated in the evaluation of IAP.

Cystic tumors of pancreas Cistoadenoma annd cistoadenocarcinoma diagnosis and practiceattitude

International Nuclear Information System (INIS)

Valinas, R.; Houry, S.; Huguier, M.

2004-01-01

Report of 16 cases of cystic tumors of pancreas(CTP) consisting of 5 serous cystoadenomas(SC), 6 mucigenous cystoadenomas(MC) and 5 cystoadenocarcinomas(CC) pertaining to11 women and 5 men.Mean age 63 years(ranging from 44 to 89).Four of these patients were asymptomatic, 6 of them had lost between 3 and 20 kilos.One patient with a CC developed jaundice.CTPS were diagnosed by ultrasound or CT scans. CTPs were topographed ten times at the level of pancreatic head, twice in its body and four in its tail.At end of preoperative explorations conducted for the purpose of diagnosis,CTPs went undetected in four cases.The exact diagnosis of tumor nature was made during preoperative in five cases:two SCs, one MC and two CCs. Unequivocal diagnosis was made through the histological study of surgical specimen in eleven cases,by the existence of liver metastases in one case and by citopunture under CT in the remainder.One patient refused to be operated.Thirteen patientys were operate:in four a cephalic duodenopancreatectomy was performed (1 SC and 4 MCs);in 2, a distal pancreatectomy was performed 1 MC and 1 CC); and 2 underwent surgical pucture (SCs).Asymptomatic SCs may remain unoperated under surveillance provided diagnosis be unequivocal.All other cystic tumors have to be resected, either,due to the fact that there is doubt as to their nature or because it is a symptomatic CS, or an MC or a CC.In the latter case, prognosis is better that in cases of exocrine non metastasic pancreatic cancer

Diagnosis and management of chronic pancreatitis

OpenAIRE

Gupta, V; Toskes, P

2005-01-01

Chronic pancreatitis represents a condition that is challenging for clinicians secondary to the difficulty in making an accurate diagnosis and the less than satisfactory means of managing chronic pain. This review emphasises the various manifestations that patients with chronic pancreatitis may have and describes recent advances in medical and surgical therapy. It is probable that many patients with chronic abdominal pain are suffering from chronic pancreatitis that is not appreciated. As the...

Cancer Stem Cells, EMT, and Developmental Pathway Activation in Pancreatic Tumors

International Nuclear Information System (INIS)

Hindriksen, Sanne; Bijlsma, Maarten F.

2012-01-01

Pancreatic cancer is a disease with remarkably poor patient survival rates. The frequent presence of metastases and profound chemoresistance pose a severe problem for the treatment of these tumors. Moreover, cross-talk between the tumor and the local micro-environment contributes to tumorigenicity, metastasis and chemoresistance. Compared to bulk tumor cells, cancer stem cells (CSC) have reduced sensitivity to chemotherapy. CSC are tumor cells with stem-like features that possess the ability to self-renew, but can also give rise to more differentiated progeny. CSC can be identified based on increased in vitro spheroid- or colony formation, enhanced in vivo tumor initiating potential, or expression of cell surface markers. Since CSC are thought to be required for the maintenance of a tumor cell population, these cells could possibly serve as a therapeutic target. There appears to be a causal relationship between CSC and epithelial-to-mesenchymal transition (EMT) in pancreatic tumors. The occurrence of EMT in pancreatic cancer cells is often accompanied by re-activation of developmental pathways, such as the Hedgehog, WNT, NOTCH, and Nodal/Activin pathways. Therapeutics based on CSC markers, EMT, developmental pathways, or tumor micro-environment could potentially be used to target pancreatic CSC. This may lead to a reduction of tumor growth, metastatic events, and chemoresistance in pancreatic cancer

Acoustic radiation force impulse shear wave elastography (ARFI) of acute and chronic pancreatitis and pancreatic tumor

Energy Technology Data Exchange (ETDEWEB)

Goertz, Ruediger S., E-mail: ruediger.goertz@uk-erlangen.de; Schuderer, Johanna, E-mail: Johanna@schuderer-floss.de; Strobel, Deike, E-mail: deike.strobel@uk-erlangen.de; Pfeifer, Lukas, E-mail: Lukas.Pfeifer@uk-erlangen.de; Neurath, Markus F., E-mail: Markus.Neurath@uk-erlangen.de; Wildner, Dane, E-mail: Dane.Wildner@uk-erlangen.de

2016-12-15

Highlights: • ARFI elastography of the pancreas is feasible. • Shear wave velocities in patients with acute or chronic pancreatitis or carcinoma are higher than those occurring in normal tissue. • ARFI values considerable overlap between different pathologies. - Abstract: Introduction: Acoustic Radiation Force Impulse (ARFI) elastography evaluates tissue stiffness non-invasively and has rarely been applied to pancreas examinations so far. In a prospective and retrospective analysis, ARFI shear wave velocities of healthy parenchyma, pancreatic lipomatosis, acute and chronic pancreatitis, adenocarcinoma and neuroendocrine tumor (NET) of the pancreas were evaluated and compared. Material and methods: In 95 patients ARFI elastography of the pancreatic head, and also of the tail for a specific group, was analysed retrospectively. Additionally, prospectively in 100 patients ARFI was performed in the head and tail of the pancreas. Results: A total of 195 patients were included in the study. Healthy parenchyma (n = 21) and lipomatosis (n = 30) showed similar shear wave velocities of about 1.3 m/s. Acute pancreatitis (n = 35), chronic pancreatitis (n = 53) and adenocarcinoma (n = 52) showed consecutively increasing ARFI values, respectively. NET (n = 4) revealed the highest shear wave velocities amounting to 3.62 m/s. ARFI elastography showed relevant differences between acute pancreatitis and chronic pancreatitis or adenocarcinoma. With a cut-off value of 1.74 m/s for the diagnosis of a malignant disease the sensitivity was 91.1% whereas the specificity amounted to 60.4%. Conclusion: ARFI shear wave velocities present differences in various pathologies of the pancreas. Acute and chronic pancreatitis as well as neoplastic lesions show high ARFI values. Very high elasticity values may indicate malignant disease of the pancreas. However, there is a considerable overlap between the entities.

Acoustic radiation force impulse shear wave elastography (ARFI) of acute and chronic pancreatitis and pancreatic tumor

International Nuclear Information System (INIS)

Goertz, Ruediger S.; Schuderer, Johanna; Strobel, Deike; Pfeifer, Lukas; Neurath, Markus F.; Wildner, Dane

2016-01-01

Highlights: • ARFI elastography of the pancreas is feasible. • Shear wave velocities in patients with acute or chronic pancreatitis or carcinoma are higher than those occurring in normal tissue. • ARFI values considerable overlap between different pathologies. - Abstract: Introduction: Acoustic Radiation Force Impulse (ARFI) elastography evaluates tissue stiffness non-invasively and has rarely been applied to pancreas examinations so far. In a prospective and retrospective analysis, ARFI shear wave velocities of healthy parenchyma, pancreatic lipomatosis, acute and chronic pancreatitis, adenocarcinoma and neuroendocrine tumor (NET) of the pancreas were evaluated and compared. Material and methods: In 95 patients ARFI elastography of the pancreatic head, and also of the tail for a specific group, was analysed retrospectively. Additionally, prospectively in 100 patients ARFI was performed in the head and tail of the pancreas. Results: A total of 195 patients were included in the study. Healthy parenchyma (n = 21) and lipomatosis (n = 30) showed similar shear wave velocities of about 1.3 m/s. Acute pancreatitis (n = 35), chronic pancreatitis (n = 53) and adenocarcinoma (n = 52) showed consecutively increasing ARFI values, respectively. NET (n = 4) revealed the highest shear wave velocities amounting to 3.62 m/s. ARFI elastography showed relevant differences between acute pancreatitis and chronic pancreatitis or adenocarcinoma. With a cut-off value of 1.74 m/s for the diagnosis of a malignant disease the sensitivity was 91.1% whereas the specificity amounted to 60.4%. Conclusion: ARFI shear wave velocities present differences in various pathologies of the pancreas. Acute and chronic pancreatitis as well as neoplastic lesions show high ARFI values. Very high elasticity values may indicate malignant disease of the pancreas. However, there is a considerable overlap between the entities.

Bombesin-stimulated serum immunoreactive trypsin in the different diagnosis between endocrine and exocrine tumors of the pancreas

International Nuclear Information System (INIS)

Bonora, G.; De Giorgio, R.; Toni, R.; Fanti, M.P.; Cariani, G.; Vezzadini, P.

1987-01-01

Bombesin administration was recently found to induce a marked increase in circulating immunoreactive trypsin (IRT), whose magnitude seems to reflect the functional capacity of pancreatic acinar cell mass. The purpose of the present study was to assess the effect of bombesin infusion on serum IRT concentration in patients with endocrine or exocrine tumors of the pancreas. Fifteen patients with pancreatic endocrine tumor, 17 patients with pancreatic exocrine carcinoma and 15 healty subjects were investigated. Serum IRT was measured by radioimmunoassay before and for 120 minutes after the start of bombesin infusion (9 ng/kg/min over 30 min). The integrated serum IRT response to bombesin administration in patients with endocrine tumor of the pancreas did not differ significantly from controls, but were significantly higher than in patients with exocrine carcinoma. In the latter the integrated IRT responses to bombesin infusion in patients with endocrine tumor can probably be explained by small tumor size and/or little invasion of the glandular parenchyma, resulting in an undetectable impairment of exocrine pancreatic function. The very low IRT responses in patients with exocrine carcinoma could reflect the presence of severe pancreatic damage. The results suggest that this newly proposed bombesin test may be useful in the preoperative differential diagnosis between endocrine and exocrine tumors of the pancreas

Inflammatory myofibroblastic tumor of the pancreatic head – a case report of a 6 months old child and review of the literature

International Nuclear Information System (INIS)

Tomazic, Ales; Gvardijancic, Diana; Maucec, Joze; Homan, Matjaz

2015-01-01

Inflammatory myofibroblastic tumors are rare in the pediatric population. Most common localizations were reported in the lungs. A localization in the pancreas needs differentiation from other tumors and chronic pancreatitis. Treatment is surgical resection, although there are reports of treatment with oral steroids and radiation therapy. A 6-month-old child was treated due to a tumor in the head of the pancreas. On admission he was jaundiced with pruritus. US and MRI confirmed pancreatic tumor. Preoperative biopsy wasn’t conclusive regarding the nature of the tumor. Duodenopancreatectomy was performed. Postoperative course was uneventful. Histologic examination confirmed the diagnosis of inflammatory myofibroblastic tumor. On follow up, he remained with no evidence of recurrence. A literature review revealed 10 cases of pancreatic inflammatory myofibroblastic tumors in the pediatric age group. Our patient is the youngest reported. Despite major resection, there were no complications. However, management of this child might be possible with steroids, but conservative treatment might be insufficient, especially in aggressive forms of tumors

Advances in the diagnosis and treatment of pancreatic neuroendocrine neoplasms in Japan.

Science.gov (United States)

Ito, Tetsuhide; Hijioka, Susumu; Masui, Toshihiko; Kasajima, Atsuko; Nakamoto, Yuji; Kobayashi, Noritoshi; Komoto, Izumi; Hijioka, Masayuki; Lee, Lingaku; Igarashi, Hisato; Jensen, Robert Thomas; Imamura, Masayuki

2017-01-01

Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20 % according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy ( 111 In-octreoscan) has also been approved in Japan. This advancement will undoubtedly contribute to the localization diagnosis, the identification of remote metastasis, and assessments of the treatment responses of PNEN. Finally, regarding the treatment strategy for PNEN, the management of liver metastasis is important. The advent of novel molecular-targeted agents has dramatically improved the prognosis of advanced PNEN. Multimodality therapy that accounts for the tumor stage, degree of tumor differentiation, tumor volume, and speed of tumor growth is required.

Radiologic diagnosis of neuroendocrine tumors

International Nuclear Information System (INIS)

Lunderquist, A.

1989-01-01

The radiologic work-up of a patient with a pancreatic endocrine tumor should follow a strict course. Ultrasonography as the first procedure should be followed by angiography, if possible. Negative ultrasonography should be followed by computed tomography (CT), which, whether positive or negative, is supplemented by angiography. Negative CT and angiography is followed by transhepatic venous sampling. In patients with suspected liver metastases from intestinal and pancreatic endocrine tumors, angiography may reveal more metastases than CT and ultrasonography. (orig.)

Pancreatic tumors in children and young adults with tuberous sclerosis complex

International Nuclear Information System (INIS)

Koc, Gonca; Sugimoto, Sam; Kammen, Bamidele F.; Karakas, S.P.; Kuperman, Rachel

2017-01-01

Pancreatic neuroendocrine tumors are not included in the diagnostic criteria for tuberous sclerosis complex, although an association has been described. To investigate the association of pancreatic neuroendocrine tumor in children and young adults with tuberous sclerosis complex and define MRI characteristics of the tumor. We retrospectively evaluated the abdominal MRI scans of 55 children and young adults with tuberous sclerosis complex for the presence of a pancreatic mass. The scans were performed over a period of 7 years to monitor renal pathology. We obtained each patient's clinical history and treatment protocol from the hospital's electronic medical records. A solid pancreatic mass was identified in 5/55 (9%, 95% confidence interval [CI] 3-20%) patients (4 male) with a mean age of 12.6 years. Four of the lesions were located in the pancreatic tail and one in the pancreatic body. All of the lesions were solid, ovoid and well demarcated, with a mean diameter of 3.1 cm. The masses uniformly demonstrated T1 and T2 prolongation, but their diffusion behavior and post-contrast enhancement varied. The two surgically resected lesions were synaptophysin (+) non-functional pancreatic neuroendocrine tumors on pathology. Two of the patients who did not have surgery were treated with everolimus; one of the lesions has shown interval decrease in size and the other has remained stable. Pancreatic tumor is relatively common in children and young adults with tuberous sclerosis complex. (orig.)

Pancreatic tumors in children and young adults with tuberous sclerosis complex

Energy Technology Data Exchange (ETDEWEB)

Koc, Gonca [Erciyes University, School of Medicine, Department of Pediatric Radiology, Melikgazi, Kayseri (Turkey); Sugimoto, Sam; Kammen, Bamidele F.; Karakas, S.P. [UCSF Benioff Children' s Hospital, Department of Diagnostic Imaging, Oakland, CA (United States); Kuperman, Rachel [UCSF Benioff Children' s Hospital, Department of Pediatric Neurology, Oakland, CA (United States)

2017-01-15

Pancreatic neuroendocrine tumors are not included in the diagnostic criteria for tuberous sclerosis complex, although an association has been described. To investigate the association of pancreatic neuroendocrine tumor in children and young adults with tuberous sclerosis complex and define MRI characteristics of the tumor. We retrospectively evaluated the abdominal MRI scans of 55 children and young adults with tuberous sclerosis complex for the presence of a pancreatic mass. The scans were performed over a period of 7 years to monitor renal pathology. We obtained each patient's clinical history and treatment protocol from the hospital's electronic medical records. A solid pancreatic mass was identified in 5/55 (9%, 95% confidence interval [CI] 3-20%) patients (4 male) with a mean age of 12.6 years. Four of the lesions were located in the pancreatic tail and one in the pancreatic body. All of the lesions were solid, ovoid and well demarcated, with a mean diameter of 3.1 cm. The masses uniformly demonstrated T1 and T2 prolongation, but their diffusion behavior and post-contrast enhancement varied. The two surgically resected lesions were synaptophysin (+) non-functional pancreatic neuroendocrine tumors on pathology. Two of the patients who did not have surgery were treated with everolimus; one of the lesions has shown interval decrease in size and the other has remained stable. Pancreatic tumor is relatively common in children and young adults with tuberous sclerosis complex. (orig.)

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

Science.gov (United States)

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.

Diffusion weighted MR imaging of pancreatic islet cell tumors

International Nuclear Information System (INIS)

Bakir, Baris; Salmaslioglu, Artur; Poyanli, Arzu; Rozanes, Izzet; Acunas, Bulent

2010-01-01

Purpose: The aim of our study is to demonstrate the feasibility of body diffusion weighted (DW) MR imaging in the evaluation of pancreatic islet cell tumors (ICTs) and to define apparent diffusion coefficient (ADC) values for these tumors. Materials and methods: 12 normal volunteers and 12 patients with histopathologically proven pancreatic ICT by surgery were included in the study. DW MR images were obtained by a body-phased array coil using a multisection single-shot echo planar sequence on the axial plane without breath holding. In addition, the routine abdominal imaging protocol for pancreas was applied in the patient group. We measured the ADC value within the normal pancreas in control group, pancreatic ICT, and surrounding pancreas parenchyma. Mann-Whitney U-test has been used to compare ADC values between tumoral tissues and normal pancreatic tissues of the volunteers. Wilcoxon Signed Ranks Test was preferred to compare ADC values between tumoral tissues and surrounding pancreatic parenchyma of the patients. Results: In 11 patients out of 12, conventional MR sequences were able to demonstrate ICTs successfully. In 1 patient an indistinct suspicious lesion was noted at the pancreatic tail. DW sequence was able to demonstrate the lesions in all of the 12 patients. On the DW images, all ICTs demonstrated high signal intensity relative to the surrounding pancreatic parenchyma. The mean and standard deviations of the ADC values (x10 -3 mm 2 /s) were as follows: ICT (n = 12), 1.51 ± 0.35 (0.91-2.11), surrounding parenchyma (n = 11) 0.76 ± 0.15 (0.51-1.01) and normal pancreas in normal volunteers (n = 12), 0.80 ± 0.06 (0.72-0.90). ADC values of the ICT were significantly higher compared with those of surrounding parenchyma (p < 0.01) and normal pancreas (p < 0.001). Conclusion: DW MR imaging does not appear to provide significant contribution to routine MR imaging protocol in the evaluation of pancreatic islet cell tumors. But it can be added to MR imaging

Application of contrast-enhanced ultrasound in the diagnosis of solid pancreatic lesions—A comparison of conventional ultrasound and contrast-enhanced CT

International Nuclear Information System (INIS)

Fan, Zhihui; Li, Ying; Yan, Kun; Wu, Wei; Yin, Shanshan; Yang, Wei; Xing, Baocai

2013-01-01

Objective: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) by comparison with conventional ultrasound (US) and contrast-enhanced CT (CECT) in solid pancreatic lesions. Method: Ninety patients with solid pancreatic focal lesions were enrolled, including 36 cases of pancreatic carcinoma, 28 cases of pancreatitis, 6 cases of pancreatic neuroendocrine tumor, 12 cases of solid pseudopapillary tumor of the pancreas, 6 cases of pancreatic metastases, 1 case of cavernous hemolymphangioma and 1 case of lymphoma. US and CEUS were applied respectively for the diagnosis of a total of 90 cases of solid pancreatic lesions. The diagnostic results were scored on a 5-point scale. Results of CEUS were compared with CECT. Results: (1) 3-score cases (undetermined) diagnosed by CEUS were obviously fewer than that of US, while the number of 1-score (definitely benign) and 5-score (definitely malignant) cases diagnosed by CEUS was significantly more than that of US. There was a significant difference in the distribution of final scores using the two methods (p < 0.001). The overall diagnostic accuracies of the 90 cases for CEUS and US were 83.33% and 44.44%, respectively, which indicated an obvious advantage for CEUS (p < 0.001). (2) The diagnostic consistency among three ultrasound doctors: the kappa values calculated for US were 0.537, 0.444 and 0.525, compared with 0.748, 0.645 and 0.795 for CEUS. The interobserver agreement for CEUS was higher than that for US. (3) The sensitivity, specificity and accuracy of the diagnosis of pancreatic carcinoma with CEUS and CECT were 91.7% and 97.2%, 87.0% and 88.9%, and 88.9% and 92.2%, respectively, while for the diagnosis of pancreatitis, the corresponding indices were 82.1% and 67.9%, 91.9% and 100%, and 88.9% and 90%, respectively, showing no significant differences (p > 0.05). Conclusion: CEUS has obvious superiority over conventional US in the general diagnostic accuracy of solid pancreatic lesions and in the

Application of contrast-enhanced ultrasound in the diagnosis of solid pancreatic lesions—A comparison of conventional ultrasound and contrast-enhanced CT

Energy Technology Data Exchange (ETDEWEB)

Fan, Zhihui, E-mail: fanzhihui_1026@163.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Li, Ying, E-mail: 18901033676@126.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Radiology, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Yan, Kun, E-mail: ydbz@sina.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Wu, Wei, E-mail: wuwei@163.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Yin, Shanshan, E-mail: yshshmd@yahoo.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Yang, Wei, E-mail: weiwei02032001@gmail.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Xing, Baocai, E-mail: xinbaocai88@sina.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Hepatic Biliary and Pancreatic Surgery, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); and others

2013-09-15

Objective: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) by comparison with conventional ultrasound (US) and contrast-enhanced CT (CECT) in solid pancreatic lesions. Method: Ninety patients with solid pancreatic focal lesions were enrolled, including 36 cases of pancreatic carcinoma, 28 cases of pancreatitis, 6 cases of pancreatic neuroendocrine tumor, 12 cases of solid pseudopapillary tumor of the pancreas, 6 cases of pancreatic metastases, 1 case of cavernous hemolymphangioma and 1 case of lymphoma. US and CEUS were applied respectively for the diagnosis of a total of 90 cases of solid pancreatic lesions. The diagnostic results were scored on a 5-point scale. Results of CEUS were compared with CECT. Results: (1) 3-score cases (undetermined) diagnosed by CEUS were obviously fewer than that of US, while the number of 1-score (definitely benign) and 5-score (definitely malignant) cases diagnosed by CEUS was significantly more than that of US. There was a significant difference in the distribution of final scores using the two methods (p < 0.001). The overall diagnostic accuracies of the 90 cases for CEUS and US were 83.33% and 44.44%, respectively, which indicated an obvious advantage for CEUS (p < 0.001). (2) The diagnostic consistency among three ultrasound doctors: the kappa values calculated for US were 0.537, 0.444 and 0.525, compared with 0.748, 0.645 and 0.795 for CEUS. The interobserver agreement for CEUS was higher than that for US. (3) The sensitivity, specificity and accuracy of the diagnosis of pancreatic carcinoma with CEUS and CECT were 91.7% and 97.2%, 87.0% and 88.9%, and 88.9% and 92.2%, respectively, while for the diagnosis of pancreatitis, the corresponding indices were 82.1% and 67.9%, 91.9% and 100%, and 88.9% and 90%, respectively, showing no significant differences (p > 0.05). Conclusion: CEUS has obvious superiority over conventional US in the general diagnostic accuracy of solid pancreatic lesions and in the

Differential diagnosis of groove pancreatic carcinomas vs. groove pancreatitis: Usefulness of the portal venous phase

International Nuclear Information System (INIS)

Ishigami, Kousei; Tajima, Tsuyoshi; Nishie, Akihiro; Kakihara, Daisuke; Fujita, Nobuhiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Irie, Hiroyuki; Nakamura, Masafumi; Takahata, Shunichi; Ito, Tetsuhide; Honda, Hiroshi

2010-01-01

Purpose: To clarify if the portal venous phase is helpful for the differential diagnosis of groove pancreatic carcinomas and groove pancreatitis. Materials and methods: MDCT and MRI of groove pancreatic carcinomas (n = 7) and groove pancreatitis (n = 15) were retrospectively reviewed by two radiologists independently. The signal intensity on T2-weighted images was subjectively assessed. The presence or absence of common bile duct (CBD) and main pancreatic duct (MPD) strictures, calcifications, and cystic lesions was evaluated. Additionally, the appearance of groove pancreatic carcinoma and that of groove pancreatitis in the portal venous phase on dynamic MDCT and MRI were compared. Results: There were no significant differences in the signal intensity on T2-weighted images and in the presence or absence of CBD and MPD strictures, calcifications, and cystic lesions between groove pancreatic carcinomas and groove pancreatitis. However, patchy focal enhancement in the portal venous phase was more commonly observed in groove pancreatitis than groove pancreatic carcinoma (Reviewers 1 and 2: 14/15 [93.3%] vs. 1/7 [14.3%], P < 0.0001). In addition, peripheral enhancement was only seen in groove pancreatic carcinomas (Reviewer 1: 4/7 [57.1%] vs. 0/15 [0%], P < 0.005, and Reviewer 2: 3/7 [42.9%] vs. 0/15 [0%], P < 0.05). Conclusion: The portal venous phase may be helpful for the differential diagnosis of groove pancreatic carcinomas and groove pancreatitis.

Contrast-enhanced helical CT of the pancreas. Optimal timing of imaging for pancreatic tumor evaluation

International Nuclear Information System (INIS)

Koide, Kazuki; Sekiguchi, Ryuzo

2001-01-01

We performed three-phase helical CT in patients suspected pancreatic tumors and investigated the optimal timing of imaging for evaluation of the pancreatic mass. The pancreatic-phase was superior in detecting pancreatic tumors, including islet cell tumors that may show strong enhancement. However, portal vein-phase imaging was also superior in 16.7% of our patients. Taking into account examination for hepatic metastasis, helical CT of any pancreatic tumor should include images obtained in the pancreatic and portal vein phases. (author)

Ultrasonographic diagnosis of pancreatic and peripancreatic cancer

International Nuclear Information System (INIS)

Park, Churl Min; Kim, Ho Kyun; Yoon, Yup; Lee, Sun Wha; Kim, Soon Yong; Ahn, Chi Yul

1982-01-01

Seventeen cases of cancers in and adjacent to the pancreas were studied by high resolution and wide field real time ultrasonographic scanner with 3.5 MHz linear array electronically focusing transducer. The result were as follows: 1. In a total of 17 cases, 7 cases were pancreatic cancers and the rests were 3 cases of ampulla of Vaster cancer, 3 cases of distal CBD cancers, and 4 cases of metastatic cancers, respectively. 2. Pancreatic cancers were located mainly in head portion, and metastatic cancers were noted in head, tail, and retropancreatic areas. 3. The sizes of all distal CBD cancer were less than 1.8 cm, usually smaller than other tumors, and the size of metastatic cancers were variable (1-6 cm). 4. The shape, margin, contour and echogenicity of the tumors were variable. 5. Pancreatic duct showed marked dilatation in one of pancreatic cancer, and mild dilatation in one of ampulla of Vater cancer. 6. The caliber of extrahepatic duct were moderately or markedly dilated in nearly all cases except 2 cases of pancreatic body cancer. 7. The pancreatic margin is partially obliterated in pancreatic and ampulla of Vater cancers but not in distal CBD cancer. 8. Gallbladder enlargement is secondary change due to the obstruction of extrahepatic bile duct. 9. Effects on the vessels are due to not only direct mass effect but direct invasion resulting in obliteration. The most commonly involved vessels are spleno-portal junction, splenic vein and portal vein. In case of pancreatic cancer in uncinate process, the superior mesenteric vessels are displaced anteriorly. 10. Surrounding metastatic lesions were suspected in pancreatic and ampulla of Vater cancer, but not seen in distal CBD cancer. 11. Ascites were seen in only two cases of metastasis

Diagnosis of pancreatic disease

International Nuclear Information System (INIS)

Bautz, W.; Skalej, M.; Kalender, W.

1990-01-01

This paper reports on CT scanners with continuously rotating measurement systems enable volume scanning of a body section when used with continuous patient transport (spiral CT). Because of its relatively small volume, the complete pancreas can be scanned in a single breathhold. For pancreatic examinations, 1 continuous, 1- second scans with a table feed of 10 mm/sec were obtained on a Siemens SOMATOM Plus. Contrast material (50 mL) was power injected immediately before the start of measurements. CT images were reconstructed from the volume data set at 2-mm intervals. Fifty-six patients with pancreatitis, carcinoma or metastases of the pancreas; endocrine-active tumors; or Echinococcus were examined with both conventional and spiral CT

Microencapsulated tumor assay: Evaluation of the nude mouse model of pancreatic cancer

Science.gov (United States)

Ma, Ming-Zhe; Cheng, Dong-Feng; Ye, Jin-Hua; Zhou, Yong; Wang, Jia-Xiang; Shi, Min-Min; Han, Bao-San; Peng, Cheng-Hong

2012-01-01

AIM: To establish a more stable and accurate nude mouse model of pancreatic cancer using cancer cell microencapsulation. METHODS: The assay is based on microencapsulation technology, wherein human tumor cells are encapsulated in small microcapsules (approximately 420 μm in diameter) constructed of semipermeable membranes. We implemented two kinds of subcutaneous implantation models in nude mice using the injection of single tumor cells and encapsulated pancreatic tumor cells. The size of subcutaneously implanted tumors was observed on a weekly basis using two methods, and growth curves were generated from these data. The growth and metastasis of orthotopically injected single tumor cells and encapsulated pancreatic tumor cells were evaluated at four and eight weeks postimplantation by positron emission tomography-computed tomography scan and necropsy. The pancreatic tumor samples obtained from each method were then sent for pathological examination. We evaluated differences in the rates of tumor incidence and the presence of metastasis and variations in tumor volume and tumor weight in the cancer microcapsules vs single-cell suspensions. RESULTS: Sequential in vitro observations of the microcapsules showed that the cancer cells in microcapsules proliferated well and formed spheroids at days 4 to 6. Further in vitro culture resulted in bursting of the membrane of the microcapsules and cells deviated outward and continued to grow in flasks. The optimum injection time was found to be 5 d after tumor encapsulation. In the subcutaneous implantation model, there were no significant differences in terms of tumor volume between the encapsulated pancreatic tumor cells and cells alone and rate of tumor incidence. There was a significant difference in the rate of successful implantation between the cancer cell microencapsulation group and the single tumor-cell suspension group (100% vs 71.43%, respectively, P = 0.0489) in the orthotropic implantation model. The former method

Evaluation of pancreatic scintigram in the diagnosis of pancreatic diseases

International Nuclear Information System (INIS)

Takai, Yukihiro; Ueda, Noriyuki; Takasago, Noritsugu; Minemoto, Hiromasa; Namiki, Masayoshi

1981-01-01

The classification of accumulative patterns with the pancreatic scintigram findings of chronic pancreatitis and carcinoma of the pancreas were compared with endoscopic retrograde pancreatography (ERP) findings and Pancreozymin-Secretin test (P-S test). I) The frequency of pancreatic cancer was 93%, whilst, the chronic pancreatitis was 88% in the abnormal pancreatic scintigram. II) In the scintigram the type II (localyzed defect shadows) of pancreatic cancer was comparatively high and it is proportional to evidence. derived from ERP. Localized diagnostic certainty is helpful, although the two tests are related. The P-S test is only restricted to the carcinoma of head, whilst, scintigram is more useful to detect the carcinoma of the body and tail of the pancreas. III) As for the chronic pancreatitis, there are various accumulative patterns. This is resemblance to that of ERP findings, but in the P-S normal test, it showed discrepancy in part of the result. Particularly, in the type I (slightly generalized low uptake with density silhouette) and type II. Therefore in order to obtain an accurate diagnosis, it is essential to have both the P-S test and scintigram. (author)

Characterization of Pancreatic Tumor Motion Using Cine MRI: Surrogates for Tumor Position Should Be Used With Caution

International Nuclear Information System (INIS)

Feng, Mary; Balter, James M.; Normolle, Daniel; Adusumilli, Saroja; Cao Yue; Chenevert, Thomas L.; Ben-Josef, Edgar

2009-01-01

Purpose: Our current understanding of intrafraction pancreatic tumor motion due to respiration is limited. In this study, we characterized pancreatic tumor motion and evaluated the application of several radiotherapy motion management strategies. Methods and Materials: Seventeen patients with unresectable pancreatic cancer were enrolled in a prospective internal review board-approved study and imaged during shallow free-breathing using cine MRI on a 3T scanner. Tumor borders were agreed on by a radiation oncologist and an abdominal MRI radiologist. Tumor motion and correlation with the potential surrogates of the diaphragm and abdominal wall were assessed. These data were also used to evaluate planning target volume margin construction, respiratory gating, and four-dimensional treatment planning for pancreatic tumors. Results: Tumor borders moved much more than expected. To provide 99% geometric coverage, margins of 20 mm inferiorly, 10 mm anteriorly, 7 mm superiorly, and 4 mm posteriorly are required. Tumor position correlated poorly with diaphragm and abdominal wall position, with patient-level Pearson correlation coefficients of -0.18-0.43. Sensitivity and specificity of gating with these surrogates was also poor, at 53%-68%, with overall error of 35%-38%, suggesting that the tumor may be underdosed and normal tissues overdosed. Conclusions: Motion of pancreatic tumor borders is highly variable between patients and larger than expected. There is substantial deformation with breathing, and tumor border position does not correlate well with abdominal wall or diaphragmatic position. Current motion management strategies may not account fully for tumor motion and should be used with caution.

From Pathogenesis, Clinical Manifestation, and Diagnosis to Treatment: An Overview on Autoimmune Pancreatitis

Directory of Open Access Journals (Sweden)

Ou Cai

2017-01-01

Full Text Available Autoimmune pancreatitis (AIP is a special type of chronic pancreatitis which is autoimmune mediated. The international consensus diagnostic criteria (ICDC 2011 proposed two types of AIP: type I is associated with histological pattern of lymphoplasmacytic sclerosing pancreatitis (LPSP, characterized by serum IgG4 elevation, whereas type 2 is named idiopathic duct-centric pancreatitis (IDCP, with granulocytic epithelial lesion (GEL and immunoglobulin G4 (IgG4 negative. The pathogenic mechanism is unclear now; based on genetic factors, disease specific or related antigens, innate and adaptive immunity may be involved. The most common clinical manifestations of AIP are obstructive jaundice and upper abdominal pain. The diagnosis can be made by a combination of parenchymal and ductal imaging, serum IgG4 concentrations, pancreatic histology, extrapancreatic disease, and glucocorticoid responsiveness according to ICDC 2011. Because of the clinical and imaging similarities with pancreatic cancer, general work-up should be done carefully to exclude pancreatic malignant tumor before empirical trial of glucocorticoid treatment. Glucocorticoid is the most common drug for AIP to induce remission, while there still exists controversy on steroid maintenance and treatment for relapse. Further studies should be done to identify more specific serum biomarkers for AIP, the pathogenic mechanisms, and the treatment for relapse.

Inhibition of pancreatic tumoral cells by snake venom disintegrins.

Science.gov (United States)

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

2015-01-01

Pancreatic cancer often has a poor prognosis, even when diagnosed early. Pancreatic cancer typically spreads rapidly and is rarely detected in its early stages, which is a major reason it is a leading cause of cancer death. Signs and symptoms may not appear until pancreatic cancer is quite advanced, and complete surgical removal is not possible. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. The importance of integrins in several cell types that affect tumor progression has made them an appealing target for cancer therapy. Some of the proteins found in the snake venom present a great potential as anti-tumor agents. In this study, we summarize the activity of two integrins antagonist, recombinant disintegrins mojastin 1 and viridistatin 2, on human pancreatic carcinoma cell line (BXPC-3). Both recombinant disintegrins inhibited some essential aspects of the metastasis process such as proliferation, adhesion, migration, and survival through apoptosis, making these proteins prominent candidates for the development of drugs for the treatment of pancreatic cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential diagnosis of small solid pancreatic lesions

DEFF Research Database (Denmark)

Dietrich, Christoph Frank; Sahai, Anand Vasante; D'Onofrio, Mirko

2016-01-01

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at a late stage. Little is known about the incidental finding of early-stage PDAC. The aim of the current study was to determine the etiology of small solid pancreatic lesions (≤15 mm) to optimize clinical......-enhanced US allowed differential diagnosis of PDAC and non-PDAC in 189 of 219 patients (86%). CONCLUSIONS: Approximately 40% of patients with small solid pancreatic lesions had very early stage PDAC. Approximately 60% of small solid pancreatic lesions ≤15 mm are not PDAC and, therefore, do not require radical...

Surgery of malignant pancreatic tumors

International Nuclear Information System (INIS)

Loos, M.; Friess, H.; Kleeff, J.

2009-01-01

Ductal adenocarcinoma is the most common malignant tumor of the pancreas. Despite great efforts in basic and clinical pancreatic cancer research, the prognosis remains poor with an overall 5-year survival rate of less than 5%. Complete surgical resection represents the only curative treatment option and 5-year survival rates of 20-25% can be achieved following curative resection and adjuvant chemotherapy. Although pancreatic surgery is considered one of the most technically demanding and challenging procedures, there has been constant progress in surgical techniques and advances in perioperative care with a modern interdisciplinary approach including anesthesiology, oncology, radiology and nursing. This has reduced morbidity and especially mortality rates in high-volume centers. Among extended resection procedures multivisceral and venous resections are technically feasible and should be considered if a complete tumor resection can be achieved. Multimodal regimens have shown promising results, however, only adjuvant chemotherapy is supported by solid evidence from randomized controlled trials. (orig.) [de

Surgical and molecular pathology of pancreatic neoplasms.

Science.gov (United States)

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.

Treatment of pancreatic neuroendocrine tumor with liver metastases

Directory of Open Access Journals (Sweden)

LI Zhao

2015-05-01

Full Text Available Pancreatic neuroendocrine tumor (pNET is a rare type of pancreatic tumors. The incidence of pNET shows a gradually increasing trend in recent years. The most common organ of distant metastases is the liver. Surgical resection is still the optimal treatment for resectable, well-differentiated liver metastases with no evidence of extrahepatic spread. For unresectable patients, a combination of multiple modalities, such as transarterial chemoembolization, radiofrequency ablation, systemic chemotherapy, and molecular targeted therapy, can prolong the survival time of patients. Liver transplantation should be strictly evaluated on an individual basis.

Primary cystic pancreatic neoplasms and tumor-like conditions. MR cholangiopancreatographic evaluation of lesions and Wirsung's duct

International Nuclear Information System (INIS)

Garcia, Adriana; Spina, Juan C. h; Rogondino, Jose; Chacon, Carolina; Gutierrez, Silvia

2003-01-01

Objective: To evaluate the contribution of single shot fast spin echo (SSFSE) in the diagnosis of cystic lesions in the pancreas, and their relation to Wirsung's duct. Material and methods: In 66 patients (33 women and 33 men; mean age: 66 years) cystic pancreatic lesions were retrospectively analyzed. The SSFSE technique was used, including an evaluation of Wirsung's duct. Conventional pancreatic sequences were added. The following lesion features were assessed: location, number, size, relation to Wirsung's duct, nature of the cystic image and signal intensity of the neoplasm or tumor-like condition. Surgical and anatomopathological correlation was obtained in 31/66 cases (47%). Results: The cystic lesions were divided in 2 groups: A) cystic lesions related to Wirsung's duct, 30 patients: all lesions measured less than 30 mm in size. Seven patients underwent surgical treatment; in 22 cases surgery was not indicated. One patient refused surgery. A mucinous papilliferous intraductal tumor was diagnosed in 3 cases, ampullar carcinoma in 1 case, pancreatic carcinoma, 1 case, autoimmune pancreatitis, 1 case, and cystic duct dilatation due to benign fibrous stenosis, 1 case. B) Cystic lesions not related to Wirsung's duct (36 patients): 7 serous cystadenomas, 7 adenocarcinomas with a cystic component, 1 mucinous cystadenoma, 1 duodenal diverticulum, 7 pseudocysts and 1 neuroendocrine tumor. In 12 patients surgery was not carried out due to clinical contraindication or patient's refusal. Conclusion: SSFSE allowed a clear differentiation between cystic lesions related (Group A) and non-related (Group B) to Wirsung's duct. The diagnosis could not be achieved by usual MRI sequences. However, benign and malignant lesions were observed in both groups. In all cases SSFSE afforded useful data either for surgical treatment or clinical follow-up. (author)

Diagnosis of pancreatic cancer using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET). Usefulness and limitations in clinical reality''

International Nuclear Information System (INIS)

Higashi, Tatsuya; Saga, Tsuneo; Ishimori, Takayoshi; Fujimoto, Koji; Doi, Ryuichiro; Imamura, Masayuki; Konishi, Junji

2003-01-01

The present review will provide an overview of the literature concerning the FDG PET diagnosis of pancreatic cancer and a summary from our experience of 231 cases of pancreatic lesions. FDG PET can effectively differentiate pancreatic cancer from benign lesion with high accuracy. Newly-developed PET scanners can detect small pancreatic cancers, up to 7 mm in diameter, by their high resolution, which could make a great contribution to the early detection of resectable and potentially curable pancreatic cancers. FDG PET is useful and cost-beneficial in the pre-operative staging of pancreatic cancer because an unexpected distant metastasis can be detected by whole-body PET in about 40% of the cases, which results in avoidance of unnecessary surgical procedures. FDG PET is also useful in evaluation of the treatment effect, monitoring after the operation and detection of recurrent pancreatic cancers. However, there are some drawbacks in PET diagnosis. A relatively wide overlap has been reported between semiquantitative uptake values obtained in cancers and those in inflammatory lesions. As for false-positive cases, active and chronic pancreatitis and autoimmune pancreatitis sometimes show high FDG accumulation and mimic pancreatic cancer with a shape of focal uptake. There were 8 false negative cases in the detection of pancreatic cancer by FDG PET, up to 33 mm in diameter, mainly because of their poor cellularity in cancer tissues. In addition, there are 19% of cancer cases with a decline in FDG uptake from 1 hr to 2 hr scan. FDG PET was recently applied to and was shown to be feasible in the differential diagnosis of cystic pancreatic lesions, such as intraductal papillary mucinous tumor of the pancreas. Further investigations are required to clarify the clinical value of FDG PET in predicting prognosis of the pancreatic patients. (author) 124 refs

Lipase or amylase for the diagnosis of acute pancreatitis?

