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Introduction: Postoperative pancreatic fistula (POPF) occurs in 25% of patients undergoing a high-risk pancreatoduodenectomy (PD) and is a driving cause of major morbidity, mortality, prolonged hospital stay and increased costs after PD. There is a need for perioperative methods to decrease these risks. In recent studies, preoperative chemoradiotherapy in patients with pancreatic ductal adenocarcinoma (PDAC) reduced the rate of POPF seemingly due to radiation-induced pancreatic fibrosis. However, patients with a high risk of POPF mostly have a non-pancreatic periampullary tumour and do not receive radiotherapy. Prospective studies using radiotherapy specifically to reduce the risk of POPF have not been performed. We aim to assess the safety, feasibility and preliminary efficacy of preoperative stereotactic radiotherapy on the future pancreatic neck transection margin to reduce the rate of POPF., Methods and Analysis: In this multicentre, single-arm, phase II trial, we aim to assess the feasibility and safety of a single fraction of preoperative stereotactic radiotherapy (12 Gy) to a 4 cm area around the future pancreatic neck transection margin in patients at high risk of developing POPF after PD aimed to reduce the risk of grade B/C POPF. Adult patients scheduled for PD for malignant and premalignant periampullary tumours, excluding PDAC, with a pancreatic duct diameter ≤3 mm will be included in centres participating in the Dutch Pancreatic Cancer Group. The primary outcome is the safety and feasibility of single-dose preoperative stereotactic radiotherapy before PD. The most relevant secondary outcomes are grade B/C POPF and the difference in the extent of fibrosis between the radiated and non-radiated (uncinate margin) pancreas. Evaluation of endpoints will be performed after inclusion of 33 eligible patients., Ethics and Dissemination: Ethical approval was obtained by the Amsterdam UMC's accredited Medical Research Ethics Committee (METC). All included patients are required to have provided written informed consent. The results of this trial will be used to determine the need for a randomised controlled phase III trial and submitted to a high-impact peer-reviewed medical journal regardless of the study outcome., Trial Registration Number: NL72913 (Central Committee on Research involving Human Subjects Registry) and NCT05641233 (ClinicalTrials)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Particle mini-beam therapy exhibits promise in sparing healthy tissue through spatial fractionation, particularly notable for heavy ions, further enhancing the already favorable differential biological effectiveness at both target and entrance regions. However, breathing-induced organ motion affects particle mini-beam irradiation schemes since the organ displacements exceed the mini-beam structure dimensions, decreasing the advantages of spatial fractionation., Purpose: In this study, the impact of breathing-induced organ motion on the dose distribution was examined at the target and organs at risk(OARs) during carbon ion mini-beam irradiation for pancreatic cancer., Methods: As a first step, the carbon ion mini-beam pattern was characterized with Monte Carlo simulations. To analyze the impact of breathing-induced organ motion on the dose distribution of a virtual pancreas tumor as target and related OARs, the anthropomorphic Pancreas Phantom for Ion beam Therapy (PPIeT) was irradiated with carbon ions. A mini-beam collimator was used to deliver a spatially fractionated dose distribution. During irradiation, varying breathing motion amplitudes were induced, ranging from 5 to 15 mm. Post-irradiation, the 2D dose pattern was analyzed, focusing on the full width at half maximum (FWHM), center-to-center distance (ctc), and the peak-to-valley dose ratio (PVDR)., Results: The mini-beam pattern was visible within OARs, while in the virtual pancreas tumor a more homogeneous dose distribution was achieved. Applied motion affected the mini-beam pattern within the kidney, one of the OARs, reducing the PVDR from 3.78  ± $\pm$  0.12 to 1.478  ± $\pm$  0.070 for the 15 mm motion amplitude. In the immobile OARs including the spine and the skin at the back, the PVDR did not change within 3.4% comparing reference and motion conditions., Conclusions: This study provides an initial understanding of how breathing-induced organ motion affects spatial fractionation during carbon ion irradiation, using an anthropomorphic phantom. A decrease in the PVDR was observed in the right kidney when breathing-induced motion was applied, potentially increasing the risk of damage to OARs. Therefore, further studies are needed to explore the clinical viability of mini-beam radiotherapy with carbon ions when irradiating abdominal regions., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: The administration of dose-escalated radiation for pancreatic adenocarcinoma remains challenging because of the proximity of dose-limiting stomach and bowel, particularly the duodenum for pancreatic head tumors. We explore whether endoscopic injection of a temporary, absorbable hydrogel into the pancreatico-duodenal (PD) groove is safe and feasible for the purpose of increasing spatial separation between pancreatic head tumors and the duodenum., Methods and Materials: Six patients with localized pancreatic adenocarcinoma underwent endoscopic injection of hydrogel into the PD groove. Safety was assessed based on the incidence of procedure-related adverse events resulting in a delay of radiation therapy initiation. Feasibility was defined as the ability to create spatial separation between the pancreas and duodenum, as assessed on simulation CT., Results: All 6 patients were able to undergo endoscopic injection of hydrogel into the PD groove. No device-related events were experienced at any point in follow-up. Presence of hydrogel in the PD groove was apparent on simulation CT in all 6 patients. Mean space created by the hydrogel was 7.7 mm +/- 2.4 mm. In 3 patients who underwent Whipple resection, presence of hydrogel in the PD groove was pathologically confirmed with no evidence of damage to the duodenum., Conclusions: Endoscopic injection of hydrogel into the PD groove is safe and feasible. Characterization of the dosimetric benefit that this technique may offer in the setting of dose-escalated radiation should also be pursued, as should the ability of such dosimetric benefit to translate into clinically improved tumor control., Competing Interests: Disclosures Amol Kumar Narang reports grants or contracts from Boston Scientific, Nanocan, and Flavocure. Theodore S. Hong reports grants or contracts from National Cancer Institute and SU2C. Received consulting fees from Synthetic Biologics, Boston Scientific, Merck, Inviata, GSK, and NextCure. Participated on a Data Safety Monitoring Board or Advisory Board for Novocure and Galera. Has stock or stock options from Panther Therapeutics. Kai Ding reports support for the present manuscript from Augmenix and Boston Scientific. Grants or contracts with NIH. Joseph Herman reports grants or contracts from 1440 Canopy Cancer Collective. Royalties or licenses from Springer Publishing. Consulting fees from Histosonics and Boston Scientific. Support for attending meetings and/or travel from Histosonics and 1440 Canopy Cancer Collective. Patents planned, issued or pending with Oncospace. Has stock or stock options from Histosonics. Jeffrey Meyer reports support for the present manuscript from Boston Scientific. Royalties or licenses from Springer and UpToDate. Manoop S. Bhutani reports support for the manuscript from Boston Scientific. Grants or contracts from Nanobiotix-Research Grant and Trisalis. Consulting fees from Oncosil Inc and Starpax Medical. Kumar Krishnan reports consulting fees from Boston Scientific and Olympus Medical. Euin Ji Shin reports consulting fees from Boston Scientific. Payment for expert testimony from US Dept of Justice. Eugene J, Koay reports support for the present manuscript from Dept of Defense and the NIH. Grants or contracts from Philips Health care, GE Health care, Stand up to Cancer, Project Purple, Elekta, and Dept of Defense. Royalties or licenses from Taylor and Francis LLC. Consulting fees from RenovoRx, AstraZeneca, and Augmenix. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Apollo Cancer Hospitals in Chennai India, Bayer Health care, Philips Health care, and Aptitude Health. Patents planned, issued or pending for the design and fabrication of 3D printed oral stents for head and neck cancer. Leadership of fiduciary role in other board, society, committee or advocacy group, paid or unpaid with International Cholangiocarcinoma Research Network. Has stock or stock options with Quantum Aurea Capital., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The aim of this article is to review unrecognized toxicities resulting from radiation therapy of digestive neoplasms. Due to their precocious occurrence, acute toxicities are well-known by radiation oncologist, and their treatment well-established. Thus, acute toxicities will not be described in this review. We will focus on incidence, diagnosis, and management of late and uncommon toxicities occurring in the digestive tract and digestive organs. Prevention, by respecting healthy tissues constraints, is the main tool to reduce incidence of those rare complications. Nonetheless, once installed, late toxicities remain a major burden in terms of quality of life and can even be life threatening. Hence, information and education about their diagnosis and management is important., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

