Adenocarcinoma Of Pancreas Research Articles

Abstract IA10: Biomarker selected therapy for pancreas ductal adenocarcinoma: an emerging reality?

Abstract Pancreas adenocarcinoma remains a major challenge hallmarked by several notables, including a rising incidence, modest effectiveness of current state-of-the-art therapies and a dearth of validated biomarkers for clinical decision making. With regard to germline genomics, about 5-8% of pancreas adenocarcinoma patients will harbor a mutation in BRCA2, BRCA1 and PALB2. These mutations amongst others lead to impaired DNA repair and are identified to be important biomarkers of genomic instability as well as of response to DNA damaging agents. Genomic instability, a result of deleterious mutations of genes functioning in homologous repair mediated DNA repair pathways, yields an exceptional vulnerability in cancer cells named synthetic lethality. Recent studies have elucidated that platinum agents and Poly-ADP-ribose polymerase (PARP) inhibitors may be effective to induce tumor regression in solid tumors bearing an unstable genome including pancreatic cancer. The impact of somatic BRCA mutations on response to DNA targeting agents is currently being investigated. A recent whole genome sequencing study by Waddell et al reported overlapping features in both somatic and germline mutations such as unstable genome along with possible DNA targeting agent sensitivity in both groups. This suggests that gained mutation of DNA repair genes throughout the oncogenesis process may also create synthetic lethality and a larger subset of patients may benefit from these evolving treatment approaches. The characteristics of genomic instability in pancreatic cancer along with its clinical implications and the utility of DNA targeting agents particularly PARP inhibitors as novel treatment approaches will be discussed. Citation Format: Eileen M. O’Reilly.{Authors}. Biomarker selected therapy for pancreas ductal adenocarcinoma: an emerging reality? [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr IA10.

IL-4 mRNA Is Downregulated in the Liver of Pancreatic Cancer Patients Suffering from Cachexia

ABSTRACTBackground. Interleukin-4 (IL-4) together with interleukin-13 (IL-13) play an important role in inflammation and wound repair, and are known to be upregulated in human skeletal muscle after strenuous physical exercise. Additionally, these cytokines may act as autocrine growth factors in pancreatic cancer cells. We hypothesize that IL-4, IL-13, and their corresponding receptors are involved in mechanism of cancer cachexia.Methods. Tissue samples from human skeletal muscle, white fat, liver, healthy pancreas, and pancreatic ductal adenocarcinoma were analyzed by quantitative real-time polymerase chain reaction for mRNA expression levels of IL-4, IL-13, IL-4 receptor α, and IL-13 receptor α1.Results. We demonstrate for the first time that liver IL-4 mRNA is downregulated in vivo in patients with pancreatic cancer and cachexia. Additionally, IL-4 mRNA in the liver inversely correlated with musculus psoas thickness.Conclusion. We speculate that suppression of IL-4 is involved in cancer cachexia, although the exact mechanisms have to be further elucidated.

Predictors and survival for pathologic tumor response grade in borderline resectable and locally advanced pancreatic cancer treated with induction chemotherapy and neoadjuvant stereotactic body radiotherapy

Background: Neoadjuvant therapy response correlates with survival in multiple gastrointestinal malignancies. To potentially augment neoadjuvant response for pancreas adenocarcinoma, we intensified treatment with stereotactic body radiotherapy (SBRT) following multi-agent chemotherapy. Using this regimen, we analyzed whether the College of American Pathology (CAP) tumor regression grade (TRG) at pancreatectomy correlated with established response biomarkers and survival.Materials and methods: We identified borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer patients treated according to our institutional clinical pathway who underwent surgical resection with reported TRG (n = 81, median follow-up after surgery 24.2 months). Patients had baseline CA19-9, computed tomography (CT), endoscopic ultrasound, and FDG positron emission tomography (PET)/CT then underwent multi-agent chemotherapy (79% with three cycles of gemcitabine, docetaxel and capecitabine) followed by 5-fraction SBRT. They then underwent restaging CT, PET/CT and CA19-9. Overall (OS) and progression-free (PFS) survival were estimated and compared by Kaplan–Meier and log-rank methods. Univariate ordinal logistic regression correlated TRG with baseline, restaging and change in CA19-9 and the PET maximum standardized uptake value (SUVmax).Results: Restaging level and decrease in CA19-9 correlated with improved TRG (p = .02 for both) as did restaging SUVmax (p < .01), yet there was no TRG correlation with decrease in SUVmax (p = .10) or CT response (p = .30). The TRG groups had similar OS and PFS except the TRG 0 (complete response) group. Compared to partial response levels (TRG 1-3, median OS 33.9 months, median PFS 13.0 months), the six (7%) patients with TRG 0 had no deaths (p = .05) and only one progression (p = .03). A group of 10 (12%) TRG 1 patients with only residual isolated tumor cells had similar outcomes to the other TRG 1-3 patients.Conclusion: Pre-operative PET-CT and CA19-9 response correlate with histopathologic tumor regression. Patients with complete pathologic response have superior outcomes, suggesting a rationale for intensification and personalization of neoadjuvant therapy in BRPC and LAPC.