Science.gov (United States)

Ismail, Ola Z; Bhayana, Vipin

2017-12-01

Acute pancreatitis is a rapid onset of inflammation of the pancreas causing mild to severe life threatening conditions [1, 2]. In Canada, acute pancreatitis is the 5th most expensive digestive disease in Canada with a considerable economic burden on the health care system [3]. The diagnosis of acute pancreatitis is usually based on the presence of abdominal pain and elevated levels of serum amylase and/or lipase. Many health care centers use either serum amylase, lipase or both to diagnose acute pancreatitis without considering which one could provide a better diagnostic accuracy. The aim of this review is to investigate whether serum lipase alone is a sufficient biomarker for the diagnosis of acute pancreatitis. We have examined various studies looking at the utilization, sensitivity, specificity and cost associated savings of lipase and amylase in the diagnosis of acute pancreatitis. When comparing different studies, serum lipase offers a higher sensitivity than serum amylase in diagnosing acute pancreatitis. Lipase also offers a larger diagnostic window than amylase since it is elevated for a longer time, thus allowing it to be a useful diagnostic biomarker in early and late stages of acute pancreatitis. Several recent evidence-based guidelines recommend the use of lipase over amylase. Nevertheless, both lipase and amylase alone lack the ability to determine the severity and etiology of acute pancreatitis. The co-ordering of both tests has shown little to no increase in the diagnostic sensitivity and specificity. Thus, unnecessary testing and laboratory expenditures can be reduced by testing lipase alone. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

pancreatic steatosis: diagnosis and clinical significance

Directory of Open Access Journals (Sweden)

Murat Daðdeviren

2017-03-01

Full Text Available Pancreatic steatosis (PS, with increased use of abdominal imaging in recent years generally appears as incidental. But it is a condition that is often overlooked. The reason for this is not yet fully demonstrated the clinical significance of PS while. However, in recent years, there are some studies conducted on the relationship with ps and other disease such as diabetes, metabolic syndrome, acute and chronic pancreatitis and pancreatic cancer. In this review, the etiology, diagnosis, treatment and clinical characteristics of ps were evaluated in the light of recent literature and current approaches. [J Contemp Med 2017; 7(1.000: 107-112

Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

Science.gov (United States)

Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

2017-09-25

von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

Endoscopic ultrasound-guided radiofrequency ablation for management of benign solid pancreatic tumors.

Science.gov (United States)

Choi, Jun-Ho; Seo, Dong-Wan; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

2018-05-04

 Radiofrequency ablation (RFA) has been increasingly employed in experimental and clinical settings for the management of pancreatic lesions. This study aimed to assess the safety and efficacy of endoscopic ultrasound (EUS)-guided RFA for benign solid pancreatic tumors.  In a single-center, prospective study, 10 patients with benign solid pancreatic tumors underwent EUS-RFA. After the RFA electrode had been inserted into the pancreatic mass, the radiofrequency generator was activated to deliver 50 W of ablation power.  Among the 10 patients, 16 sessions of EUS-RFA were successfully performed. Diagnoses included nonfunctioning neuroendocrine tumor (n = 7), solid pseudopapillary neoplasm (n = 2), and insulinoma (n = 1); the median largest diameter of the tumors was 20 mm (range 8 - 28 mm). During follow-up (median 13 months), radiologic complete response was achieved in seven patients. Two adverse events (12.4 %; 1 moderate and 1 mild) occurred.  EUS-RFA may be a safe and potentially effective treatment option in selected patients with benign solid pancreatic tumors. Multiple sessions may be required if there is a remnant tumor, and adverse events must be carefully monitored. © Georg Thieme Verlag KG Stuttgart · New York.

18F-fluorodeoxyglucose positron emission tomography in management of pancreatic cystic tumors

International Nuclear Information System (INIS)

Zhang Yaojun; Frampton, Adam E.; Martin, Jack L.; Kyriakides, Charis; Bong, Jan Jin; Habib, Nagy A.; Vlavianos, Panagiotis; Jiao, Long R.

2012-01-01

Objectives: To evaluate the effectiveness of PET in differentiating malignant from benign pancreatic cystic tumors. Methods: Between 2009 and 2010, all patients with pancreatic cystic tumors who had PET, triple phase contrast computed tomography (CT) and endoscopic ultrasound (EUS) were reviewed. Clinicopathological characteristics and final histology were correlated with preoperative PET, CT and EUS to assess the value of each modality in detecting malignant from benign lesions for clinical decision-making. Results: Twenty of a total of 116 patients with pancreatic cystic tumors had 18F-FDG PET because of diagnostic difficulties after evaluation with conventional modalities. Sensitivity and specificity of PET in differentiating malignant from benign pancreatic cystic tumors were 100% and 93.75%, with an accuracy of 95%. PET had the best sensitivity, specificity and accuracy for detecting malignant cystic tumors compared with CT and EUS. In 5 cases, the PET results altered the treatment options completely to follow-up instead of surgery (n = 2), limited resection instead of Whipple's resection (n = 1), and surgery instead of follow-up (n = 2). Conclusions: PET is an accurate, non-invasive method to distinguish malignant from benign pancreatic cystic tumors and can be used as an adjunct to facilitate clinical decision making.

Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

Energy Technology Data Exchange (ETDEWEB)

Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L. [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, BP 915,13288 Marseille cedex 9 (France)

2010-12-16

Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.

Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

International Nuclear Information System (INIS)

Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L.

2010-01-01

Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis

Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice.

Science.gov (United States)

Jiang, Shu-Heng; Li, Jun; Dong, Fang-Yuan; Yang, Jian-Yu; Liu, De-Jun; Yang, Xiao-Mei; Wang, Ya-Hui; Yang, Min-Wei; Fu, Xue-Liang; Zhang, Xiao-Xin; Li, Qing; Pang, Xiu-Feng; Huo, Yan-Miao; Li, Jiao; Zhang, Jun-Feng; Lee, Ho-Young; Lee, Su-Jae; Qin, Wen-Xin; Gu, Jian-Ren; Sun, Yong-Wei; Zhang, Zhi-Gang

2017-07-01

Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras G12D/+ /Trp53 R172H/+ /Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses. In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels

Hypotonic duodenography and endoscopic retrograde pancreatography in the diagnosis of pancreatic disease

International Nuclear Information System (INIS)

Lukes, P.J.; Rolny, P.; Nilson, A.E.; Gamklou, R.

1981-01-01

Hypotonic duodenography and endoscopic retrograde pancreatography were performed in 45 non-icteric patients with suggested pancreatic disease or long-standing upper gastrointestinal symptoms. The accuracy of each method in the diagnosis of pancreatic disease was compared. Hypotonic duodenography revealed pancreatitis in 48 per cent and ERP in 83 per cent of the cases. All 6 pancreatic tumours were detected at ERP and 3 at duodenography. The role of hypotonic duodenography and endoscopic retrograde pancreatography in the diagnosis of pancreatic disease is discussed. (Auth.)

[Autoimmune pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group].

Science.gov (United States)

Dubravcsik, Zsolt; Farkas, Gyula; Hegyi, Péter; Hritz, István; Kelemen, Dezső; Lásztity, Natália; Morvay, Zita; Oláh, Attila; Pap, Ákos; Párniczky, Andrea; Sahin-Tóth, Miklós; Szentkereszti, Zsolt; Szmola, Richárd; Takács, Tamás; Tiszlavicz, László; Szücs, Ákos; Czakó, László

2015-02-22

Autoimmune pancreatitis is a rare disease which can even mimic pancreatic tumor, however, unlike the latter, it requires not surgical but conservative management. Correct diagnosis and differential diagnosis of autoimmune pancreatitis and treatment of these patients requires up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidences. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. 29 relevant clinical questions in 4 topics were defined (Basics; Diagnosis; Differential diagnostics; Therapy). Evidence was classified according to the UpToDate(®) grading system. The draft of the guidelines was presented and discussed at the consensus meeting on September 12, 2014. All clinial questions were accepted with almost total (more than 95%) agreement. The present guideline is the first evidence based autoimmune pancreatitis guideline in Hungary. The guideline may provide very important and helpful data for tuition of autoimmune pancreatitis, for everyday practice and for establishing proper finance. Therefore, the authors believe that these guidelines will widely become a basic reference in Hungary.

Hypothyroidism in Pancreatic Cancer: Role of Exogenous Thyroid Hormone in Tumor Invasion—Preliminary Observations

Directory of Open Access Journals (Sweden)

Konrad Sarosiek

2016-01-01

Full Text Available According to the epidemiological studies, about 4.4% of American general elderly population has a pronounced hypothyroidism and relies on thyroid hormone supplements daily. The prevalence of hypothyroidism in our patients with pancreatic cancer was much higher, 14.1%. A retrospective analysis was performed on patients who underwent pancreaticoduodenectomy (Whipple procedure or distal pancreatectomy and splenectomy (DPS at Thomas Jefferson University Hospital, Philadelphia, from 2005 to 2012. The diagnosis of hypothyroidism was correlated with clinicopathologic parameters including tumor stage, grade, and survival. To further understand how thyroid hormone affects pancreatic cancer behavior, functional studies including wound-induced cell migration, proliferation, and invasion were performed on pancreatic cancer cell lines, MiaPaCa-2 and AsPC-1. We found that hypothyroid patients taking exogenous thyroid hormone were more than three times likely to have perineural invasion, and about twice as likely to have higher T stage, nodal spread, and overall poorer prognostic stage (P<0.05. Pancreatic cancer cell line studies demonstrated that exogenous thyroid hormone treatment increased cell proliferation, migration, and invasion (P<0.05. We conclude that exogenous thyroid hormone may contribute to the progression of pancreatic cancer.

Everolimus for Advanced Pancreatic Neuroendocrine Tumors.

NARCIS (Netherlands)

Yao, James C.; Shah, Manisha H.; Ito, Tetsuhide; Bohas, Catherine Lombard; Wolin, Edward M.; Van Cutsem, Eric; Hobday, Timothy J.; Okusaka, Takuji; Capdevila, Jaume; de Vries, Elisabeth G. E.; Tomassetti, Paola; Pavel, Marianne E.; Hoosen, Sakina; Haas, Tomas; Lincy, Jeremie; Lebwohl, David; Oberg, Kjell

2011-01-01

Background: Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors, in two phase 2 studies. We evaluated the agent in a prospective, randomized, phase 3 study. Methods: We randomly assigned 410

Pancreatic Sarcoma Mimicking Pseudocyst After Pancreatitis: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Cheng-Chi Lee

2015-09-01

Full Text Available A 45-year-old female presented with abdominal pain for 3 days without trauma history. The pain was located over the epigastric area with radiation to the back. A pancreatic pseudocyst was impressed initially according to clinical symptoms, laboratory data, and image studies. However, rapid progression of the lesions was noted later after discharge. Following image studies showed circumscribed tumors in the head, body, and tail regions of the pancreas. Surgery with the Whipple operation was performed during the second admission. The post operation course was uneventful. Pathologic results showed sarcoma of the pancreas. Primary pancreatic sarcomas are extremely rare lesions accounting for < 0.1% of all pancreatic malignancies. Pancreatic sarcomas tend to be aggressive and have a poor prognosis. In addition, < 5% of pancreatic tumors are cystic. The rarest cystic neoplasm is also the primary pancreatic sarcoma, with only a few cases having been documented. However, it should be considered in the differential diagnosis of pancreatic cystic lesions.

Pancreatic sarcoidosis discovered during Whipple procedure.

Science.gov (United States)

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.

SU-D-201-04: Study On the Impact of Tumor Shape and Size On Drug Delivery to Pancreatic Tumors

International Nuclear Information System (INIS)

Soltani, M; Bazmara, H; Sefidgar, M; Subramaniam, R; Rahmim, A

2015-01-01

Purpose: Drug delivery to solid tumors can be expressed physically using transport phenomena such as convection and diffusion for the drug of interest within extracellular matrices. We aimed to carefully model these phenomena, and to investigate the effect of tumor shape and size on drug delivery to solid tumors in the pancreas. Methods: In this study, multiple tumor geometries as obtained from clinical PET/CT images were considered. An advanced numerical method was used to simultaneously solve fluid flow and solute transport equations. Data from n=45 pancreatic cancer patients with non-resectable locoregional disease were analyzed, and geometrical information from the tumors including size, shape, and aspect ratios were classified. To investigate effect of tumor shape, tumors with similar size but different shapes were selected and analyzed. Moreover, to investigate effect of tumor size, tumors with similar shapes but different sizes, ranging from 1 to 77 cm 3 , were selected and analyzed. A hypothetical tumor similar to one of the analyzed tumors, but scaled to reduce its size below 0.2 cm 3 , was also analyzed. Results: The results showed relatively similar average drug concentration profiles in tumors with different sizes. Generally, smaller tumors had higher absolute drug concentration. In the hypothetical tumor, with volume less than 0.2 cm 3 , the average drug concentration was 20% higher in comparison to its counterparts. For the various real tumor geometries, however, the maximum difference between average drug concentrations was 10% for the smallest and largest tumors. Moreover, the results demonstrated that for pancreatic tumors the shape is not significant. The negligible difference of drug concentration in different tumor shapes was due to the minimum effect of convection in pancreatic tumors. Conclusion: In tumors with different sizes, smaller tumors have higher drug delivery; however, the impact of tumor shape in the case of pancreatic tumors is not

SU-D-201-04: Study On the Impact of Tumor Shape and Size On Drug Delivery to Pancreatic Tumors

Energy Technology Data Exchange (ETDEWEB)

Soltani, M [ohns Hopkins University School of Medicine, Baltimore, Maryland, and KNT university, Tehran (Iran, Islamic Republic of); Bazmara, H [KNT university, Tehran (Iran, Islamic Republic of); Sefidgar, M [IKI University, Qazvin (Iran, Islamic Republic of); Subramaniam, R; Rahmim, A [Johns Hopkins University School of Medicine, Baltimore, MD (United States)

2015-06-15

Purpose: Drug delivery to solid tumors can be expressed physically using transport phenomena such as convection and diffusion for the drug of interest within extracellular matrices. We aimed to carefully model these phenomena, and to investigate the effect of tumor shape and size on drug delivery to solid tumors in the pancreas. Methods: In this study, multiple tumor geometries as obtained from clinical PET/CT images were considered. An advanced numerical method was used to simultaneously solve fluid flow and solute transport equations. Data from n=45 pancreatic cancer patients with non-resectable locoregional disease were analyzed, and geometrical information from the tumors including size, shape, and aspect ratios were classified. To investigate effect of tumor shape, tumors with similar size but different shapes were selected and analyzed. Moreover, to investigate effect of tumor size, tumors with similar shapes but different sizes, ranging from 1 to 77 cm{sup 3}, were selected and analyzed. A hypothetical tumor similar to one of the analyzed tumors, but scaled to reduce its size below 0.2 cm{sup 3}, was also analyzed. Results: The results showed relatively similar average drug concentration profiles in tumors with different sizes. Generally, smaller tumors had higher absolute drug concentration. In the hypothetical tumor, with volume less than 0.2 cm{sup 3}, the average drug concentration was 20% higher in comparison to its counterparts. For the various real tumor geometries, however, the maximum difference between average drug concentrations was 10% for the smallest and largest tumors. Moreover, the results demonstrated that for pancreatic tumors the shape is not significant. The negligible difference of drug concentration in different tumor shapes was due to the minimum effect of convection in pancreatic tumors. Conclusion: In tumors with different sizes, smaller tumors have higher drug delivery; however, the impact of tumor shape in the case of pancreatic

Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors.

Science.gov (United States)

Bonnavion, Rémy; Teinturier, Romain; Jaafar, Rami; Ripoche, Doriane; Leteurtre, Emmanuelle; Chen, Yuan-Jia; Rehfeld, Jens F; Lepinasse, Florian; Hervieu, Valérie; Pattou, François; Vantyghem, Marie-Christine; Scoazec, Jean-Yves; Bertolino, Philippe; Zhang, Chang Xian

2015-10-01

The cells of origin of pancreatic gastrinomas remain an enigma, since no gastrin-expressing cells are found in the normal adult pancreas. It was proposed that the cellular origin of pancreatic gastrinomas may come from either the pancreatic cells themselves or gastrin-expressing cells which have migrated from the duodenum. In the current study, we further characterized previously described transient pancreatic gastrin-expressing cells using cell lineage tracing in a pan-pancreatic progenitor and a pancreatic endocrine progenitor model. We provide evidence showing that pancreatic gastrin-expressing cells, found from embryonic day 12.5 until postnatal day 7, are derived from pancreatic Ptf1a(+) and neurogenin 3-expressing (Ngn3(+)) progenitors. Importantly, the majority of them coexpress glucagon, with 4% coexpressing insulin, indicating that they are a temporary subpopulation of both alpha and beta cells. Interestingly, Men1 disruption in both Ngn3 progenitors and beta and alpha cells resulted in the development of pancreatic gastrin-expressing tumors, suggesting that the latter developed from islet cells. Finally, we detected gastrin expression using three human cohorts with pancreatic endocrine tumors (pNETs) that have not been diagnosed as gastrinomas (in 9/34 pNETs from 6/14 patients with multiple endocrine neoplasia type 1, in 5/35 sporadic nonfunctioning pNETs, and in 2/20 sporadic insulinomas), consistent with observations made in mouse models. Our work provides insight into the histogenesis of pancreatic gastrin-expressing tumors. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Solid pancreatic pseudopapillary tumor managed laparoscopically: A case report and review of the literature

Directory of Open Access Journals (Sweden)

D. Cuccurullo

Full Text Available Background: Solid pancreatic pseudopapillary tumors are a rare neoplasms, about 1–3% of all pancreatic neoplasms. This cancer mainly affects women between the third and fourth decade of life.They are not well known; the molecular origins represent a low degree of malignancy, in which the complete resection is curative. We report our experience with a case report of SPT in a young man. Presentation of case: Thirty-six years old male patient with a mass about 10 cm in the pancreatic tail and splenic ilum. After following CT and MR, the patient was subjected to surgery. Histophatological result was solid tumor pseudopapillary of pancreas with no pathological lymph nodes. Discussion and conclusion: Solid pseudopapillary neoplasm shows histological characteristic solid and pseudopapillary proliferation. Immunohistochemistry detects, among the causes of tumor development, a correlation between the Beta-catenin mutations, alteration of the E-cadherin. In the most cases, therapy is surgical treatment with laparoscopic. Keywords: Pancreatic pseudopapillary neoplasm, Pancreatic tumor, Laparoscopic surgery

Applicative Value of Serum CA19-9, CEA, CA125 and CA242 in Diagnosis and Prognosis for Patients with Pancreatic Cancer Treated by Concurrent Chemoradiotherapy.

Science.gov (United States)

Gu, Yu-Lei; Lan, Chao; Pei, Hui; Yang, Shuang-Ning; Liu, Yan-Fen; Xiao, Li-Li

2015-01-01

To evaluate the application value of serum CA19-9, CEA, CA125 and CA242 in diagnosis and prognosis of pancreatic cancer cases treated with concurrent chemotherapy. 52 patients with pancreatic cancer, 40 with benign pancreatic diseases and 40 healthy people were selected. The electrochemiluminescence immunoassay method was used for detecting levels of CA19-9, CEA and CA125, and a CanAg CA242 enzyme linked immunoassay kit for assessing the level of CA242. The Kaplan-Meier method was used for analyzing the prognostic factors of patients with pancreatic cancer. The Cox proportional hazard model was applied for analyzing the hazard ratio (HR) and 95% confidential interval (CI) for survival time of patients with pancreatic cancer. The levels of serum CA19-9, CEA, CA125 and CA242 in patients with pancreatic cancer were significantly higher than those in patients with benign pancreatic diseases and healthy people (PCEA. The specificity of CA242 is the highest, followed by CA125, CEA and CA19-9. The sensitivity and specificity of joint detection of serum CA19-9, CEA, CA125and CA242 were 90.4% and 93.8%, obviously higher than single detection of those markers in diagnosis of pancreatic cancer. The median survival time of 52 patients with pancreatic cancer was 10 months (95% CI7.389~12.611).. Patients with the increasing level of serum CA19-9, CEA, CA125, CA242 had shorter survival times (P=0.047. 0.043, 0.0041, 0.029). COX regression analysis showed that CA19-9 was an independent prognostic factor for patients with pancreatic cancer (P=0.001, 95%CI 2.591~38.243). The detection of serum tumor markers (CA19.9, CEA, CA125 and CA242) is conducive to the early diagnosis of pancreatic cancer and joint detection of tumor markers helps improve the diagnostic efficiency. Moreover, CA19-9 is an independent prognostic factor for patients with pancreatic cancer.

Neuroendocrine tumors of the pancreas.

LENUS (Irish Health Repository)

Davies, Karen

2009-04-01

Pancreatic endocrine tumors are rare neoplasms accounting for less than 5% of pancreatic malignancies. They are broadly classified into either functioning tumors (insulinomas, gastrinomas, glucagonomas, VIPomas, and somatostatinomas) or nonfunctioning tumors. The diagnosis of these tumors is difficult and requires a careful history and examination combined with laboratory tests and radiologic imaging. Signs and symptoms are usually related to hormone hypersecretion in the case of functioning tumors and to tumor size or metastases with nonfunctioning tumors. Surgical resection remains the treatment of choice even in the face of metastatic disease. Further development of novel diagnostic and treatment modalities offers potential to greatly improve quality of life and prolong disease-free survival for patients with pancreatic endocrine tumors.

Neuroendocrine tumors of the pancreas.

LENUS (Irish Health Repository)

Davies, Karen

2012-02-01

Pancreatic endocrine tumors are rare neoplasms accounting for less than 5% of pancreatic malignancies. They are broadly classified into either functioning tumors (insulinomas, gastrinomas, glucagonomas, VIPomas, and somatostatinomas) or nonfunctioning tumors. The diagnosis of these tumors is difficult and requires a careful history and examination combined with laboratory tests and radiologic imaging. Signs and symptoms are usually related to hormone hypersecretion in the case of functioning tumors and to tumor size or metastases with nonfunctioning tumors. Surgical resection remains the treatment of choice even in the face of metastatic disease. Further development of novel diagnostic and treatment modalities offers potential to greatly improve quality of life and prolong disease-free survival for patients with pancreatic endocrine tumors.

Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth

International Nuclear Information System (INIS)

Ohkura, Yu; Sasaki, Kazunari; Matsuda, Masamichi; Hashimoto, Masaji; Fujii, Takeshi; Watanabe, Goro

2015-01-01

Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth is extremely rare. Diagnosis of pancreatic cancer on preoperative imaging is difficult when the pancreatic parenchyma is compressed by a pseudocyst and becomes unclear. Despite advances in imaging techniques, accurate preoperative diagnosis of cystic lesions of the pancreas remains difficult. In this case, it was challenging to diagnose pancreatic cancer preoperatively as we could not accurately assess the pancreatic parenchyma, which had been compressed by a moderate-sized cystic lesion with extrapancreatic growth. A 63-year-old woman underwent investigations for epigastric abdominal pain. She had no history of pancreatitis. Although we suspected pancreatic ductal carcinoma with a pancreatic cyst, there was no mass lesion or low-density area suggestive of pancreatic cancer. We did not immediately suspect pancreatic cancer, as development of a moderate-sized cyst with extrapancreatic growth is extremely rare and known tumor markers were not elevated. Therefore, we initially suspected that a massive benign cyst (mucinous cyst neoplasm, serous cyst neoplasm, or intraductal papillary mucinous neoplasm) resulted in stenosis of the main pancreatic duct. We were unable to reach a definitive diagnosis prior to the operation. We had planned a pancreaticoduodenectomy to reach a definitive diagnosis. However, we could not remove the tumor because of significant invasion of the surrounding tissue (portal vein, superior mesenteric vein, etc.). The fluid content of the cyst was serous, and aspiration cytology from the pancreatic cyst was Class III (no malignancy), but the surrounding white connective tissue samples were positive for pancreatic adenocarcinoma on pathological examination during surgery. We repeated imaging (CT, MRI, endoscopic ultrasound, etc.) postoperatively, but there were neither mass lesions nor a low-density area suggestive of pancreatic cancer. In retrospect, we think

Involvement of host stroma cells and tissue fibrosis in pancreatic tumor development in transgenic mice.

Directory of Open Access Journals (Sweden)

Itai Spector

Full Text Available INTRODUCTION: Stroma cells and extracellular matrix (ECM components provide the pivotal microenvironment for tumor development. The study aimed to evaluate the importance of the pancreatic stroma for tumor development. METHODS: Pancreatic tumor cells were implanted subcutaneously into green fluorescent protein transgenic mice, and stroma cells invading the tumors were identified through immunohistochemistry. Inhibition of tumor invasion by stroma cells was achieved with halofuginone, an inhibitor of TGFβ/Smad3 signaling, alone or in combination with chemotherapy. The origin of tumor ECM was evaluated with species-specific collagen I antibodies and in situ hybridization of collagen α1(I gene. Pancreatic fibrosis was induced by cerulean injection and tumors by spleen injection of pancreatic tumor cells. RESULTS: Inhibition of stroma cell infiltration and reduction of tumor ECM levels by halofuginone inhibited development of tumors derived from mouse and human pancreatic cancer cells. Halofuginone reduced the number only of stroma myofibroblasts expressing both contractile and collagen biosynthesis markers. Both stroma myofibroblasts and tumor cells generated ECM that contributes to tumor growth. Combination of treatments that inhibit stroma cell infiltration, cause apoptosis of myofibroblasts and inhibit Smad3 phosphorylation, with chemotherapy that increases tumor-cell apoptosis without affecting Smad3 phosphorylation was more efficacious than either treatment alone. More tumors developed in fibrotic than in normal pancreas, and prevention of tissue fibrosis greatly reduced tumor development. CONCLUSIONS: The utmost importance of tissue fibrosis and of stroma cells for tumor development presents potential new therapy targets, suggesting combination therapy against stroma and neoplastic cells as a treatment of choice.

Metastatic Insulinoma Following Resection of Nonsecreting Pancreatic Islet Cell Tumor

Directory of Open Access Journals (Sweden)

Anoopa A. Koshy MD

2013-01-01

Full Text Available A 56-year-old woman presented to our clinic for recurrent hypoglycemia after undergoing resection of an incidentally discovered nonfunctional pancreatic endocrine tumor 6 years ago. She underwent a distal pancreatectomy and splenectomy, after which she developed diabetes and was placed on an insulin pump. Pathology showed a pancreatic endocrine neoplasm with negative islet hormone immunostains. Two years later, computed tomography scan of the abdomen showed multiple liver lesions. Biopsy of a liver lesion showed a well-differentiated neuroendocrine neoplasm, consistent with pancreatic origin. Six years later, she presented to clinic with 1.5 years of recurrent hypoglycemia. Laboratory results showed elevated proinsulin, insulin levels, and c-peptide levels during a hypoglycemic episode. Computed tomography scan of the abdomen redemonstrated multiple liver lesions. Repeated transarterial catheter chemoembolization and microwave thermal ablation controlled hypoglycemia. The unusual features of interest of this case include the transformation of nonfunctioning pancreatic endocrine tumor to a metastatic insulinoma and the occurrence of atrial flutter after octreotide for treatment.

Ligand stimulation of ErbB4 and a constitutively-active ErbB4 mutant result in different biological responses in human pancreatic tumor cell lines

International Nuclear Information System (INIS)

Mill, Christopher P.; Gettinger, Kathleen L.; Riese, David J.

2011-01-01

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Indeed, it has been estimated that 37,000 Americans will die from this disease in 2010. Late diagnosis, chemoresistance, and radioresistance of these tumors are major reasons for poor patient outcome, spurring the search for pancreatic cancer early diagnostic and therapeutic targets. ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases (RTKs), a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3. These RTKs play central roles in many human malignancies by regulating cell proliferation, survival, differentiation, invasiveness, motility, and apoptosis. In this report we demonstrate that human pancreatic tumor cell lines exhibit minimal ErbB4 expression; in contrast, these cell lines exhibit varied and in some cases abundant expression and basal tyrosine phosphorylation of EGFR, ErbB2, and ErbB3. Expression of a constitutively-dimerized and -active ErbB4 mutant inhibits clonogenic proliferation of CaPan-1, HPAC, MIA PaCa-2, and PANC-1 pancreatic tumor cell lines. In contrast, expression of wild-type ErbB4 in pancreatic tumor cell lines potentiates stimulation of anchorage-independent colony formation by the ErbB4 ligand Neuregulin 1β. These results illustrate the multiple roles that ErbB4 may be playing in pancreatic tumorigenesis and tumor progression.

Pancreatic Carcinoma With Hepatic Metastasis And Early Signs Of ...

African Journals Online (AJOL)

Pancreatic carcinoma is one of the lethal neoplasms. Involvement of pancreatic body and tail are uncommon compared to that of the head and neck. Sinistral portal hypertension is a rare complication of pancreatic tumor which results from obstruction of portal vein tributaries. Imaging may be the only clue to diagnosis.

Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts

Energy Technology Data Exchange (ETDEWEB)

Lohse, Ines; Lourenco, Corey; Ibrahimov, Emin; Pintilie, Melania [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Tsao, Ming-Sound [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Pathology, University Health Network, 200 Elizabeth Street, Toronto, ON M5G2C4 (Canada); Department of Laboratory Medicine and Pathobiology, 27 King’s College Circle, University of Toronto, Toronto, ON M5S1A1 (Canada); Hedley, David W., E-mail: david.hedley@uhn.ca [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medical Biophysics University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medicine, University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, 610 University Ave., Toronto, ON M5G2M9 (Canada)

2014-02-26

The unusually dense stroma of pancreatic cancers is thought to play an important role in their biological aggression. The presence of hypoxia is also considered an adverse prognostic factor. Although it is usually assumed that this is the result of effects of hypoxia on the epithelial component, it is possible that hypoxia exerts indirect effects via the tumor stroma. We therefore measured hypoxia in the stroma of a series of primary pancreatic cancer xenografts. Nine patient-derived pancreatic xenografts representing a range of oxygenation levels were labeled by immunohistochemistry for EF5 and analyzed using semi-automated pattern recognition software. Hypoxia in the tumor and stroma was correlated with tumor growth and metastatic potential. The extent of hypoxia varied from 1%–39% between the different models. EF5 labeling in the stroma ranged from 0–20% between models, and was correlated with the level of hypoxia in the tumor cell area, but not microvessel density. Tumor hypoxia correlated with spontaneous metastasis formation with the exception of one hypoxic model that showed disproportionately low levels of hypoxia in the stroma and was non-metastatic. Our results demonstrate that hypoxia exists in the stroma of primary pancreatic cancer xenografts and suggest that stromal hypoxia impacts the metastatic potential.

Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: buscail.l@chu-toulouse.fr [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)

2011-02-24

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.

Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

International Nuclear Information System (INIS)

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

uPAR-controlled oncolytic adenoviruses eliminate cancer stem cells in human pancreatic tumors.

Science.gov (United States)

Sobrevals, Luciano; Mato-Berciano, Ana; Urtasun, Nerea; Mazo, Adela; Fillat, Cristina

2014-01-01

Pancreatic tumors contain cancer stem cells highly resistant to chemotherapy. The identification of therapies that can eliminate this population of cells might provide with more effective treatments. In the current work we evaluated the potential of oncolytic adenoviruses to act against pancreatic cancer stem cells (PCSC). PCSC from two patient-derived xenograft models were isolated from orthotopic pancreatic tumors treated with saline, or with the chemotherapeutic agent gemcitabine. An enrichment in the number of PCSC expressing the cell surface marker CD133 and a marked enhancement on tumorsphere formation was observed in gemcitabine treated tumors. No significant increase in the CD44, CD24, and epithelial-specific antigen (ESA) positive cells was observed. Neoplastic sphere-forming cells were susceptible to adenoviral infection and exposure to oncolytic adenoviruses resulted in elevated cytotoxicity with both Adwt and the tumor specific AduPARE1A adenovirus. In vivo, intravenous administration of a single dose of AduPARE1A in human-derived pancreatic xenografts led to a remarkable anti-tumor effect. In contrast to gemcitabine AduPARE1A treatment did not result in PCSC enrichment. No enrichment on tumorspheres neither on the CD133(+) population was detected. Therefore our data provide evidences of the relevance of uPAR-controlled oncolytic adenoviruses for the elimination of pancreatic cancer stem cells. © 2013.

Magnetic resonance imaging in the diagnosis of pancreatic diseases

International Nuclear Information System (INIS)

Yamaguchi, Taketo; Ebara, Masaaki; Saisho, Hiromitsu

1987-01-01

Fifty patients with various pancreatic diseases and 22 without pancreatic disease were studied by a magnetic resonance imaging (MRI) to compare its diagnostic capability with that by an X-ray CT scan. To differentiate pancreas clearly from the bowel, an iron solution was orally administered as contrast medium, resulting in a usefullness, especially to differentiate the head of the pancreas from the bowel. The head of the pancreas could be identified in 89 % after iron solution but only in 62 % without it. MRI was inferior to CT in terms of visualization of the pancreatic duct and pancreatic stones, but was superior in a visualization of vessels around the pancreas. MRI was considered to be useful for a detection of carcinoma infiltrating to vessels. Pancreatic carcinoma was differentiated from chronic pancreatitis in terms of a local enlargement and disappearance of fat around the pancreas shown on MRI findings. The present results also showed statistically significant differences in T 1 relaxation times among normal pancreas, chronic pancreatitis and pancreatic carcinoma, suggesting a useful marker in the differential diagnosis of pancreatic diseases. (author)

Primary pancreatic non-Hodgkin's lymphoma

Directory of Open Access Journals (Sweden)

Čolović Nataša

2005-01-01

Full Text Available Diffuse large-cell B lymphoma of the pancreas is a rare disease, representing less than 1% of all non-Hodgkin's lymphomas and less than 0.9% of all malignant tumors of the pancreas. About 150 cases of the disease have been observed so far. The tumors are more frequent in the head of the pancreas then in other parts of the organ. They are usually larger (average size of 8 cm and are non-resectionable. As a rule, exact diagnosis is based on the histology and the immunohistology of the specimen taken during open surgery performed for general diagnosis of the pancreatic tumor. Very rarely can a very reliable and experienced cytopathologist establish a proper diagnosis based on material obtained from a fine needle biopsy. The disease usually responds positively to immunochemotherapy according to protocol R-CHOP. Occasionally, additional radiotherapy may be required. We present two women, 66 and 49 years old, in whom a diagnosis of large-cell B lymphoma of the pancreas was established, based on the histology and the immunohistochemistry of a specimen taken during open surgery performed in order to remove pancreatic tumors, which turned out to be non-resectionable. After immunochemotherapy, the symptoms disappeared and the tumors shrank, in one patient after additional radiotherapy. The authors would like to point out the importance of a proper histological diagnosis, which permitted the application of immunochemotherapy alone or together with additional radiotherapy with at least temporarily favorable results.

A pancreatic neuroendocrine tumor diagnosed during the ...

African Journals Online (AJOL)

Pancreatic neuroendocrine tumors (PNET) are increasingly being discovered. A case of PNET diagnosed and treated during the management of acute appendicitis is presented and discussed. The importance of imaging modalities in patients with acute abdominal pain is emphasized. To the best our knowledge, this is the ...

Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

Science.gov (United States)

Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

2003-01-01

Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor.

Science.gov (United States)

Jilesen, Anneke P J; van Eijck, Casper H J; Busch, Olivier R C; van Gulik, Thomas M; Gouma, Dirk J; van Dijkum, Els J M Nieveen

2016-03-01

Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of pancreatic insufficiency were analyzed. Retrospective all resected patients from two academic hospitals in The Netherlands between 1992 and 2013 were included. Postoperative complications were scored by both ISGPS and Clavien-Dindo criteria. Based on tumor location, operations were compared. Independent risk factors for overall complications were identified. During long-term follow-up, pancreatic insufficiency and recurrent disease were analyzed. Tumor enucleation was performed in 60/205 patients (29%), pancreatoduodenectomy in 65/205 (31%), distal pancreatectomy in 72/205 (35%) and central pancreatectomy in 8/205 (4%) patients. Overall complications after tumor enucleation of the pancreatic head and pancreatoduodenectomy were comparable, 24/35 (69%) versus 52/65 (80%). The same was found after tumor enucleation and resection of the pancreatic tail (36 vs.58%). Number of re-interventions and readmissions were comparable between all operations. After pancreatoduodenectomy, 33/65 patients had lymph node metastasis and in patients with tumor size ≤2 cm, 55% had lymph node metastasis. Tumor in the head and BMI ≥25 kg/m(2) were independent risk factors for complications after enucleation. During follow-up, incidence of exocrine and endocrine insufficiency was significant higher after pancreatoduodenectomy (resp. 55 and 19%) compared to the tumor enucleation and distal pancreatectomy (resp. 5 and 7% vs. 8 and 13%). After tumor enucleation 19% developed recurrent disease. Since the complication rate, need for re-interventions and readmissions were comparable for all resections, tumor enucleation may be regarded as high risk. Appropriate operation should be based on tumor size, location, and

Indications for surgical resection of benign pancreatic tumors; Indikationen zur chirurgischen Therapie benigner Pankreastumoren

Energy Technology Data Exchange (ETDEWEB)

Isenmann, R.; Henne-Bruns, D. [Chirurgische Universitaetsklinik, Klinik fuer Allgemein-, Viszeral- und Transplantationschirurgie, Ulm (Germany)

2008-08-15

Benign pancreatic tumors should undergo surgical resection when they are symptomatic or - in the case of incidental discovery - bear malignant potential. This is the case for the majority of benign pancreatic tumors, especially for intraductal papillary mucinous neoplasms or mucinous cystic adenomas. In addition, resection is indicated for all tumors where preoperative diagnostic fails to provide an exact classification. Several different operative techniques are available. The treatment of choice depends on the localization of the tumor, its size and on whether there is evidence of malignant transformation. Partial duodenopancreatectomy is the oncological treatment of choice for tumors of the pancreatic head whereas for tumors of the pancreatic tail a left-sided pancreatectomy is appropriate. Middle pancreatectomy or duodenum-preserving resection of the pancreatic head is not a radical oncologic procedure. They should only be performed in cases of tumors without malignant potential. (orig.) [German] Die Indikationsstellung zur Resektion benigner Pankreastumoren ist gegeben, wenn es sich um einen symptomatischen Tumor handelt oder - bei einem Zufallsbefund - um einen Tumor mit Potenzial zur malignen Entartung. Dies besteht bei der Mehrzahl der benignen Pankreastumoren, insbesondere bei der intraduktalen papillaeren muzinoesen Neoplasie (IPMN) oder muzinoesen Zystadenomen. Operativer Abklaerung beduerfen auch Tumoren, die unter Ausschoepfung aller diagnostischer Moeglichkeiten nicht eindeutig klassifizierbar sind. An chirurgischen Therapieverfahren stehen verschiedene Techniken zur Verfuegung. Die Wahl des Verfahren haengt von der Groesse und Lokalisation des Tumors ab und von der Frage, ob eine maligne Entartung bereits stattgefunden hat. Das onkologisch korrekte Standardresektionsverfahren bei Tumoren des Pankreaskopfes ist die partielle Duodenopankreatektomie, bei Tumoren des Pankreasschwanzes die Pankreaslinksresektion. Eine segmentale Resektion des

Acute pancreatitis following granulosa cell tumor removal in a mare

Science.gov (United States)

Gomez, Diego E.; Radtke, Catherine L.; Russell, Lauren A.; Lopez, Alfonso; Wichtel, Maureen W.