At diagnosis, about 15% of patients with pancreatic cancer present with a resectable tumour, 50% have a metastatic tumour, and 35% a locally advanced tumour, non-metastatic but unresectable due to vascular invasion, or borderline resectable. Despite the technical progress made in the field of radiation therapy and the improvement of the efficacy of chemotherapy, the prognosis of these patients remains very poor. Recently, the role of radiation therapy in the management of pancreatic cancer has been much debated. This review aims to evaluate the role of radiation therapy for patients with locally advanced tumours.

Purpose: Ablative techniques have emerged as new potential therapeutic options for patients with locally advanced pancreatic cancer (LAPC). We explored the safety and feasibility of using TRANBERG|Thermal Therapy System (Clinical Laserthermia Systems AB, Lund, Sweden) in feedback mode for immunostimulating Interstitial Laser Thermotherapy (imILT) protocol, the newest ablative technique introduced for the treatment of LAPC., Methods: The safety and feasibility results after the use of imILT protocol treatment in 15 patients of a prospective series of postsystemic therapy LAPC in two high-volume European institutions, the General and Pancreatic Unit of the Pancreas Institute, of the University of Verona, Italy, and the Department of Surgical Oncology of the Institut Paoli-Calmettes of Marseille, France, were assessed., Results: The mean age was 66 ± 5 years, with a mean tumor size of 34.6 (±8) mm. The median number of cycles of pre-imILT chemotherapy was 6 (6-12). The procedure was performed in 13 of 15 (86.6%) cases; indeed, in two cases, the procedure was not performed; in one, the procedure was considered technically demanding; in the other, liver metastases were found intraoperatively. In all treated cases, the procedure was completed. Three late pancreatic fistulas developed over four overall adverse events (26.6%) and were attributed to imILT. Mortality was nil. A learning curve is necessary to interpret and manage the laser parameters., Conclusions: Safety, feasibility, and device handling outcomes of using TRANBERG|Thermal Therapy System with temperature probes in feedback mode and imILT protocol on LAPC were not satisfactory. The metastatic setting may be appropriate to evaluate the hypothetic abscopal effect.#NCT02702986 and #NCT02973217., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To perform a comparison of the different stereotactic body radiotherapy (SBRT) plans between the Varian EDGE and CyberKnife (CK) systems for locally advanced unresectable pancreatic cancer. Fifteen patients with pancreatic cancer were selected in this study. The median planning target volume (PTV) was 28.688 cm 3 (5.736-49.246 cm 3 ). The SBRT plans for the EDGE and CK were generated in the Eclipse and Multiplan systems respectively with the same contouring and dose constrains for PTV and organs at risk (OARs). Dose distributions in PTV were evaluated in terms of coverage, conformity index (CI), new conformity index (nCI), homogeneity index (HI), and gradient index (GI). OARs, including spinal cord, bowel, stomach, duodenum and kidneys were statistically evaluated by different dose-volume metrics and equivalent uniform dose (EUD). The volume covered by the different isodose lines (ISDL) ranging from 10 to 100% for normal tissue were also analyzed. All SBRT plans for EDGE and CK met the dose constraints for PTV and OARs. For the PTV, the dosimetric metrics in EDGE plans were lower than that in CK, except that D 99 and GI were slightly higher. The EDGE plans with lower CI, nCI and HI were superior to generate more conformal and homogeneous dose distribution for PTV. For the normal tissue, the CK plans were better at OARs sparing. The radiobiological indices EUD of spinal cord, duodenum, stomach, and kidneys were lower for CK plans, except that liver were higher. The volumes of normal tissue covered by medium ISDLs (with range of 20-70%) were lower for CK plans while that covered by high and low ISDLs were lower for EDGE plans. This study indicated that both EDGE and CK generated equivalent plan quality, and both systems can be considered as beneficial techniques for SBRT of pancreatic cancer. EDGE plans offered more conformal and homogeneous dose distribution for PTV, while the CK plans could minimize the exposure of OARs.