Predisposing factors for pancreatic adenocarcinoma: What is the role of imaging?

Early detection of pancreatic adenocarcinoma is the goal of imaging, enabling curative surgery. The identification of high-grade dysplastic precursor lesions is even more beneficial. Two forms are now better known: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). To detect these lesions with imaging, we need to know the patterns associated with them. A screening program could then be used to pinpoint them. This program could not be applied to the entire population. Identifying patients with an increased risk of pancreas adenocarcinoma is the first step of such screening.

PCN274 - Recommended vs Reimbursed vs Actually used Chemiotherapeutics in Pancreatic Adenocarcinoma in Poland

To compare drugs that are recommended in national and international clinical guidelines with those reimbursed and actually used in the treatment of pancreatic adenocarcinoma in Poland. Websites of relevant clinical associations, the List of reimbursed drugs authorized by the Ministry of Health in Poland (LMoH) and database made available by Polish public payer as of October 2015 were screened in search for drugs used in the treatment of pancreatic adenocarcinoma. All guidelines consequently recommended gemcitabine or its doublets with nab-paclitaxel (with the highest category of evidence) and in patients with good performance status – FOLFIRINOX (oxaliplatin, irinotecan and fluorouracil). Some also indicated gemcitabine in combination with erlotinib, capecitabine or cisplatin, as well as doublets of oxaliplatin with fluoropiridine (classified as less effective). According to LMoH the following chemotherapeutics were reimbursed in the treatment of adenocarcinomas of pancreas: carboplatin, cisplatin, cyclophosphamide, dacarbazine, doxorubicin, etoposide, fluorouracil, gemcitabine, ifosfamide, irinotecan, mitomicin, oxaliplatin, vinblastine, vincristine and vinorelbine. Database of Polish public payer showed that from 2013 to 2015 (as for first half of the year) 1138 patients with the mentioned malignancies were treated with reimbursed drugs and gemcitabine was used in a great majority of them (n=923). Among less commonly utilized drugs were fluorouracil (n=224), oxaliplatin (n=189) and cisplatin (n=125). Other were administered to single patients (irinotecan n=23, etoposide n=11, carboplatin, vinorelbine n=4 each, doxorubicin n=3, cyclophosphamide, vinblastine and vinorelbine n=1 each). There were also 20 patients from 2014 to 2015 treated with nab-paclitaxel reimbursed outside standard fashion (i.e. outside LMoH). There is a strong adherence of recommended, reimbursed and actually used drugs in pancreatic adenocarcinoma if it comes to gemcitabine, fluorouracil, oxaliplatin and cisplatin in Poland.

Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study

ObjectiveA history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes...

Can Serum Pancreatic Amylase and Lipase Levels Be Used as Diagnostic Markers to Distinguish Between Patients With Mucinous Cystic Lesions of the Pancreas, Chronic Pancreatitis, and Pancreatic Ductal Adenocarcinoma?

This study aimed to assess the presence of pancreatic hyperenzymemia in patients with pancreatic cystic lesions as compared to other chronic diseases of the pancreas. Ninety-one patients were studied: 32 had mucinous cystic lesions, 35 had chronic pancreatitis (CP), and 24 had pancreatic ductal adenocarcinoma (PDAC). Surgery was carried out in 10 of the 32 patients with mucinous cystic lesion (7 of them had severe dysplasia), in 5 patients with CP, and in 9 patients with PDAC. Abnormally high serum pancreatic isoamylase activity was present in 11 (34.4%) patients with mucinous cystic lesions, in 14 (40.0%) patients with CP, and none in patients with PDAC (P = 0.002); whereas serum lipase activity was abnormally high in 8 (25.0%) patients with mucinous cystic lesion, in 17 (48.6%) patients with CP, and in 3 (12.5%) patients with PDAC (P = 0.009). In 7 patients with mucinous cystic lesions and histologically confirmed severe dysplasia, abnormally high levels of both serum pancreatic amylase and lipase were present in 3 (42.9%) patients. High serum concentrations of pancreatic amylase and lipase were found in no more than half of the patients with mucinous cystic lesions. High levels of pancreatic enzymes were not associated with a greater risk of malignancy.