2015-01-01

Acute pancreatitis is a rare disease in horses and is often associated with gastrointestinal disorders. Accurate diagnosis is challenging due to the presence of nonspecific clinical signs. This case represents the first documentation of acute pancreatitis in a horse following surgery of the reproductive tract. PMID:26483579

Autoimmune pancreatitis: An illustrated guide to diagnosis

International Nuclear Information System (INIS)

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

2013-01-01

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

[Clinical significance of the tests used in the diagnosis of pancreatic diseases].

Science.gov (United States)

Lenti, G; Emanuelli, G

1976-11-14

Different methods available for investigating patients for pancreatic disease are discussed. They first include measurement of pancreatic enzymes in biological fluids. Basal amylase and/or lipase in blood are truly diagnostic in acute pancreatitis but their utility is low in chronic pancreatic diseases. Evocative tests have been performed to increase the sensitivity of blood enzyme measurement. The procedure is based on enzyme determination following administration of pancreozymin and secretin, and offers a valuable aid in diagnosis of chronic pancreatitis and cancer of the pancreas. They are capable of discerning pancreatic lesions but are not really discriminatory because similar changes are observed in both diseases. The measurement of urinary enzyme levels in patients with acute pancreatitis is a sensitive indicator of disease. The urinary amylase excretion rises to abnormal levels and persists at significant values for a longer period of time than the serum amylase in acute pancreatitis. The fractional urinary amylase escretion seems to be more sensitive than daily urinary measurement. The pancreatic exocrin function can be assessed by examining the duodenal contents after intravenous administration of pancreozymin and secretin. Different abnormal secretory patterns can be determinated. Total secretory deficiency is observed in patients with obstruction of excretory ducts by tumors of the head of the pancreas and in the end stage of chronic pancreatitis. Low volume with normal bicarbonate and enzyme concentration is another typical pattern seen in neoplastic obstruction of escretory ducts. In chronic pancreatitis the chief defect is the inability of the gland to secrete a juice with a high bicarbonate concentration; but in the advanced stage diminution of enzyme and volume is also evident. Diagnostic procedures for pancreatic diseases include digestion and absorption tests. The microscopic examination and chemical estimation of the fats in stool specimens in

Radiation diagnosis of different forms of acute pancreatitis

International Nuclear Information System (INIS)

Stashuk, G.A.; Dubrova, S.Eh.; Emel'yanova, L.N.; Tripatkhi, S.

1999-01-01

Using the data on 123 patient with different forms of pancreatitis the ultrasonic and computerized tomographic semiotics of these states is described. It is shown that ultrasonography and computerized tomography are highly informative in diagnosis of different forms of the disease and its complications. Both methods not only assess the pancreatic parenchyma state, the spreading of process into adjacent anatomic structures, but also the dynamic control and perform diagnostic and treatment measures under visual control [ru

Selective tumor irradiation without normal tissue exposure in non-resectable pancreatic cancer

International Nuclear Information System (INIS)

Order, S.E.; Siegel, J.A.; Lustig, R.A.; Principato, L.S.; Zeiger, L.; Lang, P.; Wallner, P.E.

1996-01-01

Purpose: To determine the maximum dose of colloidal 32 P that may be interstitially infused in non-resectable pancreatic cancer prior to external radiation [60 Gy + 5FU]. Materials and Methods: Forty-seven patients with non-resectable pancreatic cancer with and without metastasis entered a dose escalation Phase I study beginning at a specific activity of 4 mCi. Under CT guidance the center of the pancreatic tumor was localized by computer the distance and angle from a grid on the abdomen to the center of the tumor mass determined. Three drugs were infused: 4 mg Decadron - 10 minute delay; 2.5 million particles of macroaggregated albumin [MAA]; and with final dose escalation two infusions of 30 mCi colloidal chromic phosphate 32 P [3.5 ml] followed by a needle cleansing dose of .25 ml of macroaggregated albumin. Bremsstrahlung scans on three separate days determined tumor localization and radiation dose. One week later infusional brachytherapy was repeated, that is Decadron, MAA, colloidal 32 P, followed by three additional bremsstrahlung scans. Two weeks later a course of 60 Gy external radiation was initiated with four doses of 5FU [500 mg] administered with every other radiation treatment day. Toxicity was recorded using RTOG cooperative group criteria. CA19-9 and CEA were used as biomarkers to evaluate tumor progression or remission in conjunction with CT scans and clinical course. Results: Completion of the Phase I study was limited, not by toxicity, but by the volume of colloidal 32 P that could be infused into the stroma of the tumor, i.e. 3.5 ml containing 30 mCi. No significant (grade 3-4) toxicity occurred in patients with pancreatic cancer only. Patients without metastasis had reduction and, in some cases, elimination of CA19-9, etc. The median survival in 28 patients within the Phase I non-resectable pancreas cancer study without metastasis was one year in 19 patients; with metastasis was 6.9 months. The two infusions of 30 mCi 32 P ordinarily yields a

Surgical strategies for treatment of malignant pancreatic tumors: extended, standard or local surgery?

Directory of Open Access Journals (Sweden)

Jacob Dietmar

2008-11-01

Full Text Available Abstract Tumor related pancreatic surgery has progressed significantly during recent years. Pancreatoduodenectomy (PD with lymphadenectomy, including vascular resection, still presents the optimal surgical procedure for carcinomas in the head of pancreas. For patients with small or low-grade malignant neoplasms, as well as small pancreatic metastases located in the mid-portion of pancreas, central pancreatectomy (CP is emerging as a safe and effective option with a low risk of developing de-novo exocrine and/or endocrine insufficiency. Total pancreatectomy (TP is not as risky as it was years ago and can nowadays safely be performed, but its indication is limited to locally extended tumors that cannot be removed by PD or distal pancreatectomy (DP with tumor free surgical margins. Consequently, TP has not been adopted as a routine procedure by most surgeons. On the other hand, an aggressive attitude is required in case of advanced distal pancreatic tumors, provided that safe and experienced surgery is available. Due to the development of modern instruments, laparoscopic operations became more and more successful, even in malignant pancreatic diseases. This review summarizes the recent literature on the abovementioned topics.

Effects of Low Intensity Continuous Ultrasound (LICU on Mouse Pancreatic Tumor Explants

Directory of Open Access Journals (Sweden)

Despina Bazou

2017-12-01

Full Text Available This paper describes the effects of low intensity continuous ultrasound (LICU on the inflammatory response of mouse pancreatic tumor explants. While there are many reports focusing on the application of low-intensity pulsed ultrasound (LIPUS on cell cultures and tissues, the effects of continuous oscillations on biological tissues have never been investigated. Here we present an exploratory study of the effects induced by LICU on mouse pancreatic tumor explants. We show that LICU causes significant upregulation of IFN-γ, IL-1β, and TNF-α on tumor explants. No detectable effects were observed on tumor vasculature or collagen I deposition, while thermal and mechanical effects were not apparent. Tumor explants responded as a single unit to acoustic waves, with spatial pressure variations smaller than their size.

MUC1 enhances tumor progression and contributes toward immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma.

Science.gov (United States)

Tinder, Teresa L; Subramani, Durai B; Basu, Gargi D; Bradley, Judy M; Schettini, Jorge; Million, Arefayene; Skaar, Todd; Mukherjee, Pinku

2008-09-01

MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune-competent host. Significant enhancement in the development of pancreatic intraepithelial preneoplastic lesions and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and IDO compared with PDA mice lacking MUC1, especially during early stages of tumor development. The increased proinflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease, which in turn regulate the immune responses. Thus, the mouse model is ideally suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer.

MUC1 enhances tumor progression and contributes towards immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma

Science.gov (United States)

Tinder, Teresa L.; Subramani, Durai B.; Basu, Gargi D.; Bradley, Judy M.; Schettini, Jorge; Million, Arefayene; Skaar, Todd

2008-01-01

MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune competent host. Significant enhancement in the development of pancreatic intraepithelial pre-neoplastic lesions (PanINs) and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and indoleamine 2,3, dioxygenase compared to PDA mice lacking MUC1, especially during early stages of tumor development. The increased pro-inflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease which in turn regulate the immune responses. Thus, the mouse model is ideally-suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer. PMID:18713982

Computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatography in the diagnosis of pancreatic disease

International Nuclear Information System (INIS)

Foley, W.D.; Stewart, E.T.; Lawson, T.L.; Maher, L.; Unger, G.F.; Geenan, J.; Loguidice, J.

1980-01-01

A prospective study was performed comparing the sensitivity of computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of pancreatic disease. Forty patients with suspected pancreatic carcinoma, acute recurrent or chronic pancreatitis, and/or jaundice were studied. CT was the most sensitive study in evaluation of pancreatitis. ERCP was most accurate in evaluation of pancreatic malignancy. Ultrasonography was the least sensitive method in detecting pancreatic disease and dilatation of the extrahepatic biliary ducts. (orig.) [de

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

Science.gov (United States)

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.

Differential Diagnosis of the pancreatic disease : significance of perivascular changes at celiac trunk and superior mesenteric artery on CT

Energy Technology Data Exchange (ETDEWEB)

Kwon, Ryang; Kim, Ki Whang; Yu, Jeong Sik; Kim, Ji Hyung; Kim, Dong Guk; Lee, Sung Il; Ahn, Chang Soo; Oh, Sei Jung [Yonsei Univ., Seoul (Korea, Republic of). Coll. of Medicine; Kim, Young Hwan [Sanggye Paik Hospital, Seoul (Korea, Republic of)

1998-03-01

The purpose of this paper is to classify perivascular change in the celiac trunk and SMA occurring in pancreatic disease and to evaluate its significance in differential diagnosis. In 73 patients with pancreatic disease (42, acute pancreatitis; 14, chronic pancreatitis; 17, pancreatic cancer) abdominal CT findings were retrospectively reviewed. We defined infiltration as linear or irregular density and thickening as presence of a soft tissue mantle surrounding the vessel, and statistically evaluated the usefulness of these factors for the differential diagnosis of pancreatic diseases. Thickening of the celiac trunk and SMA is a valuable finding in the differential diagnosis of pancreatic inflammatory disease and pancreatic cancer. When applied to the differential diagnosis of pancreatic disease, perivascular change should be classified as either infiltration or thickening. (author). 10 refs., 1 tab., 2 figs.

Differential Diagnosis of the pancreatic disease : significance of perivascular changes at celiac trunk and superior mesenteric artery on CT

International Nuclear Information System (INIS)

Kwon, Ryang; Kim, Ki Whang; Yu, Jeong Sik; Kim, Ji Hyung; Kim, Dong Guk; Lee, Sung Il; Ahn, Chang Soo; Oh, Sei Jung

1998-01-01

The purpose of this paper is to classify perivascular change in the celiac trunk and SMA occurring in pancreatic disease and to evaluate its significance in differential diagnosis. In 73 patients with pancreatic disease (42, acute pancreatitis; 14, chronic pancreatitis; 17, pancreatic cancer) abdominal CT findings were retrospectively reviewed. We defined infiltration as linear or irregular density and thickening as presence of a soft tissue mantle surrounding the vessel, and statistically evaluated the usefulness of these factors for the differential diagnosis of pancreatic diseases. Thickening of the celiac trunk and SMA is a valuable finding in the differential diagnosis of pancreatic inflammatory disease and pancreatic cancer. When applied to the differential diagnosis of pancreatic disease, perivascular change should be classified as either infiltration or thickening. (author). 10 refs., 1 tab., 2 figs

Magnetic resonance (MR) in the diagnosis of pancreatic disease

International Nuclear Information System (INIS)

Anacker, H.; Rupp, N.; Reiser, M.; Technische Univ. Muenchen

1984-01-01

New methods of examination are measured in terms of the efficiency of their predecessors. The introduction of endoscopic retrograde cholangiopancreatography (ERCP) and computerised tomography (CT) constituted a turning point in the diagnosis of pancreatic disease. In this incipient stages as a clinical diagnostic method, the question is raised whether or not there is evidence that magnetic resonance (MR) can supplement, improve upon or replace the customary methods. It must, however, be taken into account that the technical development of MR is still in progress and that clinical experience with MR in the diagnosis of pancreatic disease, as in other areas, is still insufficient. At this point it is only possible to survey the trends. (orig.)

Immunohistochemical study of tumor markers (CEA, TPA, CA19-9, POA and Ferritin) and pancreatic exocrine enzymes(Amylase and Elastase 1) in pancreatic tumors

OpenAIRE

脇谷, 勇夫

1987-01-01

The distribution of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), carbohydrate antigen 19-9 (CA19-9), pancreatic oncofetal antigen (POA), Ferritin, Amylase and Elastase 1 was studied immunohistochemically using an immunoperoxidase method in 26 conventional histopathologic sections of pancreatic tumor. CEA and CA19-9 were regarded as markers secreted into the glandular lumina from cancer cells, but TPA and POA were not. The expression of these markers was different from one...

Pancreatic candidiasis that mimics a malignant pancreatic cystic tumor on magnetic resonance imaging: A case report in an immunocompetent patient

International Nuclear Information System (INIS)

Seong, Min Jung; Kang, Tae Wook; Ha, Sang Yun

2015-01-01

Candida is a commensal organism that is frequently found in the human gastrointestinal tract. It is the most common organism that causes pancreatic fungal infections. However, magnetic resonance imaging findings of Candida infection in the pancreas have not been described. We report imaging findings of pancreatic candidiasis in a patient in immunocompetent condition. It presented as a multi-septated cystic mass with a peripheral solid component in the background of pancreatitis and restricted diffusion on diffusion-weighted image that mimicked a malignant pancreatic cystic tumor

Pancreatic candidiasis that mimics a malignant pancreatic cystic tumor on magnetic resonance imaging: A case report in an immunocompetent patient

Energy Technology Data Exchange (ETDEWEB)

Seong, Min Jung; Kang, Tae Wook; Ha, Sang Yun [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2015-12-15

Candida is a commensal organism that is frequently found in the human gastrointestinal tract. It is the most common organism that causes pancreatic fungal infections. However, magnetic resonance imaging findings of Candida infection in the pancreas have not been described. We report imaging findings of pancreatic candidiasis in a patient in immunocompetent condition. It presented as a multi-septated cystic mass with a peripheral solid component in the background of pancreatitis and restricted diffusion on diffusion-weighted image that mimicked a malignant pancreatic cystic tumor.

Diagnosis and classification of pancreatic and duodenal injuries in emergency radiology.

Science.gov (United States)

Linsenmaier, Ulrich; Wirth, Stefan; Reiser, Maximilian; Körner, Markus

2008-10-01

Pancreatic and duodenal injuries after blunt abdominal trauma are rare; however, delays in diagnosis and treatment can significantly increase morbidity and mortality. Multidetector computed tomography (CT) has a major role in early diagnosis of pancreatic and duodenal injuries. Detecting the often subtle signs of injury with whole-body CT can be difficult because this technique usually does not include a dedicated protocol for scanning the pancreas. Specific injury patterns in the pancreas and duodenum often have variable expression at early posttraumatic multidetector CT: They may be hardly visible, or there may be considerable exudate, hematomas, organ ruptures, or active bleeding. An accurate multidetector CT technique allows optimized detection of subtle abnormalities. In duodenal injuries, differentiation between a contusion of the duodenal wall or mural hematoma and a duodenal perforation is vital. In pancreatic injuries, determination of involvement of the pancreatic duct is essential. The latter conditions require immediate surgical intervention. Use of organ injury scales and a surgical classification adapted for multidetector CT enables classification of organ injuries for trauma scoring, treatment planning, and outcome control. In addition, multidetector CT reliably demonstrates potential complications of duodenal and pancreatic injuries, such as posttraumatic pancreatitis, pseudocysts, fistulas, exudates, and abscesses. (c) RSNA, 2008.

18F-fluorodeoxyglucose positron tomography is useful in evaluating the efficacy of multidisciplinary treatments for so-called borderline unresectable pancreatic head cancers

International Nuclear Information System (INIS)

Murakami, Makoto; Katayama, Kanji; Yamaguchi, Akio; Iida, Atsushi; Goi, Takanori; Hirono, Yasuo; Nagano, Hideki; Koneri, Kenji

2011-01-01

Currently, computed tomography (CT) is widely used to evaluate the efficacy of treatments on tumor regression in unresectable pancreatic head carcinomas. Recently, 18 F-fluorodeoxyglucose positron emission tomography (PET) examination has been used for the initial diagnosis of pancreatic tumors, for diagnosis of distant metastasis, and for recurrences of pancreatic carcinomas. PET has also been used for the qualitative diagnosis of existing tumors. The current study was designed to observe if PET examination can be used to gauge the efficacy of multidisciplinary treatments, and to estimate the prognosis for unresectable pancreatic head carcinomas in similar clinical stages and during therapy. This was a prospective cohort study and included 18 cases. All cases were unresectable pancreatic head cancers diagnosed as TNM classification stage 3, and had undergone identical multidisciplinary treatment regimens. The level of tumor markers, tumor-size reduction, and maximum standardized uptake values (SUV max ) were correlated with prognosis. Pearson's correlation and Kaplan-Meyer survival rate curves were used for statistical analysis. Tumor-size reduction in CTs and the transition of tumor markers were not related to patient prognosis. Cases in which post-treatment SUV max values were reduced to <3.0 were correlated with a more favorable prognosis and demonstrated extended survival rates. PET examination can be used to estimate the prognosis of unresectable pancreatic head carcinomas which have undergone multidisciplinary treatments. (author)

Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

Science.gov (United States)

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

2017-02-23

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

Two-stage resection of a bilateral pheochromocytoma and pancreatic neuroendocrine tumor in a patient with von Hippel-Lindau disease: A case report

Directory of Open Access Journals (Sweden)

Yutaka Endo

Full Text Available Introduction: von Hippel-Lindau disease (vHL disease is a hereditary disease in which tumors and cysts develop in many organs, in association with central nervous system hemangioblastomas, pheochromocytomas, and pancreatic tumors. We herein report a case of vHL disease (type 2A associated with bilateral pheochromocytomas, pancreatic neuroendocrine tumors (PNET, and cerebellar hemangioblastomas treated via pancreatectomy after adrenalectomy. Case presentation: A 51-year-old woman presented with a cerebellar tumor, bilateral hypernephroma, and pancreatic tumor detected during a medical checkup. 18F-fluorodeoxyglucose positron emission tomography–computed tomography revealed a bilateral adrenal gland tumor and a tumor in the head of the pancreas, while an abdominal computed tomography examination revealed a 30-mm tumor with strong enhancement in the head of the pancreas. Cranial magnetic resonance imaging showed a hemangioblastoma in the cerebellum. Therefore, a diagnosis of vHL disease (type 2A was made. Her family medical history included renal cell carcinoma in her father and bilateral adrenal pheochromocytoma and spinal hemangioblastoma in her brother. A detailed examination of endocrine function showed that the adrenal mass was capable of producing catecholamine. Treatment of the pheochromocytoma was prioritized, and therefore, laparoscopic left adrenalectomy and subtotal resection of the right adrenal gland were performed. Once the postoperative steroid levels were replenished, subtotal stomach-preserving pancreatoduodenectomy was performed for the PNET. After a good postoperative course, the patient was discharged in remission on the 11th day following surgery. Histopathological examination findings indicated NET G2 (MIB-1 index 10–15% pT3N0M0 Stage II A and microcystic serous cystadenoma throughout the resected specimen. The patient is scheduled to undergo treatment for the cerebellar hemangioblastoma. Conclusion: A two-staged resection

Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis.

Directory of Open Access Journals (Sweden)

Hiromitsu Ito

Full Text Available Patients with pancreatic cancer typically develop tumor invasion and metastasis in the early stage. These malignant behaviors might be originated from cancer stem cells (CSCs, but the responsible target is less known about invisible CSCs especially for invasion and metastasis. We previously examined the proteasome activity of CSCs and constructed a real-time visualization system for human pancreatic CSCs. In the present study, we found that CSCs were highly metastatic and dominantly localized at the invading tumor margins in a liver metastasis model. Microarray and siRNA screening assays showed that doublecortin-like kinase 1 (DCLK1 was predominantly expressed with histone modification in pancreatic CSCs with invasive and metastatic potential. Overexpression of DCLK1 led to amoeboid morphology, which promotes the migration of pancreatic cancer cells. Knockdown of DCLK1 profoundly suppressed in vivo liver metastasis of pancreatic CSCs. Clinically, DCLK1 was overexpressed in the metastatic tumors in patients with pancreatic cancer. Our studies revealed that DCLK1 is essential for the invasive and metastatic properties of CSCs and may be a promising epigenetic and therapeutic target in human pancreatic cancer.

Molecular biology of pancreatic cancer.

Science.gov (United States)

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.

Radiologic features of cystic, endocrine and other pancreatic neoplasms

International Nuclear Information System (INIS)

Balci, N. Cem; Semelka, Richard C.

2001-01-01

This article presents imaging features of cystic, endocrine and other pancreatic neoplasms. Microcystic adenoma which is composed of small cysts ( 2 cm) are accounted for mucinous cystic neoplasms, its variant along pancreatic duct is ductectatic mucinous cystic neoplasm. Endocrine tumors of pancreas are hypervascular and can be depicted on early dynamic enhanced crosssectional imaging modalities or on angiography when they are <1 cm. Pancreatic metastases and lymphomas are rare neoplasms which should also be included in differential diagnosis for pancreatic masses

Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts.

Science.gov (United States)

José, Anabel; Sobrevals, Luciano; Miguel Camacho-Sánchez, Juan; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

2013-01-01

Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

99mTc-HYNIC-TOC imaging in the evaluation of pancreatic masses which are potential neuroendocrine tumors.

Science.gov (United States)

Qiao, Zhen; Zhang, Jingjing; Jin, Xiaona; Huo, Li; Zhu, Zhaohui; Xing, Haiqun; Li, Fang

2015-05-01

The aim of this investigation was to determine the accuracy of the findings and the diagnoses of Tc-hydrazinonicotinyl-Tyr3-octreotide scan (Tc-HYNIC-TOC imaging) in patients with pancreatic masses which were potential neuroendocrine tumors. Records of total 20 patients with pancreatic masses were retrospectively reviewed. All of the patients had been revealed by abdominal contrast CT and possibility of neuroendocrine tumors could not be excluded by CT imaging before Tc-HYNIC-TOC imaging. Tc-HYNIC-TOC imaging was performed at 1 and 4 hours post-tracer injection, and SPECT/CT images of the abdomen were also acquired. The image findings were compared to final diagnoses which were made from pathological examination. Among all 20 pancreatic masses evaluated, there were 16 malignant lesions which included 1 ductal adenocarcinoma and 15 neuroendocrine tumors. Tc-HYNIC-TOC imaging identified 14 of 15 pancreatic neuroendocrine tumors and excluded 4 of 5 lesions which were not neuroendocrine tumors. The overall sensitivity, specificity, and accuracy was therefore 93.3% (14 of 15), 80% (4 of 5), and 90.0% (18 of 20), respectively, in our patient population. Tc-HYNIC-TOC imaging provides reasonable accuracy in the evaluation pancreatic mass suspected to be neuroendocrine tumors.

MRI-based tumor motion characterization and gating schemes for radiation therapy of pancreatic cancer

International Nuclear Information System (INIS)

Heerkens, Hanne D.; Vulpen, Marco van; Berg, Cornelis A.T. van den; Tijssen, Rob H.N.; Crijns, Sjoerd P.M.; Molenaar, Izaak Q.; Santvoort, Hjalmar C. van; Reerink, Onne; Meijer, Gert J.

2014-01-01

Background and purpose: To characterize pancreatic tumor motion and to develop a gating scheme for radiotherapy in pancreatic cancer. Materials and methods: Two cine MRIs of 60 s each were performed in fifteen pancreatic cancer patients, one in sagittal direction and one in coronal direction. A Minimum Output Sum of Squared Error (MOSSE) adaptive correlation filter was used to quantify tumor motion in craniocaudal, lateral and anteroposterior directions. To develop a gating scheme, stability of the breathing phases was examined and a gating window assessment was created, incorporating tumor motion, treatment time and motion margins. Results: The largest tumor motion was found in craniocaudal direction, with an average peak-to-peak amplitude of 15 mm (range 6–34 mm). Amplitude of the tumor in the anteroposterior direction was on average 5 mm (range 1–13 mm). The least motion was seen in lateral direction (average 3 mm, range 2–5 mm). The end exhale position was the most stable position in the breathing cycle and tumors spent more time closer to the end exhale position than to the end inhale position. On average, a margin of 25% of the maximum craniocaudal breathing amplitude was needed to achieve full target coverage with a duty cycle of 50%. When reducing the duty cycle to 50%, a margin of 5 mm was sufficient to cover the target in 11 out of 15 patients. Conclusion: Gated delivery for radiotherapy of pancreatic cancer is best performed around the end exhale position as this is the most stable position in the breathing cycle. Considerable margin reduction can be established at moderate duty cycles, yielding acceptable treatment efficiency. However, motion patterns and amplitude do substantially differ between individual patients. Therefore, individual treatment strategies should be considered for radiotherapy in pancreatic cancer

Low accuracy of tumor markers for diagnosing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 patients

NARCIS (Netherlands)

de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

2013-01-01

Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

Low Accuracy of Tumor Markers for Diagnosing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 Patients

NARCIS (Netherlands)

de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

2013-01-01

Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

Pancreatic Serous Cystadenoma with Compression of the Main Pancreatic Duct: An Unusual Entity

Directory of Open Access Journals (Sweden)

Stéphanie Truant

2011-01-01

Full Text Available Serous cystadenoma is a common benign neoplasm that can be managed without surgery in asymptomatic patients provided that the diagnosis is certain. We describe a patient, whose pancreatic cyst exhibited a radiological appearance distinct from that of typical serous cystadenoma, resulting in diagnostic difficulties. CT and MRI showed a 10 cm-polycystic tumor with upstream dilatation of the main pancreatic duct (MPD, suggestive of intraductal papillary mucinous tumor (IPMT. Ultrasonographic aspect and EUS-guided fine-needle aspiration gave arguments for serous cystadenoma. ERCP showed a communication between cysts and the dilated MPD, compatible with IPMT. The patient underwent left pancreatectomy with splenectomy. Pathological examination concluded in a serous cystadenoma, with only a ductal obstruction causing proximal dilatation.

Cystic pancreatic neuroendocrine tumors (cPNETs: a systematic review and meta-analysis of case series

Directory of Open Access Journals (Sweden)

Luis Hurtado-Pardo

Full Text Available Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387 were sporadic tumors and 10.3% (n = 40 corresponded to multiple endocrine neoplasia type 1. Were diagnosed incidentally 44.6% (n = 135. Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338, and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb, and 12.2% were advanced (III-IV. Disease-free survival at 5 years in stages (I-IIIa and (IIIb-IV was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001 in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5% and multifocal (28.1% tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.

Systematic review on the role of serum tumor markers in the detection of recurrent pancreatic cancer.

Science.gov (United States)

Daamen, Lois A; Groot, Vincent P; Heerkens, Hanne D; Intven, Martijn P W; van Santvoort, Hjalmar C; Molenaar, I Quintus

2018-04-01

Biomarker testing can be helpful to monitor disease progression after resection of pancreatic cancer. This systematic review aims to give an overview of the literature on the diagnostic value of serum tumor markers for the detection of recurrent pancreatic cancer during follow-up. A systematic search was performed to 2 October 2017. All studies reporting on the diagnostic value of postoperatively measured serum biomarkers for the detection of pancreatic cancer recurrence were included. Data on diagnostic accuracy of tumor markers were extracted. Forest plots and pooled values of sensitivity and specificity were calculated. Four articles described test results of CA 19-9. A pooled sensitivity and specificity of respectively 0.73 (95% CI 0.66-0.80) and 0.83 (95% CI 0.73-0.91) were calculated. One article reported on CEA, showing a sensitivity of 50% and specificity of 65%. No other serum tumor markers were discussed for surveillance purposes in the current literature. Although testing of serum CA 19-9 has considerable limitations, CA 19-9 remains the most used serum tumor marker for surveillance after surgical resection of pancreatic cancer. Further studies are needed to assess the role of serum tumor marker testing in the detection of recurrent pancreatic cancer and to optimize surveillance strategies. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Computer-aided diagnosis of pancreatic and lung cancer

Directory of Open Access Journals (Sweden)

B. Luis Lancho Tofé

2008-12-01

Full Text Available When we talk about cancer diagnosis the most important thing is early diagnosis to prevent cancer cells from spreading. We may also consider the high cost of diagnostic tests. Our approach seeks to address both problems. It uses a software based on Bayesian networks that simulates the causeeffect relationships and gets the chance of suffering a pancreatic cancer or lung cancer. This software would support doctors and save a lot of time and resources.

Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor

NARCIS (Netherlands)

Jilesen, Anneke P. J.; van Eijck, Casper H. J.; Busch, Olivier R. C.; van Gulik, Thomas M.; Gouma, Dirk J.; van Dijkum, Els J. M. Nieveen

2016-01-01

Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of pancreatic

Spiral (Helical) computed tomographic imaging for the diagnosis of bile duct cancer. Vascular and pancreatic invasions

International Nuclear Information System (INIS)

Kon, Masanori

1997-01-01

The development of several imaging techniques for diagnosing bile duct cancer have improved, however, its diagnosis at the early stage is still difficult. We discuss the significance of the spiral (helical) computed tomography (SCT) imaging for the diagnosis of bile duct cancer at an early stage. We performed, as a preoperative examination, SCT under intravenous angiography (IV-SCT) for all cases, which included 233 cases of benign bile duct diseases, 42 cases of gallbladder cancer and 22 cases of bile duct cancer. The accuracy rate of diagnosis ability of 42 cases of gallbladder cancer by IV-SCT was 91%, and that of portal vein invasion was 91%. In the cases of bile duct cancer, IV-SCT showed destructive images of the bile duct wall and the tumor images invaded into the pancreatic parenchyma, in the cases of invasion at the splenic vein and confluence site of the portal vein, IV-SCT gave clearer 3D images than conventional angiography. The accuracy rate of diagnosing pancreatic invasion in bile duct cancer by IV-SCT was 80%. However, it is still difficult to determine completely the layer structures of the bile duct and the invasion into the walls along the long axis. As the future development of SCT for the diagnosis of bile duct cancer, we expect further progression of diagnosis ability of bile duct cancer and the invasion level by the applying high resolution thin-section CT images or endoscopical images of the luminal organs in examining the bile duct. (K.H.)

Computed tomographic criteria for differential diagnosis between exacerbation of focal chronic pancreatitis and carcinoma located in the head of the pancreas

International Nuclear Information System (INIS)

Ivanov, A.; Tonchev, Z.

1995-01-01

A group of 126 patients with CT-finding of tumor mass in the head of the pancreas is studied. Signs of acute exacerbation of focal chronic pancreatitis are found in 28 of them. Carcinoma of the head of pancreas is diagnosed in 98 patients. Surgical and histological verification is performed in 84 (86%) patients with carcinoma of the pancreas. In 77 (92%) cases the computed tomographic diagnosis coincides with the histological one, while in the remaining 7 (8%) it fails to coincide. The morphological and densitometric changes were analyzed with respect to their frequency. On account of the nonspecific character of the computed tomographic signs a symptom constellation is developed which facilitates the differential diagnosis of the acute exacerbation of focal pancreatitis and the carcinoma. The changes in density of lesions observed after application of contrast media were found to be of significant value. 16 refs., 6 figs. (author)

Retrograde cholangiopancreatography in the diagnosis of biliary and pancreatic duct diseases

International Nuclear Information System (INIS)

Vasil'ev, Yu.D.; Sedletskaya, T.N.

1980-01-01

Results of retrograde cannulation with the aid of flexible fibroduodenoscopes with subsequent introduction of a contrast substance into biliary and pancreatic ducts are presented. The investigation is carried out on 120 patients with different diseases of hepatopancreatoduodenal zone. The standard technique of X-ray examination has been applied permitting to obtain the most exhaustive information. Using retrograde cholangiopancreatography revealed have been choledocholithiasis, deformation of biliary ducts after surgical intervention, pancreatic cyst, tumor of the main pancreatic duct etc. Results of investigation of biliary and pancreatic ducts using retrograde cannulation are reaffirmed with the data of operations on biliary tract in 72 patients. Intraoperational cholangiography has been carried out on 36 of them during operation. An attempt to cannulate big duodenal papilla in 12 patients proved to be ineffective. No complications have been observed during examination

Multidetector computer tomography in the pancreatic adenocarcinoma assessment: an update

Directory of Open Access Journals (Sweden)

Vincenza Granata

2016-11-01

Full Text Available Abstract Ductal adenocarcinoma of the pancreas is one of the most aggressive forms of cancer, with only a minority of cases being resectable at the moment of their diagnosis. The accurate detection and characterization of pancreatic carcinoma is very important for patient management. Multidetector-row computed tomography (MDCT has become the cross-sectional modality of choice in the diagnosis, staging, treatment planning, and follow-up of patients with pancreatic tumors. However, approximately 11% of ductal adenocarcinomas still remain undetected at MDCT because of the lack of attenuation gradient between the lesion and the adjacent pancreatic parenchyma. In this systematic literature review we investigate the current evolution of the CT technique, limitations, and perspectives in the evaluation of pancreatic carcinoma.

Salinomycin nanoparticles interfere with tumor cell growth and the tumor microenvironment in an orthotopic model of pancreatic cancer.

Science.gov (United States)

Daman, Zahra; Faghihi, Homa; Montazeri, Hamed

2018-05-02

Recently, salinomycin (SAL) has been reported to inhibit proliferation and induce apoptosis in various tumors. The aim of this study was to deliver SAL to orthotopic model of pancreatic cancer by the aid of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The NPs were physico-chemically characterized and evaluated for cytotoxicity on luciferase-transduced AsPC-1 cells in vitro as well as implanted orthotopically into the pancreas of nude mice. SAL (3.5 mg/kg every other day) blocked tumor growth by 52% compared to the control group after 3 weeks of therapy. Western blotting of tumor protein extracts indicated that SAL treatment leads to up-regulation of E-cadherin, β-catenin, and transforming growth factor beta receptor (TGFβR) expressions in AsPC-1 orthotopic tumor. Noteworthy, immunofluorescence staining of adjacent tumor sections showed that treatment with SAL NPs cause significant apoptosis in the tumor cells rather than the stroma. Further investigations also revealed that TGFβR2 over-expression was induced in stroma cells after treatment with SAL NPs. These results highlight SAL-loaded PLGA NPs as a promising system for pancreatic cancer treatment, while the mechanistic questions need to be subsequently tested.

An Intra-Abdominal Desmoid Tumor, Embedded in the Pancreas, Preoperatively Diagnosed as an Extragastric Growing Gastrointestinal Stromal Tumor

Directory of Open Access Journals (Sweden)

Mari Mizuno

2017-04-01

Full Text Available A 45-year-old woman was found to have a pancreatic tumor by abdominal ultrasound performed for a medical check-up. Abdominal contrast-enhanced computed tomography showed a hypovascular tumor measuring 30 mm in diameter in the pancreatic tail. Endoscopic ultrasound-guided fine needle aspiration was performed. An extragastric growing gastrointestinal stromal tumor was thereby diagnosed preoperatively, and surgical resection was planned. Laparoscopic surgery was attempted but conversion to open surgery was necessitated by extensive adhesions, and distal pancreatectomy, splenectomy, and partial gastrectomy were performed. The histological diagnosis was an intra-abdominal desmoid tumor. A desmoid tumor is a fibrous soft tissue tumor arising in the fascia and musculoaponeurotic tissues. It usually occurs in the extremities and abdominal wall, and only rarely in the abdominal cavity. We experienced a case with an intra-abdominal desmoid tumor that was histologically diagnosed after laparotomy, which had been preoperatively diagnosed as an extragastric growing gastrointestinal stromal tumor. Although rare, desmoid tumors should be considered in the differential diagnosis of intra-abdominal tumors. Herein, we report this case with a literature review.

Diagnosis of mild chronic pancreatitis (Cambridge classification): comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography.

Science.gov (United States)

Sai, Jin-Kan; Suyama, Masafumi; Kubokawa, Yoshihiro; Watanabe, Sumio

2008-02-28

To investigate the usefulness of secretin injection-MRCP for the diagnosis of mild chronic pancreatitis. Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge Classification), using endoscopic retrograde cholangiopancreatography (ERCP) for comparison. The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44% and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver agreement (kappa statistics) concerning the diagnosis of an abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent. Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

Directory of Open Access Journals (Sweden)

Robert Grützmann

2010-11-01

Full Text Available Pancreatic neuroendocrine tumors (PNETs are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET or by symptoms related to tumor bulk effects (non-functional PNET. So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management.

Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

International Nuclear Information System (INIS)

Ehehalt, Florian; Franke, Ellen; Pilarsky, Christian; Grützmann, Robert

2010-01-01

Pancreatic neuroendocrine tumors (PNETs) are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET) or by symptoms related to tumor bulk effects (non-functional PNET). So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management

[Application of second generation dual-source computed tomography dual-energy scan mode in detecting pancreatic adenocarcinoma].

Science.gov (United States)

Xue, Hua-dan; Liu, Wei; Sun, Hao; Wang, Xuan; Chen, Yu; Su, Bai-yan; Sun, Zhao-yong; Chen, Fang; Jin, Zheng-yu

2010-12-01

To analyze the clinical value of multiple sequences derived from dual-source computed tomography (DSCT) dual-energy scan mode in detecting pancreatic adenocarcinoma. Totally 23 patients with clinically or pathologically diagnosed pancreatic cancer were enrolled in this retrospective study. DSCT (Definition Flash) was used and dual-energy scan mode was used in their pancreatic parenchyma phase scan (100kVp/230mAs and Sn140kVp/178mAs) . Mono-energetic 60kev, mono-energetic 80kev, mono-energetic 100kev, mono-energetic 120kev, linear blend image, non-linear blend image, and iodine map were acquired. pancreatic parenchyma-tumor CT value difference, ratio of tumor to pancreatic parenchyma, and pancreatic parenchyma-tumor contrast to noise ratio were calculated. One-way ANOVA was used for the comparison of diagnostic values of the above eight different dual-energy derived sequences for pancreatic cancer. The pancreatic parenchyma-tumor CT value difference, ratio of tumor to pancreatic parenchyma, and pancreatic parenchyma-tumor contrast to noise ratio were significantly different among eight sequences (P<0.05) . Mono-energetic 60kev image showed the largest parenchyma-tumor CT value [ (77.53 ± 23.42) HU] , and iodine map showed the lowest tumor/parenchyma enhancement ratio (0.39?0.12) and the largest contrast to noise ratio (4.08 ± 1.46) . Multiple sequences can be derived from dual-energy scan mode with DSCT via multiple post-processing methods. Integration of these sequences may further improve the sensitivity of the multislice spiral CT in the diagnosis of pancreatic cancer.

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

Science.gov (United States)

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.

Amenorrhea as a rare drug-related adverse event associated with everolimus for pancreatic neuroendocrine tumors.