Radon therapy has been traditionally performed globally for oxidative stress-related diseases. Many researchers have studied the beneficial effects of radon exposure in living organisms. However, the effects of thoron, a radioisotope of radon, have not been fully examined. In this study, we aimed to compare the biological effects of radon and thoron inhalation on mouse organs with a focus on oxidative stress. Male BALB/c mice were randomly divided into 15 groups: sham inhalation, radon inhalation at a dose of 500 Bq/m 3 or 2000 Bq/m 3 , and thoron inhalation at a dose of 500 Bq/m 3 or 2000 Bq/m 3 were carried out. Immediately after inhalation, mouse tissues were excised for biochemical assays. The results showed a significant increase in superoxide dismutase and total glutathione, and a significant decrease in lipid peroxide following thoron inhalation under several conditions. Additionally, similar effects were observed for different doses and inhalation times between radon and thoron. Our results suggest that thoron inhalation also exerts antioxidative effects against oxidative stress in organs. However, the inhalation conditions should be carefully analyzed because of the differences in physical characteristics between radon and thoron.

Objectives: The goal of this study was to compare outcomes of patients with borderline and resectable pancreatic cancer treated with neoadjuvant stereotactic body radiation therapy (SBRT) versus fractionated chemoradiation., Methods: Patients with borderline or resectable pancreatic cancer treated with neoadjuvant intent between November 2011 and December 2017 were reviewed. The SBRT volume/dose was 33 Gy in 5 fractions to gross tumor plus abutting vessel with or without 25 Gy in 5 fractions to pancreatic head/body and celiac/superior mesenteric artery. Fractionated chemoradiation volume/dose was 50.4 Gy in 28 fractions to gross tumor, superior mesenteric/celiac arteries, and enlarged lymph nodes with concurrent bolus 5-FU, leucovorin, oxaliplatin, irinotecan or gemcitabine/nab-paclitaxel. Failure patterns, local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival were assessed., Results: Forty-three patients were reviewed (18 SBRTs and 25 fractionated). Among patients who underwent resection, patients treated with fractionated chemoradiation had improved LRFS (12-month LRFS, 86% vs 62%, P = 0.003) and PFS (median PFS, 23 months vs 11 months, P = 0.006) compared with SBRT. There was no difference in overall survival., Conclusions: Stereotactic body radiation therapy may result in inferior LRFS and PFS compared with fractionated chemoradiation, likely because of under coverage of high-risk vascular targets.

Objectives: Locally advanced pancreatic cancer (LAPC) is managed with multimodality therapy. We aim to evaluate the outcome of single-modality radiation therapy for LAPC., Methods: Locally advanced pancreatic cancer patients were identified between 2004 and 2013 using the National Cancer Database excluding patients who received chemotherapy or surgery., Results: A total of 6590 patients were included. The mean age was 73.5 (range, 28-90) years, 83.2% were white, and 54.4% were female. Tumors of 4 cm or greater (>T3 stage) accounted for 52.7%. The median radiation dose was 39.6 Gy. Stereotactic body radiation (SBRT) delivered to 64 patients and external-beam/intensity modulated radiotherapy in 416 patients. Radiation therapy was associated with improved overall survival (OS) compared with no treatment in univariate and multivariable analyses. The medians OS for patients who received SBRT, external-beam/intensity modulated radiotherapy, or no radiation were 8.6, 6.7, and 3.4 months, respectively (P < 0.001). There is a significant difference in 12-month OS for the SBRT cohort (31.9%; 95% confidence interval [CI], 20.9%-43.5%) compared with patients who received no radiation (15.1%; 95% CI, 14.2%-16.0%), and on multivariable analysis (hazard ratio, 0.50; 95% CI, 0.38-0.65; P < 0.001)., Conclusions: The current study suggests potential benefit for radiation therapy alone in comparison with no treatment in LAPC.

Background: Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for diabetes mellitus, but the association between risk and radiation dose and volume is unclear., Methods: Participants included 20 762 5-year survivors of childhood cancer (4568 exposed to abdRT) and 4853 siblings. For abdRT, we estimated maximum dose to abdomen; mean doses for whole pancreas, pancreatic head, body, tail; and percent pancreas volume receiving no less than 10, 20, and 30 Gy. Relative risks (RRs) were estimated with a Poisson model using generalized estimating equations, adjusted for attained age. All statistical tests were two-sided., Results: Survivors exposed to abdRT (median age = 31.6 years, range = 10.2-58.3 years) were 2.92-fold more likely than siblings (95% confidence interval [CI] = 2.02 to 4.23) and 1.60-times more likely than survivors not exposed to abdRT (95%CI = 1.24 to 2.05) to develop diabetes. Among survivors treated with abdRT, greater attained age (RRper 10 years = 2.11, 95% CI = 1.70 to 2.62), higher body mass index (RRBMI 30+ = 5.00, 95% CI = 3.19 to 7.83 with referenceBMI 18.5-24.9), and increasing pancreatic tail dose were associated with increased diabetes risk in a multivariable model; an interaction was identified between younger age at cancer diagnosis and pancreatic tail dose with much higher diabetes risk associated with increasing pancreatic tail dose among those diagnosed at the youngest ages (P < .001). Radiation dose and volume to other regions of the pancreas were not statistically significantly associated with risk., Conclusions: Among survivors treated with abdRT, diabetes risk was associated with higher pancreatic tail dose, especially at younger ages. Targeted interventions are needed to improve cardiometabolic health among those at highest risk., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pancreatic adenocarcinoma is one of the most lethal cancers in oncology. Pancreatic cancer is the third most common cause of cancer-related mortality in the United States. As the years have progressed, the importance of a multidisciplinary and multimodal approach to pancreatic cancer care has been recognized and is now recommended in all major society guidelines. A subset of pancreatic cancer, borderline resectable pancreatic cancer (BRPC), has emerged as a distinct clinical entity for which specialized treatment plans are now being developed. The medical oncologist, surgical oncologist, and radiation oncologist must work jointly to help deliver the best clinical outcome for the patient with pancreatic cancer. In this discussion, we describe the current state of surgical, locoregional therapies and systemic therapy in BRPC.