Second pancreatectomy for recurrent pancreatic ductal adenocarcinoma in the remnant pancreas: A pooled analysis

ObjectivesThe aim of this study was to examine the outcomes of second pancreatectomy for the treatment of recurrent pancreatic ductal adenocarcinoma (PDAC) in the remnant pancreas. MethodSearch of the PubMed database was undertaken to identify relevant English language studies. Pooled individually data were examined for clinical outcomes after second pancreatectomy for recurrent PDAC. ResultsA total of 19 articles involving 55 patients were eligible for inclusion. The median disease-free interval after initial resection was 33 (range 7–143) months. Of the 55 patients reported, 52 (94.5%) patients underwent completion total pancreatectomy in the second operation for recurrences, including 15 patients who developed recurrences more than 5 years after the initial operation. There was no perioperative death. The 1-, 3- and 5-year overall survival rate after the second pancreatectomy was 82.2%, 49.2% and 40.6% respectively. ConclusionSecond pancreatectomy for recurrent PDAC can be performed safely with long-term survival in selected patients.

Behind Recurrent Thromboembolic Events.

We describe the case of a 68-year-old man, who presented with an ischemic stroke due to cardiac embolization related to mitral valve endocarditis. Blood cultures were always negative and post-operative valve histology did not show microorganisms. The patient also presented further recurrent peripheral embolic events. These clinical aspects were the first sign of a pancreas adenocarcinoma, which was only diagnosed in the clinical autopsy. In conclusion, these clinical findings of recurrent thromboembolic events with no microorganisms isolated suggests the diagnostic of a marantic endocarditis.LEARNING POINTSMarantic endocarditis is characterized by the deposition of fibrin and thrombi on heart valves in the absence of microorganisms.Is associated with higher incidence of thromboembolic events and most commonly found in patients with neoplasia in post-mortem studies.It is a diagnostic challenge to distinguish from infective endocarditis and a high clinical suspicion is crucial to confirm the diagnosis.

Performance Status Key to Treatment for Pancreas Adenocarcinoma

Performance Status Key to Treatment for Pancreas Adenocarcinoma

Macrophage PI3Kγ Drives Pancreatic Ductal Adenocarcinoma Progression

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low 5-year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here, we report that inhibitory targeting of PI3Kγ, a key macrophage lipid kinase, stimulates antitumor immune responses, leading to improved survival and responsiveness to standard-of-care chemotherapy in animal models of PDAC. PI3Kγ selectively drives immunosuppressive transcriptional programming in macrophages that inhibits adaptive immune responses and promotes tumor cell invasion and desmoplasia in PDAC. Blockade of PI3Kγ in PDAC-bearing mice reprograms tumor-associated macrophages to stimulate CD8(+) T-cell-mediated tumor suppression and to inhibit tumor cell invasion, metastasis, and desmoplasia. These data indicate the central role that macrophage PI3Kγ plays in PDAC progression and demonstrate that pharmacologic inhibition of PI3Kγ represents a new therapeutic modality for this devastating tumor type. We report here that PI3Kγ regulates macrophage transcriptional programming, leading to T-cell suppression, desmoplasia, and metastasis in pancreas adenocarcinoma. Genetic or pharmacologic inhibition of PI3Kγ restores antitumor immune responses and improves responsiveness to standard-of-care chemotherapy. PI3Kγ represents a new therapeutic immune target for pancreas cancer. Cancer Discov; 6(8); 870-85. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 803.