Science.gov (United States)

Kawaguchi, Yoshiaki; Maruno, Atsuko; Kawashima, Yohei; Ito, Hiroyuki; Ogawa, Masami; Mine, Tetsuya

2014-11-14

The patient was an asymptomatic 43-year-old woman. Abdominal ultrasonography and enhanced computed tomography showed a tumor lesion accompanied by multiple cystic changes in the liver and the pancreatic tail. Endoscopic ultrasound-fine needle aspiration was performed on the pancreatic tumor lesion and revealed pancreatic neuroendocrine tumor (PNET). As it was unresectable due to multiple liver metastases, the decision was made to initiate treatment with everolimus and transcatheter arterial chemoembolization. The patient ceased menstruating after the start of everolimus administration. When the administration was discontinued due to interstitial lung disease, menstruation resumed, but then again stopped with everolimus resumption. An association between everolimus and amenorrhea was highly suspected. Amenorrhea occurred as a rare adverse event of everolimus. As the younger women might be included in PNETs patients, we should put this adverse event into consideration.

CT classification of chronic pancreatitis and the significance for differential diagnosis

International Nuclear Information System (INIS)

Hu Xueling

2006-01-01

Objective: To study the CT characteristics of chronic pancreatitis and a classification based on the CT manifestations was established. Methods: In total 59 patients with chronic pancreatitis, 43 males and 16 females, with an average age of 40 years old were enrolled in the study. History of acute pancreatitis was positive in 36 patients. Non contrast enhanced and contrast enhanced CT scans were performed. The sizes of lesions, contour of pancreas, as well as the number, density and margin of lesions were investigated on the CT images. Results: Atrophy of the entire pancreas was revealed in 27 patients (46%), complicated with different degree of calcification. Solitary cyst with amorphous wall calcification was demonstrated in 13 patients (22%); multiple intra-pancreatic and peri-pancreatic pseudo-cysts were shown in 7 patients (12%); dilated pancreatic duct was seen in 7 patients (12%); and regional well demarcated bulging of pancreas was presented in 5 patients (8%). Conclusion: The CT findings of chronic pancreatitis in our study could be classified into 5 types: atrophy type, solitary cystic type, multicystic type, pure pancreatic duct dilatation type and mass type. The classification had certain significance for the differential diagnosis and the etiological analysis of chronic pancreatitis. (authors)

Perioperative high dose rate (HDR brachytherapy in unresectable locally advanced pancreatic tumors

Directory of Open Access Journals (Sweden)

Brygida Białas

2011-07-01

Full Text Available Purpose: The aim of the study was to present an original technique of catheter implantation for perioperative HDR-Ir192 brachytherapy in patients after palliative operations of unresectable locally advanced pancreatic tumors and to estimate the influence of perioperative HDR-Ir192 brachytherapy on pain relief in terminal pancreatic cancer patients. Material and methods: Eight patients with pancreatic tumors located in the head of pancreas underwent palliative operations with the use of HDR-Ir192 brachytherapy. All patients qualified for surgery reported pain of high intensity and had received narcotic painkillers prior to operation. During the last phase of the surgery, the Nucletron® catheters were implanted in patients to prepare them for later perioperative brachytherapy. Since the 6th day after surgery HDR brachytherapy was performed. Before each brachytherapy fraction the location of implants were checked using fluoroscopy. A fractional dose was 5 Gy and a total dose was 20 Gy in the area of radiation. A comparative study of two groups of patients (with and without brachytherapy with stage III pancreatic cancer according to the TNM scale was taken in consideration. Results and Conclusions: The authors claim that the modification of catheter implantation using specially designed cannula, facilitates the process of inserting the catheter into the tumor, shortens the time needed for the procedure, and reduces the risk of complications. Mean survival time was 5.7 months. In the group of performed brachytherapy, the mean survival time was 6.7 months, while in the group of no brachytherapy performed – 4.4 months. In the group of brachytherapy, only one patient increased the dose of painkillers in the last month of his life. Remaining patients took constant doses of medicines. Perioperative HDR-Ir192 brachytherapy could be considered as a practical application of adjuvant therapy for pain relief in patients with an advanced pancreatic cancer.

Evaluating the efficacy of tumor markers CA 19-9 and CEA to predict operability and survival in pancreatic malignancies.

Science.gov (United States)

Mehta, Jay; Prabhu, Ramkrishna; Eshpuniyani, Priya; Kantharia, Chetan; Supe, Avinash

2010-01-01

Using CA 19-9 and CEA (elevated > 2 times of normal) as predictors in determining operability and survival in pancreatic tumors. Levels of CA 19-9 and CEA were measured (pre and post operatively) in 49 patients of pancreatic malignancy. CECT was performed for diagnosis and staging. An experienced surgeon determined the operability. The levels of tumor markers were correlated with the operability and the survival based on CECT and intra-operative findings. 16/24 (67%) patients with CA 19-9 levels (CEA levels (CEA levels (p = 0.003) were found to be non-resectable. Of the 27 patients, found resectable on CECT, 5 were non-resectable intra-operatively. All of these had elevated levels of CA 19-9 and 4/5 (80%) had elevated levels of CEA. Only 5/21 (23%) non-resectable patients, with elevated levels of CA 19-9 reported at 1 year follow up. None of the non-resectable patients with CA 19-9 levels > 1000 U/ml reported at 6 month follow-up. None of the resectable patients pre-operatively showed evidence of recurrence. All achieved normal values post surgery. Elevated levels of CA 19-9 and CEA (> 2 times) predict increased chances of inoperability and poor survival in pancreatic tumors. Levels > 3 times had increased risk of inoperability even in patients deemed resectable on CT-Scan. Diagnostic laparoscopy would be beneficial in these patients. Levels of CA 19-9 (> 1000 U/ml) indicate a dismal survival in non-resectable group of patients.

Therapy of metastatic pancreatic neuroendocrine tumors (pNETs). Recent insights and advances

International Nuclear Information System (INIS)

Ito, Tetsuhide; Igarashi, Hisato; Jensen, R.T.

2012-01-01

Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. (author)

MUC1 selectively targets human pancreatic cancer in orthotopic nude mouse models.

Directory of Open Access Journals (Sweden)

Jeong Youp Park

Full Text Available The goal of this study was to determine whether MUC1 antibody conjugated with a fluorophore could be used to visualize pancreatic cancer. Anti-MUC1 (CT2 antibody was conjugated with 550 nm or 650 nm fluorophores. Nude mouse were used to make subcutaneous and orthotopic models of pancreatic cancer. Western blot and flow cytometric analysis confirmed the expression of MUC1 in human pancreatic cancer cell lines including BxPC-3 and Panc-1. Immunocytochemistry with fluorophore conjugated anti-MUC1 antibody demonstrated fluorescent areas on the membrane of Panc-1 cancer cells. After injecting the conjugated anti-MUC1 antibodies via the tail vein, subcutaneously transplanted Panc-1 and BxPC-3 tumors emitted strong fluorescent signals. In the subcutaneous tumor models, the fluorescent signal from the conjugated anti-MUC1 antibody was noted around the margin of the tumor and space between the cells. The conjugated anti-MUC1 antibody bound the tumor in orthotopically-transplanted Panc-1 and BxPC-3 models enabling the tumors to be imaged. This study showed that fluorophore conjugated anti-MUC1 antibodies could visualize pancreatic tumors in vitro and in vivo and may help to improve the diagnosis and treatment of pancreatic cancer.

Pancreatic Exocrine Insufficiency in Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Miroslav Vujasinovic

2017-02-01

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

Radioimmunoassays for tumor diagnosis

International Nuclear Information System (INIS)

Dressler, J.

1983-01-01

Aside from imaging techniques several (radio-)immunological analyses are used for tumor diagnosis. Oncofetal antigens, for instance the carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP), have become the most important substances for many malignancies. However, nearly all of the so-called tumor markers are not suitable for early diagnosis or screening either because of low sensitivity or low tumor specifity. On the other hand follow-up measurements give a very sensitive index of the success of treatment and may indicate tumor progression when other signs are still not present. In some carcinomas and under some clinical circumstances tumorspecific markers are available and mandatory for detection and/or staging: AFP in hepatoma, acid phosphatase in metastasizing carcinoma of the prostate and serum thyreoglobulin in differentiated thyroid cancer. (orig.) [de

Islet Cell Tumors of the Pancreas: A Variety of Multiphase Dynamic Imaging Findings with Pathologic Correlations Focusing on Nonfunctioning Tumors and Insulinomas

International Nuclear Information System (INIS)

Hong, Yoo Jin; Yu, Jeong Sik; Park, Chan Il; Kwon, Ji Eun; Chung, Jae Joon; Kim, Joo Hee; Kim, Ki Whang

2010-01-01

Islet cell tumors (ICTs) are rare pancreatic neoplasms of neuroendocrine origin, posing a diagnostic challenge to radiologists. We illustrated a spectrum of features of pancreatic ICTs that could be found on multiphase dynamic CT or MRI, and elucidated the histopathologic characteristics by determining the contrast enhancement pattern of the lesions. Various enhancement patterns were dependant on the internal composition of the tumor, that is, the proportion of vascular densities for early enhancement and non-hypervascular interstitial tissue for late enhancement regardless of the size or functional behavior. This knowledge of the imaging-pathologic spectrum of ICTs could be helpful for the proper differential diagnosis from other pancreatic tumors

Secretin-enhanced magnetic resonance cholangiopancreaticography: value for the diagnosis of chronic pancreatitis

International Nuclear Information System (INIS)

Heverhagen, J.T.; Burbelko, M.; Schenck zu Schweinsberg, T.; Funke, C.; Wecker, C.; Walthers, E.M.; Rominger, M.

2007-01-01

Endoscopic retrograde cholangiopancreaticography (ERCP) is the morphologic gold standard for the diagnosis of chronic pancreatitis. Magnetic Resonance Imaging (MRI) enables the visualization of not only the pancreatic duct but also the surrounding parenchyma using T2- and T1-weighted sequences before and after the application of a contrast agent. Moreover, it allows the depiction of ductal segments distal to a stenosis or occlusion. However, conventional Magnetic Resonance Cholangiopancreaticography (MRCP) was not able to achieve accuracy similar to that of ERCP. Despite many technological innovations, such as fast breath-hold acquisitions or respiratory-gated 3D sequences, this drawback could not be overcome. In recent years, secretin-enhanced MRCP has been used for the diagnosis of chronic pancreatitis. A recent study showed that secretin not only improves the visibility of the pancreatic duct and its side branches but it also enhances the diagnostic accuracy of MRCP. The sensitivity, specificity, and positive and negative predictive values were improved by the application of secretin. Moreover, the agreement between independent observers increased after the use of secretin. In addition, quantitative post-processing tools have been developed that enable the measurement of the exocrine pancreatic output non-invasively using secretin-enhanced MRCP. These tools facilitate applications, such as functional follow-up after pancreaticogastrostomy and pancreaticogastric anastomoses, evaluation of the functional status of the graft after pancreas transplantation and follow-up of pancreatic drainage procedures and duct disruption. (orig.)

Diagnosis and treatment of ampullary tumors

Directory of Open Access Journals (Sweden)

YIN Tao

2017-02-01

Full Text Available Ampullary tumors mainly manifest as obstructive jaundice and ampullary mass in clinical practice and are difficult to be identified in early stage due to a complex structure of the anatomical site, a deep location, and hidden symptoms. Sometimes a qualitative diagnosis cannot be made. Based on the experience in the treatment of ampullary tumors for many years in our center, this article summarizes the features of ampullary tumors from the aspects of clinical manifestations, diagnosis, treatment, and prognosis, especially the issues regarding imaging evaluation of ampullary tumors, selection of surgical procedure, and prognosis. An early diagnosis is the key to the treatment of ampullary tumors, and early identification and treatment of lesions have great impacts on patients′ prognosis. Accurate preoperative imaging evaluation, a professional diagnosis and treatment team, accurate preoperative and intraoperative pathological analysis, and implementation of reasonable therapeutic strategy are the key to patients′ recovery.

Pancreatic cancer risk in hereditary pancreatitis

Directory of Open Access Journals (Sweden)

Frank Ulrich Weiss

2014-02-01

Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

Characterization of a pancreatic islet cell tumor in a polar bear (Ursus maritimus).

Science.gov (United States)

Fortin, Jessica S; Benoit-Biancamano, Marie-Odile

2014-01-01

Herein, we report a 25-year-old male polar bear suffering from a pancreatic islet cell tumor. The aim of this report is to present a case of this rare tumor in a captive polar bear. The implication of potential risk factors such as high carbohydrate diet or the presence of amyloid fibril deposits was assessed. Necropsy examination revealed several other changes, including nodules observed in the liver, spleen, pancreas, intestine, and thyroid glands that were submitted for histopathologic analysis. Interestingly, the multiple neoplastic nodules were unrelated and included a pancreatic islet cell tumor. Immunohistochemistry of the pancreas confirmed the presence of insulin and islet amyloid polypeptide (IAPP) within the pancreatic islet cells. The IAPP gene was extracted from the paraffin-embedded liver tissue and sequenced. IAPP cDNA from the polar bear exhibits some differences as compared to the sequence published for several other species. Different factors responsible for neoplasms in bears such as diet, infectious agents, and industrial chemical exposure are reviewed. This case report raised several issues that further studies may address by evaluating the prevalence of cancers in captive or wild animals. © 2014 Wiley Periodicals, Inc.

Disseminated carcinomatosis of the bone marrow from pancreatic cancer: a case report

International Nuclear Information System (INIS)

Namikawa, Hiroki; Takemoto, Yasuhiko; Makuuchi, Ayako; Kobayashi, Masanori; Kinuhata, Shigeki; Morimura, Mina; Ikebe, Takashi; Tanaka, Hiromu; Shuto, Taichi

2016-01-01

Most cases of disseminated carcinomatosis of the bone marrow (DCBM) arise from gastric cancer. DCBM from pancreatic cancer is very rare. We herein present a case of DCBM from pancreatic cancer. A 57-year-old man was referred to our hospital for severe lumbago. Laboratory data indicated that he suffered from disseminated intravascular coagulation (DIC). Non-contrast abdominal computed tomography (CT) revealed multiple bone masses but no other abnormal findings. Left iliac bone marrow biopsy revealed poorly differentiated adenocarcinoma cells. Positron emission tomography (PET)-CT showed diffuse abnormal uptake in the bones and tail of the pancreas. Contrast whole-body CT showed a tumor measuring approximately 28 mm in diameter with poor enhancement in the tail of the pancreas. The patient’s final diagnosis was pancreatic cancer located in the tail of the pancreas with diffuse bone metastases and DIC. His DCBM was thus believed to originate from the pancreatic cancer. He succumbed to the disease approximately 2 months after admission to our hospital. We herein describe a case of pancreatic cancer located in the tail of the pancreas with diffuse bone metastases and DIC, which, in our case, was DCBM. Therefore, in cases of DCBM with an unknown primary tumor, pancreatic cancer should be considered during differential diagnosis

Pancreatic Tuberculosis or Autoimmune Pancreatitis

Directory of Open Access Journals (Sweden)

Ayesha Salahuddin

2014-01-01

Full Text Available Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.

A Man with Pancreatic Head Mass Lesion on Endoscopic Ultrasound and Granuloma on Cytopathology

Directory of Open Access Journals (Sweden)

Neda Rad

2016-12-01

Full Text Available Primary pancreatic lymphoma is an unlikely malignancy accounting for less than 0.5% of pancreatic tumors. Clinical presentation is often nonspecific and may be clinically misdiagnosed as pancreatic adenocarcinoma. Here we present an Iranian case of primary pancreatic lymphoma in a 47-year-old male suffering from jaundice and 20% weight loss. Endoscopic ultrasound revealed a mixed echoic mass lesion at the head of pancreas. The patient underwent endoscopic ultrasound-guided fine needle aspiration of solid pancreatic mass and histopathologic diagnosis revealed granuloma. Computed tomography-guided core needle biopsy was performed and eventually histological examination showed granuloma that was coherent with the diagnosis of primary pancreatic lymphoma. Primary pancreatic lymphoma is a rare entity presenting with nonspecific symptoms, laboratory and radiological findings. Computed tomography results in combination with clinical and radiological studies generally provide guidance for appropriate investigation.

A Man with Pancreatic Head Mass Lesion on Endoscopic Ultrasound and Granuloma on Cytopathology.

Science.gov (United States)

Rad, Neda; Heidarnezhad, Arash; Soheili, Setareh; Mohammad-Alizadeh, Amir Houshang; Nikmanesh, Arash

2016-01-01

Primary pancreatic lymphoma is an unlikely malignancy accounting for less than 0.5% of pancreatic tumors. Clinical presentation is often nonspecific and may be clinically misdiagnosed as pancreatic adenocarcinoma. Here we present an Iranian case of primary pancreatic lymphoma in a 47-year-old male suffering from jaundice and 20% weight loss. Endoscopic ultrasound revealed a mixed echoic mass lesion at the head of pancreas. The patient underwent endoscopic ultrasound-guided fine needle aspiration of solid pancreatic mass and histopathologic diagnosis revealed granuloma. Computed tomography-guided core needle biopsy was performed and eventually histological examination showed granuloma that was coherent with the diagnosis of primary pancreatic lymphoma. Primary pancreatic lymphoma is a rare entity presenting with nonspecific symptoms, laboratory and radiological findings. Computed tomography results in combination with clinical and radiological studies generally provide guidance for appropriate investigation.

Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer: a phase I study

International Nuclear Information System (INIS)

Order, Stanley E.; Siegel, Jeffry A.; Principato, Robert; Zeiger, Louis E.; Johnson, Elizabeth; Lang, Patricia; Lustig, Robert; Wallner, Paul E.

1996-01-01

Purpose: Selective high-dose radiation of solid tumors has been a goal of radiation oncology. The physiological barriers of solid tumors (high interstitial tumor pressure, reduced tumor vascularity, and poor perfusion) have been major barriers in achieving significant tumor dose of systemically infused radioconjugates. Direct tumor infusional brachytherapy overcomes these barriers and leads to selective high tumor doses. Methods and Materials: The development of interstitial tumor infusion of macroaggregated albumin (MAA) followed by colloidal chromic phosphate 32 P has overcome solid tumor obstacles in 47 patients with nonresectable pancreatic cancer in a Phase I dose escalation study. The colloidal 32 P infusion was followed by external radiation and five fluorouracil. Results: Of the 28 patients with cancer limited to the pancreas, 15 of 16 patients retained 86-100% (mean 96%) of the infused colloidal 32 P isotope. While the other 12 patients had partial shunting to the liver, shunting to the liver was due to high interstitial resistance with tumor dose deposition of 17-88% (mean 52%). Of the 19 patients with metastatic pancreas cancer, colloidal 32 P tumor deposition ranged from 22 to 100% of the infused dose (mean 79%). The less than optimal tumor deposition led to our increasing the MAA from 600,000 to 1.5-2.5 million particles. Interstitial dexamethasone 2 mg and later 4 mg was infused first and prevented liver shunting by somehow reducing tumor resistance. The median survival in 28 Phase I patients with nonresectable pancreas cancer without metastasis, was 12 months. No significant toxicity occurred when treatment was limited to two infusions with as much as 30 mCi each. The maximum tumor dose was 17,000 Gy (1.700,000 cGy). In 19 non-resectable pancreatic cancer patients with metastasis, a 6.9 months median survival was observed. Conclusions: Infusional brachytherapy is an outpatient procedure that delivers high-dose radiation selectively to pancreatic

In Vivo Loss of Function Screening Reveals Carbonic Anhydrase IX as a Key Modulator of Tumor Initiating Potential in Primary Pancreatic Tumors

Directory of Open Access Journals (Sweden)

Nabendu Pore

2015-06-01

Full Text Available Reprogramming of energy metabolism is one of the emerging hallmarks of cancer. Up-regulation of energy metabolism pathways fuels cell growth and division, a key characteristic of neoplastic disease, and can lead to dependency on specific metabolic pathways. Thus, targeting energy metabolism pathways might offer the opportunity for novel therapeutics. Here, we describe the application of a novel in vivo screening approach for the identification of genes involved in cancer metabolism using a patient-derived pancreatic xenograft model. Lentiviruses expressing short hairpin RNAs (shRNAs targeting 12 different cell surface protein transporters were separately transduced into the primary pancreatic tumor cells. Transduced cells were pooled and implanted into mice. Tumors were harvested at different times, and the frequency of each shRNA was determined as a measure of which ones prevented tumor growth. Several targets including carbonic anhydrase IX (CAIX, monocarboxylate transporter 4, and anionic amino acid transporter light chain, xc- system (xCT were identified in these studies and shown to be required for tumor initiation and growth. Interestingly, CAIX was overexpressed in the tumor initiating cell population. CAIX expression alone correlated with a highly tumorigenic subpopulation of cells. Furthermore, CAIX expression was essential for tumor initiation because shRNA knockdown eliminated the ability of cells to grow in vivo. To the best of our knowledge, this is the first parallel in vivo assessment of multiple novel oncology target genes using a patient-derived pancreatic tumor model.

A case of positive 68Ga-DOTATOC-PET/CT pancreatic heterotopia mimicking an intestinal neuroendocrine tumor.

Science.gov (United States)

Zilli, Alessandra; Fanetti, Ilaria; Conte, Dario; Massironi, Sara

Gallium-68 DOTA-peptide positron emission tomography/computed tomography ( 68 Ga-PET/CT) has emerged as a promising tool for the diagnosis and staging of gastro-entero-pancreatic neoplasms, thanks to its high sensitivity and specificity. Heterotopic pancreas, which is relatively rare, has never been reported as a possible cause of false positives of 68 Ga-PET/CT. We report on the first case of a heterotopic pancreas showing pathological uptake at 68 Ga-PET/CT, thus mimicking an intestinal neuroendocrine tumor. The present case suggests that heterotopic pancreas should be included among the possible causes of false positives at 68 Ga PET. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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.

Endocrine carcinoma of the pancreatic tail exhibiting gastric variceal bleeding

Directory of Open Access Journals (Sweden)

Si-Yuan Wu

2014-01-01

Full Text Available Nonfunctional endocrine carcinoma of the pancreas is uncommon. Without excess hormone secretion, it is clinically silent until the enlarging or metastatic tumor causes compressive symptoms. Epigastric pain, dyspepsia, jaundice, and abdominal mass are the usual symptoms, whereas upper gastrointestinal (GI bleeding is rare. Here, we describe the case of a 24-year-old man with the chief complaint of hematemesis. Upper GI panendoscopy revealed isolated gastric varices at the fundus and upper body. Ultrasonography and computed tomography showed a tumor mass at the pancreatic tail causing a splenic vein obstruction, engorged vessels near the fundus of the stomach, and splenomegaly. After distal pancreatectomy and splenectomy, the bleeding did not recur. The final pathologic diagnosis was endocrine carcinoma of the pancreas. Gastric variceal bleeding is a possible manifestation of nonfunctional endocrine carcinoma of the pancreas if the splenic vein is affected by a tumor. In non-cirrhotic patients with isolated gastric variceal bleeding, the differential diagnosis should include pancreatic disorders.

Two avirulent, lentogenic strains of Newcastle disease virus are cytotoxic for some human pancreatic tumor lines in vitro.

Science.gov (United States)

Walter, Robert J; Attar, Bashar M; Rafiq, Asad; Delimata, Megan; Tejaswi, Sooraj

2012-09-10

Pancreatic cancer is the fourth leading cause of cancer death in the U.S. Highly infectious Newcastle disease virus (NDV) strains are known to be very cytotoxic for an array of human tumor cell types in vitro and in vivo but the effects of these and avirulent NDV strains on pancreatic neoplasms are little known. Here, the direct cytolytic effects of the avirulent Hitchner-B1 (B1) and Ulster (U) NDV strains on 7 human pancreatic tumor cell lines and 4 normal human cell lines were studied. Cytotoxicity assays used serially diluted NDV to determine minimum cytotoxic plaque forming unit (PFU) doses. For NDV-B1, normal human cells were killed only by relatively high doses (range: 471-3,724 PFU) whereas NDV-U killed these cells at low PFU (range: 0.32-1.60 PFU). Most pancreatic cancer cell types were killed by much lower NDV-B1 doses (range: 0.40-2.60 PFU) while NDV-U killed Capan-1 and SU.86.86 cultures at very low doses (0.00041 PFU and 0.0034 PFU, respectively). On average, 1,555 times more NDV-B1 was needed to kill normal cells than most pancreatic tumor cells and 558 times more NDV-U to kill the two most sensitive pancreatic cancer lines. These innately-targeted lentogenic viruses may have meaningful potential in treating pancreatic cancer.

Comparison of Oct4, Sox2 and Nanog Expression in Pancreatic Cancer Cell Lines and Human Pancreatic Tumor

Directory of Open Access Journals (Sweden)

Vahideh Assadollahi

2015-12-01

Full Text Available Background: Genes are involved in the control of stem cell self-renewal as a new class of molecular markers of cancer. Objectives: In this study, the expression of Oct4, Nanog and Sox2 in cell lines MIA Paca-2, PA-TU-8902 and AsPC-1 and pancreatic cancer tissue were examined. Materials and Methods: In this experimental study, cell lines, MIA Paca-2, PA-TU-8902 and AsPC-1, were cultured in DMEM (Dulbecco’s Modified Eagles Medium and RPMI-1640 (Roswell Park Memorial Institute containing FBS 10% (fetal bovine serum in a 37°C incubator containing Co2 5% and humidity 90%. Samples of tumor and non-cancer pancreatic tumor were purchased Iran tumor bank. Extraction of RNA and synthesis of cDNA was performed. Expression levels of Oct4, Nanog and Sox2 were determined using Real-time PCR. The protein expression levels of target genes in the cell lines were studied by flow cytometry and immunocytochemistry. Results: The expression rate of Oct4, Nanog and Sox2 is more in the cancer cell lines than those in the control (normal tissue samples. The protein expression levels of target genes in the cell lines were confirmed by flow cytometry and immunocytochemistry. Conclusions: The genes are involved in stem cell self-renewal as a new class of molecular markers of cancer that detected in the pancreatic cell lines. Maybe, these genes play important role in the uncontrolled proliferation of cancer cells.

Organoid Models of Human and Mouse Ductal Pancreatic Cancer

Science.gov (United States)

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

Road Accident due to a Pancreatic Insulinoma

Science.gov (United States)

Parisi, Amilcare; Desiderio, Jacopo; Cirocchi, Roberto; Grassi, Veronica; Trastulli, Stefano; Barberini, Francesco; Corsi, Alessia; Cacurri, Alban; Renzi, Claudio; Anastasio, Fabio; Battista, Francesca; Pucci, Giacomo; Noya, Giuseppe; Schillaci, Giuseppe

2015-01-01

Abstract Insulinoma is a rare pancreatic endocrine tumor, typically sporadic and solitary. Although the Whipple triad, consisting of hypoglycemia, neuroglycopenic symptoms, and symptoms relief with glucose administration, is often present, the diagnosis may be challenging when symptoms are less typical. We report a case of road accident due to an episode of loss of consciousness in a patient with pancreatic insulinoma. In the previous months, the patient had occasionally reported nonspecific symptoms. During hospitalization, endocrine examinations were compatible with an insulin-producing tumor. Abdominal computerized tomography and magnetic resonance imaging allowed us to identify and localize the tumor. The patient underwent a robotic distal pancreatectomy with partial omentectomy and splenectomy. Insulin-producing tumors may go undetected for a long period due to nonspecific clinical symptoms, and may cause episodes of loss of consciousness with potentially lethal consequences. Robot-assisted procedures can be performed with the same techniques of the traditional surgery, reducing surgical trauma, intraoperative blood loss, and hospital stays. PMID:25816027

Quality of life and performance status in patients with pancreatic and periampullary tumors

International Nuclear Information System (INIS)

Velanovich, V.; Wollner, I.

2011-01-01

The background of this study was to determine if pretreatment quality of life is associated with performance status in patients with pancreatic and periampullary tumors. Eighty consecutive patients evaluated for surgical treatment of pancreatic or periampullary tumors completed the social functioning SF-36, a generic quality of life instrument. This instrument measures 8 domains of quality of life: physical functioning (PF), role-physical (RP), role-emotional, bodily pain, vitality, mental health, social functioning, and general health (GH). The best possible score is 100 and the worst possible score is 0. Each patient was then assigned a Karnofsky performance score (KPS), with the best possible score of 100 (normal, no complaints, no evidence of disease) and worst score of 0 (dead). Data recorded included age, gender, pathology, stage, resection, use of chemotherapy, and radiation therapy. Statistical analysis was done using single and multiple linear regression analysis, correlation coefficients (r) and coefficient of determination (r 2 ). KPS was significantly associated with all domains of the SF-36 by single linear regression. By multiple linear regression, KPS was significantly associated with the PF domain (p 2 values) suggest that there are additional factors determining both quality of life and performance status in patients with pancreatic and periampullary tumors. (author)

Multiphoton microscopy as a diagnostic imaging modality for pancreatic neoplasms without hematoxylin and eosin stains

Science.gov (United States)

Chen, Youting; Chen, Jing; Chen, Hong; Hong, Zhipeng; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Yanling; Chen, Jianxin

2014-09-01

Hematoxylin and eosin (H&E) staining of tissue samples is the standard approach in histopathology for imaging and diagnosing cancer. Recent reports have shown that multiphoton microscopy (MPM) provides better sample interface with single-cell resolution, which enhances traditional H&E staining and offers a powerful diagnostic tool with potential applications in oncology. The purpose of this study was to further expand the versatility of MPM by establishing the optical parameters required for imaging unstained histological sections of pancreatic neoplasms, thereby providing an efficient and environmentally sustainable alternative to H&E staining while improving the accuracy of pancreatic cancer diagnoses. We found that the high-resolution MPM images clearly distinguish between the structure of normal pancreatic tissues compared with pancreatic neoplasms in unstained histological sections, and discernable differences in tissue architecture and cell morphology between normal versus tumorigenic cells led to enhanced optical diagnosis of cancerous tissue. Moreover, quantitative assessment of the cytomorphological features visualized from MPM images showed significant differences in the nuclear-cytoplasmic ratios of pancreatic neoplasms compared with normal pancreas, as well as further distinguished pancreatic malignant tumors from benign tumors. These results indicate that the MPM could potentially serve as an optical tool for the diagnosis of pancreatic neoplasms in unstained histological sections.

Benzyl isothiocyanate suppresses pancreatic tumor angiogenesis and invasion by inhibiting HIF-α/VEGF/Rho-GTPases: pivotal role of STAT-3.

Directory of Open Access Journals (Sweden)

Srinivas Reddy Boreddy

Full Text Available Our previous studies have shown that benzyl isothiocyanate (BITC suppresses pancreatic tumor growth by inhibiting STAT-3; however, the exact mechanism of tumor growth suppression was not clear. Here we evaluated the effects and mechanism of BITC on pancreatic tumor angiogenesis. Our results reveal that BITC significantly inhibits neovasularization on rat aorta and Chicken-Chorioallantoic membrane. Furthermore, BITC blocks the migration and invasion of BxPC-3 and PanC-1 pancreatic cancer cells in a dose dependant manner. Moreover, secretion of VEGF and MMP-2 in normoxic and hypoxic BxPC-3 and PanC-1 cells was significantly suppressed by BITC. Both VEGF and MMP-2 play a critical role in angiogenesis and metastasis. Our results reveal that BITC significantly suppresses the phosphorylation of VEGFR-2 (Tyr-1175, and expression of HIF-α. Rho-GTPases, which are regulated by VEGF play a crucial role in pancreatic cancer progression. BITC treatment reduced the expression of RhoC whereas up-regulated the expression of tumor suppressor RhoB. STAT-3 over-expression or IL-6 treatment significantly induced HIF-1α and VEGF expression; however, BITC substantially suppressed STAT-3 as well as STAT-3-induced HIF-1α and VEGF expression. Finally, in vivo tumor growth and matrigel-plug assay show reduced tumor growth and substantial reduction of hemoglobin content in the matrigel plugs and tumors of mice treated orally with 12 µmol BITC, indicating reduced tumor angiogenesis. Immunoblotting of BITC treated tumors show reduced expression of STAT-3 phosphorylation (Tyr-705, HIF-α, VEGFR-2, VEGF, MMP-2, CD31 and RhoC. Taken together, our results suggest that BITC suppresses pancreatic tumor growth by inhibiting tumor angiogenesis through STAT-3-dependant pathway.

New concepts in diagnosis and therapy of pancreatic adenocarcinoma

International Nuclear Information System (INIS)

Laghi, Andrea

2011-01-01

This book adopts a multidisciplinary approach to examine in detail a range of interesting new concepts in the diagnosis and therapy of pancreatic adenocarcinoma. Its primary goals are to offer a valuable source of information for clinicians involved in the management of patients with pancreatic adenocarcinoma and to provide a modern guide to the disease for those who are interested in updating their knowledge, including fellows and senior residents. The book is divided into three parts. The first part provides an epidemiological and clinical overview of the disease, followed by an update on pathological findings, including new discoveries in the area of molecular biology. The second part, on diagnosis, offers detailed and comprehensive information on the advantages and disadvantages of different imaging techniques, including nuclear medicine and endoscopic ultrasound. Each diagnostic strategy is critically reviewed with regard to cost-effectiveness. The concluding part of the book, on therapy, gives a panoramic overview of the various therapeutic options, from surgery to chemotherapy and palliative approaches based on interventional endoscopy and radiology. (orig.)

Epithelial-to-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma and Pancreatic Tumor Cell Lines: The Role of Neutrophils and Neutrophil-Derived Elastase

Directory of Open Access Journals (Sweden)

Thomas Große-Steffen

2012-01-01

Full Text Available Pancreatic ductal adenocarcinoma (PDAC is frequently associated with fibrosis and a prominent inflammatory infiltrate in the desmoplastic stroma. Moreover, in PDAC, an epithelial-to-mesenchymal transition (EMT is observed. To explore a possible connection between the infiltrating cells, particularly the polymorphonuclear neutrophils (PMN and the tumor cell transition, biopsies of patients with PDAC (n=115 were analysed with regard to PMN infiltration and nuclear expression of β-catenin and of ZEB1, well-established indicators of EMT. In biopsies with a dense PMN infiltrate, a nuclear accumulation of β-catenin and of ZEB1 was observed. To address the question whether PMN could induce EMT, they were isolated from healthy donors and were cocultivated with pancreatic tumor cells grown as monolayers. Rapid dyshesion of the tumor cells was seen, most likely due to an elastase-mediated degradation of E-cadherin. In parallel, the transcription factor TWIST was upregulated, β-catenin translocated into the nucleus, ZEB1 appeared in the nucleus, and keratins were downregulated. EMT was also induced when the tumor cells were grown under conditions preventing attachment to the culture plates. Here, also in the absence of elastase, E-cadherin was downmodulated. PMN as well as prevention of adhesion induced EMT also in liver cancer cell line. In conclusion, PMN via elastase induce EMT in vitro, most likely due to the loss of cell-to-cell contact. Because in pancreatic cancers the transition to a mesenchymal phenotype coincides with the PMN infiltrate, a contribution of the inflammatory response to the induction of EMT and—by implication—to tumor progression is possible.

Usefulness of percutaneous elastography by acoustic radiation force impulse for the non-invasive diagnosis of chronic pancreatitis

Directory of Open Access Journals (Sweden)

Camilo Julio Llamoza-Torres

Full Text Available Objective: To determine the accuracy of the acoustic radiation force impulse (ARFI technique for the diagnosis of chronic pancreatitis. Materials and methods: We present an observational, single-center study that included patients with suspected chronic pancreatitis in the period between October 2012 and September 2015 who underwent endoscopic ultrasound (EUS and were classified according to the standard and Rosemont criteria. The same group of patients was assessed by the ARFI technology using ACUSON S2000™ equipment with Virtual Touch™ Quantification software for the assessment of pancreatic stiffness by obtaining the shear wave velocity (SWV in the head, body and tail of the pancreas. Data were analyzed using ANOVA and nonparametric correlation methods. Diagnostic accuracy was obtained by analyzing receiver operating characteristic (ROC curve. Results: A total of thirty-three patients were studied (45.5% women; mean age was 58.3 ± 11.8 years. Seventeen with a diagnosis of chronic pancreatitis and sixteen classified as normal according to standard criteria. A significant difference was detected between the means of SWV in pancreatic body of patients without (SWV: 1.27 m/s and with chronic pancreatitis (SWV 1.57 m/s, p = 0.037. The area under the ROC curve was 71.3% (95% CI 0.532-0.895 and the accuracy of ARFI for diagnosing chronic pancreatitis was 69.7% for a SWV of 1.4 m/s in the pancreatic body. The SWV means in head (r = 0.421, p < 0.05 and body (r = 0.455, p < 0.05 of the pancreas showed a significant correlation with the number of EUS criteria for chronic pancreatitis. Conclusion: Quantification of pancreatic stiffness with ARFI elastography technique has proven to be useful for the non-invasive diagnosis of chronic pancreatitis.

Imaging Tumor Variation in Response to Photodynamic Therapy in Pancreatic Cancer Xenograft Models

International Nuclear Information System (INIS)

Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; O'Hara, Julia A.; Hoopes, P. Jack; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

2010-01-01

Purpose: A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. Methods and Materials: Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. Results: There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. Conclusions: The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.

Tumor markers CA19-9, CA242 and CEA in the diagnosis of pancreatic cancer: a meta-analysis.

Science.gov (United States)

Zhang, Yimin; Yang, Jun; Li, Hongjuan; Wu, Yihua; Zhang, Honghe; Chen, Wenhu

2015-01-01

Pancreatic cancer has the worst prognosis and early detection is crucial for improving patient prognosis. Therefore, we performed a meta-analysis to evaluate and compare the sensitivity and specificity of single test of CA19-9, CA242, and CEA, as well as combination test in pancreatic cancer detection. We searched PubMed, Embase, Medline, and Wanfang databases for studies that evaluated the diagnostic validity of CA19-9, CA242, and CEA between January 1990 and September 2014. Data were analyzed by Meta-Disc and STATA software. A total of 21 studies including 3497 participants, which fulfilled the inclusion criteria were considered for analysis. The pooled sensitivities for CA19-9, CA242, and CEA were 75.4 (95% CI: 73.4-77.4), 67.8 (95% CI: 65.5-70), and 39.5 (95% CI: 37.3-41.7), respectively. The pooled specificities of CA19-9, CA242, and CEA were 77.6 (95% CI: 75.4-79.7), 83 (95% CI: 81-85), and 81.3 (95% CI: 79.3-83.2), respectively. Parallel combination of CA19-9+CA242 has a higher sensitivity (89, 95% CI: 80-95) without impairing the specificity (75, 95% CI: 67-82). Our meta-analysis showed that CA242 and CA19-9 have better performance in the diagnosis of pancreatic cancer than CEA. Furthermore, parallel combination test of CA19-9+CA242 could be of better diagnostic value than individual CA242 or CA19-9 test.

Optimizing 4-Dimensional Magnetic Resonance Imaging Data Sampling for Respiratory Motion Analysis of Pancreatic Tumors

Energy Technology Data Exchange (ETDEWEB)

Stemkens, Bjorn, E-mail: b.stemkens@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Tijssen, Rob H.N. [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Senneville, Baudouin D. de [Imaging Division, University Medical Center Utrecht, Utrecht (Netherlands); L' Institut de Mathématiques de Bordeaux, Unité Mixte de Recherche 5251, Centre National de la Recherche Scientifique/University of Bordeaux, Bordeaux (France); Heerkens, Hanne D.; Vulpen, Marco van; Lagendijk, Jan J.W.; Berg, Cornelis A.T. van den [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands)

2015-03-01

Purpose: To determine the optimum sampling strategy for retrospective reconstruction of 4-dimensional (4D) MR data for nonrigid motion characterization of tumor and organs at risk for radiation therapy purposes. Methods and Materials: For optimization, we compared 2 surrogate signals (external respiratory bellows and internal MRI navigators) and 2 MR sampling strategies (Cartesian and radial) in terms of image quality and robustness. Using the optimized protocol, 6 pancreatic cancer patients were scanned to calculate the 4D motion. Region of interest analysis was performed to characterize the respiratory-induced motion of the tumor and organs at risk simultaneously. Results: The MRI navigator was found to be a more reliable surrogate for pancreatic motion than the respiratory bellows signal. Radial sampling is most benign for undersampling artifacts and intraview motion. Motion characterization revealed interorgan and interpatient variation, as well as heterogeneity within the tumor. Conclusions: A robust 4D-MRI method, based on clinically available protocols, is presented and successfully applied to characterize the abdominal motion in a small number of pancreatic cancer patients.