Advanced cancer patients exhibit cachexia, a condition characterized by a significant reduction in the body weight predominantly from loss of skeletal muscle and adipose tissue. Cachexia is one of the major causes of morbidity and mortality in cancer patients. Decreased food intake and multi-organ energy imbalance in cancer patients worsen the cachexia syndrome. Cachectic cancer patients have a low tolerance for chemo- and radiation therapies and also have a reduced quality of life. The presence of tumors and the current treatment options for cancer further exacerbate the cachexia condition, which remains an unmet medical need. The onset of cachexia involves crosstalk between different organs leading to muscle wasting. Recent advancements in understanding the molecular mechanisms of skeletal muscle atrophy/hypertrophy and adipose tissue wasting/browning provide a platform for the development of new targeted therapies. Therefore, a better understanding of this multifactorial disorder will help to improve the quality of life of cachectic patients. In this review, we summarize the metabolic mediators of cachexia, their molecular functions, affected organs especially with respect to muscle atrophy and adipose browning and then discuss advanced therapeutic approaches to cancer cachexia., Competing Interests: Declaration of competing interest SKB is one of the co-founders of Sanguine Diagnostics and Therapeutics, Inc. The other authors declare no competing interests. The authors have declared that the submitted manuscript is original, is not under consideration by another journal, and has not been published previously in any form. Every author is aware of and has agreed to the content of this paper., (Copyright © 2020. Published by Elsevier B.V.)

The tolerability and efficacy of low-frequency, low-intensity therapeutic ultrasound-induced insulin release was investigated in a pre-clinical in vivo murine model. The treatment groups received a single 5-min continuous sonication at 1 MHz and 1.0 W/cm 2 . Insulin and glucagon levels in the serum were determined using enzyme-linked immunosorbent assay. The pancreas was excised and sectioned for histologic analysis. In terminal studies, we observed a moderate (∼50 pM) but significant increase in blood insulin concentration in vivo immediately after sonication compared with a decrease of approximately 60 pM in sham animals (n < 6, p < 0.005). No difference was observed in the change in glucose or glucagon concentrations between groups. Comparisons of hematoxylin and eosin-stained terminal and survival pancreatic tissue revealed no visible differences or evidence of damage. This study is the first step in assessing the translational potential of therapeutic ultrasound as a treatment for early stages of type 2 diabetes., (Copyright © 2019. Published by Elsevier Inc.)

Pulsed focused ultrasound (pFUS) utilizes short cycles of sound waves to mechanically shake cells within tissues which, in turn, causes transient local increases in cytokines, growth factors and cell adhesion molecules. Although the effect of pFUS has been investigated in several different organs including the kidney, muscle and heart, its effect on the pancreas has not been investigated. In the present work, we applied pFUS to the rodent pancreas with the following parameters: 1.1-MHz frequency, 5-Hz pulse repetition frequency, 5% duty cycle, 10-ms pulse length, 160-s duration. Low-intensity pFUS had a spatial average temporal average intensity of 11.5 W/cm 2 and a negative peak pressure of 3 MPa; high-intensity pFUS had a spatial average temporal average intensity of 18.5 W/cm 2 and negative peak pressure of 4 MPa. Here we found that pFUS changed the expression of several cytokines while having no effect on the underlying tissue histology or health of pancreatic cells (as reflected by no significant change in plasma levels of amylase and lipase). Furthermore, we found that this effect on cytokine expression in the pancreas was acoustic intensity dependent; while pFUS at low intensities turned off the expression of several cytokines, at high intensities it had the opposite effect and turned on the expression of these cytokines. The ability to non-invasively manipulate the microenvironment of the pancreas using sound waves could have profound implications for priming and modulating this organ for the application of cellular therapies in the context of both regenerative medicine (i.e., diabetes and pancreatitis) and oncology (i.e., pancreatic cancer)., Competing Interests: Conflict of interest disclosure The authors declare no competing interests., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident., Materials and Methods: Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated., Results: A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %., Conclusion: Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment., (E. O. Sarkisova, V. O. Sushko, A. A. Chumak, L. M. Ovsyannikova, O. V. Nosach, S. M. Alyokhina, T. O. Shyiko.)

Purpose: To investigate the image quality, diagnostic accuracy, and dose reduction potential of a split-bolus protocol(SBP) compared with a multiphasic protocol(MPP) in the detection of recurrent or progressive pancreatic ductal adenocarcinoma(PDAC) or cholangiocarcinoma(CC) using contrast- enhanced computed tomography(CECT)., Materials and Methods: This prospective study included 56 patients who underwent CECT, 28 with our institutional standard MPP(100 ml contrast bolus) and 28 with a novel SBP(110 ml). Radiation exposure was determined in terms of total dose- length product(DLP) and computed tomography dose index(CTDI). Image quality was measured objectively by analysis of attenuation in Hounsfield units(HU) in regions of interest(ROIs) and subjectively by two blinded readers using a Likert scale. Diagnostic accuracy and interreader variability were tested., Results: The total DLP of the SBP group(498.1 ± 43.7 mGy*cm) was significantly lower than in the MPP group(1,092.5 ± 106.9 mGy*cm; p < 0.001). The SBP showed higher contrast enhancement of all critical anatomical structures including portal vein, liver, and pancreas compared with the MPP, except for the aorta(SBP: 326.9 ± 15.7 HU vs. MPP: 246.7 ± 12.2 HU; p < 0.001). Subjective analysis revealed poorer image quality ratings for important landmarks with the MPP (resection surface: p = 0.624, portal vein: p = 0.395, liver p = 0.361). The two blinded readers correlated significantly. Sensitivity, specificity, positive and negative predictive values (PPV/NPV), and overall interreader variabilities correlated significantly. Furthermore, significantly fewer slices per exam were required for the SBP(1,823 vs. 3,235; p < 0.001)., Conclusion: The SBP provides the same image quality and diagnostic accuracy as an MPP while significantly lowering radiation exposure in CT follow-up of PDAC or CC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background/aim: The significance of the anatomical variations of proximal jejunal vein [the so-called 1st jejunal vein (J1v)] has been reported from a technical standpoint. The aim of this study was to retrospectively investigate the prognostic impact of the anatomical variations of J1v in the surgical treatment of resectable pancreatic cancer (PC)., Patients and Methods: A total of 49 patients with resectable PC located in the uncinate process were included in this study. The J1v converging pattern was divided into 2 groups in terms of its relation to the SMA (i.e., the J1v status): i) group D: the J1v travels posterior to the SMA; ii) group V: the J1v travels anterior to the SMA. The associations between the J1v status and surgical outcome were assessed., Results: The 5-year survival rate after resection in group V (35%) was significantly lower than that in group D (70%) (p=0.029), and the J1v status of group V was the only independent negative prognostic factor (HR=5.49; 95% CI=1.69-19.3; p=0.005)., Conclusion: The J1v converging pattern is a significant prognostic variable in patients with PC located in the uncinate process: the J1v status of group V was significantly associated with impaired survival., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