Abstract 1310: Targetingprolactin signaling to suppress pancreatic cancer stem cells

Abstract Background: Pancreatic cancer (PCa) is a major cause of cancer related mortality in United States with &amp;lt; 6% survival rate. It is an aggressive and devastating disease, which is characterized by poor prognosis, invasiveness, rapid progression, profound resistance to drug treatment and recurrance after surgery. Presently, single agent based chemotherapy (e.g. Gemcitabine) is the major treatment for metastatic adenocarcinoma of pancreas but it has a tumor response rate of below 10%. Moreover combination therapy of gemcitabine and erlotinib only marginally improved survival rate. Hence, there is a dire need to identify novel ways to inhibit pancreatic cancer growth. Methods: PCa cells (MiaPaCa-2 and PanC-1) were grown to 70-80% of confluency and treated with and without prolactin (PRL) and JAK2, STAT3 and ERK phosphorylation in presence and absence of antipsychotic compound were evaluated by western blot. Growth of PCa lines (MiaPaCa-2, PanC-1, BxPC-3, AsPC-1) and normal ductal epithelial cells (HPNE) was measured by hexosaminidase and clonogenicity, respectively. Pancosphere formation was used to identify effects on stem cells. Results: We have recently identified that the receptor for the pituitary hormone prolactin is overexpressed in pancreatic cancers, and in pancreatic cancer cell lines. When prolactin (PRL) binds its cognate receptor (PRLR), it induces various downstream events including the JAK-STAT and ERK MAPK pathways. In pancreatic cancer cell lines, we observe that PRL treatment induced dose- and time-dependent JAK2, STAT3, and ERK1/2 phosphorylation. Furthermore, there was an increase in the expression of cancer stem cell (CSC) markers DCLK1 (doublecortin calmodulin like kinase 1) and CD44. In addition, PRL-induced pancosphere formation further suggesting that PRL affects stem cells. Based on these data, we conclude that PRL signaling enhances stemness in pancreatic cancers, and therefore we decided to target it for therapeutic intervention. For this, we developed a homology model for the C-terminal intracellular region of the receptor and performed a virtual screening in silico with FDA approved drugs. One compound, a first generation antipsychotic drug diphenylbutylpiperidine, also called Penfluridol was found to interact with the region of the receptor that also binds site for JAK2. The compound has a long half-life, and is used in the treatment of chronic schizophrenia and similar psychotic disorders. We have further determined that Penfluridol inhibits PRL-induced STAT3 and ERK phosphorylation. In addition, the compound reduced proliferation, colony formation, and spheroid formation. Moreover, it induced cells to undergo autophagy by activating LC3B and increasing expression of autophagy-related genes ATG5, 7 and 12. Conclusions: PRL signaling through its cognate PRLR receptor is critical for aggressive pancreatic cancer behavior, and therefore may be an effective therapeutic strategy. Citation Format: Prasad Dandawate, Gaurav Kaushik, Dharmalingam Subramaniam, Prabhu Ramamoorthy, Scott J. Weir, Roy A. Jensen, Shrikant Anant. Targetingprolactin signaling to suppress pancreatic cancer stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1310.

Predictive Factors for the Metachronous Development of High-risk Lesions in the Remnant Pancreas After Partial Pancreatectomy for Intraductal Papillary Mucinous Neoplasm.

To identify factors predicting the development of high-risk lesions in the remnant pancreas after surgery for intraductal papillary mucinous neoplasm (IPMN). IPMN has unique features, including multifocality, adenoma-carcinoma sequence, and the development of distinct pancreatic ductal adenocarcinoma (PDAC) in the same pancreas. Careful attention should, therefore, be paid to the metachronous occurrence of high-risk lesions, including high-grade dysplasia or invasive carcinoma (HGD/INV) of IPMN and concomitant PDAC in the remnant pancreas after partial pancreatectomy for IPMN. Clinicopathologic and surveillance data for 195 patients who underwent partial pancreatectomy for IPMN were reviewed retrospectively. Thirteen patients exhibited metachronous development of high-risk lesions including 6 HGD/INV and 7 concomitant PDACs in the remnant pancreas. The 5- and 10-year cumulative incidences of metachronous high-risk lesions in the remnant pancreas were 7.8% and 11.8%, respectively. Twelve of 13 patients had high-risk lesions at the time of initial surgery, and 10 of the 13 IPMNs were located in the distal pancreas. The IPMN subtypes initially resected were gastric in 6 patients, intestinal in 5, and pancreatobililary in the remaining 2. Univariate and multiple regression analyses identified pathologic results of HGD/INV and IPMN located in the distal pancreas as independent predictive factors for metachronous HGD/INV of IPMN, and the pancreatobiliary subtype of IPMN and presence of concomitant PDAC for metachronous PDAC. Patients undergoing partial pancreatectomy for IPMN are at high risk of developing lesions requiring surgery in the remnant pancreas, and close, long-term surveillance should be considered in these patients.