Critical appraisal of the role of everolimus in advanced neuroendocrine tumors of pancreatic origin

Directory of Open Access Journals (Sweden)

Mulet-Margalef N

2012-09-01

Full Text Available Núria Mulet-Margalef, Jaume CapdevilaMedical Oncology Department, Vall d'Hebron University Hospital, Barcelona, SpainAbstract: For many years, the treatment of advanced pancreatic neuroendocrine tumors (pNETs has been limited almost entirely to somatostatin analogs and streptozocin-based chemotherapy, with modest benefit. Increasing knowledge of the biologic features of pNETs has allowed the design of molecular-based clinical trials, which have taken a step forward in the management of these tumors. In this review, we discuss the molecular rationale for the development of everolimus for patients with advanced pNETs, critically review the clinical data obtained by the main studies in this setting, and discuss essential considerations based on recent findings in pNET biology for future drug development involving the phosphatidylinositol 3' kinase-AKT-mTOR pathway.Keywords: pancreatic neuroendocrine tumors, everolimus, targeted therapies

Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma.

Science.gov (United States)

Zhao, Xianda; Fan, Wei; Xu, Zhigao; Chen, Honglei; He, Yuyu; Yang, Gui; Yang, Gang; Hu, Hanning; Tang, Shihui; Wang, Ping; Zhang, Zheng; Xu, Peipei; Yu, Mingxia

2016-12-06

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are still unclear. To identify the targeting values of TNF-α in PDAC, we measured TNF-α expression in different stages of PDAC initiation and evaluated its prognostic significance in a pancreatic cancer cohort. We found that TNF-α expression elevated in PDAC initiation process, and high expression of TNF-α was an independent prognostic marker of poor survival. We further evaluated anti-tumor effects of anti-TNF-α treatments in PDAC. Anti-TNF-α treatments resulted in decreased cell viability in both PDAC tumor cells and pancreatic satellite cells in similar dose in vitro. In vivo, anti-TNF-α treatments showed effects in reducing desmoplasia and the tumor promoting inflammatory microenvironment in PDAC. Combination of anti-TNF-α treatments with chemotherapy partly overcame chemoresistance of PDAC tumor cells and prolonged the survival of PDAC mouse model. In conclusion, our findings indicated that TNF-α in PDAC can be a prognostic and therapeutic target. Inhibition of TNF-α synergized with chemotherapy in PDAC resulted in better pre-clinical responses via killing tumor cells as well as diminishing desmoplasia and inflammation in PDAC tumor stroma.

Spiral CT during pharmacoangiography with angiotensin II in patients with pancreatic disease. Technique and diagnostic efficacy

Energy Technology Data Exchange (ETDEWEB)

Kuroda, C.; Mihara, N.; Hosomi, N.; Inoue, E.; Fujita, M. [Osaka Medical Center for Cancer and Cardiovascular Diseases (Japan). Dept. of Diagnostic Radiology; Ohigashi, H.; Ishikawa, O. [Osaka Medical Center for Cancer and Cardiovascular Diseases (Japan). Dept. of Surgery; Nakaizumi, A. [Osaka Medical Center for Cancer and Cardiovascular Deseases (Japan). Dept. of Internal Medicine; Ishiguro, S. [Osaka Medical Center for Cancer and Cardiovascular Diseases (Japan). Dept. of Pathology

1998-03-01

Purpose: To compare the diagnostic efficacy of pancreatic pharmacoangiographic CT using angiotensin II with conventional angiographic CT. Material and Methods: Eighteen patients with space-occupying pancreatic disease were examined in this study. Pharmacoangiographic CT was performed with a 1-3-{mu}/6-ml solution of angiotensin II injected through a catheter into the celiac artery during spiral CT. Results: In 17 of the 18 (94%) patients, the area of pancreatic parenchymal enhancement was the same or larger at pharmacoangiographic CT than at conventional angiographic CT. The attenuation value of the pancreatic parenchyma was significantly increased at pharmacoangiographic CT (p=0.0010). Although the attenuation value of tumors was also increased on images obtained after the injection of angiotensin II, the tumor-to-pancreas contrast was significantly greater at pharmacoangiographic CT (p=0.0479). The mean differences in attenuation between tumor and pancreas at angiographic CT with and without angiotensin II were respectively 182 HU and 115 HU. Conclusion: Pharmacoangiographic CT with angiotensin II proved superior to conventional angiographic CT in the diagnosis of pancreatic disease. We therefore recommend it as a supplementary technique at the angiographic examination of patients with suspected pancreatic tumor. (orig.).

Curcumin Inhibits Tumor Growth and Angiogenesis in an Orthotopic Mouse Model of Human Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Sabrina Bimonte

2013-01-01

Full Text Available Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The best chemotherapeutic agent used to treat pancreatic cancer is the gemcitabine. However, gemcitabine treatment is associated with many side effects. Thus novel strategies involving less toxic agents for treatment of pancreatic cancer are necessary. Curcumin is one such agent that inhibits the proliferation and angiogenesis of a wide variety of tumor cells, through the modulation of many cell signalling pathways. In this study, we investigated whether curcumin plays antitumor effects in MIA PaCa-2 cells. In vitro studies showed that curcumin inhibits the proliferation and enhances apoptosis of MIA PaCa-2 cells. To test whether the antitumor activity of curcumin is also observed in vivo, we generated an orthotopic mouse model of pancreatic cancer by injection of MIA PaCa-2 cells in nude mice. We placed mice on diet containing curcumin at 0.6% for 6 weeks. In these treated mice tumors were smaller with respect to controls and showed a downregulation of the transcription nuclear factor NF-κB and NF-κB-regulated gene products. Overall, our data indicate that curcumin has a great potential in treatment of human pancreatic cancer through the modulation of NF-κB pathway.

Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice

Science.gov (United States)

Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

2016-01-01

Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. Methods We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2–12 Gy and analyzed by flow cytometry. Results Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Conclusions Radiation exposure causes macrophages in PDAs

Extragastrointestinal Stromal Tumor: A Differential Diagnosis of Compressive Upper Abdominal Tumor

Directory of Open Access Journals (Sweden)

Clara Kimie Miyahira

2018-01-01

Full Text Available Introduction. Extragastrointestinal stromal tumors (EGIST are rare mesenchymal tumor lesions located outside the gastrointestinal tract. A rare compressing tumor with difficult diagnosis is reported. Presentation of the Case. A male patient, 63 years old, was admitted in the emergency room complaining of stretching and continuous abdominal pain for one day. He took Hyoscine, with partial improvement of symptoms, but got worse due to hyporexia, and the abdominal pain persisted. The patient also reported early satiety and ten-pound weight loss over the last month. Discussion. EGIST could be assessed by CT-guided biopsy, leading to diagnosis and proper treatment with surgical resection or Imatinib. Conclusion. This case report highlights the importance of considering EGIST an important differential diagnosis of compressing upper abdominal tumors.

Appearance of the aging pancreas on CT scans: Implications in diagnosis of pancreatic carcinoma

International Nuclear Information System (INIS)

Mattison, G.R.; Francis, I.R.; Glazer, G.M.; Trenkner, S.W.

1986-01-01

Because early pancreatic cancer may not appear on CT as a frank mass, the CT-based diagnosis relies on detection of subtle changes such as focal loss of lobulation or asymmetry in the distribution of tissue. The author studied the normal pancreas in 140 patients of different ages to determine if there is an overlap in the appearance of the normal aging pancreas and subtle signs of pancreatic cancer. Both contour lobulation and fatty infiltration were found to increase with age and involved the pancreatic body and tail more than the head. These normal age-related changes should be recognized to avoid overdiagnosing pancreatic head masses

Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

International Nuclear Information System (INIS)

Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

2012-01-01

We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present

MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment.

Science.gov (United States)

Mukherjee, P; Ginardi, A R; Madsen, C S; Tinder, T L; Jacobs, F; Parker, J; Agrawal, B; Longenecker, B M; Gendler, S J

2001-01-01

Pancreatic cancer is a highly aggressive, treatment refractory disease and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas over-express altered forms of a tumor-associated antigen, MUC1 (an epithelial mucin glycoprotein), which is a target for immunotherapy. Using a clinically relevant mouse model of pancreas cancer that demonstrates peripheral and central tolerance to human MUC1 and develops spontaneous tumors of the pancreas, we have previously reported the presence of functionally active, low affinity, MUC1-specific precursor cytotoxic T cells (pCTLs). Hypothesis for this study is that MUC1-based immunization may enhance the low level MUC1-specific immunity that may lead to an effective anti-tumor response. Data demonstrate that MUC1 peptide-based immunization elicits mature MUC1-specific CTLs in the peripheral lymphoid organs. The mature CTLs secrete IFN-gamma and are cytolytic against MUC1-expressing tumor cells in vitro. However, active CTLs that infiltrate the pancreas tumor microenvironment become cytolytically anergic and are tolerized to MUC1 antigen, allowing the tumor to grow. We demonstrate that the CTL tolerance could be reversed at least in vitro with the use of anti-CD40 co-stimulation. The pancreas tumor cells secrete immunosuppressive cytokines, including IL-10 and TGF-beta that are partly responsible for the down-regulation of CTL activity. In addition, they down-regulate their MHC class I molecules to avoid immune recognition. CD4+ CD25+ T regulatory cells, which secrete IL-10, were also found in the tumor environment. Together these data indicate the use of several immune evasion mechanisms by tumor cells to evade CTL killing. Thus altering the tumor microenvironment to make it more conducive to CTL killing may be key in developing a successful anti-cancer immunotherapy.

Recent advances of CT in the diagnosis of abdominal malignancies

Energy Technology Data Exchange (ETDEWEB)

Itai, Y [Tokyo Univ. (Japan). Faculty of Medicine

1980-08-01

Advantages and limitations of CT in the diagnosis of abdominal malignancies are discussed in liver, pancreas, adrenal gland and recurrent tumor. As to hepatocellular carcinoma, main tumors were clearly demonstrated in 83%, equivocally in 9% and negatively in 8%. Rapid injection of contrast material was useful in dividing hepatic masses into hyper- and hypovascular tumors. Sensitivity of pancreatic cancer was high enough, but CT was of limited value in detecting a resectable one. CT was highly effective in diagnosis of adrenal tumors and recurrent tumors.

Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

Directory of Open Access Journals (Sweden)

Sala Abdalla

2016-01-01

Full Text Available Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions.

Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.

Science.gov (United States)

Kirkegård, Jakob; Mortensen, Frank Viborg; Cronin-Fenton, Deirdre

2017-09-01

Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic pancreatitis decreased when the lag period was increased to 5 years (EE: 7.90; 95% CI: 4.26-14.66) or a minimum of 9 years (EE: 3.53; 95% CI: 1.69-7.38). In conclusion, chronic pancreatitis increases the risk of pancreatic cancer, but the association diminishes with long-term follow-up. Five years after diagnosis, chronic pancreatitis patients have a nearly eight-fold increased risk of pancreatic cancer. We suggest that common practice on inducing a 2-year lag period in these studies may not be sufficient. We also recommend a close follow-up in the first years following a diagnosis of chronic pancreatitis to avoid overlooking a pancreatic cancer.

Endoscopic ultrasound-guided fine-needle aspiration diagnosis of secondary tumors involving the pancreas: An institution′s experience

Directory of Open Access Journals (Sweden)

Ahmed K Alomari

2016-01-01

Full Text Available Background: Pancreatic masses may seldom represent a metastasis or secondary involvement by lymphoproliferative disorders. Recognition of this uncommon occurrence may help render an accurate diagnosis and avoid diagnostic pitfalls during endoscopic ultrasound-guided fine needle aspiration (EUS-FNA. In this study, we review our experience in diagnosing secondary tumors involving the pancreas. Materials and Methods: The electronic database of cytopathology archives was searched for cases of secondary tumors involving the pancreas at our institution and a total of 31 cases were identified. The corresponding clinical presentations, imaging study findings, cytological diagnoses, the results of ancillary studies, and surgical follow-up, if available, were reviewed. Results: Nineteen of the patients were male and 12 female, with a mean age of 66 years. Twenty-three patients (74% had a prior history of malignancy, with the latency ranging from 6 months to 19 years. The secondary tumors involving the pancreas included metastatic carcinoma (24 cases, metastatic sarcoma (3 cases, diffuse large B-cell lymphoma (2 cases, and plasma cell neoplasm (2 cases. The most common metastatic tumors were renal cell carcinoma (8 cases and lung carcinoma (7 cases. Correct diagnoses were rendered in 29 cases (94%. The remaining two cases were misclassified as primary pancreatic carcinoma. In both cases, the patients had no known history of malignancy, and no ancillary studies were performed. Conclusions: Secondary tumors involving the pancreas can be accurately diagnosed by EUS-FNA. Recognizing uncommon cytomorphologic features, knowing prior history of malignancy, and performing ancillary studies are the keys to improve diagnostic performance and avoid diagnostic pitfalls.

A Suspicious Pancreatic Mass in Chronic Pancreatitis: Pancreatic Actinomycosis

Directory of Open Access Journals (Sweden)

F. de Clerck

2015-01-01

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

CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth.

Science.gov (United States)

Golubovskaya, Vita; Berahovich, Robert; Zhou, Hua; Xu, Shirley; Harto, Hizkia; Li, Le; Chao, Cheng-Chi; Mao, Mike Ming; Wu, Lijun

2017-10-21

CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. In addition, CD47-CAR-T cells significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral injection into NSG mice. Moreover, we humanized mouse CD47 ScFv and showed that it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also specifically killed ovarian, pancreatic, and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can be used as a novel cellular therapeutic agent for treating different types of cancer.

Neoadjuvant Treatment of Nonfunctioning Pancreatic Neuroendocrine Tumors with [177Lu-DOTA0,Tyr3]Octreotate

NARCIS (Netherlands)

van Vliet, Esther I.; van Eijck, Casper H.; de Krijger, Ronald R.; Nieveen van Dijkum, Elisabeth J.; Teunissen, Jaap J.; Kam, Boen L.; de Herder, Wouter W.; Feelders, Richard A.; Bonsing, Bert A.; Brabander, Tessa; Krenning, Eric P.; Kwekkeboom, Dik J.

2015-01-01

Pancreatic neuroendocrine tumors (NETs) are rare neoplasms for which surgery has almost the only potential for cure. When surgery is not possible because of tumor size and vascular involvement, neoadjuvant treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) may be an option. We

Assessment of biophysical tumor response to PDT in pancreatic cancer using localized reflectance spectroscopy

Science.gov (United States)

Isabelle, Martin; Klubben, William; He, Ting; Laughney, Ashley M.; Glaser, Adam; Krishnaswamy, Venkataramanan; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

2011-02-01

Biophysical changes such as inflammation and necrosis occur immediately following PDT and may be used to assess the treatment response to PDT treatment in-vivo. This study uses localized reflectance measurements to quantify the scatter changes in tumor tissue occurring in response to verteporfin-based PDT treatment in xenograft pancreas tumors. Nude mice were implanted with subcutaneous AsPC-1 pancreatic tumors cells in matrigel, and allowed to establish solid tumors near 100mm3 volume. The mice were sensitized with 1mg/kg of the active component of verteporfin (benzoporphryin derivative, BPD), one hour before light delivery. The optical irradiation was performed using a 1 cm cylindrical interstitial diffusing tip fiber with 20J of red light (690nm). Tumor tissue was excised progressively and imaged, from 1 day to 4 weeks, after PDT treatment. The tissue sections were stained and analyzed by an expert veterinary pathologist, who provided information on tissue regions of interest. This information was correlated with variations in scattering and absorption parameters elucidated from the spectral images and the degree of necrosis and inflammation involvement was identified. Areas of necrosis and dead cells exhibited the lowest average scatter irradiance signature (3.78 and 4.07 respectively) compared to areas of viable pancreatic tumor cells and areas of inflammation (5.81 and 7.19 respectively). Bilirubin absorbance parameters also showed a lower absorbance value in necrotic tissue and areas of dead cells (0.05 and 0.1 respectively) compared to tissue areas for viable pancreatic tumor cells and areas of inflammation (0.28 and 0.35). These results demonstrate that localized reflectance spectroscopy is an imaging modality that can be used to identify tissue features associated with PDT treatment (e.g. necrosis and inflammation) that can be correlated with histopathologically-reviewed H&E stained slides. Further study of this technique may provide means for automated

Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma.

Directory of Open Access Journals (Sweden)

Nina V Chaika

Full Text Available Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a five-year survival rate of 6%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. However, the contribution of metabolic interrelationships between tumor cells and cells of the surrounding microenvironment to the progression of cancer is not well understood. We evaluated differential expression of metabolic genes and, hence, metabolic pathways in primary tumor and metastases of patients with pancreatic adenocarcinoma.We analyzed the metabolic gene (those involved in glycolysis, tri-carboxylic acid pathway, pentose-phosphate pathway and fatty acid metabolism expression profiles of primary and metastatic lesions from pancreatic cancer patients by gene expression arrays. We observed two principal results: genes that were upregulated in primary and most of the metastatic lesions; and genes that were upregulated only in specific metastatic lesions in a site-specific manner. Immunohistochemical (IHC analyses of several metabolic gene products confirmed the gene expression patterns at the protein level. The IHC analyses also revealed differential tumor and stromal expression patterns of metabolic enzymes that were correlated with the metastasis sites.Here, we present the first comprehensive studies that establish differential metabolic status of tumor and stromal components and elevation of aerobic glycolysis gene expression in pancreatic cancer.

Radiolabeling of substance P with Lutetium-177 and biodistribution study in AR42J pancreatic tumor xenografted Nude mice

International Nuclear Information System (INIS)

Araujo, Bortoleti de; Pujatti, Priscilla Brunelli; Barrio, Ofelia; Caldeira, Jose S.; Mengatti, Jair; Suzuki, Miriam F.

2008-01-01

Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. In recent years, new developments in targeted therapies have emerged and the presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands. Substance P, an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin 1 and 2 receptors (NKr), may play a role in the pathogenesis of PT, because approximately 10% of these tumors over express NKr. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with Lutetium-177 ( 177 Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice in other to verify if SP can be used in this pancreatic tumor detection and treatment. 177 Lu (half-life 6.7 days) has both β and γ-emissions suitable for radiotherapy and imaging respectively. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 4 deg C and 24 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, 177 Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor. (author)

Apoptosis: Targets in Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Kalthoff Holger

2003-01-01

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

Clinical Value of Dual-energy CT in Detection of Pancreatic Adenocarcinoma: Investigation of the Best Pancreatic Tumor Contrast to Noise Ratio.

Science.gov (United States)

He, Yong-Lan; Zhang, Da-Ming; Xue, Hua-Dan; Jin, Zheng-Yu

2013-01-01

Objective To quantitatively compare and determine the best pancreatic tumor contrast to noise ratio (CNR) in different dual-energy derived datasets. Methods In this retrospective, single center study, 16 patients (9 male, 7 female, average age 59.4±13.2 years) with pathologically diagnosed pancreatic cancer were enrolled. All patients received an abdominal scan using a dual source CT scanner 7 to 31 days before biopsy or surgery. After injection of iodine contrast agent, arterial and pancreatic parenchyma phase were scanned consequently, using a dual-energy scan mode (100 kVp/230 mAs and Sn 140 kVp/178 mAs) in the pancreatic parenchyma phase. A series of derived dual-energy datasets were evaluated including non-liner blending (non-linear blending width 0-500 HU; blending center -500 to 500 HU), mono-energetic (40-190 keV), 100 kVp and 140 kVp. On each datasets, mean CT values of the pancreatic parenchyma and tumor, as well as standard deviation CT values of subcutaneous fat and psoas muscle were measured. Regions of interest of cutaneous fat and major psoas muscle of 100 kVp and 140 kVp images were calculated. Best CNR of subcutaneous fat (CNRF) and CNR of the major psoas muscle (CNRM) of non-liner blending and mono-energetic datasets were calculated with the optimal mono-energetic keV setting and the optimal blending center/width setting for the best CNR. One Way ANOVA test was used for comparison of best CNR between different dual-energy derived datasets. Results The best CNRF (4.48±1.29) was obtained from the non-liner blending datasets at blending center -16.6±103.9 HU and blending width 12.3±10.6 HU. The best CNRF (3.28±0.97) was obtained from the mono-energetic datasets at 73.3±4.3 keV. CNRF in the 100 kVp and 140 kVp were 3.02±0.91 and 1.56±0.56 respectively. Using fat as the noise background, all of these images series showed significant differences (Pbest CNRF of mono-energetic image sets vs. CNRF of 100 kVp image (P=0.460). Similar results were

Origin of induced pancreatic islet tumors: a radioautographic study

International Nuclear Information System (INIS)

Michels, J.E.; Bauer, G.E.; Dixit, P.K.

1987-01-01

Endocrine tumors of the pancreas are induced in a high percentage of young rats by injections of streptozotocin and nicotinamide (SZ/NA). Benign tumors first appear 20 to 36 weeks after drug injections. To determine the possible site of their origin, the incorporation of [ 3 H]thymidine into islets, ducts, acini, microtumors, and gross tumors was examined by radioautography of histologic sections at 1 to 36 weeks after drug injection. Drug treatment led to early (1- to 6-week) increases in nuclear 3 H labeling of exocrine pancreatic structures (ductal and acinar cells), which may involve DNA repair processes. A secondary increase in labeling of duct cells during the period of tumor emergence supports the assumption that SZ/NA-induced tumors are of ductal origin. Microtumors and gross tumors also exhibited markedly elevated rates of [ 3 H]thymidine incorporation compared to control islets. Nontumorous islet tissue, which exhibited a gradual decrease in volume due to B-cell destruction by the drug injection, showed about 10-fold higher 3 H labeling than islets of controls at all time points. The results suggest that in addition to ductal precursors, islets that survive SZ/NA-induced injury may also provide sites of focal endocrine cell differentiation to tumor tissue. Once established, both microtumors and gross tumors continue to grow by accelerated cell division

Comparison of Scintigraphic and Radiological Results in the Diagnosis of Pancreatic Diseases

Energy Technology Data Exchange (ETDEWEB)

Deininger, H. K.; Sielaff, H. J. [Strahlenklinik der Staedt. Krankenanstalten Heilbronn, Heilbronn, Federal Republic of Germany (Germany)

1969-05-15

The results obtained by pancreas scanning and standard radiological diagnostic methods are compared. The roentgenographic examinations of the stomach, intestine, colon, biliary tract and kidneys were performed by standard X-ray methods and by abdominal tomography with pneumoretroperitoneum. Special methods of a radiological pancreatic diagnosis, e.g. selective angiography and intra-operative pancreatography, are intentionally not considered. So far 192 pancreas scans have been carried out after administration of {sup 75}Se-1 -selenomethionine. The patients were prepared either with a special diet or a fasting period. The quality of the pancreas scans depended on the functional state of the pancreatic tissue and a comparison with phantom studies allowed an approximate estimation of the extent of the parenchymatous lesions. Of the 87 cases with proven pancreatic diseases the results were compared with the scintigraphical and radiological findings. This comparative research illustrates the superiority of pancreas scanning over the conventional rontgenographic methods in the exclusion or detection of pancreatic diseases. (author)

Pancreatic Carcinoma: the Disease that Kills.

Science.gov (United States)

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

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

Science.gov (United States)

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.

Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

Science.gov (United States)

Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

2016-06-01

The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Radiation treatment causes macrophages

Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

Science.gov (United States)

Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro

2017-04-01

The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

Abdominal leimyosarcoma simulating a pancreatic cystoadenocarcinoma. A case report and clinical-anatomo radiological correlation

International Nuclear Information System (INIS)

Montagnini, A.L.; Machado, M.C.C.; Zerbini, C.; Cerri, G.G.; Magalhaes, A.; Pinotti, H.W.

1989-01-01

The authors present one case of a large abdominal leiomyosarcoma. Due its localization and echographic and tomographic characteristics it was initially thought to be of pancreatic origin. The diagnosis was performed by laparotomy that showed a tumor not related to the pancreas, but the origin of the tumor has not been established. (author)

Cystic tumors of the pancreas

International Nuclear Information System (INIS)

Brambs, H.J.; Juchems, M.

2008-01-01

Cystic lesions of the pancreas encompass a broad spectrum of benign, premalignant, and malignant tumors which are primarily cystic or result from cystic necroses of solid neoplasms. Because of the wide use of cross-sectional imaging techniques they are increasingly being identified in asymptomatic patients as well as in patients presenting with abdominal pain, jaundice or pancreatitis. Among these lesions, intraductal papillary mucinous neoplasms, serous cystic neoplasms and mucinous cystic neoplasms represent the majority of cases. With increasing experience with these tumors, a refinement of our understanding of their morphology and of their natural course has emerged. It is important to be familiar with the CT and MR imaging features of these lesions to differentiate these tumors and to orient the diagnosis towards benign or malignant forms. Because characterization of cystic tumors of the pancreas can sometimes be difficult due to overlapping imaging features, additional criteria such as clinical symptoms, localization, age and gender have to be taken into account. If appropriately treated, these tumors can usually be cured by resection and the decreasing risk of pancreatic surgery has led to an increasing number of resections of pancreatic tumors. The management of cystic tumors of the pancreas has not yet been standardized and the correct evaluation and subsequent management of the disease in asymptomatic patients have not been fully defined. (orig.) [de

Pancreatic trauma.

Science.gov (United States)

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

United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU).

Science.gov (United States)

Löhr, J Matthias; Dominguez-Munoz, Enrique; Rosendahl, Jonas; Besselink, Marc; Mayerle, Julia; Lerch, Markus M; Haas, Stephan; Akisik, Fatih; Kartalis, Nikolaos; Iglesias-Garcia, Julio; Keller, Jutta; Boermeester, Marja; Werner, Jens; Dumonceau, Jean-Marc; Fockens, Paul; Drewes, Asbjorn; Ceyhan, Gürlap; Lindkvist, Björn; Drenth, Joost; Ewald, Nils; Hardt, Philip; de Madaria, Enrique; Witt, Heiko; Schneider, Alexander; Manfredi, Riccardo; Brøndum, Frøkjer J; Rudolf, Sasa; Bollen, Thomas; Bruno, Marco

2017-03-01

There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and Evaluation Directorate). After a final round of adjustments based on these comments, a draft version was sent out to external reviewers. The 101 recommendations covered 12 topics related to the clinical management of chronic pancreatitis: aetiology (working party (WP)1), diagnosis of chronic pancreatitis with imaging (WP2 and WP3), diagnosis of pancreatic exocrine insufficiency (WP4), surgery in chronic pancreatitis (WP5), medical therapy (WP6), endoscopic therapy (WP7), treatment of pancreatic pseudocysts (WP8), pancreatic pain (WP9), nutrition and malnutrition (WP10), diabetes mellitus (WP11) and the natural course of the disease and quality of life (WP12). Using the Grading of Recommendations Assessment, Development and Evaluation system, 70 of the 101 (70%) recommendations were rated as 'strong' and plenary voting revealed 'strong agreement' for 99 (98%) recommendations. The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects

Pancreatic Adenocarcinoma Therapeutic Targets Revealed by Tumor-Stroma Cross-Talk Analyses in Patient-Derived Xenografts

Directory of Open Access Journals (Sweden)

Rémy Nicolle

2017-11-01

Full Text Available Preclinical models based on patient-derived xenografts have remarkable specificity in distinguishing transformed human tumor cells from non-transformed murine stromal cells computationally. We obtained 29 pancreatic ductal adenocarcinoma (PDAC xenografts from either resectable or non-resectable patients (surgery and endoscopic ultrasound-guided fine-needle aspirate, respectively. Extensive multiomic profiling revealed two subtypes with distinct clinical outcomes. These subtypes uncovered specific alterations in DNA methylation and transcription as well as in signaling pathways involved in tumor-stromal cross-talk. The analysis of these pathways indicates therapeutic opportunities for targeting both compartments and their interactions. In particular, we show that inhibiting NPC1L1 with Ezetimibe, a clinically available drug, might be an efficient approach for treating pancreatic cancers. These findings uncover the complex and diverse interplay between PDAC tumors and the stroma and demonstrate the pivotal role of xenografts for drug discovery and relevance to PDAC.

The Adnectin CT-322 is a novel VEGF receptor 2 inhibitor that decreases tumor burden in an orthotopic mouse model of pancreatic cancer

Directory of Open Access Journals (Sweden)

Miller Andrew F

2008-11-01

Full Text Available Abstract Background Pancreatic cancer continues to have a 5-year survival of less than 5%. Therefore, more effective therapies are necessary to improve prognosis in this disease. Angiogenesis is required for tumor growth, and subsequently, mediators of angiogenesis are attractive targets for therapy. Vascular endothelial growth factor (VEGF is a well-characterized mediator of tumor angiogenesis that functions primarily by binding and activating VEGF receptor 2 (VEGFR2. In this study, we evaluate the use of CT-322, a novel biologic (Adnectin. This small protein is based on a human fibronectin domain and has beneficial properties in that it is fully human, stable, and is produced in bacteria. CT-322 binds to and inhibits activation of VEGFR2. Methods The efficacy of CT-322 was evaluated in vivo using two orthotopic pancreatic tumor models. The first model was a human tumor xenograft where MiaPaCa-2 cells were injected into the tail of the pancreas of nude mice. The second model was a syngeneic tumor using Pan02 cells injected into pancreas of C57BL/6J mice. In both models, therapy was initiated once primary tumors were established. Mice bearing MiaPaCa-2 tumors were treated with vehicle or CT-322 alone. Gemcitabine alone or in combination with CT-322 was added to the treatment regimen of mice bearing Pan02 tumors. Therapy was given twice a week for six weeks, after which the animals were sacrificed and evaluated (grossly and histologically for primary and metastatic tumor burden. Primary tumors were also evaluated by immunohistochemistry for the level of apoptosis (TUNEL, microvessel density (MECA-32, and VEGF-activated blood vessels (Gv39M. Results Treatment with CT-322 was effective at preventing pancreatic tumor growth and metastasis in orthotopic xenograft and syngeneic models of pancreatic cancer. Additionally, CT-322 treatment increased apoptosis, reduced microvessel density and reduced the number of VEGF-activated blood vessels in tumors

Four-dimensional measurement of intrafractional respiratory motion of pancreatic tumors using a 256 multi-slice CT scanner

International Nuclear Information System (INIS)

Mori, Shinichiro; Hara, Ryusuke; Yanagi, Takeshi; Sharp, Gregory C.; Kumagai, Motoki; Asakura, Hiroshi; Kishimoto, Riwa; Yamada, Shigeru; Kandatsu, Susumu; Kamada, Tadashi

2009-01-01

Purpose: To quantify pancreas and pancreatic tumor movement due to respiratory motion using volumetric cine CT images. Materials and methods: Six patients with pancreatic tumors were scanned in cine mode with a 256 multi-slice CT scanner under free breathing conditions. Gross tumor volume (GTV) and pancreas were manually contoured on the CT data set by a radiation oncologist. Intrafractional respiratory movement of the GTV and pancreas was calculated, and the results were compared between the respiratory ungated and gated phases, which is a 30% duty cycle around exhalation. Results: Respiratory-induced organ motion was observed mainly in the anterior abdominal side than the posterior side. Average GTV displacement (ungated/gated phases) was 0.7 mm/0.2 mm in both the left and right directions, and 2.5 mm/0.9 mm in the anterior, 0.1 mm/0 mm in the posterior, and 8.9 mm/2.6 mm in the inferior directions. Average pancreas center of mass displacement relative to that at peak exhalation was mainly in the inferior direction, at 9.6 mm in the ungated phase and 2.3 mm in the gated phase. Conclusions: By allowing accurate determination of the margin, quantitative analysis of tumor and pancreas displacement provides useful information in treatment planning in all radiation approaches for pancreatic tumors.

A model for cell migration in non-isotropic fibrin networks with an application to pancreatic tumor islets.

Science.gov (United States)

Chen, Jiao; Weihs, Daphne; Vermolen, Fred J

2018-04-01

Cell migration, known as an orchestrated movement of cells, is crucially important for wound healing, tumor growth, immune response as well as other biomedical processes. This paper presents a cell-based model to describe cell migration in non-isotropic fibrin networks around pancreatic tumor islets. This migration is determined by the mechanical strain energy density as well as cytokines-driven chemotaxis. Cell displacement is modeled by solving a large system of ordinary stochastic differential equations where the stochastic parts result from random walk. The stochastic differential equations are solved by the use of the classical Euler-Maruyama method. In this paper, the influence of anisotropic stromal extracellular matrix in pancreatic tumor islets on T-lymphocytes migration in different immune systems is investigated. As a result, tumor peripheral stromal extracellular matrix impedes the immune response of T-lymphocytes through changing direction of their migration.

Diagnosis and treatment of solid pseudopapillary tumor of the pancreas: experience of one single institution from Turkey

Science.gov (United States)

2013-01-01

Background Solid pseudopapillary neoplasia (SPN) of the pancreas is an extremely rare epithelial tumor of low malignant potential. SPN accounts for less than 1% to 2% of exocrine pancreatic tumors. The aim of this study is to report our experience with SPN of the pancreas. It includes a summary of the current literature to provide a reference for the management of this rare clinical entity. Methods A retrospective analysis was performed of all patients diagnosed and treated for SPN in our hospital over the past 15 years (1998 to 2013). A database of the characteristics of these patients was developed, including age, gender, tumor location and size, treatment, and histopathological and immunohistochemical features. Results During this time period, 255 patients with pancreatic malignancy (which does not include ampulla vateri, distal choledocal and duodenal tumor) were admitted to our department, only 10 of whom were diagnosed as having SPN (2.5%). Nine patients were women (90%) and one patient was a man (10%). Their median age was 38.8 years (range 18 to 71). The most common symptoms were abdominal pain and dullness. Seven patients (70%) presented with abdominal pain or abdominal dullness and three patient (30%) were asymptomatic with the diagnosis made by an incidental finding on routine examination. Abdominal computed tomography and/or magnetic resonance imaging showed the typical features of solid pseudopapillary neoplasm in six (60%) of the patients. Four patients underwent distal pancreatectomy with splenectomy, one patient underwent a total mass excision, and one patient underwent total pancreatic resection. Two required extended distal pancreatectomy with splenectomy. Two underwent spleen-preserving distal pancreatectomy. Conclusions SPN is a rare neoplasm that primarily affects young women. The prognosis is favorable even in the presence of distant metastasis. Although surgical resection is generally curative, a close follow-up is advised in order to

Clinical significance of magnetic resonance cholangiopancreatography for the diagnosis of cystic tumor of the pancreas compared with endoscopic retrograde cholangiopancreatography and computed tomography

International Nuclear Information System (INIS)

Mera, Kiyomi; Tajiri, Hisao; Muto, Manabu

1999-01-01

Cystic tumor of the pancreas has been investigated by a variety of imaging techniques. Magnetic resonance cholangiopancreatography (MRCP) is being widely used as a non-invasive diagnostic modality for investigation of the biliary tree and pancreatic duct system. The purpose of this study was to compare MRCP images with those of endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) in order to clarify the diagnostic efficacy of MRCP for cystic tumor of the pancreas. We retrospectively studied 15 patients with cystic tumor of the pancreas that had been surgically resected and histopathologically confirmed. There were five cases of intraductal papillary adenocarcinoma, five of intraductal papillary adenoma, two of serous cyst adenoma, two of retention cyst associated with invasive ductal adenocarcinoma and one of solid cystic tumor. In all cases MRCP correctly identified the main pancreatic duct (MPD) and showed the entire cystic tumor and the communication between the tumor and the MPD. On the other hand, the detection rate by ERCP of the cystic tumor and the communication between the cystic tumor and the MPD was only 60%. Although the detection rates by CT for the septum and solid components inside the cystic tumor were 100 and 90.0%, respectively, those of MRCP for each were 58.3 and 20.0%. MRCP is capable of providing diagnostic information superior to ERCP for the diagnosis of cystic tumor of the pancreas. Although MRCP may provide complementary information about the whole lesion of interest, the characteristic internal features of cystic tumor of the pancreas should be carefully diagnosed in combination with CT. (author)

Relationship of pancreatic mass size and diagnostic yield of endoscopic ultrasound-guided fine needle aspiration.

Science.gov (United States)

Siddiqui, Ali A; Brown, Lauren J; Hong, Shih-Kuang S; Draganova-Tacheva, Rossitza A; Korenblit, Jason; Loren, David E; Kowalski, Thomas E; Solomides, Charalambos

2011-11-01

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is central to discerning the diagnosis of solid pancreatic tumors through tissue acquisition. Test performance is affected by a number of factors including location of mass within the pancreas, presence of onsite cytology technologist, and number of passes with the needle. The influence of tumor size has not been well studied. The objective of the current study was to determine whether the size of mass affects the diagnostic accuracy for solid pancreatic lesions aspirated under EUS guidance. Data were collected retrospectively on all patients with solid pancreatic masses undergoing EUS-FNA from June 2003 to August 2010. The cytology samples were reported as positive, suspicious for malignancy, atypical, negative, or nondiagnostic. The gold standard for a cytological diagnosis was histological confirmation or clinical follow-up of more than 6 months with repeat imaging. Patients were divided into five groups based upon lesion size as follows: (a) less than 1 cm, (b) 1-2 cm, (c) 2-3 cm, (d) 3-4 cm, and (e) greater than 4 cm. Performance characteristics of EUS-FNA including sensitivity, specificity, and accuracy were compared for each group. Accuracy was defined as the ratio of the sum of true-positive and true-negative values divided by the number of lesions. We identified 583 patients with solid pancreatic lesions in which EUS-FNA was performed and adequate cellularity was obtained (47% men, mean age 65 ± 1.4 (SE) years). Overall, 486 (83%) of lesions were pancreatic adenocarcinoma, 18 (3%) were neuroendocrine tumors, 12 (2%) were lymphomas, and 67 (12%) were benign lesions. The median size of the mass was 3 cm (range, 0.5-7 cm). A mean of 4.9 passes (range, 1-9 passes) was needed to obtain adequate samples from lesions. The overall yield of obtaining adequate samples for diagnosis was 85%. When stratified by size, the EUS-FNA sensitivity for lesions with size 4 cm was 40, 75.9, 86.9, 93

Spectral CT imaging in differential diagnosis of pancreatic serous oligocystic adenoma and mucinous cystic neoplasms

International Nuclear Information System (INIS)

Lin Xiaozhu; Chen Kemin; Wu Zhiyuan; Tao Ran; Guo Yan; Zhang Jing; Li Jianying; Shen Yun

2011-01-01

Objective: To investigate the CT spectral imaging features of pancreatic serous oligocystic adenoma and mucinous cystic neoplasms and to assess the value of spectral CT in differentiating between pancreatic serous oligocystic adenoma and mucinous cystic neoplasms. Methods: From Feb. 2010 to Dec. 2010, 27 patients with cystic neoplasms of the pancreas (group one with 15 serous oligocystic adenomas and group two with 12 mucinous cystic neoplasms) underwent dual-phase CT spectral imaging followed by surgery. Quantitative values (age, tumor size, CT value change as function of photon energy, effective-Z, iodine-water concentration, and calcium-water concentration) were compared with independent samples t test and Mann-Whitney test and non-quantitative parameters (gender, symptom, and tumor location) were compared with Chi-square test (Fisher exact). The parameters with significant differences between two groups were analyzed further and the performance of multiple parameters for joint differential diagnosis was evaluated with discriminant analysis. Results: Compared to patients with mucinous cystic neoplasms, patients with serous oligocystic adenoma had younger age, lower frequency of being symptomatic and smaller tumor size. The CT values on 40 keV to 60 keV (with 10 keV increment) in late arterial phase [(36±13) HU vs. (62±23) HU, (26±8) HU vs. (40±15) HU, and (19±6) HU vs. (27±10) HU respectively] and 40 keV to 50 keV (with 10 keV increment) in portal venous phase [(43±14) HU vs. (61±25) HU and (30±10) HU vs. (40±16) HU respectively], effective-Z (late arterial phase 7.80± 0.16 vs. 8.05±0.21, and portal venous phase 7.87±0.15 vs 8.02±0.22), concentration of calcium (water) [late arterial phase (5±3) g/L vs. (11±4) g/L, t=-3.836, P=0.001 and portal venous phase (7±3) g/L vs. (10±5) g/L, t=-2.071, P=0.049] and iodine (water) [late arterial phase (0.38±0.24) g/L vs. (0.78±0.32) g/L, t=-3.755, P=0.001 and portal venous phase (0.48± 0.24) g/L vs. (0

HDAC gene expression in pancreatic tumor cell lines following treatment with the HDAC inhibitors panobinostat (LBH589) and trichostatine (TSA).