BackgroundChange in tumor size at CT is insufficient for reliable assessment of treatment response after neoadjuvant chemotherapy and radiation therapy (CRT) and shows poor correlation with histologic grading of response.PurposeTo investigate the use of perfusion CT to predict the response of pancreatic ductal adenocarcinoma (PDA) to CRT.Materials and MethodsBetween June 2016 and May 2018, study participants with biopsy-proven PDA were prospectively recruited to undergo perfusion CT before and after planned CRT. Blood flow (BF), blood volume (BV), and permeability-surface area product (PSP) were quantified from CT images. Participants were categorized into responders and nonresponders according to therapy response. The Mann-Whitney test was used to compare the baseline perfusion values between responders and nonresponders, and the Wilcoxon matched-pairs signed rank test was used to compare perfusion values before and after CRT.ResultsThe final cohort of 21 participants (median age, 68 years; interquartile range [IQR], 65-72 years; eight men) underwent dynamic perfusion (dual-source) CT before neoadjuvant CRT. All participants underwent pancreatectomy. Eighteen participants underwent post-CRT perfusion CT. Baseline BF was higher in responders ( n = 10) than in nonresponders ( n = 11) (median, 44 [IQR, 39-56] vs 28 [IQR, 16-52] mL/100 g/min; P = .04), while BV and PSP were similar between groups (median BV, 4.3 [IQR, 3.5-6.9] vs 2.0 [IQR, 1.6-6.5] mL/100 g, P = .15; median PSP, 25 [IQR, 21-30] vs 20 [IQR, 10-34] mL/100 g/min, P = .31). Response Evaluation Criteria in Solid Tumors (RECIST) and carbohydrate antigen (CA) 19-9 showed no correlation with perfusion parameters (eg, RECIST and BF: r = 0.05, P = .84, 95% confidence interval [CI]: -0.40, 0.48; CA 19-9 and BF: r = 0.06, P = .78, 95% CI: -0.39, 0.49) or histopathologic response ( r = 0.16, P = .47, 95% CI: -0.3, 0.57 and r = 0.09, P = .71, 95% CI: -0.37, 0.51, respectively). For responders, perfusion parameters increased after CRT (eg, median BF, 54 [IQR, 42-73] vs 43 [IQR, 28-53] mL/100 g/min; P = .04). The perfusion change in nonresponders was not significant (median BF, 43 [IQR, 28-53] vs 33 [IQR, 16-52] mL/100 g/min; P = .06).ConclusionPerfusion CT may be useful in helping predict the histopathologic response to therapy in pancreatic ductal adenocarcinoma.© RSNA, 2019See also the editorial by Sinitsyn in this issue.

Objective: To evaluate the relationship of sarcopenia with the pancreatic dose-volume histogram (DVH) in gastric cancer patients treated with adjuvant chemoradiotherapy (CRT) after radical gastrectomy., Methods: A retrospective study was performed on the data in Zhongnan Hospital of Wuhan University from January 2008 to December 2016. Skeletal muscle index (SMI) was analyzed by cross-sectional areas of body composition at the level of third lumbar (L3) vertebrae, which was measured using single-slice computer tomograph (CT) prior to CRT, at 6 months and 12 months after CRT respectively. Logistic regression analysis was conducted to explore the potential clinical risk factors of sarcopenia in this patients cohort. Regarding the dosimetrics of pancreas, the sarcopenia rate was compared between the two groups divided according to the cut-off value determined by the receiver operating characteristic (ROC) curves., Results: One hundred and fifty-three gastric cancer patients were eligible in this study. The median postoperative follow-up was 36 (7-115) months. The mean dose of pancreas was 4399.7 ± 396.0 cGy. The incidence of sarcopenia prior to CRT, at 6 months and 12 months later were 29.4% (45/153), 27.3% (35/128) and 37.0% (37/100). Both sarcopenia at 6 months (HR = 2.038, 95%CI = 1.084-3.833, P = 0.027) and sarcopenia at 12 months (HR = 2.216, 95%CI = 1.007-4.873, P = 0.048) were the independent prognostic factor of gastric cancer patients. V46 remained to be the only independent risk factor of sarcopenia at 6 months (OR = 3.889, 95%CI = 1.099-13.764, P = 0.035) and 12 months (OR = 6.067, 95%CI = 1.687-21.821, P = 0.006) in multivariate logistic regression analysis. Among the dosimetric parameters used for ROC analysis, the V46 showed the highest area under the curve (AUC = 0.707). Here is the relationship between sarcopenia rate and the cut-off value for V46. Higher sarcopenia rate at 6 months was noted in 42.6% patients with V46 ≥ 57% compared with 9% of patients with V46 < 57% (P < 0.001). The sarcopneia rate at 12 months was 52% with V46 ≥ 57% and 25% with V46 < 57% (P = 0.010)., Conclusion: Gastric cancer with sarcopenia after adjuvant CRT had poorer survival. Higher dose and larger irradiated volume of pancreas correlated with higher risk of sarcopenia. Appropriated administration of pancreas dose-volume may be conducive to reduce the risk of sarcopenia and improve survival in gastric cancer patients treated with adjuvant CRT., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Abdominal organ motion seriously compromises the targeting accuracy for particle therapy in patients with pancreatic adenocarcinoma. This study compares three different abdominal corsets regarding their ability to reduce pancreatic motion and their potential usability in particle therapy., Materials and Methods: A patient-individualized polyurethane (PU), a semi-individualized polyethylene (PE), and a patient-individualized three-dimensional-scan based polyethylene (3D-PE) corset were manufactured for one healthy volunteer. Time-resolved volumetric four-dimensional-magnetic resonance imaging (4D-MRI) and single-slice two-dimensional (2D) cine-MRI scans were acquired on two consecutive days to compare free-breathing motion patterns with and without corsets. The corset material properties, such as thickness variance, material homogeneity in Hounsfield units (HU) on computed tomography (CT) scans, and manufacturing features were compared. The water equivalent ratio (WER) of corset material samples was measured using a multi-layer ionization chamber for proton energies of 150 and 200 MeV., Results: All corsets reduced the pancreatic motion on average by 9.6 mm in inferior-superior and by 3.2 mm in anterior-posterior direction. With corset, the breathing frequency was approximately doubled and the day-to-day motion variations were reduced. The WER measurements showed an average value of 0.993 and 0.956 for the PE and 3DPE corset, respectively, and of 0.298 for the PU corset. The PE and 3DPE corsets showed a constant thickness of 2.8 ± 0.2 and 3.8 ± 0.2 mm, respectively and a homogeneous material composition with a standard deviation (SD) of 31 and 32 HU, respectively. The PU corset showed a variable thickness of 4.2 - 25.6 mm and a heterogeneous structure with air inclusions with an SD of 113 HU., Conclusion: Abdominal corsets may be effective devices to reduce pancreatic motion. For particle therapy, PE-based corsets are preferred over PU-based corset due to their material homogeneity and constant thickness., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background/aim: Irreversible electroporation (IRE) has recently been used as an experimental ablation treatment following systemic chemotherapy in locally advanced pancreatic cancer (LAPC). The primary aim of this study was to evaluate survival of LAPC patients after IRE prior to chemotherapy. The secondary aim was to examine the complication rates., Patients and Methods: Twenty-four patients with LAPC were included and treated with percutaneous ultrasound-guided IRE under general anesthesia. Survival data from the National Quality Registry for Pancreatic and Periampullary Cancer for LAPC during the same period were used for comparison., Results: The median survival after diagnosis was 13.3 months in the IRE group compared to 9.9 months in the registry group (p=0.511). Six patients had a severe complication after IRE treatment., Conclusion: No obvious gain in survival was observed with IRE as the first line treatment of LAPC and IRE was associated with severe complications. This study does not support percutaneous IRE in this setting., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Locally advanced pancreatic cancer (LAPC) represents more than one third of pancreatic cancers and owns poor survival after the standard chemotherapy. Irreversible electroporation (IRE) is a novel method and has been recently used in LAPC. The aim of this study was to compare the efficacy of IRE and radiotherapy after induction chemotherapy for patients with LAPC., Methods: From August 2015 to August 2017, a total of 76 patients with biopsy proven LAPC and who had received IRE or radiotherapy after chemotherapy were included. Thirty-two pairs of patients were selected through propensity score matching (PSM) analysis and the efficacy of two treatments was compared., Results: Before PSM analysis, after induction chemotherapy, patients with LAPC benefited more in terms of overall survival (OS) and progression free survival (PFS) from IRE, compared with radiotherapy (2-year OS rates, 53.5% vs 26.9%, p = 0.039; 2-year PFS rates, 28.4% vs 13.3%, p = 0.045). After PSM analysis, the survival benefits of OS and PFS of patients after induction chemotherapy followed by IRE were more obvious than those of patients treated with radiotherapy (2-year OS rates, 53.5% vs 20.7%, p = 0.011; 2-year PFS rates, 28.4% vs 5.6%, p = 0.004). Multivariate Cox regression analysis indicated that IRE after induction chemotherapy was identified as a significant favourable factor for both OS and PFS in both the whole and matched cohort., Conclusions: Induction chemotherapy followed by IRE is superior to induction chemotherapy followed by radiotherapy for treating LAPC. A randomized clinical trial comparing the efficacy of IRE and radiotherapy after the induction chemotherapy is therefore considerable.