Can serum amylase and lipase levels be used as diagnostic markers to distinguish between patients with mucinous cystic lesions of the pancreas, chronic pancreatitis and pancreatic ductal adenocarcinoma?

Can serum amylase and lipase levels be used as diagnostic markers to distinguish between patients with mucinous cystic lesions of the pancreas, chronic pancreatitis and pancreatic ductal adenocarcinoma?

Diyabetik sıçanların karaciğer ve böbrekleri üzerinde Caralluma tuberculata’nın hipoglisemik ve hipolipidemik etkisi ve güvenliği / Liquidambar orientalis Mill. reçine ekstraktlarının antioksidan, sitotoksik ve iNOS aktiviteleri

Abstract Objective: The aim of this study is to investigate the in vitro cytotoxicity and iNOS (inducible nitric oxide synthase) inhibitory, and antioxidant activity in order to assess the traditional usage of Liquidambar orientalis Mill resin extract. Methods: Different solvent extracts of Liquidambar orientalis Mill resin were prepared. The cytotoxicity of extracts was determined using MTT (3-(4,5-dimethyl-2-thiazolyl)- 2,5-diphenyl-2H-tetrazoliumbromide) assay. HeLa (Human cervix adenocarcinoma), A-549 (Human alveolar adenocarcinoma), MCF-7 (Human breast adenocarcinoma), CaCo-2 (Human colon colorectal adenocarcinoma), mPANC96 (Human pancreas adenocarcinoma), PC-3 (Human prostate adenocarcinoma), U87MG (Human glioblastoma- astrocytoma) and as a normal cell line HEK293 (Human embryonic kidney cells) and Vero (African green monkey kidney epithelial cells) were used for testing cytotoxicity. RAW 264.7 (murine macrophage cell lines) was used to determine the inhibition levels of inducible nitric oxide synthase (iNOS). HL-60 (human acute myeloid leukemia) was used to determine antioxidant activity as DCF production per cent. Results: Hexane, dichloromethane, methanol and water extracts were prepared, and their iNOS inhibitory, cytotoxic and antioxidant activity were investigated. The estimated IC50 values of extracts varied from 6.68 to 48.90 μg/ ml after treatment with different doses of extracts for 48 h. Inhibition of the hexane, dichloromethane, methanol, and water extracts on LPS-induced NO production in RAW 264.7 macrophage were showed that the all extracts inhibited NO production in activated RAW 264.7 cells, except methanol extract. Hexane, dichloromethane and methanol extracts inhibited NO production with IC50 values of 22 μg/ml, 22 μg/ml, and 21/ml μg, respectively. The antioxidant activity was determined by the production of DCF in HL-60 cells. The extracts showed a potent antioxidant effect, with an IC50 of in between from 19.01 to 39.77 μg/ml. Conclusion: This study is the first report showing the potential of Liquidambar orientalis Mill resin extracts for cytotoxicity, iNOS inhibition and the antioxidant activity as an alternative therapeutic approach for traditional uses. The results demonstrated that Liquidambar orientalis dichloromethane resin extracts showed strongest cytotoxic effect while all extracts except methanolic extracts exhibited moderate iNOS inhibition. All extracts other than hexane have a potent antioxidant effect in the cellular-based assay. In conclusion, further studies should focus on the purification of the active components of this extracts and to investigate the possible mode of action to obtain a better understanding of their potential use as cytotoxic, anti-inflammatory and antioxidant agents.

Influence of age on outcomes in pancreas adenocarcinoma (PAC): A single institution experience.

e15744Background: The mean age at diagnosis of PAC is 71. However, many apply age rather than performance status and organ function to decide therapy. Additionally, the elderly are underrepresented...