Science.gov (United States)

Mehdi, Ouaïssi; Françoise, Silvy; Sofia, Costa Lima; Urs, Giger; Kevin, Zemmour; Bernard, Sastre; Igor, Sielezneff; Anabela, Cordeiro-da-Silva; Dominique, Lombardo; Eric, Mas; Ali, Ouaïssi

2012-01-01

In this study, the effect of LBH589 and trichostatin (TSA), a standard histone deacetylase inhibitor (HDACi) toward the growth of pancreatic cancer cell lines was studied. Thus, we examined for the first time, the HDAC family gene expression levels before and after drug treatment. Several human pancreatic cancer cell lines (Panc-1, BxPC-3, SOJ-6) and a normal human pancreatic duct immortalized epithelial cell line (HPDE/E6E7) were used as target cells. The cell growth was measured by MTT assay, cell cycle alteration, membrane phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane potential loss, RT-PCR and Western blots were done using standard methods. The effect of drugs on tumor growth in vivo was studied using subcutaneous xenograft model. Except in the case of certain HDAC gene/tumor cell line couples: (SIRT1/HPDE-SOJ6/TSA- or LBH589-treated cells; LBH589-treated Panc-1 Cells; HDAC2/BxPC-3/LBH589-treated cells or TSA-treated SOJ-6-1 cells), there were no major significant changes of HDACs genes transcription in cells upon drug treatment. However, significant variation in HDACs and SIRTs protein expression levels could be seen among individual cell samples. The in vivo results showed that LBH589 formulation exhibited similar tumor reduction efficacy as the commercial drug gemcitabine. Our data demonstrate that LBH589 induced the death of pancreatic tumor cell by apoptosis. In line with its in vitro activity, LBH589 achieved a significant reduction in tumor growth in BxPC-3 pancreatic tumor cell line subcutaneous xenograft mouse model. Furthermore, exploring the impact of LBH589 on HDACs encoding genes expression revealed for the first time that some of them, depending on the cell line considered, seem to be regulated during translation. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Pancreatic adenocarcinoma: combination of MR imaging, MR angiography and MR cholangiopancreatography for the diagnosis and assessment of resectability

International Nuclear Information System (INIS)

Catalano, C.; Pavone, P.; Laghi, A.; Panebianco, V.; Scipioni, A.; Fanelli, F.; Brillo, R.; Passariello, R.

1998-01-01

The purpose of this study was to determine the possibility of integrating MR cholangiopancreatography (MRCP) and MR angiography (MRA) to conventional MR images in the diagnosis and assessment of resectability of pancreatic adenocarcinoma. Twenty-three patients with pancreatic adenocarcinoma were prospectively examined with MR. Conventional MR images were acquired in all patients. Three-dimensional MRCP and MRA images were acquired in all patients with suspected biliary and vascular involvement. Acquisition time was less than 45 min in all cases. Images were independently evaluated by two radiologists, with final reading decided by consensus among readers. Diagnosis was confirmed with surgery in 16 patients and with percutaneous biopsy in 7. Concordance among readers was high with a kappa value of 0.83. Pancreatic adenocarcinoma was observed in all patients. Correct assessment of unresectability due to vascular involvement was found in 22 of 23 patients. Biliary obstruction was evident in 13 patients, involving the biliary and pancreatic ducts in 9 and the biliary ducts only in 4. Technical advances permit extensive use of MRI in the evaluation of abdominal pathologies. The combination of MR imaging, MRCP, and MRA can provide sufficient information for the diagnosis and assessment of resectability of pancreatic adenocarcinoma, which otherwise would require three different exams. (orig.)

Road accident due to a pancreatic insulinoma: a case report.

Science.gov (United States)

Parisi, Amilcare; Desiderio, Jacopo; Cirocchi, Roberto; Grassi, Veronica; Trastulli, Stefano; Barberini, Francesco; Corsi, Alessia; Cacurri, Alban; Renzi, Claudio; Anastasio, Fabio; Battista, Francesca; Pucci, Giacomo; Noya, Giuseppe; Schillaci, Giuseppe

2015-03-01

Insulinoma is a rare pancreatic endocrine tumor, typically sporadic and solitary. Although the Whipple triad, consisting of hypoglycemia, neuroglycopenic symptoms, and symptoms relief with glucose administration, is often present, the diagnosis may be challenging when symptoms are less typical. We report a case of road accident due to an episode of loss of consciousness in a patient with pancreatic insulinoma. In the previous months, the patient had occasionally reported nonspecific symptoms. During hospitalization, endocrine examinations were compatible with an insulin-producing tumor. Abdominal computerized tomography and magnetic resonance imaging allowed us to identify and localize the tumor. The patient underwent a robotic distal pancreatectomy with partial omentectomy and splenectomy. Insulin-producing tumors may go undetected for a long period due to nonspecific clinical symptoms, and may cause episodes of loss of consciousness with potentially lethal consequences. Robot-assisted procedures can be performed with the same techniques of the traditional surgery, reducing surgical trauma, intraoperative blood loss, and hospital stays.

Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.

Science.gov (United States)

Casar-Borota, Olivera; Botling, Johan; Granberg, Dan; Stigare, Jerker; Wikström, Johan; Boldt, Henning Bünsow; Kristensen, Bjarne Winther; Pontén, Fredrik; Trouillas, Jacqueline

2017-09-01

Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

Prognostic significance of new onset ascites in patients with pancreatic cancer

Directory of Open Access Journals (Sweden)

Luzardo German

2006-03-01

Full Text Available Abstract Background The purpose of this study was to determine risk factors for development of malignant ascites and its prognostic significance in patients with pancreatic cancer. Methods A prospective database was queried to identify patients with pancreatic cancer who develop ascites. Stage at presentation, size, and location of primary tumor, treatment received and length of survival after onset of ascites were determined. Results A total of 15 patients were identified. Of which 4 patients (1 stage II, 3 stage III underwent pancreaticoduodenectomy and manifested with ascites 2, 3, 24 and 47 months after surgery (tumor size 2.9 ± 1.32 cm. All but one of the remaining 11 patients (tumor size 4.4 ± 3.38 cm presented with metastatic disease, and all developed malignant ascites 9 months after diagnosis, dying 2 months later. Resected patients lived longer before the onset of ascites, but not after. Conclusion Once diagnosed, ascites in pancreatic cancer patients heralds imminent death. Limited survival should be considered when determining the aggressiveness of further intervention.

Neuroendocrine Tumor, diagnostic difficulties

Directory of Open Access Journals (Sweden)

Pedro Oliveira

2017-06-01

Full Text Available Ectopic adrenocorticotropic hormone (ACTH secretion is a rare disease. A 51 years old woman, with a Cushing syndrome secondary to ectopic ACTH secretion, diagnosed in 2009, with mediastinal lymphadenopathy, whose biopsy was compatible with lung small cell carcinoma, staged as IIIB using TNM classification. No other lesions were found in patient study. The patient was submitted to chemotherapy, associated to ketoconazole 200 mg twice daily, with partial remission of both conditions. Three years later was admitted with an aggravation of Cushing syndrome. There was no evidence of progression of pulmonary disease. A cystic lesion in the pancreatic uncinated process was found by abdominal CT scan and with avid uptake by DOTANOC PET discreet in anterior mediastinal lymphadenopathy. Biopsy of pancreatic mass revealed a neuroendocrine tumor. Pulmonary masses were biopsied again and was in favor of neuroendocrine tumor. It was assumed the diagnosis of pancreatic neuroendocrine tumor with mediastinal metastasis. The patient initiated lanreotid (120 mg, monthly, subcutaneous in association with ketoconazole. After 5 months of therapy, patient died with sepsis secondary to pneumonia. Neuroendocrine tumours are rare, difficult to diagnose and with poor prognosis when associated with ectopic ACTH secreting Cushing syndrome.

Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells

Science.gov (United States)

ZHAO, LU; ZHAO, YUE; SCHWARZ, BETTINA; MYSLIWIETZ, JOSEF; HARTIG, ROLAND; CAMAJ, PETER; BAO, QI; JAUCH, KARL-WALTER; GUBA, MAKUS; ELLWART, JOACHIM WALTER; NELSON, PETER JON; BRUNS, CHRISTIANE JOSEPHINE

2016-01-01

Tumor side population (SP) cells display stem-like properties that can be modulated by treatment with the calcium channel blocker verapamil. Verapamil can enhance the cytotoxic effects of chemotherapeutic drugs and multi-drug resistance by targeting the transport function of the P-glycoprotein (P-gp). This study focused on the therapeutic potential of verapamil on stem-like SP tumor cells, and further investigated its chemosensitizing effects using L3.6pl and AsPC-1 pancreatic carcinoma models. As compared to parental L3.6pl cells (0.9±0.22%), L3.6pl gemcitabine-resistant cells (L3.6plGres) showed a significantly higher percentage of SP cells (5.38±0.99%) as detected by Hoechst 33342/FACS assays. The L3.6plGres SP cells showed stable gemcitabine resistance, enhanced colony formation ability and increased tumorigenicity. Verapamil effectively inhibited L3.6plGres and AsPC-1 SP cell proliferation in vitro. A pro-apoptotic effect of verapamil was observed in L3.6pl cells, but not in L3.6plGres cells, which was linked to their differential expression of P-gp and equilibrative nucleoside transporter-1 (ENT-1). In an orthotopic pancreatic cancer mouse model, both low and high dose verapamil was shown to substantially reduce L3.6plGres-SP cell tumor growth and metastasis, enhance tumor apoptosis, and reduce microvascular density. PMID:27177126

Recurrence of Solid Pseudopapillary Tumor: A Rare Pancreatic Tumor

Directory of Open Access Journals (Sweden)

Chandra Punch

2016-01-01

Full Text Available Solid pseudopapillary tumor of the pancreas (SPTP is a rare disease of young females that does not usually recur after resection. Here we report a case of an elderly female with history of SPTP ten years ago who presented with anorexia and a palpable left lower quadrant abdominal mass. Imaging revealed metastatic disease and US-guided biopsy of the liver confirmed the diagnosis of SPTP. Due to her advanced age and comorbidities, she elected to undergo hospice care. The objective of this case report is to increase awareness of this tumor and its possibility of recurrence, necessitating further guidelines for follow-up.

Short- and long-term outcomes after enucleation of pancreatic tumors: An evidence-based assessment.

Science.gov (United States)

Zhou, Yanming; Zhao, Min; Wu, Lupeng; Ye, Feng; Si, Xiaoying

Enucleation of pancreatic tumors is rarely performed. The aim of this study was to evaluate the published evidence for its short- and long-term outcomes. PubMed (MEDLINE) and EMBASE databases were searched from 1990 to March 2016. Studies including at least ten patients who underwent enucleation of pancreatic lesions were included. Data on the outcomes were synthesized and meta-analyzed where appropriate. Twenty-seven studies involving 1316 patients were included in the systematic review. The postoperative mortality was 0.3%, and the postoperative morbidity was 50.3%, mainly represented by pancreatic fistula (38.1%). Endocrine insufficiency, exocrine insufficiency and tumor recurrence was observed in 2.4%, 1.1% and 2.3% of the patients respectively. Compared with typical resection, the operation time, blood loss, length of hospital stay, and the incidence of endocrine and exocrine insufficiency were all significantly reduced after enucleation. The occurrence of pancreatic fistula was significantly higher in enucleation group, but overall morbidity, the reoperation rate and mortality were comparable between the two groups. There was no significant difference in disease recurrence between the two groups. Compared with central pancreatectomy, enucleation had a shorter operation time, lower blood loss, less morbidity, and better pancreatic function. Compared with open enucleation, minimally invasive enucleation had a shorter operation time and a shorter length of hospital stay. Enucleation is an appropriate surgical procedure in selected patients with benign or low-malignant lesions of the pancreas. The benefits of minimally invasive approach need to be validated in further investigations with larger groups of patients. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

The radiological diagnosis of bone tumors

International Nuclear Information System (INIS)

Freyschmidt, J.

1979-01-01

Since the definitive diagnosis of very many bone tumors is not only histological but also radiological it is important that the latter examination be of high quality. Prior to biopsy the differential diagnosis should be narrowed down as far as possible radiologically. The radiological procedures include conventional X-ray examination in two projections, tomography, angiography, and computerized tomography. Tomography can reveal the borders of the tumor and minute clacifications within the tumor. Angiography may show atypically vascularized areas and thus be helpful in choosing the best site for biopsy and in making a prognosis. It might reveal, for example, unusual vascularization or penetration of tumor into blood vessels. Computerized tomography allows precise delineation of the intraosseous and extraosseous borders of the tumor, and is particularly useful in this respect in regions in which angiography has its technical limitations, such as the pelvis and the spine. The radiological assessment of a tumor or tumor-like lesion should take account of the structural changes, the site of the lesion, and the age and sex of the patient. The report should include a statement about the malignancy of the lesion. (orig.) [de

Clinicopathological features of pancreatic mucinous cystic neoplasm and influencing factors for its malignancy

Directory of Open Access Journals (Sweden)

HOU Liyan

2017-08-01

Full Text Available ObjectiveTo investigate the clinicopathological features of pancreatic mucinous cystic neoplasm (MCN and influencing factors for benign and malignant MCN. MethodsA retrospective analysis was performed for the clinical data of 43 patients with pathologically confirmed pancreatic MCN who were treated from January 2013 to December 2015, and according to the results of pathological diagnosis, the patients were divided into benign group (mucinous cystadenoma and pancreatic MCN with low/middle-grade dysplasia and malignant group (MCN with high-grade dysplasia and MCN with invasive carcinoma. The clinicopathological features and radiological features were summarized, and the risk factors for malignant transformation of pancreatic MCN were analyzed. The independent samples t-test was used for comparison of continuous data between groups, the chi-square test or Fisher's exact test was used for comparison of categorical data between groups, and a multivariate logistic regression analysis was used to identify risk factors. ResultsThere were 14 male and 29 female patients aged 22-81 years (median 58.53 years. Of all patients, 30 (69.8% had clinical symptoms. The maximum tumor diameter was 4.8 cm (range 1.2-16 cm. Of all patients, 18 (41.9% had MCN in the head of the pancreas, 3 (7.0% had MCN in the neck of the pancreas, 20 (46.5% had MCN in the body and tail of the pancreas, and 2 (4.6% had multiple MCNs. There were significant differences between the two groups in age, tumor nature, tumor location, texture, tumor markers, heterogeneous enhancement of the cyst wall, heterogeneous enhancement of solid components, and cyst wall thickness ＞0.2 cm. The multivariate logistic regression analysis showed that age and increased tumor markers were independent predictive factors for malignant pancreatic MCN (P ＜0.05. ConclusionAge, tumor nature, tumor location, texture, increased tumor markers, heterogeneous enhancement of the cyst wall, heterogeneous enhancement

An exceptional collision tumor: gastric calcified stromal tumor and ...

African Journals Online (AJOL)

The authors report an exceptional case of collision tumor comprised of a gastric calcified stromal tumor and a pancreatic adenocarcinoma. The pancreatic tumor was detected fortuitously on the histological exam of resection specimen. Key words: Collision tumor, stromal tumor, adenocarcinoma ...

Two-step Raman spectroscopy method for tumor diagnosis

Science.gov (United States)

Zakharov, V. P.; Bratchenko, I. A.; Kozlov, S. V.; Moryatov, A. A.; Myakinin, O. O.; Artemyev, D. N.

2014-05-01

Two-step Raman spectroscopy phase method was proposed for differential diagnosis of malignant tumor in skin and lung tissue. It includes detection of malignant tumor in healthy tissue on first step with identification of concrete cancer type on the second step. Proposed phase method analyze spectral intensity alteration in 1300-1340 and 1640-1680 cm-1 Raman bands in relation to the intensity of the 1450 cm-1 band on first step, and relative differences between RS intensities for tumor area and healthy skin closely adjacent to the lesion on the second step. It was tested more than 40 ex vivo samples of lung tissue and more than 50 in vivo skin tumors. Linear Discriminant Analysis, Quadratic Discriminant Analysis and Support Vector Machine were used for tumors type classification on phase planes. It is shown that two-step phase method allows to reach 88.9% sensitivity and 87.8% specificity for malignant melanoma diagnosis (skin cancer); 100% sensitivity and 81.5% specificity for adenocarcinoma diagnosis (lung cancer); 90.9% sensitivity and 77.8% specificity for squamous cell carcinoma diagnosis (lung cancer).

Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor

NARCIS (Netherlands)

A.P.J. Jilesen (Anneke P. J.); C.H.J. van Eijck (Casper); O.R.C. Busch (Olivier); T.M. van Gulik (Thomas); D.J. Gouma (Dirk); E.J.M.N. Van Dijkum (Els J. M. Nieveen)

2016-01-01

textabstractBackground: Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of

Potential dosimetric benefits of adaptive tumor tracking over the internal target volume concept for stereotactic body radiation therapy of pancreatic cancer.

Science.gov (United States)

Karava, Konstantina; Ehrbar, Stefanie; Riesterer, Oliver; Roesch, Johannes; Glatz, Stefan; Klöck, Stephan; Guckenberger, Matthias; Tanadini-Lang, Stephanie

2017-11-09

Radiotherapy for pancreatic cancer has two major challenges: (I) the tumor is adjacent to several critical organs and, (II) the mobility of both, the tumor and its surrounding organs at risk (OARs). A treatment planning study simulating stereotactic body radiation therapy (SBRT) for pancreatic tumors with both the internal target volume (ITV) concept and the tumor tracking approach was performed. The two respiratory motion-management techniques were compared in terms of doses to the target volume and organs at risk. Two volumetric-modulated arc therapy (VMAT) treatment plans (5 × 5 Gy) were created for each of the 12 previously treated pancreatic cancer patients, one using the ITV concept and one the tumor tracking approach. To better evaluate the overall dose delivered to the moving tumor volume, 4D dose calculations were performed on four-dimensional computed tomography (4DCT) scans. The resulting planning target volume (PTV) size for each technique was analyzed. Target and OAR dose parameters were reported and analyzed for both 3D and 4D dose calculation. Tumor motion ranged from 1.3 to 11.2 mm. Tracking led to a reduction of PTV size (max. 39.2%) accompanied with significant better tumor coverage (p<0.05, paired Wilcoxon signed rank test) both in 3D and 4D dose calculations and improved organ at risk sparing. Especially for duodenum, stomach and liver, the mean dose was significantly reduced (p<0.05) with tracking for 3D and 4D dose calculations. By using an adaptive tumor tracking approach for respiratory-induced pancreatic motion management, a significant reduction in PTV size can be achieved, which subsequently facilitates treatment planning, and improves organ dose sparing. The dosimetric benefit of tumor tracking is organ and patient-specific.

Pancreatic endocrine tumors or apudomas Tumores endocrinos o apudomas pancreáticos

Directory of Open Access Journals (Sweden)

Modesto Varas

2011-04-01

Full Text Available Introduction and objective: pancreatic endocrine tumors (PET are difficult to diagnose. Their accurate localization using imaging techniques is intended to provide a definite cure. The goal of this retrospective study was to review a PET series from a private institution. Patients and methods: the medical records of 19 patients with PETs were reviewed, including 4 cases of MEN-1, for a period of 17 years (1994-2010. A database was set up with ten parameters: age, sex, symptoms, imaging techniques, size and location in the pancreas, metastasis, surgery, complications, adjuvant therapies, definite diagnosis, and survival or death. Results: a total of 19 cases were analyzed. Mean age at presentation was 51 years (range: 26-67 y (14 males, 5 females, and tumor size was 5 to 80 mm (X: 20 mm. Metastatic disease was present in 37% (7/19. Most underwent the following imaging techniques: ultrasounds, computed tomography (CT and magnetic resonance imaging (MRI. Fine needle aspiration punction (FNA was performed for the primary tumor in 4 cases. Non-functioning: 7 cases (37%, insulinoma: 2 cases [1 with possible multiple endocrine neoplasia (MEN], Zollinger-Ellison syndrome (ZES from gastrinoma: 5 (3 with MEN-1, glucagonoma: 2 cases, 2 somatostatinomas; carcinoid: 1 case with carcinoide-like syndrome. Most patients were operated upon: 14/19 (73%. Four (4/14: 28% has postoperative complications following pancreatectomy: pancreatitis, pseudocyst, and abdominal collections. Some patients received chemotherapy (4, somatostatin (3 and interferon (2 before or after surgery. Median follow-up was 48 months. Actuarial survival during the study was 73.6% (14/19. Conclusions: age was similar to that described in the literature. Males were predominant. Most cases were non-functioning (37%. Most patients underwent surgery (73% with little morbidity (28% and an actuarial survival of 73.6% at the time of the study.Introducción y objetivo: los tumores endocrinos pancre

Development of a novel preclinical pancreatic cancer research model: bioluminescence image-guided focal irradiation and tumor monitoring of orthotopic xenografts.

Science.gov (United States)

Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; Deweese, Theodore L; Herman, Joseph M

2012-04-01

We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response.

“Stealth dissemination” of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma

Science.gov (United States)

Circulating tumor cells (CTCs) appear to be involved in early dissemination of many cancers, although which characteristics are important in metastatic spread are not clear. Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal a...

TUMOR-SPECIFIC EXPRESSION AND ALTERNATIVE SPLICING OF THE COL6A3 GENE IN PANCREATIC CANCER

Science.gov (United States)

Arafat, Hwyda; Lazar, Melissa; Salem, Khalifa; Chipitsyna, Galina; Gong, Qiaoke; Pan, Te-Cheng; Zhang, Rui-Zhu; Yeo, Charles J.; Chu, Mon-Li

2011-01-01

Introduction Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease in which a prominent desmoplastic reaction is a defining characteristic. Fibrillar collagens, such as collagen I and to a lesser extent, collagen III and V comprise the majority of this stromal fibrosis. Type VI collagen (COL6) forms a microfibrillar network associated with type I collagen fibrils. The expression of COL6 has been linked to inflammation and survival. Importantly, tumor-specific alternative splicing in COL6A3 has been identified in several cancers by genome exon arrays. We evaluated the expression and localization of COL6A3 in PDA and premalignant lesions and explored the presence of alternative splicing events. Methods We analyzed paired PDA-normal (n=18), IPMN (n=5), pancreatic cystadenoma (n=5), and eight PDA cell lines with RT-PCR, using unique primers that identify total COL6A3 gene and alternative splicing sites in several of its exons. Western blot analysis and immunohistochemistry were used to analyze the expression levels and localization of COL6A3 protein in the different lesions, and in two animal models of PDA. Results COL6A3 protein levels were significantly upregulated in 77% of the paired PDA-adjacent tissue examined. COL6A3 was mainly present in the desmoplastic stroma of PDA, with high deposition around the malignant ducts and in between the sites of stromal fatty infiltration. Analysis of the COL6A3 splice variants showed tumor-specific consistent inclusion of exons 3 and 6 in 17 of the 18 (94%) paired PDA-adjacent tissues. Inclusion of exon 4 was exclusively tumor-specific, with barely detectable expression in the adjacent tissues. IPMN and pancreatic cystadenomas showed no expression of any of the examined exons. Total COL6A3 mRNA and exon 6 were identified in six PDA cell lines, but only two cell lines (MIA PACA-2 and ASPC-1) expressed exons 3 and 4. In both the xenograft and transgenic models of PDA, COL6A3 immunoreactivity was present in the stroma

Comparison of conventional and 3-dimensional computed tomography against histopathologic examination in determining pancreatic adenocarcinoma tumor size: Implications for radiation therapy planning

International Nuclear Information System (INIS)

Qiu Haoming; Wild, Aaron T.; Wang Hao; Fishman, Elliot K.; Hruban, Ralph H.; Laheru, Daniel A.; Kumar, Rachit; Hacker-Prietz, Amy; Tuli, Richard; Tryggestad, Erik; Schulick, Richard D.; Cameron, John L.; Edil, Barish H.; Pawlik, Timothy M.; Wolfgang, Christopher L.; Herman, Joseph M.

2012-01-01

Background and purpose: This study seeks to: (a) quantify radiologic-pathologic discrepancy for pancreatic adenocarcinoma by comparing tumor size on conventional computed tomography (C-CT) and 3-dimensional CT (3D-CT) to corresponding pathologic specimens; and (b) to identify clinico-pathologic characteristics predictive of radiologic-pathologic discrepancy to assist radiotherapy planning. Materials and methods: Sixty-three patients with pancreatic adenocarcinoma and preoperative C-CT and volume-rendered 3D-CT imaging within 6 weeks of resection were identified. Maximum tumor diameter (MTD) was measured on pathology, C-CT, and 3D-CT and compared for each patient as well as among different clinico-pathologic subgroups. Results: There was a trend toward C-CT underestimation of MTD compared to final pathology (p = 0.08), but no significant difference between 3D-CT MTD and pathology (p = 0.54). Pathologic tumor size was significantly underestimated by C-CT in patients with larger pathologic tumor size (>3.0 cm, p = 0.0001), smaller tumor size on C-CT ( 90 U/mL, p = 0.008), and location in the pancreatic head (p = 0.015). A model for predicting pathologic MTD using C-CT MTD and CA19-9 level was generated. Conclusions: 3D-CT may allow for more accurate contouring of pancreatic tumors than C-CT. Patients with the above clinico-pathologic characteristics may require expanded margins relative to tumor size estimates on C-CT during radiotherapy planning.

Obstructive jaundice secondary to pancreatic head adenocarcinoma in a young teenage boy: a case report

Directory of Open Access Journals (Sweden)

Khattab Mohammed

2011-09-01

Full Text Available Abstract Introduction Pancreatic adenocarcinoma is extremely rare in childhood. We report a case of metastatic pancreatic adenocarcinoma in a 13-year-old boy, revealed by jaundice. Case presentation A 13-year-old Moroccan boy was admitted with obstructive jaundice to the children's Hospital of Rabat, Department of Pediatric Oncology. Laboratory study results showed a high level of total and conjugated bilirubin. Computerized tomography of the abdomen showed a dilatation of the intra-hepatic and extra-hepatic bile ducts with a tissular heterogeneous tumor of the head of the pancreas and five hepatic lesions. Biopsy of a liver lesion was performed, and a histopathological examination of the sample confirmed the diagnosis of metastatic ductal adenocarcinoma of the pancreas. Our patient underwent a palliative biliary derivation. After that, chemotherapy was administered (5-fluorouracil and epirubicin, however no significant response to treatment was noted and our patient died six months after diagnosis. Conclusion Malignant pancreatic tumors, especially ductal carcinomas, are exceedingly rare in the pediatric age group and their clinical features and treatment usually go unappreciated by most pediatric oncologists and surgeons.

Development of a Novel Preclinical Pancreatic Cancer Research Model: Bioluminescence Image-Guided Focal Irradiation and Tumor Monitoring of Orthotopic Xenografts1

OpenAIRE

Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; DeWeese, Theodore L; Herman, Joseph M

2012-01-01

PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. B...

Evaluation of 99mTc-HYNIC-βAla-Bombesin(7-14 as an agent for pancreas tumor detection in mice

Directory of Open Access Journals (Sweden)

F.N. Carlesso

2015-01-01

Full Text Available Pancreatic adenocarcinoma is important in oncology because of its high mortality rate. Deaths may be avoided if an early diagnosis could be achieved. Several types of tumors overexpress gastrin-releasing peptide receptors (GRPr, including pancreatic cancer cells. Thus, a radiolabeled peptide derivative of gastrin-releasing peptide (GRP may be useful as a specific imaging probe. The purpose of the present study was to evaluate the feasibility of using 99mTc-HYNIC-βAla-Bombesin(7-14 as an imaging probe for Capan-1 pancreatic adenocarcinoma. Xenographic pancreatic tumor was developed in nude mice and characterized by histopathological analysis. Biodistribution studies and scintigraphic images were carried out in tumor-bearing nude mice. The two methods showed higher uptake by pancreatic tumor when compared to muscle (used as control, and the tumor-to-muscle ratio indicated that 99mTc-HYNIC-βAla-Bombesin(7-14 uptake was four-fold higher in tumor cells than in other tissues. Scintigraphic images also showed a clear signal at the tumor site. The present data indicate that 99mTc-HYNIC-βAla-Bombesin(7-14 may be useful for the detection of pancreatic adenocarcinoma.

Tumor-Targeting Salmonella typhimurium A1-R Promotes Tumoricidal CD8+ T Cell Tumor Infiltration and Arrests Growth and Metastasis in a Syngeneic Pancreatic-Cancer Orthotopic Mouse Model.

Science.gov (United States)

Murakami, Takashi; Hiroshima, Yukihiko; Zhang, Yong; Zhao, Ming; Kiyuna, Tasuku; Hwang, Ho Kyoung; Miyake, Kentaro; Homma, Yuki; Mori, Ryutaro; Matsuyama, Ryusei; Chishima, Takashi; Ichikawa, Yasushi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

2018-01-01

The present study determined the effect of the tumor-targeting strain Salmonella typhimurium A1-R (S. typhimurium A1-R) on CD8 + tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic-cancer orthotopic mouse model. The effect of tumor-targeting S. typhimurium A1-R on CD8 + TILs was determined on the Pan02 murine pancreatic-adenocarcinoma implanted orthotopically in the pancreatic tail of C57BL/6 immunocompromised mice. Three weeks after orthotopic implantation, mice were randomized as follows G1: untreated control group (n = 8); and G2: S. typhimurium A1-R-treatment group (n = 8, 1 × 10 7 colony forming units [CFU]/body, iv, weekly, 3 weeks). On the 22nd day from initial treatment, all mice were sacrificed and tumors were harvested. The tumor-volume ratio was defined as ratio of tumor volume on the 22nd day relative to the 1st day. The tumor volume ratio was significantly lower in the S. typhimurium A1-R-treated group (G2) (3.0 ± 2.8) than the untreated control (G1) (39.9 ± 30.7, P R-treated mice (G2). Six mice in G1 had peritoneal dissemination, whereas no mice showed peritoneal dissemination in G2 (P R promotes CD8 + T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634-639, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Compositions and methods involving methyladenosine phosphorylase in the diagnosis and treatment of proliferative disorders

Science.gov (United States)

Olopade, Olufunmilayo I.

2007-03-20

Disclosed are novel nucleic acid and peptide compositions comprising methylthioadenosine phosphorylase (MTAP) and methods of use for MTAP amino acid sequences and DNA segments comprising MTAP in the diagnosis of human cancers and development of MTAP-specific antibodies. Also disclosed are methods for the diagnosis and treatment of tumors and other proliferative cell disorders, and identification of tumor suppressor genes and gene products from the human 9p21-p22 chromosome region. Such methods are useful in the diagnosis of multiple tumor types such as bladder cancer, lung cancer, breast cancer, pancreatic cancer, brain tumors, lymphomas, gliomas, melanomas, and leukemias.

Acute pancreatitis: The role of imaging in diagnosis and management

Energy Technology Data Exchange (ETDEWEB)

Bharwani, Nishat, E-mail: nishat.bharwani@nhs.ne [Imaging Department, Barts and The London NHS Trust, St Bartholomew' s Hospital, Ground Floor, King George V Wing, London EC1A 7BE (United Kingdom); Patel, Shilpa; Prabhudesai, Shirish; Fotheringham, Tim; Power, Niall [Imaging Department, Barts and The London NHS Trust, St Bartholomew' s Hospital, Ground Floor, King George V Wing, London EC1A 7BE (United Kingdom)

2011-02-15

Acute pancreatitis is one of the more commonly encountered aetiologies in the emergency setting and its incidence is rising. Presentations range from a mild-self limiting condition which usually responds to conservative management to one with significant morbidity and mortality in its most severe forms. While clinical criteria are necessary to make the initial diagnosis, contrast-enhanced CT is the mainstay of imaging and has a vital role in assessing the extent and evolution of the disease and its associated complications. The purpose of this article is to summarise the natural course of acute severe pancreatitis, clarify confusing nomenclature, demonstrate the morphological stages in conjunction with radiological scoring systems and illustrate the complications. We will review and illustrate the increasing and significant role interventional radiology has in the management of these patients, which are often life-saving and surgery-sparing.

Acute recurrent pancreatitis: Etiopathogenesis, diagnosis and treatment

Science.gov (United States)

Testoni, Pier Alberto

2014-01-01

Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches. PMID:25493002

Pancreatic ductal adenocarcinoma mice lacking mucin 1 have a profound defect in tumor growth and metastasis.

Science.gov (United States)

Besmer, Dahlia M; Curry, Jennifer M; Roy, Lopamudra D; Tinder, Teresa L; Sahraei, Mahnaz; Schettini, Jorge; Hwang, Sun-Il; Lee, Yong Y; Gendler, Sandra J; Mukherjee, Pinku

2011-07-01

MUC1 is overexpressed and aberrantly glycosylated in more than 60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In this study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared with both KC and KCM. Cell lines derived from KCKO tumors have significantly less tumorigenic capacity compared with cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared with mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor, platelet-derived growth factor, or matrix metalloproteinase 9. Further, significantly less KCKO cells entered the G(2)-M phase of the cell cycle compared with the KCM cells. Proteomics and Western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of mitogen-activated protein kinase (MAPK), as well as a significant decrease in nestin and tubulin-α2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. ©2011 AACR

Evaluation of radiological prognostic factors of hepatic metastases in patients with non-functional pancreatic neuroendocrine tumors

Energy Technology Data Exchange (ETDEWEB)

Denecke, Timm [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Baur, Alexander D.J., E-mail: alexander.baur@charite.de [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Ihm, Claudia; Steffen, Ingo G. [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Tischer, Elisabeth [Medizinische Klinik m.S. Hepatologie Gastroenterologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Arsenic, Ruza [Institut für Pathologie, Campus Charité Mitte, Charité - Universitätsmedizin Berlin (Germany); Pascher, Andreas [Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Wiedenmann, Bertram; Pavel, Marianne [Medizinische Klinik m.S. Hepatologie Gastroenterologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany)

2013-10-01

Purpose: There are different therapeutic options in non-functional well to moderately differentiated (G1 and G2) pancreatic neuroendocrine tumors (pNET) with unresectable hepatic metastases including systemic chemotherapy and novel molecular targeted therapies. Treatment with somatostatin analogs (SSA) as antiproliferative agents is optional. At initial diagnosis watchful waiting until tumor progression is a well-established approach. Goal of this study was to evaluate imaging features as potential prognostic factors predicting early tumor progression in order to select patients that might benefit from an earlier initiation of medical treatment. Patients and methods: In 44 patients we correlated tumor grade, chromogranin A (CgA) levels, treatment with SSA and imaging features of hepatic metastases on contrast-enhanced multiphase CT and MR imaging with time to tumor progression (TTP) according to RECIST 1.0. Results: In the total patient cohort none of the tested imaging features was found to be a statistically significant prognostic factor for TTP. Since treatment with SSA was associated with an increased TTP we also analyzed a subgroup of 30 patients not treated with SSA. In this subgroup of patients hypoenhancement of hepatic metastases during early contrast phases was found to be a negative prognostic factor for early tumor progression within 12 months (p = 0.039). The other evaluated parameters including hepatic tumor load, number of metastases, and presence of regressive morphological changes did not reveal significant results. Conclusion: Hypovascularization of liver metastases from G1 and G2 pNET reflected by hypoenhancement during the early contrast phases seems to be associated with early tumor progression. In patients with hypoenhancing metastases repeated biopsy for reassessment of grading of these metastases, and early initiation of therapy should be considered.

Research on perfusion weighted imaging and diffusion weighted imaging of pancreatic masses at 3.0 T MR

International Nuclear Information System (INIS)

Yao Xiuzhong; Zeng mengsu; Rao Shengxiang; Ji Yuan

2011-01-01

Objective: To investigate the value of MR perfusion parameters and ADC in the diagnosis of pancreatic cancer and pancreatic mass at 3.0 T MR. Methods: Twenty healthy volunteers and 25 patients with pancreatic cancers proven by pathological results underwent MR PWI at a 3.0 T scanner. A two-compartment model was used to quantify K trans , K ep and V e in the pancreatic cancer, adjacent pancreatic tissue, distal inflammatory pancreatic tissue and normal pancreatic tissue. All parameters among different tissues were analyzed and compared with ANONA. Fifteen normal volunteers and 58 patients, including 30 patients with pancreatic cancer (proven histopathologically), 9 patients with pancreatitis pseudotumor (4 patients proven by histopathological results, 5 patients proven by follow-up after treatment), 9 patients with solid pseudopapillary tumor of pancreas (SPTP, proven histopathologically) and 10 patients with pancreatic neuroendocrine tumor (PET, proven by histopathology), underwent respiratory-triggered DWI on 3.0 T. ADC values of normal pancreas and all types of pancreatic lesions were statistically analyzed and compared with ANONA. ROC curve was used to analyze the diagnostic power of ADC value. Results: K trans of pancreatic cancer, adjacent pancreatic tissue, distal inflammatory pancreatic tissue and normal pancreatic tissue were (1.66±1.25), (3.77±2.67), (1.16±0.94) and (2.69±1.46 )/min respectively (F= 8. 160, P ep of pancreatic cancer, adjacent pancreatic tissue, distal inflammatory pancreatic tissue and normal pancreatic tissue were (2. 53 +1. 55) , (5.64±2.64), (1.70±0.91) and (4.28±1.64)/min respectively (F=4.544, P ep in pancreatic cancer was statistically lower than that in normal pancreatic tissue (P= 0.035) and adjacent pancreatic tissue (P=0.041). The median of V e among the pancreatic cancer, adjacent pancreatic tissue, distal inflammatory pancreatic tissue and normal pancreatic tissue were 0.926, 0.839, 0.798 and 0.659 respectively (χ 2 =12

A Novel Ras Inhibitor (MDC-1016 Reduces Human Pancreatic Tumor Growth in Mice

Directory of Open Access Journals (Sweden)

Gerardo G Mackenzie

2013-10-01

Full Text Available Pancreatic cancer has one of the poorest prognoses among all cancers partly because of its persistent resistance to chemotherapy. The currently limited treatment options for pancreatic cancer underscore the need for more efficient agents. Because activating Kras mutations initiate and maintain pancreatic cancer, inhibition of this pathway should have a major therapeutic impact. We synthesized phospho-farnesylthiosalicylic acid (PFTS; MDC-1016 and evaluated its efficacy, safety, and metabolism in preclinical models of pancreatic cancer. PFTS inhibited the growth of human pancreatic cancer cells in culture in a concentration- and time-dependent manner. In an MIA PaCa-2 xenograft mouse model, PFTS at a dose of 50 and 100 mg/kg significantly reduced tumor growth by 62% and 65% (P < .05 vs vehicle control. Furthermore, PFTS prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. PFTS appeared to be safe, with the animals showing no signs of toxicity during treatment. Following oral administration, PFTS was rapidly absorbed, metabolized to FTS and FTS glucuronide, and distributed through the blood to body organs. Mechanistically, PFTS inhibited Ras-GTP, the active form of Ras, both in vitro and in vivo, leading to the inhibition of downstream effector pathways c-RAF/mitogen-activated protein-extracellular signal-regulated kinase (ERK kinase (MEK/ERK1/2 kinase and phosphatidylinositol 3-kinase/AKT. In addition, PFTS proved to be a strong combination partner with phospho-valproic acid, a novel signal transducer and activator of transcription 3 (STAT3 inhibitor, displaying synergy in the inhibition of pancreatic cancer growth. In conclusion, PFTS, a direct Ras inhibitor, is an efficacious agent for the treatment of pancreatic cancer in preclinical models, deserving further evaluation.