Purpose: Peptide receptor radionuclide therapy (PRRT) with the radiolabeled somatostatin analogue [Lutetium-177-DOTA0-Tyr3]octreotate (177Lu-DOTATATE) is widely applied for inoperable metastatic small intestinal and nonfunctioning pancreatic neuroendocrine tumors (pNETs). The aim of this study is to describe the safety and efficacy of the treatment of functioning pNETs., Methods: Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gbq per cycle. Radiological (Response Evaluation Criteria in Solid Tumors 1.1), symptomatic, and biochemical response were analyzed retrospectively for all patients with a functioning pNET (insulinoma, gastrinoma, VIPoma, and glucagonoma) treated with 177Lu-DOTATATE. Quality of life (QOL) was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Module questionnaire., Results: Thirty-four patients with a metastatic functioning pNET (European Neuroendocrine Tumor Society grade 1 or 2) were included: 14 insulinomas, 5 VIPomas, 7 gastrinomas, and 8 glucagonomas. Subacute hematological toxicity, grade 3 or 4 occurred in 4 patients (12%) and a hormonal crisis in 3 patients (9%). PRRT resulted in partial or complete response in 59% of patients and the disease control rate was 78% in patients with baseline progression. 71% of patients with uncontrolled symptoms had a reduction of symptoms and a more than 80% decrease of circulating hormone levels was measured during follow-up. After PRRT, median progression-free survival was 18.1 months (interquartile range: 3.3 to 35.7) with a concurrent increase in QOL., Conclusion: Treatment with 177Lu-DOTATATE is a safe and effective therapy resulting in radiological, symptomatic and biochemical response in a high percentage of patients with metastatic functioning pNETs. Hormonal crises occur relatively frequent and preventive therapy should be considered before and/or during PRRT., (Copyright © 2019 Endocrine Society.)

Competing Interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Volumetric shrinkage of normal tissues such as salivary glands, kidneys, hippocampus are observed after radiotherapy. We aimed to assess the alterations in pancreatic volume of patients who received abdominal radiotherapy and define pancreas as an organ at risk for radiation treatment planning., Material-Methods: Forty-nine patients operated for gastric adenocarcinoma who received adjuvant abdominal radiotherapy were in the study group, 27 patients with early stage disease who did not need adjuvant treatment after surgery comprised the control group. An experienced radiologist contoured the pancreas of all the patients from computed tomographies imported to the planning system obtained either for radiation planning purpose or for follow-up after surgery. The same procedure was repeated one year later for both groups. Measured volume of the pancreas was expressed in cm 3 ., Results: Mean pancreatic volumes were similar in both groups at the onset of the study, 51,34 ± 20,33 cm 3 , and 50,12 ± 23,75 cm 3 in the irradiated and the control groups respectively (p = 0,63). One year later, mean pancreatic volumes were significantly decreased in each group; 22,48 ± 10,53 cm 3 , 44,18 ± 23,08 cm 3 respectively, p < 0,001. However, the decrease in pancreatic volume was significantly more pronounced in the irradiated group in comparison to the control group, p < 0,001., Conclusion: Volumetric decrease in normal tissues after radiotherapy is responsible for loss of organ function and radiation related late side effects. Although pancreas is a radiation sensitive organ losing its volume and function after radiation exposure, it is not yet considered as an organ at risk for radiation treatment planning. Pancreas should be contoured as an organ at risk, dose-volume histogram for the organ should be created, and safe organ doses should be determined. This is the first study declaring pancreas as an organ at risk for radiation toxicity and the necessity of defining dose constraints for the organ.