Pancreas Adenocarcinoma: Ascites, Clinical Manifestations, and Management Implications

BackgroundAscites develops in a subset of patients with pancreatic adenocarcinoma (PAC) at presentation or as the disease advances. Limited data exist on the prognostic importance of malignant ascites in PAC. Our hypothesis is that this information will provide an understanding of the natural history and facilitate management decisions. MethodsWe conducted a retrospective analysis of 180 patients treated at Memorial Sloan Kettering Cancer Center diagnosed between January 1, 2009 and December 31, 2014, with PAC and with ascites either at presentation or that developed during the disease course. ResultsFor the 180 patients, the overall survival was 15 months. The time from diagnosis to ascites presentation was 11 months, and the survival time after ascites development was 1.8 months (range, 1.6-2.3 months; 95% confidence interval). Of 62 patients (34%) who had ascitic fluid analyzed, 36 (58%) had positive cytology. Fifty-one (82%) patients had a serum ascites albumin gradient ≥ 1, and 11 (18%) had serum ascites albumin gradient < 1. Sixty-four (36%) patients had their ascites managed solely by serial paracenteses. A total of 116 patients required a catheter; of these, 108 (93%) had a Tenckhoff catheter, 4 (3%) a Pleurx catheter, 4 (3%) a pigtail catheter, and 1 (1%) a Denver catheter. Eight (7%) patients required 2 catheters to be placed, and in 6 (5%), Tenckhoff catheters had to be removed. The main observed complications were spontaneous bacterial peritonitis in 7 (11%) managed with paracenteses versus 26 (23%) who had a catheter placed, catheter malfunction in 8 (7%), and acute renal failure in 6 (3%). After ascites development, 79 (44%) patients received active anti-cancer therapy, and 101 (56%) patients were managed with supportive care alone. ConclusionsIn patients with PAC who presented with or developed ascites, serial paracenteses and indwelling catheters are common methods used for providing symptomatic relief. The complication rate was higher with indwelling catheters, primarily related to infection (eg, bacterial peritonitis). Overall, ascites has a significantly negative prognostic import with a short median survival.

Human anti-MUC1 antibodies elicited by a prophylactic cancer vaccine for CAR T cell immunotherapy.

Abstract Hypoglycosylated MUC1 is a tumor-associated protein that is expressed on over 80% of all human cancers including adenocarcinomas of the colon, pancreas, breast, lung, prostate, and ovary, and multiple myeloma. In our recent clinical trial, individuals at-risk for colon adenocarcinoma received a prophylactic MUC1 cancer vaccine. Many individuals responded producing high titers of anti-MUC1 IgG antibodies with no detectable toxicity. This trial provided a rare source of human antibodies elicited and affinity-matured in a healthy human host to abnormal MUC1. Using our recently developed proteomics method, we isolated and identified 13 anti-MUC1 antibodies representing 7 different clonotypes. These antibodies bind to several different epitopes on the MUC1 vaccine peptide with a range of affinities (15.7μM to 130pM). They also stain MUC1 on human cancer cell lines and colon, breast, lung, and pancreas adenocarcinoma tissue sections while showing no reactivity against a large panel of normal tissues that express MUC1. We constructed lentiviral vectors encoding chimeric antigen receptors (CARs) using scFv’s of several of the antibodies as antigen binding regions and a variety of co-signaling domain architectures. Several of the scFv’s were able to retarget human primary T cells to become activated and produce cytokines in a MUC1-dependent manner and to lyse a variety of MUC1+ human tumor cell lines. Preclinical testing in mouse tumor xenograftgrafts is underway. Being of fully human origin and showing a high-degree of tumor specificity and efficacy in preclinical experiments, these antibodies will be tested in future clinical trials for potential approval for therapy of cancer patients.

Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy

Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology. Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRT was used for clinical correlation. A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively. In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection.

Pancreatic biopsies technically difficult: benefits of percutaneous access!

Solid masses localized in the pancreas usually represent malignant lesions, and primary adenocarcinoma is the most common. However some of these injuries can be difficult to be differentiated from benign lesions by laboratory testing and imaging. In this scenario, the pancreatic biopsies are often needed for initial diagnosis and can be performed during surgery, endoscopic and percutaneous, this guided by CT scan or ultrasound. Objectives: To examine the effectiveness and safety in patients undergoing percutaneous biopsy of the pancreas through the different access and literature review. Methods: A retrospective analysis of patients undergoing biopsy of the pancreas through percutaneous access in our institution. Results: Among the observed histological diagnoses, pancreas adenocarcinoma it was the most frequent and are not observed in the sample analyzed cases of false negative. There were no post-procedure complications in the patients studied. Discussion: Percutaneous biopsy pancreatic masses is effective and safe method in different locations, with the main advantage and possibility of reduced invasiveness of pancreatic body and tail approach when compared with surgical biopsies or guided by US-endoscopic approach. Conclusion: The biopsy of pancreatic lesions with percutaneous access proves to be safe and versatile and should be considered as an initial choice in the diagnosis of injuries where the image is nonspecific.