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

Energy Technology Data Exchange (ETDEWEB)

Kim, Su Jin [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); New Drug Development Center, Osong Medical Innovation Foundation, Cheongwon, Chungbuk (Korea, Republic of); Chang, Suhwan [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Yangsoon; Kim, Na Young; Hwang, Yeonsil; Min, Hye Jin; Yoo, Kyung-Sook; Park, Eun Hye; Kim, Seokho [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Chung, Young-Hwa [BK21-plus, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Koh, Sang Seok, E-mail: sskoh@dau.ac.kr [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Department of Biological Sciences, Dong-A University, Busan (Korea, Republic of)

2014-11-07

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

A case of pancreatic neuroendocrine tumor in a patient with neurofibromatosis-1

Directory of Open Access Journals (Sweden)

Nishi Takeshi

2012-07-01

Full Text Available Abstract Patients with neurofibromatosis-1 (NF-1 sometime develop neuroendocrine tumors (NET. Although these NETs usually occur in the duodenum or peri-ampullary region, they occasionally grow in the pancreas (PNET. A 62-year-old man with NF-1 had mild liver dysfunction and was admitted to our hospital for further examination. An abdominal contrast-enhanced computed tomography scan demonstrated a 30-mm tumor in the head of the pancreas. The scan showed an invasion of the tumor into the duodenum, and biopsy under an endoscopic ultrasonography indicated that the tumor was a NET. A subtotal stomach-preserving pancreaticoduodenectomy was performed. Macroscopically, the pancreatic tumor was white and elastic hard. Microscopically, tumor cells were composed of ribbons, cords, and solid nests with an acinus-like structure. The tumor was diagnosed as NET G2 according to the WHO classification (2010. The product of theNF-1 gene, i.e., neurofibromin, was weakly positive in the tumor cells, suggesting that the tumor was induced by a mutation in the NF-1 gene. This is the seventh case of PNET arising in NF-1 patients worldwide.

Quantitative CT analysis for the preoperative prediction of pathologic grade in pancreatic neuroendocrine tumors

Science.gov (United States)

Chakraborty, Jayasree; Pulvirenti, Alessandra; Yamashita, Rikiya; Midya, Abhishek; Gönen, Mithat; Klimstra, David S.; Reidy, Diane L.; Allen, Peter J.; Do, Richard K. G.; Simpson, Amber L.

2018-02-01

Pancreatic neuroendocrine tumors (PanNETs) account for approximately 5% of all pancreatic tumors, affecting one individual per million each year.1 PanNETs are difficult to treat due to biological variability from benign to highly malignant, indolent to very aggressive. The World Health Organization classifies PanNETs into three categories based on cell proliferative rate, usually detected using the Ki67 index and cell morphology: low-grade (G1), intermediate-grade (G2) and high-grade (G3) tumors. Knowledge of grade prior to treatment would select patients for optimal therapy: G1/G2 tumors respond well to somatostatin analogs and targeted or cytotoxic drugs whereas G3 tumors would be targeted with platinum or alkylating agents.2, 3 Grade assessment is based on the pathologic examination of the surgical specimen, biopsy or ne-needle aspiration; however, heterogeneity in the proliferative index can lead to sampling errors.4 Based on studies relating qualitatively assessed shape and enhancement characteristics on CT imaging to tumor grade in PanNET,5 we propose objective classification of PanNET grade with quantitative analysis of CT images. Fifty-five patients were included in our retrospective analysis. A pathologist graded the tumors. Texture and shape-based features were extracted from CT. Random forest and naive Bayes classifiers were compared for the classification of G1/G2 and G3 PanNETs. The best area under the receiver operating characteristic curve (AUC) of 0:74 and accuracy of 71:64% was achieved with texture features. The shape-based features achieved an AUC of 0:70 and accuracy of 78:73%.

Methylthioadenosine phosphorylase compositions and methods of use in the diagnosis and treatment of proliferative disorders

Science.gov (United States)

Olopade, Olufunmilayo I.

2005-03-22

Disclosed are novel nucleic acid and peptide compositions comprising methythlioadenosine phosphorylase (MTAP) and methods of use for MTAP amino acid sequences and DNA segments comprising MTAP in the diagnosis of human cancers and development of MTAP-specific antibodies. Also disclosed are methods for the diagnosis and treatment of tumors and other proliferative cell disorders, and idenification tumor suppressor genes and gene products from the human 9p21-p22 chromosome region. Such methods are useful in the diagnosis of multiple tumor types such as bladder cancer, lung cancer, breast cancer, pancreatic cancer, brain tumors, lymphomas, gliomas, melanomas, and leukemias.

Prognostic factors of non-functioning pancreatic neuroendocrine tumor revisited: The value of WHO 2010 classification.

Science.gov (United States)

Bu, Jiyoung; Youn, Sangmin; Kwon, Wooil; Jang, Kee Taek; Han, Sanghyup; Han, Sunjong; You, Younghun; Heo, Jin Seok; Choi, Seong Ho; Choi, Dong Wook

2018-02-01

Various factors have been reported as prognostic factors of non-functional pancreatic neuroendocrine tumors (NF-pNETs). There remains some controversy as to the factors which might actually serve to successfully prognosticate future manifestation and diagnosis of NF-pNETs. As well, consensus regarding management strategy has never been achieved. The aim of this study is to further investigate potential prognostic factors using a large single-center cohort to help determine the management strategy of NF-pNETs. During the time period 1995 through 2013, 166 patients with NF-pNETs who underwent surgery in Samsung Medical Center were entered in a prospective database, and those factors thought to represent predictors of prognosis were tested in uni- and multivariate models. The median follow-up time was 46.5 months; there was a maximum follow-up period of 217 months. The five-year overall survival and disease-free survival rates were 88.5% and 77.0%, respectively. The 2010 WHO classification was found to be the only prognostic factor which affects overall survival and disease-free survival in multivariate analysis. Also, pathologic tumor size and preoperative image tumor size correlated strongly with the WHO grades ( p <0.001, and p <0.001). Our study demonstrates that 2010 WHO classification represents a valuable prognostic factor of NF-pNETs and tumor size on preoperative image correlated with WHO grade. In view of the foregoing, the preoperative image size is thought to represent a reasonable reference with regard to determination and development of treatment strategy of NF-pNETs.

The role of volume perfusion CT in the diagnosis of pathologies of the pancreas; Die Rolle des Volumenperfusions-CT in der Diagnostik von Pankreaspathologika

Energy Technology Data Exchange (ETDEWEB)

Groezinger, G.; Groezinger, A.; Horger, M. [Universitaetsklinik Tuebingen (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie

2014-12-15

The review discusses the potential role of volume perfusion CT (VPCT) in the diagnosis and follow-up of different pathologies of the pancreas. VPCT enables a differentiation of different pancreatic tumors like adenocarcinoma or neuroendocrine tumors based on functional parameters like blood flow, blood volume and permeability. Furthermore, the article discusses the potential indications for VPCT imaging of inflammatory diseases of the pancreas such as acute or chronic pancreatitis and autoimmune pancreatitis.

The role of contrast-enhanced endoscopic ultrasound in pancreatic adenocarcinoma

DEFF Research Database (Denmark)

Saftoiu, Adrian; Vilmann, Peter; Bhutani, Manoop S

2016-01-01

contrast agents for early detection, tridimensional and fusion techniques for enhanced staging and resectability assessment but also novel applications of perfusion imaging for monitoring ablative therapy, improved local detection through EUS-guided sampling of portal vein flow or enhanced drug delivery......Contrast-enhanced endoscopic ultrasound (CE-EUS) allows characterization, differentiation, and staging of focal pancreatic masses. The method has a high sensitivity and specificity for the diagnosis of pancreatic adenocarcinoma which is visualized as hypo-enhanced as compared to the rest...... of the parenchyma while chronic pancreatitis and neuroendocrine tumors are generally either iso-enhanced or hyper-enhanced. The development of contrast-enhanced low mechanical index harmonic imaging techniques used in real time during endoscopic ultrasound (EUS) allowed perfusion imaging and the quantification...

Evaluation of {sup 99m}Tc-HYNIC-βAla-Bombesin{sub (7-14)} as an agent for pancreas tumor detection in mice

Energy Technology Data Exchange (ETDEWEB)

Carlesso, F.N.; Fuscaldi, L.L.; Araujo, R.S.; Teixeira, C.S.; Oliveira, M.C.; Fernandes, S.O.A.; Cassali, G.D.; Reis, D.C.; Barros, A.L.B.; Cardoso, V.N., E-mail: valbertcardoso@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

2015-10-15

Pancreatic adenocarcinoma is important in oncology because of its high mortality rate. Deaths may be avoided if an early diagnosis could be achieved. Several types of tumors overexpress gastrin-releasing peptide receptors (GRPr), including pancreatic cancer cells. Thus, a radiolabeled peptide derivative of gastrin-releasing peptide (GRP) may be useful as a specific imaging probe. The purpose of the present study was to evaluate the feasibility of using {sup 99m}Tc-HYNIC--βAla-Bombesin{sub (7-14)} as an imaging probe for Capan-1 pancreatic adenocarcinoma. Xenographic pancreatic tumor was developed in nude mice and characterized by histopathological analysis. Biodistribution studies and scintigraphic images were carried out in tumor-bearing nude mice. The two methods showed higher uptake by pancreatic tumor when compared to muscle (used as control), and the tumor-to-muscle ratio indicated that {sup 99m}Tc-HYNIC--βAla-Bombesin{sub (7-14)} uptake was four-fold higher in tumor cells than in other tissues. Scintigraphic images also showed a clear signal at the tumor site. The present data indicate that {sup 99m}Tc-HYNIC--βAla-Bombesin{sub (7-14)} may be useful for the detection of pancreatic adenocarcinoma. (author)

THE RUSSIAN CONSENSUS ON DIAGNOSIS AND TREATMENT OF CHRONIC PANCREATITIS: POINTS OF DEBATE

Directory of Open Access Journals (Sweden)

I. E. Khat'kov

2016-01-01

Full Text Available The most controversial provisions of the Russian Consensus on Diagnosis and Treatment of Chronic Pancreatitis (hereinafter, the Consensus are presented. The debate has been initiated by the Russian Pancreatic Club and performed with the use of the Delphi system, based on interdisciplinary approach with participation of leading gastroenterologists, surgeons and pediatricians. This paper is the first in the series of the Consensus-related publications. Here we discuss the most controversial issues of Chapter 5 "Treatment of acute episodes" and Chapter 8 "Strategies of pain syndrome management". While discussing the conventional recommendation of a period of starvation for patients with clinical symptom of exacerbation of chronic pancreatitis, it was noted that for a long time it had been virtually the only way to provide functional rest for the pancreas. However, patients with chronic pancreatitis are frequently in malnutrition, therefore, starving may aggravate nutritional deficit that significantly affects the prognosis; therefore, early nutritional support is indicated. To alleviate functional strain of the pancreas, it is reasonable to use enteral nutrition elemental and semi-elemental formulas. The transition from formulas to conventional nutrition should be accompanied by administration of adequate pancreatin doses. The role of pancreatic enzymes, spasmolytics and proton pump inhibitors in the management of pain syndrome was also controversial.

Research advances in tumor markers for the diagnosis of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

YANG Guimin

2018-01-01

Full Text Available Hepatocellular carcinoma (HCC is a malignant tumor with a high fatality rate in the world, and alpha-fetoprotein (AFP is the most commonly used tumor marker for HCC diagnosis. However, AFP does not have a satisfactory sensitivity or specificity and may lead to missed diagnosis when the tumor is small in the early stage of HCC. This article summarizes the clinical value of new tumor markers in the diagnosis, treatment monitoring, and prognosis judgment of HCC and analyzes the future prospects of the measurement of tumor markers for HCC. It is pointed out that combined determination of several tumor markers helps to improve the sensitivity and specificity of HCC diagnosis, and the screening and optimization of combined determination of tumor markers, noninvasive and efficient tumor markers, and individualized treatment are research hotspots in future.

Dynamic MRI of pancreatic neoplasms

International Nuclear Information System (INIS)

Furukawa, Nobuyoshi; Takayasu, Ken-ichi; Muramatu, Yukio

1995-01-01

The usefulness of dynamic MRI study using contrast media is studied on pancreatic tumors. This method was useful in detecting small lesion of pancreatic tumor, however, T1-weighted SE method was more useful in detecting swelling lesions or diagnosing degree of tumors. Although endocrine tumors are depicted by contrast media, careful attention is needed since there are some hypovascular cases. T2-weighted image is commonly performed to detect the morphology of cystic content and the correlation between the pancreas and bile duct in cystic tumors, however, dynamic study was more useful in proving vascularity of serous cystadenoma and differentiating malignant or benign mucous cystic tumors by depicting intracystic torous components. In performing MR imaging on pancreatic diseases, it is necessary to select appropriate imaging procedure, and dynamic study should be included and used in a rational manner. (S.Y.)

Mesenchymal Stem Cells Promote Pancreatic Tumor Growth by Inducing Alternative Polarization of Macrophages

Directory of Open Access Journals (Sweden)

Esha Mathew

2016-03-01

Significance: Targeting the stroma is emerging as a new paradigm in pancreatic cancer; however, efforts to that effect are hampered by our limited understanding of the nature and function of stromal components. Here, we uncover previously unappreciated heterogeneity within the stroma and identify interactions among stromal components that promote tumor growth and could be targeted therapeutically.

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

Science.gov (United States)

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.

Development of a Novel Preclinical Pancreatic Cancer Research Model: Bioluminescence Image-Guided Focal Irradiation and Tumor Monitoring of Orthotopic Xenografts1

Science.gov (United States)

Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; DeWeese, Theodore L; Herman, Joseph M

2012-01-01

PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. RESULTS: Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. CONCLUSIONS: We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response. PMID:22496923

Vascular Targeting in Pancreatic Cancer: The Novel Tubulin-Binding Agent ZD6126 Reveals Antitumor Activity in Primary and Metastatic Tumor Models

Directory of Open Access Journals (Sweden)

Axel Kleespies

2005-10-01

Full Text Available ZD6126 is a novel vascular-targeting agent that acts by disrupting the tubulin cytoskeleton of an immature tumor endothelium, leading to an occlusion of tumor blood vessels and a subsequent tumor necrosis. We wanted to evaluate ZD6126 in primary and metastatic tumor models of human pancreatic cancer. Nude mice were injected orthotopically with L3.6pl pancreatic cancer cells. In single and multiple dosing experiments, mice received ZD6126, gemcitabine, a combination of both agents, or no treatment. For the induction of metastatic disease, additional groups of mice were injected with L3.6pl cells into the spleen. Twenty-four hours after a single-dose treatment, ZD6126 therapy led to an extensive central tumor necrosis, which was not seen after gemcitabine treatment. Multiple dosing of ZD6126 resulted in a significant growth inhibition of primary tumors and a marked reduction of spontaneous liver and lymph node metastases. Experimental metastatic disease could be significantly controlled by a combination of ZD6126 and gemcitabine, as shown by a reduction of the number and size of established liver metastases. As shown by additional in vitro and in vivo experiments, possible mechanisms involve antivascular activities and subsequent antiproliferative and proapoptotic effects of ZD6126 on tumor cells, whereas direct activities against tumor cells seem unlikely. These data highlight the antitumor and antimetastatic effects of ZD6126 in human pancreatic cancer and reveal benefits of adding ZD6126 to standard gemcitabine therapy.

Pancreatic Gastrointestinal Stromal Tumor after Upper Gastrointestinal Hemorrhage and Performance of Whipple Procedure: A Case Report and Literature Review.

Science.gov (United States)

Aziret, Mehmet; Çetinkünar, Süleyman; Aktaş, Elife; İrkörücü, Oktay; Bali, İlhan; Erdem, Hasan

2015-08-03

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal system. These types of tumors originate from any part of the tract as well as from the intestine, colon, omentum, mesentery or retroperitoneum. GIST is a rare tumor compared to other types of tumors, accounting for less than 1% of all gastrointestinal tumors. A 56-year-old male patient was hospitalized due to an upper gastrointestinal hemorrhage and the start of abdominal pain on the same day. In the upper gastrointestinal endoscopy that was performed, a solitary mass was found in the second section of the duodenum and a blood vessel (Forrest type 2a) was seen. The extent and location of the mass was detected by abdominal tomography. After hemodynamic recovery, a Whipple procedure was performed without any complications. A subsequent histopathological examination detected a c-kit-positive (CD117) pancreatic GIST with high mitotic index. The most effective treatment method for GISTs is surgical resection. In patients with a head of pancreatic GIST, the Whipple procedure can be used more safely and effectively.

Preventive medicine for von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

Science.gov (United States)

Krauss, Tobias; Ferrara, Alfonso Massimiliano; Links, Thera P; Wellner, Ulrich; Bancos, Irina; Kvachenyuk, Andrey; Villar Gómez de Las Heras, Karina; Yukina, Marina; Petrov, Roman; Bullivant, Garrett; von Duecker, Laura; Jadhav, Swati S; Ploeckinger, Ursula; Welin, Staffan; Schalin-Jantti, Camilla; Gimm, Oliver; Pfeifer, Marija; Ngeow, Joanne; Hasse-Lazar, Kornelia; Sanso, Gabriela; Qi, Xiao-Ping; Ugurlu, Umit; Diaz, Rene Eduardo; Wohllk, Nelson; Peczkowska, Mariola; Aberle, Jens; Lourenço, Delmar Muniz; Pereira, Maria Adelaide; Fragoso, Maria Candida Barisson Villares; Hoff, Ana O; Almeida, Madson Queiroz; Violante, Alice H D; Quidute, Ana R P; Zhang, Zheiwei; Recasens, Monica; Robles Diaz, Luis; Kunavisarut, Tada; Wannachalee, Taweesak; Sirinvaravong, Sirinart; Jonasch, Eric; Grozinsky-Glasberg, Simona; Fraenkel, Merav; Beltsevich, Dmitry; Egorov, Viacheslav I; Bausch, Dirk; Schott, Matthias; Tiling, Nikolaus; Pennelli, Gianmaria; Zschiedrich, Stefan; Därr, Roland; Ruf, Juri; Denecke, Timm; Link, Karl-Heinrich; Zovato, Stefania; von Dobschuetz, Ernst; Yaremchuk, Svetlana; Amthauer, Holger; Makay, Ozer; Patocs, Attila; Walz, Martin K; Huber, Tobias B; Seufert, Jochen; Hellman, Per; Kim, Raymond H; Kuchinskaya, Ekaterina; Schiavi, Francesca; Malinoc, Angelica; Reisch, Nicole; Jarzab, Barbara; Barontini, Marta; Januszewicz, Andrzej; Shah, Nalini; Young, William; Opocher, Giuseppe; Eng, Charis; Neumann, Hartmut P H; Bausch, Birke

2018-05-10

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2,330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8cm vs ≥2.8 cm (94% vs 85% by 10 years; P=0.020; 80% vs 50% at 10 years; P=0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

Role of CT in evaluation of the extension of pancreatic cancer

International Nuclear Information System (INIS)

Fujita, Nobuyuki

1990-01-01

CT findings of 39 lesions from 37 cases of pancreas cancer were correlated with surgical and/or pathological findings. Each finding was recorded following 'General rules for surgical and pathological studies on cancer of the pancras' proposed by Japanese pancreatic society. CT employed in this study is Somatom II (Siemens) with scan time of 5 seconds and slice thickness of 8 mm. Contrast study with bolus injection of contrast medium is a basic procedure in all the cases. The results are as follows. T factor (size of the tumor) was underestimated in 9 lesions, no overestimation was observed. It is because that the contrast enhancement surrounding low density was not included in the size of the tumor. No positive results were observed in lymph node group of no.17, but many false positive in no.12. Results of diagnosis of lymph node metastasis was poor, the total accuracy was 65.5%. CT was very effective in the diagnosis of V factor, total accuracy was 95.5%. In S (serosal invasion) and RP (retroperitoneal infiltration) factors, the total accuracy was 81.0%, and 87.1% respectively, when the protrusions into and the disappearance of the surrounding fat plane were taken into account. CT is not effective in the diagnosis of CH (bile duct invasion) factor, because of undifferentiation between compression and invasion from the surrounding pancreas tumor. Results of CT were good in Du (duodenal invasion) factor. Finally, it was concluded that CT is effective in the staging diagnosis of pancreatic cancer. (author)

Autoimmune pancreatitis: Assessment of the enhanced duct sign on multiphase contrast-enhanced computed tomography

International Nuclear Information System (INIS)

Kawai, Yuichi; Suzuki, Kojiro; Itoh, Shigeki; Takada, Akira; Mori, Yoshine; Naganawa, Shinji

2012-01-01

Purpose: To assess the usefulness of the computed tomography (CT) finding of main pancreatic duct (MPD) wall enhancement, termed the “enhanced duct sign”, for diagnosis of autoimmune pancreatitis (AIP) in comparison with diagnosis of pancreatic carcinoma and chronic pancreatitis. Materials and methods: Two radiologists independently evaluated the presence or absence of the enhanced duct sign on multiphase contrast-enhanced CT in patients with AIP (n = 55), pancreatic carcinoma (n = 50), and chronic pancreatitis (n = 50). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of AIP were calculated. In patients demonstrating the enhanced duct sign, additional findings were evaluated by consensus. Results: The enhanced duct sign was more frequently observed in patients with AIP (37/55, 67%) than in patients with pancreatic carcinoma (5/50, 10%) or chronic pancreatitis (0/50, 0%) (P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the finding were 0.67, 0.95, 0.85, 0.88, and 0.84, respectively. In AIP, the lumen within the enhanced duct was completely or partially invisible in 29 of 37 (78%) patients, and the enhanced duct was observed within the affected pancreatic parenchyma in 35 of 37 (95%) patients. In pancreatic carcinoma, the lumen within the enhanced duct was visible in all patients (5/5, 100%), and the enhanced duct was observed downstream of the tumor (5/5, 100%). Conclusion: The enhanced duct sign is highly specific of AIP.

Autoimmune pancreatitis: Assessment of the enhanced duct sign on multiphase contrast-enhanced computed tomography

Energy Technology Data Exchange (ETDEWEB)

Kawai, Yuichi, E-mail: kawai.yuichi@a.mbox.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Suzuki, Kojiro, E-mail: kojiro@med.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Itoh, Shigeki, E-mail: shigeito@nagoya-1st.jrc.or.jp [Department of Diagnostic Radiology, Japan Red Cross Nagoya Daiichi Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya 453-8511 (Japan); Takada, Akira, E-mail: takadaa@med.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Mori, Yoshine, E-mail: yoshine@med.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Naganawa, Shinji, E-mail: naganawa@med.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

2012-11-15

Purpose: To assess the usefulness of the computed tomography (CT) finding of main pancreatic duct (MPD) wall enhancement, termed the 'enhanced duct sign', for diagnosis of autoimmune pancreatitis (AIP) in comparison with diagnosis of pancreatic carcinoma and chronic pancreatitis. Materials and methods: Two radiologists independently evaluated the presence or absence of the enhanced duct sign on multiphase contrast-enhanced CT in patients with AIP (n = 55), pancreatic carcinoma (n = 50), and chronic pancreatitis (n = 50). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of AIP were calculated. In patients demonstrating the enhanced duct sign, additional findings were evaluated by consensus. Results: The enhanced duct sign was more frequently observed in patients with AIP (37/55, 67%) than in patients with pancreatic carcinoma (5/50, 10%) or chronic pancreatitis (0/50, 0%) (P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the finding were 0.67, 0.95, 0.85, 0.88, and 0.84, respectively. In AIP, the lumen within the enhanced duct was completely or partially invisible in 29 of 37 (78%) patients, and the enhanced duct was observed within the affected pancreatic parenchyma in 35 of 37 (95%) patients. In pancreatic carcinoma, the lumen within the enhanced duct was visible in all patients (5/5, 100%), and the enhanced duct was observed downstream of the tumor (5/5, 100%). Conclusion: The enhanced duct sign is highly specific of AIP.

Pancreatic Ductal Adenocarcinoma (PDA) mice lacking Mucin 1 have a profound defect in tumor growth and metastasis

Science.gov (United States)

Besmer, Dahlia M.; Curry, Jennifer M.; Roy, Lopamudra D.; Tinder, Teresa L.; Sahraei, Mahnaz; Schettini, Jorge; Hwang, Sun-Il; Lee, Yong Y.; Gendler, Sandra J.; Mukherjee, Pinku

2011-01-01

MUC1 is over expressed and aberrantly glycosolated in >60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In the present study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared to both KC and KCM. Cell lines derived from KCKO tumors have significantly lower tumorigenic capacity compared to cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared to mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or matrix metalloproteinase-9 (MMP9). Further, significantly fewer KCKO cells entered the G2M phase of the cell cycle compared to the KCM cells. Proteomics and western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of MAPK, as well as a significant decrease in Nestin and Tubulin α-2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse in order to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. PMID:21558393

[Duodenum-preserving total pancreatic head resection and pancreatic head resection with segmental duodenostomy].

Science.gov (United States)

Takada, Tadahiro; Yasuda, Hideki; Nagashima, Ikuo; Amano, Hodaka; Yoshiada, Masahiro; Toyota, Naoyuki

2003-06-01

A duodenum-preserving pancreatic head resection (DPPHR) was first reported by Beger et al. in 1980. However, its application has been limited to chronic pancreatitis because of it is a subtotal pancreatic head resection. In 1990, we reported duodenum-preserving total pancreatic head resection (DPTPHR) in 26 cases. This opened the way for total pancreatic head resection, expanding the application of this approach to tumorigenic morbidities such as intraductal papillary mucinous tumor (IMPT), other benign tumors, and small pancreatic cancers. On the other hand, Nakao et al. reported pancreatic head resection with segmental duodenectomy (PHRSD) as an alternative pylorus-preserving pancreatoduodenectomy technique in 24 cases. Hirata et al. also reported this technique as a new pylorus-preserving pancreatoduodenostomy with increased vessel preservation. When performing DPTPHR, the surgeon should ensure adequate duodenal blood supply. Avoidance of duodenal ischemia is very important in this operation, and thus it is necessary to maintain blood flow in the posterior pancreatoduodenal artery and to preserve the mesoduodenal vessels. Postoperative pancreatic functional tests reveal that DPTPHR is superior to PPPD, including PHSRD, because the entire duodenum and duodenal integrity is very important for postoperative pancreatic function.

Acute pancreatitis: current perspectives on diagnosis and management

Science.gov (United States)

Shah, Adarsh P; Mourad, Moustafa M; Bramhall, Simon R

2018-01-01

The last two decades have seen the emergence of significant evidence that has altered certain aspects of the management of acute pancreatitis. While most cases of acute pancreatitis are mild, the challenge remains in managing the severe cases and the complications associated with acute pancreatitis. Gallstones are still the most common cause with epidemiological trends indicating a rising incidence. The surgical management of acute gallstone pancreatitis has evolved. In this article, we revisit and review the methods in diagnosing acute pancreatitis. We present the evidence for the supportive management of the condition, and then discuss the management of acute gallstone pancreatitis. Based on the evidence, our local institutional pathways, and clinical experience, we have produced an outline to guide clinicians in the management of acute gallstone pancreatitis. PMID:29563826

X-ray pathological-anatomical diagnosis of bone tumors

International Nuclear Information System (INIS)

Adler, C.P.

1983-01-01

The diagnosis of bone tumors is particularly difficult and requires specific knowledge and experience. This is done not only of clinical workers and X-ray specialists but also of pathologists, who are mostly unable to gather enough experience because those diseases are relatively rare. The specialities of the diagnosis of bone tumors are pointed out and the indispensable co-operation between the fields of work of clinical specialists, radiologists and pathologists is emphasized. Bone growths are classified according to the proposals of the World Health Organization, forming the basis for the subsequent therapy. An absolute pre-requisite for an exact diagnosis in the synopsis of the X-ray structures and the histologic findings. In various cases the dignity of a bone tumor cannot be determined; in such instances radical removal is recommended to preclude recidivation and possible malignity. In difficult cases a reference centre for bone tumors should be consulted. (orig.) [de

Pancreatic Cancer—Patient Version

Science.gov (United States)

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.

The FDG-PET diagnosis of head and neck malignant tumor

International Nuclear Information System (INIS)

Kada, Shinpei; Hayashi, Masahiko; Okazawa, Hidehiko

2003-01-01

We investigated the utility of whole body FDG-PET in patients with head and neck malignant tumor, retrospectively. Fifty four FDG-PET studies were performed in 45 patients. Regarding the primary tumor and nodal metastasis, we compared the diagnosis of only FDG-PET with diagnosis using CT, MRI, and physical examination without FDG-PET (diagnosis without FDG-PET). These FDG-PET images were evaluated with visual interpretation qualitatively. At the primary tumor, sensitivity and specificity of FDG-PET diagnoses were 90% and 93%, and those of the diagnoses without FDG-PET were 95% and 100%, respectively; for nodal metastasis, sensitivity and specificity of FDG-PET diagnoses were 90% and 84%, and those of the diagnoses without FDG-PET were 72% and 80%, respectively. In nodal metastasis, the diagnosis of FDG-PET was superior to the diagnosis without FDG-PET. However, it is important to be careful of false positive findings of FDG-PET such as inflammatory lymph nodes, and false negative findings such as very thin tumors. By combining the FDG-PET diagnosis with other examinations, we could achieve almost perfect diagnosis. Farthermore, we perform FDG-PET repeatedly to improve diagnosis accuracy. (author)

Homogeneous pancreatic cancer spheroids mimic growth pattern of circulating tumor cell clusters and macrometastases: displaying heterogeneity and crater-like structure on inner layer.

Science.gov (United States)

Feng, Hao; Ou, Bao-Chi; Zhao, Jing-Kun; Yin, Shuai; Lu, Ai-Guo; Oechsle, Eva; Thasler, Wolfgang E

2017-09-01

Pancreatic cancer 3D in vitro models including multicellular tumor spheroid (MCTS), single cell-derived tumor spheroid (SCTS), tissue-derived tumor spheroid, and organotypic models provided powerful platforms to mimic in vivo tumor. Recent work supports that circulating tumor cell (CTC) clusters are more efficient in metastasis seeding than single CTCs. The purpose of this study is to establish 3D culture models which can mimic single CTC, monoclonal CTC clusters, and the expansion of macrometastases. Seven pancreatic ductal adenocarcinoma cell lines were used to establish MCTS and SCTS using hanging drop and ultra-low attachment plates. Spheroid immunofluorescence staining, spheroid formation assay, immunoblotting, and literature review were performed to investigate molecular biomarkers and the morphological characteristics of pancreatic tumor spheroids. Single cells experienced different growth patterns to form SCTS, like signet ring-like cells, blastula-like structures, and solid core spheroids. However, golf ball-like hollow spheroids could also be detected, especially when DanG and Capan-1 cells were cultivated with fibroblast-conditioned medium (p cell lines could also establish tumor spheroid with hanging drop plates by adding methylated cellulose. Tumor spheroids derived from pancreatic cancer cell line DanG possessed asymmetrically distributed proliferation center, immune-checkpoint properties. ß-catenin, Ki-67, and F-actin were active surrounding the crater-like structure distributing on the inner layer of viable rim cover of the spheroids, which was relevant to well-differentiated tumor cells. It is possible to establish 3D CTC cluster models from homogenous PDA cell lines using hanging drop and ultra-low attachment plates. PDA cell line displays its own intrinsic properties or heterogeneity. The mechanism of formation of the crater-like structure as well as golf ball-like structure needs further exploration.

Radiation induces invasiveness of pancreatic cancer via up-regulation of heparanase

International Nuclear Information System (INIS)

Lerner, I.; Bensoussan, E.; Meirovitz, A.; Elkin, M.; Vlodavsky, I.

2013-01-01

The full text of the publication follows. Pancreatic cancer is one of the most aggressive neoplasms with an extremely low survival rate. Because most pancreatic carcinoma patients miss the opportunity for complete surgical resection at the time of diagnosis, radiotherapy remains a major component of treatment modalities. However, pancreatic cancer often shows resistance to radiation therapy. Ionizing radiation (IR)-induced aggressiveness is emerging as one of the important mechanisms responsible for the limited benefit of radiation therapy in pancreatic cancer, but the identity of downstream effectors responsible for this effect remains poorly investigated. Here we report that IR promotes pancreatic cancer aggressiveness through up-regulation of the heparanase. Heparanase is a predominant mammalian enzyme capable of degrading heparan sulfate (HS), the main polysaccharide component of the basement membrane and other types of extracellular matrix (ECM). Cleavage of HS by heparanase leads to disassembly of ECM, enables cell invasion, releases HS-bound angiogenic and growth factors from the ECM depots, and generates bioactive HS fragments. We found that clinically relevant doses of IR augment invasive ability of pancreatic cells in vitro and in vivo via induction of heparanase. Our results indicate that the effect of IR on heparanase expression is mediated by Egr1 transcription factor. Moreover, specific inhibitor of heparanase enzymatic activity abolished IR-induced invasiveness of pancreatic carcinoma cells in vitro, while combined treatment with IR and the heparanase inhibitor, but not IR alone, attenuated ortho-topic pancreatic tumor progression in vivo. The proposed up-regulation of heparanase by IR represents a new molecular pathway through which IR may promote pancreatic tumor aggressiveness, providing explanation for the limited benefit from radiation therapy in pancreatic cancer. Our research is expected to offer a new approach to improve the efficacy of

In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

Energy Technology Data Exchange (ETDEWEB)

Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

2017-01-01

Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

Endoscopic Ultrasound-Guided Fine Needle Aspiration versus Percutaneous Ultrasound-Guided Fine Needle Aspiration in Diagnosis of Focal Pancreatic Masses.

Science.gov (United States)

Okasha, Hussein Hassan; Naga, Mazen Ibrahim; Esmat, Serag; Naguib, Mohamed; Hassanein, Mohamed; Hassani, Mohamed; El-Kassas, Mohamed; Mahdy, Reem Ezzat; El-Gemeie, Emad; Farag, Ali Hassan; Foda, Ayman Mohamed

2013-10-01

Pancreatic carcinoma is one of the leading cancer morbidity and mortality world-wide. Controversy has arisen about whether the percutaneous approach with computed tomography/ultrasonography-guidance fine needle aspiration (US-FNA) or endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the preferred method to obtain diagnostic tissue. Our purpose of this study is to compare between the diagnostic accuracy of EUS-FNA and percutaneous US-FNA in diagnosis of pancreatic cancer. A total of 197 patients with pancreatic masses were included in the study, 125 patients underwent US-FNA (Group 1) and 72 patients underwent EUS-FNA (Group 2). EUS-FNA has nearly the same accuracy (88.9%) as US-FNA (87.2%) in diagnosis of pancreatic cancer. The sensitivity, specificity, positive predictive value and negative predictive value for EUS-FNA was 84%, 100%, 100%, 73.3% respectively. It was 85.5%, 90.4%, 94.7%, 76% respectively for US-FNA. EUS-FNA had a lower complication rate (1.38%) than US-FNA (5.6%). EUS-FNA has nearly the same accuracy as US-FNA of pancreatic masses with a lower complication rate.

The Key Genes of Chronic Pancreatitis which Bridge Chronic Pancreatitis and Pancreatic Cancer Can be Therapeutic Targets.

Science.gov (United States)

Li, Shuang; Li, Rui; Wang, Heping; Li, Lisha; Li, Huiyu; Li, Yulin

2018-04-01

An important question in systems biology is what role the underlying molecular mechanisms play in disease progression. The relationship between chronic pancreatitis and pancreatic cancer needs further exploration in a system view. We constructed the disease network based on gene expression data and protein-protein interaction. We proposed an approach to discover the underlying core network and molecular factors in the progression of pancreatic diseases, which contain stages of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and pancreatic cancer core network and key factors were revealed and then verified by gene set enrichment analysis of pathways and diseases. The key factors provide the microenvironment for tumor initiation and the change of gene expression level of key factors bridge chronic pancreatitis and pancreatic cancer. Some new candidate genes need further verification by experiments. Transcriptome profiling-based network analysis reveals the importance of chronic pancreatitis genes and pathways in pancreatic cancer development on a system level by computational method and they can be therapeutic targets.

Pancreatic neuroendocrine neoplasms; Neuroendokrine Neoplasien des Pankreas

Energy Technology Data Exchange (ETDEWEB)

Beiderwellen, K.; Lauenstein, T.C. [Universitaetsklinikum Essen, Institut fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie, Essen (Germany); Sabet, A.; Poeppel, T.D. [Universitaetsklinikum Essen, Klinik fuer Nuklearmedizin, Essen (Germany); Lahner, H. [Universitaetsklinikum Essen, Klinik fuer Endokrinologie und Stoffwechselerkrankungen, Essen (Germany)

2016-04-15

Pancreatic neuroendocrine neoplasms (NEN) account for 1-2 % of all pancreatic neoplasms and represent a rare differential diagnosis. While some pancreatic NEN are hormonally active and exhibit endocrine activity associated with characteristic symptoms, the majority are hormonally inactive. Imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) or as combined PET/CT play a crucial role in the initial diagnosis, therapy planning and control. Endoscopic ultrasound (EUS) and multiphase CT represent the reference methods for localization of the primary pancreatic tumor. Particularly in the evaluation of small liver lesions MRI is the method of choice. Somatostatin receptor scintigraphy and somatostatin receptor PET/CT are of particular value for whole body staging and special aspects of further therapy planning. (orig.) [German] Neuroendokrine Neoplasien (NEN) des Pankreas stellen mit einem Anteil von 1-2 % aller pankreatischen Tumoren eine seltene Differenzialdiagnose dar. Ein Teil der Tumoren ist hormonell aktiv und faellt klinisch durch charakteristische Symptome auf, wohingegen der ueberwiegende Anteil hormonell inaktiv ist. Bildgebende Verfahren wie Sonographie, Computertomographie (CT), Magnetresonanztomographie (MRT) und nicht zuletzt Positronenemissionstomographie (PET oder kombiniert als PET/CT) spielen eine zentrale Rolle fuer Erstdiagnose, Therapieplanung und -kontrolle. Die Endosonographie und die multiphasische CT stellen die Referenzmethoden zur Lokalisation des Primaertumors dar. Fuer die Differenzierung insbesondere kleiner Leberlaesionen bietet die MRT die hoechste Aussagekraft. Fuer das Ganzkoerperstaging und bestimmte Aspekte der Therapieplanung lassen sich die Somatostatinrezeptorszintigraphie und v. a. die Somatostatinrezeptor-PET/CT heranziehen. (orig.)

Fluorescence diagnosis of pre-tumor and tumor pathology of endometrium

Directory of Open Access Journals (Sweden)

E. V. Filonenko

2014-01-01

Full Text Available The technique of fluorescence hysteroscopy with Alasens includes visual assessment of fluorescence of Alasens-induced protoporphyrin IX and local fluorescence spectroscopy. The technique allows to improve the efficacy of early diagnosis for endometrial pathology including early endometrial cancer, to assess definitely an extent of pre-tumor and tumor process. The sensitivity of fluorescence hysteroscopy accounts for 100%, the specificity – 98%. 

Histopathological diagnosis of eyelid tumors in Chiang Mai University Hospital.

Science.gov (United States)

Nithithanaphat, Chanut; Ausayakhun, Sakarin; Wiwatwongwana, Damrong; Mahanupab, Pongsak

2014-10-01

To report the histopathological diagnosis ofeyelid tumors and to study the prevalence of eyelid tumors in Chiang Mai University Hospital Chiang Mai, Thailand. A retrospective review of medical and pathological records ofpatients diagnosed as eyelid tumor that underwent histopathological biopsy between January 2007 and December 2013 in Chiang Mai University Hospital was done. Three hundred sixteen cases of eyelid tumors were reviewed. The mean age at diagnosis was 54.2 +/- 19.6 years (range 1 month-99 years), women were 59.5% (n = 188) and men 40.5% (n = 128). The tumor sites were left lower eyelid (27.5%), right upper eyelid (24.4%), right lower eyelid (21.2%), and left upper eyelid (18.7%). There were 204 (64.6%) benign tumors and 112 (35.4%) malignant tumors. Nevi were the most common in benign group (16.4%) and basal cell carcinoma was the most common eyelid malignancy (18.0%). The most common histopathological diagnosis for benign eyelid tumor was nevus, while the most common malignant eyelid tumor was basal cell carcinoma at Chiang Mai University Hospital.

[Pancreatic trauma].