Background/purpose: Stereotactic-magnetic-resonance-guided-online-adaptive-radiotherapy (SMART) is a promising tool for pancreas stereotactic-body-radiotherapy. Our online-adaptive-radiotherapy (On-ART) process relies on daily image overview by the managing radiation-oncologist, who determines the need for creating a predicted plan if significant interfractional anatomical changes are noted. Predicted plans are achieved through applying the baseline plan on deformed and manually adjusted contours based on daily imaging. If the dose to the target volume or organs-at-risk (OARs) violate constraints, an adapted plan is generated and delivered for treatment. In-depth review of daily images and deformed contours is limited by time and inter-observer variations. This study evaluates the reliability of our On-ART decision-making process. All fractions retrospectively underwent a predicted plan for off-line decision-making to adapt (Off-ART). Decisions to adapt were compared using On-ART and Off-ART approaches., Material/methods: Thirty-five sets of daily images were analyzed from seven patients who underwent five fractions of SMART. Each OAR was fully re-contoured off-line by the same physician for each fraction. Off-ART decision was re-evaluated for each fraction., Results: N = 14/35 fractions were adapted based on On-ART decision-making versus N = 25/35 with Off-ART. The concordance between On-ART and Off-ART decision was 87.5% for the 16 fractions using a predicted plan online and 42% for the 19 fractions using only visual image review for On-ART decision-making., Conclusions: Daily-image visual review is not reliable to determine benefit or not for adaptive radiation-therapy. Online predicted plan, based on deformed and manually adjusted contours, should be generated for every fraction that is delivered using SMART in order to reliably optimize treatment plans daily., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The necrosis-fibrosis hypothesis describes a continuum between single attacks of acute pancreatitis (SAP), recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) with endocrine and exocrine pancreatic insufficiency. For prevention purposes we evaluated clinico-radiological parameters and pancreatic volumetry to compare SAP and RAP and provide prognostic relevance on short-term mortality, need for intervention and the hospitalization duration., Materials and Methods: We retrospectively investigated 225 consecutive patients (150 males, range 19-97years) with acute pancreatitis (74%SAP, 26%RAP) according to the revised Atlanta classification. All patients received an intravenous contrast-enhanced CT after a median time of 5 (IQR 5-7) days after onset of symptoms. Two experienced observers rated the severity of AP by 3 CT scores (CTSI, mCTSI, EPIC). Moreover, total pancreatic volumes and additional parenchymal necrosis volumes were assessed, when appropriate. Clinical parameters were etiology of AP, lipase on admission, CRP 48 hours after admission (CRP48), and the presence of organ dysfunction, assessed by the modified Marshall score. The modified Marshall score included systolic blood pressure, serum creatinine, and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2 ratio) and was assessed on admission and 48 hours after admission to find patients with persistent organ failure. Outcome parameters were total hospitalization duration, short-term mortality and need for intervention., Results: Lipase, CRP48, etiology of AP, EPIC, PaO2/FiO2 ratio, and the presence of a pleural effusion differed significantly in both groups (p<0.05). In 109 patients with interstitial edematous AP, the total pancreatic volume was significantly smaller in patients with RAP compared to those with SAP (69±35cm3; (RAP) vs 106±45cm3; (SAP), p<0.001). All outcome parameters including the mortality rates (SAP vs. RAP: 15% vs. 7%) were comparable in both groups (p>0.05). In the necrotizing RAP group, only the necrotic volume correlated significantly with total hospitalization time (r = 0.72, p<0.001), whereas the systolic blood pressure was the only, but weak predictor for short-term mortality (β-coefficient: -0.05, p = 0.03) and the need for intervention (β-coefficient: -0.02, p = 0.048) in the total RAP group. In patients with SAP, the modified Marshall score was the strongest predictor of short-term mortality, followed by the mCTSI on multivariate logistic regression (Marshall score: β-coefficient: 1.79, p<0.001; mCTSI: β-coefficient: 0.40, p<0.001). CTSI was the best predictor for required intervention in necrotizing SAP (β-coefficient: 0.46, p<0.001), followed by the volume of intrapancreatic necrosis (β-coefficient: 0.17, p = 0.03)., Conclusion: Total pancreatic volume differed significantly between interstitial RAP and SAP and intrapancreatic necrosis volume revealed prognostic value for the total hospitalization duration in necrotizing RAP. Although all outcome parameters were comparable between SAP and RAP, only systolic blood pressure and pancreatic volumetry were prognostic in RAP. In SAP, only the modified Marshall score and mCTSI revealed prognostic value for short-term mortality, whereas CTSI was predictive for the need for intervention., Competing Interests: The authors have declared that no competing interests exist.

Pancreatic radiation effect (PRE) can be a component of gastrointestinal tract (GIT) radiotoxicity. This inter-organ correlation between the GIT and the pancreas was assessed through a rat model. Separate local irradiation to the abdomen and the pelvis was applied concurrently for 8-week-old male Sprague Dawley rats. Abdominal irradiation was categorized into pancreatic shield (PS) and non-pancreatic shield (NPS) irradiation. After 5 Gy and 15 Gy irradiation, the rectal mucosa was analyzed at the first week (early phase, Ep) and the 14th week (late phase, Lp). A slow gain in body weight was observed initially, particularly in the NPS group receiving a 15 Gy dose (P < 0.001). The large number of apoptotic bodies after 15 Gy at Ep decreased at Lp. At Ep for the 5-Gy group, the NPS group revealed more fibrotic change than the PS group (P = 0.002). Cleaved caspase-3 (CCP3) expression was greater at Lp, and the Ep-Lp increase was prominent in the NPS-15-Gy group (P = 0.010). At Lp, for 15 Gy irradiation, CCP3 was expressed more in the NPS group than in the PS group (P = 0.032). Despite no direct toxicity difference between the PS and NPS groups, small changes in parameters such as fibrosis or CCP3 expression suggest that pancreatic shielding does have an effect on the radiation response in the rectal mucosa, which suggests a need for a multi-organ effect-based approach in GIT radiotoxicity assessment.