Science.gov (United States)

Arvieux, C; Guillon, F; Létoublon, Ch; Oughriss, M

2003-10-01

Early diagnosis of pancreatic trauma has always been challenging because of the lack of correlation between the initial clinical symptomatology, radiologic and laboratory findings, and the severity of the injury. Thanks to the improved performance of spiral CT scanning and magnetic resonance pancreatography, it is now often possible to make an early diagnosis of pancreatic contusion, to localize the site of the injury, and (most importantly) to identify injury to the main pancreatic duct which has major implications for the management of the case. When the trauma victim is unstable, radiologic work-up may be impossible and urgent laparotomy is required. Control of hemorrhage is the primary concern here and a damage control approach with packing may be appropriate; if the pancreatic head has been destroyed, a pancreaticoduodenectomy with delayed reconstruction may be required. If the trauma victim is stable, the treatment strategy will be governed by a variety of parameters--age, clinical condition, associated local anatomic findings (pancreatitis, injury to the duodenum or biliary tract), involvement of the pancreatic duct, and localization of the injury within the gland (to right or left of the mesenteric vessels).

Preoperative clinical radioimmunodetection of pancreatic cancer by 111In-labeled chimeric monoclonal antibody Nd2

International Nuclear Information System (INIS)

Sawada, Tetsuji; Nishihara, Tamahiro; Yamamoto, Atsushi

1999-01-01

The present study was carried out with the purpose of evaluating the clinical usefulness of radioimmunodetection (RAID) with 111 In-labeled murine/human chimeric monoclonal antibody, Nd2 (c-Nd2) in patients with pancreatic cancer. Nineteen patients suspected to have pancreatic cancer were administered intravenously 74 MBq/2 mg 111 In-labeled c-Nd2 in 100 ml of saline containing 2% albumin over 30 min. A scintigram was obtained on the 3rd day after infusion by using single photon emission computed tomography (SPECT) imaging. Of the 14 patients finally diagnosed as having pancreatic cancer on the basis of surgical specimens or progress of disease, specific focal uptake at the site of the tumor was detected in 12 (true positive cases), representing a sensitivity of 85.7% (12/14), and liver metastasis was found in one case with metastasis. Of the 5 patients diagnosed with tumor-forming pancreatitis (TFP), 4 patients demonstrated true negative imaging, but one patient whose tumor demonstrated interesting findings in histology and immunostaining, showed false positive imaging. Of patients investigated for human anti-chimeric antibody (HACA) response, none showed HACA response, and no allergic reaction was seen in any of the patients administered c-Nd2. These results suggest that RAID with 111 In-labeled c-Nd2 is useful for differential preoperative diagnosis between invasive pancreatic cancer and TFP. (author)

Multidetector Computed Tomography and Neuroendocrine Pancreaticoduodenal Tumors

International Nuclear Information System (INIS)

Rappeport, E.D.; Palnaes Hansen, C.; Kjaer, A.; Knigge, U.

2006-01-01

Purpose: To investigate the accuracy of dedicated pancreatic multidetector computed tomography (MDCT) in the diagnosis of neuroendocrine pancreaticoduodenal tumors (NPTs). Material and Methods: MDCT and other imaging studies in patients with suspected NPTs were identified. Thirty dedicated MDCT studies were done in 23 patients. Fourteen patients (16 operations) subsequently had surgery. Imaging reports were reviewed and findings compared with surgical findings and findings in other imaging studies. Results: Patients with surgery : 19 NPTs (16 extrapancreatic gastrinomas and 3 pancreatic NPTs) were identified at surgery. MDCT identified 16 and somatostatin receptor scintigraphy (SRS) 11 out of 19 tumors. Endoscopic ultrasound detected 11 out of 14 NPTs. Patients without surgery : In 4 out of 9 patients, no NPTs were identified at MDCT. Conclusion: Dedicated MDCT of the pancreas can identify many NPTs, including small duodenal and periduodenal tumors, and the detection rate is better than reported in the older literature on CT

Role of endoscopic ultrasound-guided fine needle aspiration and ultrasound-guided fine-needle aspiration in diagnosis of cystic pancreatic lesions

Science.gov (United States)

Okasha, Hussein Hassan; Ashry, Mahmoud; Imam, Hala M. K.; Ezzat, Reem; Naguib, Mohamed; Farag, Ali H.; Gemeie, Emad H.; Khattab, Hani M.

2015-01-01

Background and Objective: The addition of fine-needle aspiration (FNA) to different imaging modalities has raised the accuracy for diagnosis of cystic pancreatic lesions. We aim to differentiate benign from neoplastic pancreatic cysts by evaluating cyst fluid carcinoembryonic antigen (CEA), carbohydrate antigen (CA19-9), and amylase levels and cytopathological examination, including mucin stain. Patients and Methods: This prospective study included 77 patients with pancreatic cystic lesions. Ultrasound-FNA (US-FNA) or endoscopic ultrasound-FNA (EUS-FNA) was done according to the accessibility of the lesion. The aspirated specimens were subjected to cytopathological examination (including mucin staining), tumor markers (CEA, CA19-9), and amylase level. Results: Cyst CEA value of 279 or more showed high statistical significance in differentiating mucinous from nonmucinous lesions with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 73%, 60%, 50%, 80%, and 65%, respectively. Cyst amylase could differentiate between neoplastic and nonneoplastic cysts at a level of 1043 with sensitivity of 58%, specificity of 75%, PPV of 73%, NPV of 60%, and accuracy of 66%. CA19-9 could not differentiate between neoplastic and nonneoplastic cysts. Mucin examination showed a sensitivity of 85%, specificity of 95%, PPV of 92%, NPV of 91%, and accuracy of 91% in differentiating mucinous from non-mucinous lesions. Cytopathological examination showed a sensitivity of 81%, specificity of 94%, PPV of 94%, NPV of 83%, and accuracy of 88%. Conclusion: US or EUS-FNA with analysis of cyst CEA level, CA19-9, amylase, mucin stain, and cytopathological examination increases the diagnostic accuracy of cystic pancreatic lesions. PMID:26020048

Histological evaluation of obliterative phlebitis for the diagnosis of autoimmune pancreatitis.

Science.gov (United States)

Miyabe, Katsuyuki; Notohara, Kenji; Nakazawa, Takahiro; Hayashi, Kazuki; Naitoh, Itaru; Okumura, Fumihiro; Shimizu, Shuya; Yoshida, Michihiro; Yamashita, Hiroaki; Takahashi, Satoru; Ohara, Hirotaka; Joh, Takashi

2014-04-01

Obliterative phlebitis is a useful pathological finding for the diagnosis of lymphoplasmacytic sclerosing pancreatitis (LPSP), or type 1 autoimmune pancreatitis. The present study evaluated histological findings of obliterative phlebitis, including the significance of adding Elastica van Gieson stain (EVG) in comparison with other pancreatic conditions. Specimens of LPSP (n = 18), chronic pancreatitis (CP; n = 24), and pancreatic ductal adenocarcinoma (PDA; n = 45) were enrolled. Obliterative venous lesions (OVLs), defined as the presence of inflammatory cells and/or fibrosis inside the tunica adventitia, were counted and compared between hematoxylin and eosin stain (H&E) and EVG. OVLs were classified into three types: OVL-1, lymphoplasmacytic infiltration and fibrosis against a loose textured background; OVL-2, dense fibrosis with minimal or no lymphoplasmacytic infiltration; and OVL-3, densely packed lymphoplasmacytic infiltration without fibrosis. OVL type and OVL size were compared between disease groups. OVL counts in LPSP, CP, and PDA were significantly higher with EVG than with H&E (p < 0.001). OVL-1 was most common in LPSP (H&E 92.4 %, EVG 79.8 %), and was identified in almost all cases of LPSP, but was less common in CP and PDA. Maximum diameter and OVL count in 1 cm(2) of OVL-1 were high for LPSP. Maximum diameter of OVL-1 ≥150 μm was observed in 17 LPSP, 0 CP, and 1 PDA cases (sensitivity 94.4 %, specificity 98.6 %). Additional EVG is useful for excluding conditions mimicking OVL-1 or detecting OVL in small specimens. The presence of OVL-1 with diameter ≥150 μm is highly diagnostic for LPSP.

Pancreatic cyst development: insights from von Hippel-Lindau disease

Directory of Open Access Journals (Sweden)

van Asselt Sophie J

2013-02-01

Full Text Available Abstract Pancreatic cysts are a heterogeneous group of lesions, which can be benign or malignant. Due to improved imaging techniques, physicians are more often confronted with pancreatic cysts. Little is known about the origin of pancreatic cysts in general. Von Hippel-Lindau (VHL disease is an atypical ciliopathy and inherited tumor syndrome, caused by a mutation in the VHL tumor suppressor gene encoding the VHL protein (pVHL. VHL patients are prone to develop cysts and neuroendocrine tumors in the pancreas in addition to several other benign and malignant neoplasms. Remarkably, pancreatic cysts occur in approximately 70% of VHL patients, making it the only hereditary tumor syndrome with such a discernible expression of pancreatic cysts. Cellular loss of pVHL due to biallelic mutation can model pancreatic cystogenesis in other organisms, suggesting a causal relationship. Here, we give a comprehensive overview of various pVHL functions, focusing on those that can potentially explain pancreatic cyst development in VHL disease. Based on preclinical studies, cilia loss in ductal cells is probably an important early event in pancreatic cyst development.

Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis

Directory of Open Access Journals (Sweden)

Nelson S. Yee

2015-03-01

Full Text Available Our previous studies in zebrafish development have led to identification of the novel roles of the transient receptor potential melastatin-subfamily member 7 (TRPM7 ion channels in human pancreatic cancer. However, the biological significance of TRPM7 channels in pancreatic neoplasms was mostly unexplored. In this study, we determined the expression levels of TRPM7 in pancreatic tissue microarrays and correlated these measurements in pancreatic adenocarcinoma with the clinicopathological features. We also investigated the role of TRPM7 channels in pancreatic cancer cell invasion using the MatrigelTM-coated transwell assay. In normal pancreas, TRPM7 is expressed at a discernable level in the ductal cells and centroacinar cells and at a relatively high level in the islet endocrine cells. In chronic pancreatitis, pre-malignant tissues, and malignant neoplasms, there is variable expression of TRPM7. In the majority of pancreatic adenocarcinoma specimens examined, TRPM7 is expressed at either moderate-level or high-level. Anti-TRPM7 immunoreactivity in pancreatic adenocarcinoma significantly correlates with the size and stages of tumors. In human pancreatic adenocarcinoma cells in which TRPM7 is highly expressed, short hairpin RNA-mediated suppression of TRPM7 impairs cell invasion. The results demonstrate that TRPM7 channels are over-expressed in a proportion of the pre-malignant lesions and malignant tumors of the pancreas, and they are necessary for invasion by pancreatic cancer cells. We propose that TRPM7 channels play important roles in development and progression of pancreatic neoplasm, and they may be explored as clinical biomarkers and targets for its prevention and treatment.

Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer

International Nuclear Information System (INIS)

Karamitopoulou, Eva

2013-01-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial–mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer.

Science.gov (United States)

Karamitopoulou, Eva

2012-01-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

Tumor Budding Cells, Cancer Stem Cells and Epithelial-Mesenchymal Transition-type Cells in Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Eva eKaramitopoulou

2013-01-01

Full Text Available Pancreatic ductal adenocarcinoma (PDAC is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4 and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with WNT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT. Emerging evidence has demonstrated that cancer stem cells (CSCs, small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5 of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric and ampullary carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs and EMT-type cells in PDAC.

Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression

Directory of Open Access Journals (Sweden)

Rute M.M. Ferreira

2017-10-01

Full Text Available The cell of origin of pancreatic ductal adenocarcinoma (PDAC has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs, duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions. Using orthotopic transplantation and chimera experiments, we demonstrate that PanIN-like lesions can be induced by PDAC as bystanders in adjacent healthy tissues, explaining the co-existence of mucinous and non-mucinous lesions and highlighting the need to distinguish between true precursor PanINs and PanIN-like bystander lesions. Our results suggest AGR2 as a tool to stratify PDAC according to cell of origin, highlight that not all PanIN-like lesions are precursors of PDAC, and add an alternative progression route to the current model of PDAC development.

External beam radiotherapy for unresectable pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Kagami, Yoshikazu; Nishio, Masamichi; Narimatsu, Naoto; Ogawa, Hajime; Betsuyaku, Takashi; Hirata, Kouji; Ikeda, Shigeyuki (Sapporo National Hospital (Japan). Hokkaido Cancer Center)

1992-04-01

Between 1980 to 1989, 24 patients with unresectable pancreatic cancer (10 with localized tumor alone and 14 with distant metastases) have been treated with external beam radiation at Sapporo National Hospital, Hokkaido Cancer Center. Response rate of pancreatic tumor treated with external beam radiation was 33.3% (7/21) with no complete response. Median survival time of the patients with localized tumor was 10 months and that of the patients with distant metastases was 3 months. Relief of pain occurred in 92.9% (12/13) of patients having pain due to pancreatic tumor and in 75% (3/4) of patients having pain due to bone metastases. Major complication was gastric ulcer which developed in 5 patients of 21 patients given stomach irradiation. We concluded that unresectable pancreatic cancer would be frequently indicated for radiotherapy. (author).

Pancreatic cancer in patients with chronic calcifying pancreatitis: Computed tomography findings – a retrospective analysis of 48 patients

Energy Technology Data Exchange (ETDEWEB)

Mohamed, Amir, E-mail: amir.med87@gmail.com [Department of Radiology, Brabois Adults Hospital, Nancy (France); Ayav, Ahmet [Department of HPB Surgery, University Hospital of Nancy (France); Belle, Arthur [Department of Hepatogastroenterologie, Brabois Adults Hospital, Nancy (France); Orry, Xavier [Department of Radiology, Brabois Adults Hospital, Nancy (France); Chevaux, Jean-Baptiste [Department of Hepatogastroenterologie, Brabois Adults Hospital, Unité Inserm U954, Nancy (France); Laurent, Valerie [Department of Radiology, Brabois Adults Hospital, Nancy (France); Laboratory IADI, INSERM u947 (France)

2017-01-15

Objective: Chronic calcifying pancreatitis (CCP) is a risk factor for pancreatic cancer (PC). Symptoms of PC are non-specific in patients with CCP, and diagnostic imaging can be difficult. Some studies have shown that diagnosis may take several months, leading to delays in treatment (Lin et al., 2015; Lennon et al., 2014) . The aim of this study was to describe the radiological signs of PC in patients with CCP. Methods: This retrospective, single-center study was conducted between January 2004 and December 2014. Patients with CCP who were being monitored for PC were included. Each patient diagnosed with PC was matched with two CCP controls who did not develop PC. Results: We studied 48 patients with CCP (30 men (62%) and 18 women (38%), mean age 69.4 years). Sixteen patients (with 18 tumor sites) who developed PC (1.52%) were compared with 32 controls who did not develop PC. A hypodense mass was observed in all of the patients with PC, predominantly in the pancreatic head (61.2%). No such masses were observed in the controls (p < 0.001). The average mass size was 36.3 mm, and the masses were observed to push aside the calcifications in all patients (p < 0.001). Calcifications were very abundant (>10) in 33.3% of the patients with PC and in 71.9% of the controls (p = 0.0076). The main pancreatic duct (MPD) was dilated in all of the patients with PC (average diameter 8.6 mm; homogeneous in 83.3%) and in only 46.9% of the controls (average 7.4 mm; homogeneous in 37.5%) (p > 0.05). Dilation of the intrahepatic bile ducts and common bile duct was observed in 15 (94.4%) of the patients with PC and in none of the controls (p < 0.0001). The average alcohol consumption was 1 g/day (0–5 g/day) in the PC group and 4.6 g/day (0–20 g/day) in the control group. In addition, the average smoking history was 14.25 pack-years (0–40 PY) in the PC group and 27.70 PY (0–60 PY) in the control group. Conclusion: The presence of a pancreatic mass in a patient with CCP is

Computed tomography findings of pancreatic metastases from renal cell carcinoma

International Nuclear Information System (INIS)

Prando, Adilson

2008-01-01

Objective: To present computed tomography findings observed in four patients submitted to radical nephrectomy for renal cell carcinoma who developed pancreatic metastases afterwards. Materials and methods: The four patients underwent radical nephrectomy for stage Tz1 (n=2) and stage T3a (n=2) renal cell carcinoma. The mean interval between nephrectomy and detection of pancreatic metastases was eight years. Two asymptomatic patients presented with solitary pancreatic metastases (confined to the pancreas). Two symptomatic patients presented with single and multiple pancreatic metastases, both with tumor recurrence in the contralateral kidney. Results: Computed tomography studies demonstrated pancreatic metastases as solitary (n=2), single (n=1) or multiple (n=1) hypervascular lesions. Partial pancreatectomy was performed in two patients with solitary pancreatic metastases and both are free of disease at four and two years after surgery. Conclusion: Pancreatic metastases from renal cell carcinoma are rare and can occur many years after the primary tumor presentation. Multiple pancreatic metastases and pancreatic metastases associated with tumor recurrence in the contralateral kidney are uncommon. Usually, on computed tomography images pancreatic metastases are visualized as solitary hypervascular lesions, simulating isletcell tumors. Surgical management should be considered for patients with solitary pancreatic lesions. (author)

Computed tomography findings of pancreatic metastases from renal cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Prando, Adilson [Hospital Vera Cruz, Campinas, SP (Brazil). Dept. of Radiology and Imaging Diagnosis]. E-mail: adilson.prando@gmail.com

2008-07-15

Objective: To present computed tomography findings observed in four patients submitted to radical nephrectomy for renal cell carcinoma who developed pancreatic metastases afterwards. Materials and methods: The four patients underwent radical nephrectomy for stage Tz1 (n=2) and stage T3a (n=2) renal cell carcinoma. The mean interval between nephrectomy and detection of pancreatic metastases was eight years. Two asymptomatic patients presented with solitary pancreatic metastases (confined to the pancreas). Two symptomatic patients presented with single and multiple pancreatic metastases, both with tumor recurrence in the contralateral kidney. Results: Computed tomography studies demonstrated pancreatic metastases as solitary (n=2), single (n=1) or multiple (n=1) hypervascular lesions. Partial pancreatectomy was performed in two patients with solitary pancreatic metastases and both are free of disease at four and two years after surgery. Conclusion: Pancreatic metastases from renal cell carcinoma are rare and can occur many years after the primary tumor presentation. Multiple pancreatic metastases and pancreatic metastases associated with tumor recurrence in the contralateral kidney are uncommon. Usually, on computed tomography images pancreatic metastases are visualized as solitary hypervascular lesions, simulating isletcell tumors. Surgical management should be considered for patients with solitary pancreatic lesions. (author)

Cooperation of Ad-hING4 and 125I seed in tumor-suppression on human pancreatic cancer xenograft in nude mice

International Nuclear Information System (INIS)

Zhai Hongyan; Fa Yihua; Su Chenghai; Yang Jicheng; Sheng Weihua; Xie Yufeng

2009-01-01

This work is to investigate the combined tumor-suppression effect of Adenovirus-mediated human ING4 (Ad-hING4) and 125 I seed on human pancreatic cancer xenograft and the possible mechanisms. Ad-hING4 recombinant adenovirus vector was transected into QBI-293A cells and high titre adenovirus was obtained. Subcutaneous tumor models were established with 25 nude mice with human pancreatic cancer cell line PANC-1. They were randomly divided into 5 groups: PBS control group, Ad carrier group, 125 I seed brachytherapy group, Ad-hING4 gene treatment group, combined 125 I seed and Ad-hING4 group. The tumor volumes were measured every 5 days after treatment, and were sacrificed on the 20th day. The tumors were measured and weighed to determine the ratio of tumor-suppression and Jin-Shi q value. Morphological changes of tumor cells,the tissue injury and apoptotic index AI were examined on pathological sections. MVD, Survivin and Caspase3 were tested in immunohistochemistry. The results show that the tumor-suppressive ratio of the 125 I seed group, Ad-hING4 group, combined treatment group were,respectively, 34.19%(P 0.05). It can be concluded that 125 I seed and Ad-hING4 inhibit the growth of PANC-1 pancreatic cancer on nude mice significantly. These indicate a synergy of the combined treatments in tumor-suppression and Ad-hING4 is a promising novel radiosensitizer. The mechanisms of tumor-suppressive may be multi-pathways such as down-regulation the expression of Survivin and up-regulation the expression of Caspase3 to induce apoptosis and inhibit angiogenesis. (authors)

Micro-positron emission tomography/contrast-enhanced computed tomography imaging of orthotopic pancreatic tumor-bearing mice using the αvβ₃ integrin tracer ⁶⁴Cu-labeled cyclam-RAFT-c(-RGDfK-)₄.

Science.gov (United States)

Aung, Winn; Jin, Zhao-Hui; Furukawa, Takako; Claron, Michael; Boturyn, Didier; Sogawa, Chizuru; Tsuji, Atsushi B; Wakizaka, Hidekatsu; Fukumura, Toshimitsu; Fujibayashi, Yasuhisa; Dumy, Pascal; Saga, Tsuneo

2013-09-01

The purpose of this study was to develop a clinically relevant orthotopic xenotransplantation model of pancreatic cancer and to perform a preclinical evaluation of a new positron emission tomography (PET) imaging probe, ⁶⁴Cu-labeled cyclam-RAFT-c(-RGDfK-)₄ peptide (⁶⁴Cu-RAFT-RGD), using this model. Varying degrees of αvβ₃ integrin expression in several human pancreatic cancer cell lines were examined by flow cytometry and Western blotting. The cell line BxPC-3, which is stably transfected with a red fluorescence protein (RFP), was used for surgical orthotopic implantation. Orthotopic xenograft was established in the pancreas of recipient nude mice. An in vivo probe biodistribution and receptor blocking study, preclinical PET imaging coregistered with contrast-enhanced computed tomography (CECT) comparing ⁶⁴Cu-RAFT-RGD and ¹⁸F-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) accumulation in tumor, postimaging autoradiography, and histologic and immunohistochemical examinations were done. Biodistribution evaluation with a blocking study confirmed that efficient binding of probe to tumor is highly αvβ₃ integrin specific. ⁶⁴Cu-RAFT-RGD PET combined with CECT provided for precise and easy detection of cancer lesions. Autoradiography, histologic, and immunohistochemical examinations confirmed the accumulation of ⁶⁴Cu-RAFT-RGD in tumor versus nontumor tissues. In comparative PET studies, ⁶⁴Cu-RAFT-RGD accumulation provided better tumor contrast to background than ¹⁸F-FDG. Our results suggest that ⁶⁴Cu-RAFT-RGD PET imaging is potentially applicable for the diagnosis of αvβ₃ integrin-expressing pancreatic tumors.

Radioimmunodetection of human pancreatic tumor xenografts using DU-PAN II monoclonal antibody

International Nuclear Information System (INIS)

Nakamura, Kayoko; Kubo, Atsushi; Hashimoto, Shozo; Furuuchi, Takayuki; Abe, Osahiko; Takami, Hiroshi.

1988-01-01

The potential of DU-PAN II, monoclonal antibody (IgM), which was raised against the human tumor cell line, was evaluated for radioimmunodetection of human pancreatic tumors (PAN-5-JCK and EXP-58) grown in nude mice. 125 I-labeled DU-PAN II was accumulated into PAN-5-JCK producing DU-PAN II antigen with a tumor-to-blood ratio of 2.72 ± 3.00, but it did not localize in EXP-58 because of insufficient DU-PAN II. There was no significant uptake of 125 I-nonimmunized IgM in PAN-5-JCK. These facts indicated the specific tumor uptake of DU-PAN II. Excellent images of the tumor PAN-5-JCK were obtained 3 days after the injection of 125 I-DU-PAN II. Gel chromatography was also investigated with respect to the plasma taken from mice injected with antibody, or incubated with antibody in vitro. The results indicate that circulating antigen affected the tumor uptake of DU-PAN II: The more the tumor grew, the higher the amount of antigen excreted into the blood, leading to the degradation of DU-PAN II before it reached the tumor sites. Consequently, the immunoscintigram of the small tumor was remarkably clear. The catabolism and the radiolysis of the labeled IgM injected are critical points in applying immunoscintigraphy. (author)

PANCREATIC CANCER

Directory of Open Access Journals (Sweden)

Alojz Pleskovič

2003-12-01

Full Text Available Background. The pancreatic cancer is quite common malignant tumor of gastointestinal tract and its incidence is increasing in well developed part of the world. Despite of all advanced diagnostic methods the disease is in most cases recognised too late when the tumor is not resectable.Conclusions. Only in 20–30% of patients with pancreatic cancer surgical resection is possible, and even in this group 5year survival is very low. In the patients where the tumor is not resectable, sometimes only palliative procedures are indicated and sometimes only simptomatic therapy is possible. The average survival period in this group of patients is 12–20 months. Adjuvant chemo and radiotherapy has not shown much of benefit and the prognosis is still very bad.

Extended pancreatectomy in pancreatic ductal adenocarcinoma: definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS)

NARCIS (Netherlands)

Hartwig, Werner; Vollmer, Charles M.; Fingerhut, Abe; Yeo, Charles J.; Neoptolemos, John P.; Adham, Mustapha; Andrén-Sandberg, Ake; Asbun, Horacio J.; Bassi, Claudio; Bockhorn, Max; Charnley, Richard; Conlon, Kevin C.; Dervenis, Christos; Fernandez-Cruz, Laureano; Friess, Helmut; Gouma, Dirk J.; Imrie, Clem W.; Lillemoe, Keith D.; Milićević, Miroslav N.; Montorsi, Marco; Shrikhande, Shailesh V.; Vashist, Yogesh K.; Izbicki, Jakob R.; Büchler, Markus W.

2014-01-01

Complete macroscopic tumor resection is one of the most relevant predictors of long-term survival in pancreatic ductal adenocarcinoma. Because locally advanced pancreatic tumors can involve adjacent organs, "extended" pancreatectomy that includes the resection of additional organs may be needed to

Marital status is an independent prognostic factor for pancreatic neuroendocrine tumors patients: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

Science.gov (United States)

Zhou, Huaqiang; Zhang, Yuanzhe; Song, Yiyan; Tan, Wulin; Qiu, Zeting; Li, Si; Chen, Qinchang; Gao, Shaowei

2017-09-01

Marital status's prognostic impact on pancreatic neuroendocrine tumors (PNET) has not been rigorously studied. We aimed to explore the relationship between marital status and outcomes of PNET. We retrospectively investigated 2060 PNET cases between 2004 and 2010 from Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by Chi 2 test, t-test as appropriate. Kaplan-Meier methods and COX proportional hazard models were used to ascertain independent prognostic factors. Married patients had better 5-year overall survival (OS) (53.37% vs. 42.27%, Pvs. 59.82%, P=0.001) comparing with unmarried patients. Multivariate analysis revealed marital status is an independent prognostic factor, with married patients showing better OS (HR=0.74; 95% CI: 0.65-0.84; Punmarried patients may be associated with a delayed diagnosis with advanced tumor stage, psychosocial and socioeconomic factors. Further studies are needed. Copyright © 2017. Published by Elsevier Masson SAS.

Pancreatic neuroendocrine tumors containing areas of iso- or hypoattenuation in dynamic contrast-enhanced computed tomography: Spectrum of imaging findings and pathological grading.

Science.gov (United States)

Hyodo, Ryota; Suzuki, Kojiro; Ogawa, Hiroshi; Komada, Tomohiro; Naganawa, Shinji

2015-11-01

To evaluate dynamic contrast-enhanced computed tomography (CT) features of pancreatic neuroendocrine tumors (PNETs) containing areas of iso- or hypoattenuation and the relationship with pathological grading. Between June 2006 and March 2014, 61 PNETs in 58 consecutive patients (29 male, 29 female; median-age 55 years), which were surgically diagnosed, underwent preoperative dynamic contrast-enhanced CT. PNETs were classified based on contrast enhancement patterns in the pancreatic phase: iso/hypo-PNETs were defined as tumors containing areas of iso- or hypoattenuation except for cystic components, and hyper-PNETs were tumors showing hyperattenuation over the whole area. CT findings and contrast-enhancement patterns of the tumors were evaluated retrospectively by two radiologists and compared with the pathological grading. Iso/hypo-PNETs comprised 26 tumors, and hyper-PNETs comprised 35 tumors. Not only hyper-PNETs but also most iso/hypo-PNETs showed peak enhancement in the pancreatic phase and a washout from the portal venous phase to the delayed phase. Iso/hypo-PNETs showed larger tumor size than the hyper-PNETs (mean, 3.7 cm vs. 1.6 cm; PIso/hypo-PNETs also showed significantly higher pathological grading (WHO 2010 classification; iso/hypo, G1=14, G2=11, G3=1; hyper, G1=34, G2=1; Piso/hypo-areas showed a rapid enhancement pattern as well as hyper-PNETs, various radiological features and higher malignant potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

International Nuclear Information System (INIS)

Chang, Aeson; Kim-Fuchs, Corina; Le, Caroline P.; Hollande, Frédéric; Sloan, Erica K.

2015-01-01

The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer

Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

Energy Technology Data Exchange (ETDEWEB)

Chang, Aeson [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Kim-Fuchs, Corina [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Visceral Surgery and Medicine, University Hospital Bern, Bern 3010 (Switzerland); Le, Caroline P. [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Hollande, Frédéric [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Pathology, University of Melbourne, Parkville 3010 (Australia); Sloan, Erica K., E-mail: erica.sloan@monash.edu [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Cousins Center for PNI, UCLA Semel Institute, Jonsson Comprehensive Cancer Center, and UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095 (United States); Peter MacCallum Cancer Centre, Division of Cancer Surgery, East Melbourne, Victoria 3002 (Australia)

2015-07-17

The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer.

Growth Factor Mediated Signaling in Pancreatic Pathogenesis

Energy Technology Data Exchange (ETDEWEB)

Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

2011-02-24

Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

Growth Factor Mediated Signaling in Pancreatic Pathogenesis

International Nuclear Information System (INIS)

Nandy, Debashis; Mukhopadhyay, Debabrata

2011-01-01

Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

Validation of full-field optical coherence tomography in distinguishing malignant and benign tissue in resected pancreatic cancer specimens.

Directory of Open Access Journals (Sweden)

Labrinus van Manen

Full Text Available Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States. The minority of patients can undergo curative-intended surgical therapy due to progressive disease stage at time of diagnosis. Nonetheless, tumor involvement of surgical margins is seen in up to 70% of resections, being a strong negative prognostic factor. Real-time intraoperative imaging modalities may aid surgeons to obtain tumor-free resection margins. Full-field optical coherence tomography (FF-OCT is a promising diagnostic tool using high-resolution white-light interference microscopy without tissue processing. Therefore, we composed an atlas of FF-OCT images of malignant and benign pancreatic tissue, and investigated the accuracy with which the pathologists could distinguish these.One hundred FF-OCT images were collected from specimens of 29 patients who underwent pancreatic resection for various indications between 2014 and 2016. One experienced gastrointestinal pathologist and one pathologist in training scored independently the FF-OCT images as malignant or benign blinded to the final pathology conclusion. Results were compared to those obtained with standard hematoxylin and eosin (H&E slides.Overall, combined test characteristics of both pathologists showed a sensitivity of 72%, specificity of 74%, positive predictive value of 69%, negative predictive value of 79% and an overall accuracy of 73%. In the subset of pancreatic ductal adenocarcinoma patients, 97% of the FF-OCT images (n = 35 were interpreted as tumor by at least one pathologist. Moreover, normal pancreatic tissue was recognised in all cases by at least one pathologist. However, atrophy and fibrosis, serous cystadenoma and neuroendocrine tumors were more often wrongly scored, in 63%, 100% and 25% respectively.FF-OCT could distinguish normal pancreatic tissue from pathologic pancreatic tissue in both processed as non-processed specimens using architectural features. The accuracy in

Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection.

Science.gov (United States)

Gilliland, Taylor M; Villafane-Ferriol, Nicole; Shah, Kevin P; Shah, Rohan M; Tran Cao, Hop S; Massarweh, Nader N; Silberfein, Eric J; Choi, Eugene A; Hsu, Cary; McElhany, Amy L; Barakat, Omar; Fisher, William; Van Buren, George

2017-03-07

Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995-2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate treatment to improve the patient's quality of life.

Rare case of pancreatic cancer with leptomeningeal carcinomatosis

Science.gov (United States)

Yoo, In Kyung; Lee, Hong Sik; Kim, Chang Duk; Chun, Hoon Jai; Jeen, Yoon Tae; Keum, Bora; Kim, Eun Sun; Choi, Hyuk Soon; Lee, Jae Min; Kim, Seung Han; Nam, Seung Joo; Hyun, Jong Jin

2015-01-01

Leptomeningeal carcinomatosis occurs very rarely in patients with pancreatic cancer. Leptomeningeal carcinomatosis is characterized by multifocal seeding of the leptomeninges by malignant cells that originate from a solid tumor. To the best of our knowledge, brain metastasis from pancreatic cancer is extremely rare. Leptomeningeal carcinomatosis is estimated to occur in 3% to 8% of cases of solid tumors. The clinical manifestation usually involves neurological symptoms, including dizziness, headache, vomiting, nausea, and hemiparesis, symptoms similar to those of meningitis or brain tumors. Diagnostic methods for leptomeningeal carcinomatosis include brain magnetic resonance imaging and cerebrospinal fluid examination. Here, we describe a case of leptomeningeal carcinomatosis in which the primary tumor was later determined to be pancreatic cancer. Brain magnetic resonance imaging findings showed mild enhancement of the leptomeninges, and cerebrospinal fluid cytology was negative at first. However, after repeated spinal taps, atypical cells were observed on cerebrospinal fluid analysis and levels of tumor markers such as carbohydrate antigen 19-9 in cerebrospinal fluid were elevated. Abdominal computed tomography, performed to determine the presence of extracerebral tumors, revealed pancreatic cancer. Pancreatic cancer was confirmed histopathologically on examination of an endoscopic ultrasound-guided fine needle aspiration specimen. PMID:25624740

Marked differences in immunocytological localization of [3H]estradiol-binding protein in rat pancreatic acinar tumor cells compared to normal acinar cells

International Nuclear Information System (INIS)

Beaudoin, A.R.; Grondin, G.; St Jean, P.; Pettengill, O.; Longnecker, D.S.; Grossman, A.

1991-01-01

[ 3 H]Estradiol can bind to a specific protein in normal rat pancreatic acinar cells. Electron microscopic immunocytochemical analysis has shown this protein to be localized primarily in the rough endoplasmic reticulum and mitochondria. Rat exocrine pancreatic tumor cell lines, whether grown in tissue culture (AR42J) or as a tumor mass after sc injection into rats (DSL-2), lacked detectable amounts of this [ 3 H]estradiol-binding protein (EBP), as determined by the dextran-coated charcoal assay. Furthermore, primary exocrine pancreatic neoplasms induced with the carcinogen azaserine contained little or no detectable [ 3 H]estradiol-binding activity. However, electron immunocytochemical studies of transformed cells indicated the presence of material that cross-reacted with antibodies prepared against the [ 3 H]EBP. The immunopositive reaction in transformed cells was localized almost exclusively in lipid granules. Such lipid organelles in normal acinar cells, although present less frequently than in transformed cells, have never been observed to contain EBP-like immunopositive material. Presumably, the aberrant localization of EBP in these acinar tumor cells results in loss of function of this protein, which in normal pancreatic acinar cells appears to exert a modulating influence on zymogen granule formation and the process of secretion

Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar-to-Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice.

Science.gov (United States)

He, Ping; Yang, Jong Won; Yang, Vincent W; Bialkowska, Agnieszka B

2018-04-01

Activating mutations in KRAS are detected in most pancreatic ductal adenocarcinomas (PDACs). Expression of an activated form of KRAS (KrasG12D) in pancreata of mice is sufficient to induce formation of pancreatic intraepithelial neoplasia (PanINs)-a precursor of PDAC. Pancreatitis increases formation of PanINs in mice that express KrasG12D by promoting acinar-to-ductal metaplasia (ADM). We investigated the role of the transcription factor Krüppel-like factor 5 (KLF5) in ADM and KRAS-mediated formation of PanINs. We performed studies in adult mice with conditional disruption of Klf5 (Klf5 fl/fl ) and/or expression of Kras G12D (LSL-Kras G12D ) via Cre ERTM recombinase regulated by an acinar cell-specific promoter (Ptf1a). Activation of Kras G12D and loss of KLF5 was achieved by administration of tamoxifen. Pancreatitis was induced in mice by administration of cerulein; pancreatic tissues were collected, analyzed by histology and immunohistochemistry, and transcriptomes were compared between mice that did or did not express KLF5. We performed immunohistochemical analyses of human tissue microarrays, comparing levels of KLF5 among 96 human samples of PDAC. UN-KC-6141 cells (pancreatic cancer cells derived from Pdx1-Cre;LSL-Kras G12D mice) were incubated with inhibitors of different kinases and analyzed in proliferation assays and by immunoblots. Expression of KLF5 was knocked down with small hairpin RNAs or CRISPR/Cas9 strategies; cells were analyzed in proliferation and gene expression assays, and compared with cells expressing control vectors. Cells were subcutaneously injected into flanks of syngeneic mice and tumor growth was assessed. Of the 96 PDAC samples analyzed, 73% were positive for KLF5 (defined as nuclear staining in more than 5% of tumor cells). Pancreata from Ptf1a-Cre ERTM ;LSL-Kras G12D mice contained ADM and PanIN lesions, which contained high levels of nuclear KLF5 within these structures. In contrast, Ptf1a-Cre ERTM ;LSL-Kras G12D ;Klf5 fl

Autoimmune pancreatitis. An update

International Nuclear Information System (INIS)

Helmberger, T.

2016-01-01

Autoimmune pancreatitis (AIP) is a rare disease, the pathophysiological understanding of which has been greatly improved over the last years. The most common form, type 1 AIP belongs to the IgG4-related diseases and must be distinguished from type 2 AIP, which is a much rarer entity associated with chronic inflammatory bowel disease. Clinically, there is an overlap with pancreatic cancer. Imaging and further criteria, such as serological and histological parameters are utilized for a differentiation between both entities in order to select the appropriate therapy and to avoid the small but ultimately unnecessary number of pancreatectomies. The diagnostics of AIP are complex, whereby the consensus criteria of the International Association of Pancreatology have become accepted as the parameters for discrimination. These encompass five cardinal criteria and one therapeutic criterion. By applying these criteria AIP can be diagnosed with a sensitivity of 84.9 %, a specificity of 100 % and an accuracy of 93.8 %. The diagnosis of AIP is accomplished by applying several parameters of which two relate to imaging. As for the routine diagnostics of the pancreas these are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Important for the differential diagnosis is the exclusion of signs of local and remote tumor spread for which CT and MRI are established. The essential diagnostic parameter of histology necessitates sufficient sample material, which cannot usually be acquired by a fine needle biopsy. CT or MRI are the reference standard methods for identification of the optimal puncture site and imaging-assisted (TruCut) biopsy. In patients presenting with unspecific upper abdominal pain, painless jaundice combined with the suspicion of a pancreatic malignancy in imaging but a mismatch of secondary signs of malignancy, AIP should also be considered as a differential diagnosis. As the diagnosis of AIP only partially relies on imaging radiologists also

Pancreatic Carcinoma: the Disease that Kills

Science.gov (United States)

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

CT of blunt pancreatic trauma-A pictorial essay

International Nuclear Information System (INIS)

Venkatesh, Sudhakar Kundapur; Wan, John Mun Chin

2008-01-01

Blunt trauma to pancreas is uncommon and clinical features are often non-specific and unreliable leading to possible delays in diagnosis and therefore increased morbidity. CT has been established as the imaging modality of choice for the diagnosis of abdominal solid-organ injury in the blunt trauma patient. The introduction of multidetector-row CT allows for high resolution scans and multiplanar reformations that improve diagnosis. Detection of pancreatic injuries on CT requires knowledge of the subtle changes produced by pancreatic injury. The CT appearance of pancreatic injury ranges from a normal initial appearance of the pancreas to active pancreatic bleeding. Knowledge of CT signs of pancreatic trauma and a high index of suspicion is required in diagnosing pancreatic injury