The physiological function of the pancreas is controlled by the circadian clock. The aim of this study was to determine whether aging-induced changes in glucose homeostasis affect properties of the circadian clock in the pancreas and/or its sensitivity to disturbances in environmental lighting conditions. mPer2 Luc mice aged 24-26 months developed hyperinsulinemic hypoglycaemia, which was likely due to the Pclo-mediated insulin hyper-secretion and Slc2a2-mediated glucose transport impairment in the pancreas, and due to the alterations in Pp1r3c-related glycogen storage and Sgk1-related glucose transport in the liver. In the pancreatic tissue, aging affected clock gene expression only marginally, it upregulated Bmal1 and downregulated Clock expression. Whereas aging significantly impaired the circadian clock in lung explants, which were used as a control tissue, the properties of the pancreatic clock in vitro were not affected. The data suggest a non-circadian role of Bmal1 in changes of pancreatic function that occur during aging. Additionally, the pancreatic clock was more sensitive to exposure of animals to constant light conditions. These findings provide an explanation for the previously demonstrated relationship between disturbances in the circadian system and disordered glucose homeostasis, including diabetes mellitus type 2, in subjects exposed to long-term shift work.

Purpose: The aim of this multi-institutional study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally advanced pancreatic cancer (LAPC)., Methods and Materials: Patients with LAPC treated with C-ion RT from April 2012 to December 2014 at 3 institutions were retrospectively analyzed. Patients with pathologically-confirmed invasive ductal adenocarcinoma of the pancreas were eligible. The prescribed dose was 52.8 Gy (relative biological effectiveness weighted absorbed dose; RBE) or 55.2 Gy (RBE) in 12 fractions. Overall survival (OS), distant metastasis-free survival (DMFS), local recurrence (LR), and toxicity were evaluated., Results: In total, 72 patients were included in this study. Tumors in the head of the pancreas were seen in 30 patients (42%), while those in the body or tail of the pancreas were seen in 42 patients (58%). Fifty-six patients (78%) received concurrent chemotherapy. The OS rates were 73% (95% confidence interval [CI], 62%-84%) at 1 year, and 46% (95% CI, 31%-61%) at 2 years with a median OS of 21.5 months (95% CI, 11.8-31.2 months). The 1- and 2-year DMFS rates were 41% (95% CI, 29%-52%) and 28% (95% CI, 16%-40%), respectively. The 1- and 2-year cumulative incidences of LR were 16% (95% CI, 9%-26%) and 24% (95% CI, 14%-36%), respectively. Nineteen patients (26%) experienced acute grade 3 or 4 hematological toxicities. Two patients (3%) had grade 3 anorexia. Late gastrointestinal (GI) grade 3 toxicity was observed in 1 patient (1%). No patients developed late grade 4 or 5 toxicity., Conclusions: The first multi-institutional analysis of C-ion RT for LAPC indicated relatively favorable outcomes with limited toxicities, especially for tumors not in close proximity to GI tract., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Inverse planning is trial-and-error iterative process. This work introduces a fully automated inverse optimization approach, where the treatment plan is closely tailored to the unique patient anatomy. The auto-optimization is applied to pancreatic stereotactic body radiotherapy (SBRT)., Materials and Methods: The automation is based on stepwise reduction of dose-volume histograms (DVHs). Five uniformly spaced points, from 1% to 70% of the organ at risk (OAR) volumes, are used. Doses to those DVH points are iteratively decreased through multiple optimization runs. With each optimization run the doses to the OARs are decreased, while the dose homogeneity over the target is increased. The iterative process is terminated when a pre-specified dose heterogeneity over the target is reached. Twelve pancreatic cases were retrospectively studied. Doses to the target, maximum doses to duodenum, bowel, stomach, and spinal cord were evaluated. In addition, mean doses to liver and kidneys were tallied. The auto-optimized plans were compared to the actual treatment plans, which are based on national protocols., Results: The prescription dose to 95% of the planning target volume (PTV) is the same for the treatment and the auto-optimized plans. The average difference for maximum doses to duodenum, bowel, stomach, and spinal cord are -4.6 Gy, -1.8 Gy, -1.6 Gy, and -2.4 Gy respectively. The negative sign indicates lower doses with the auto-optimization. The average differences in the mean doses to liver and kidneys are -0.6 Gy, and -1.1 Gy to -1.5 Gy respectively., Conclusions: Automated inverse optimization holds great potential for personalization and tailoring of radiotherapy to particular patient anatomies. It can be utilized for normal tissue sparing or for an isotoxic dose escalation.

Background/aim: Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that allows accurate irradiation with reduced damage to surrounding tissues. Here, we analyzed borderline-resectable pancreatic cancer (BRPC) with arterial abutment (BR-A) patients with IMRT as neoadjuvant therapy and performed comparisons with patients with conventional RT to clarify the advantages of IMRT as a neoadjuvant therapy., Patients and Methods: Thirty BR-A patients treated at our hospital between January 2012 and December 2015 were divided into two groups: 12 patients underwent conventional 3D-RT before resection (RT group); and 18 patients underwent IMRT before resection (IMRT group). We analyzed safety, tumor resection rate, histological classification of the tumor and overall survival., Results: The R0 rate was 84% for the IMRT group and 83% for the RT group. Local therapeutic effects as assessed by Evans classification showed a higher local control rate in the IMRT group (Grade: 1, 0%; 2a, 25%; 2b, 41.6%; 3, 17%; 4, 8%) than in the RT group (Grade: 1, 17%; 2a, 50%; 2b, 17%; 3, 17%; 4, 0%). The cumulative dose of S1 treatment as adjuvant therapy was much smaller in the RT group (18.3%) compared to that in the IMRT group (57.1%, p=0.047), and with better subsequent overall survival rate (MST 32 months vs. 13.8 months, p=0.0273)., Conclusion: The IMRT group showed a better control rate than the RT group. The neoadjuvant IMRT has advantages of higher completion rate of adjuvant chemotherapy with better nutritional status and better subsequent overall survival rate (OS)., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To develop a Monte Carlo model for patient-specific dosimetry of 32 P microparticle localized internal radionuclide therapy for advanced pancreatic cancer., Methods and Materials: Spherical tumor geometries and a pancreatic phantom were modeled, as well as different 3-dimensional non-uniform clinical pancreatic geometries based on patient-specific ultrasound images. The dosimetry simulations modeled the dose distribution due to the energy spectrum of emitted beta particles., Results: The average dose for small (3-cm diameter) and large (6-cm diameter) spherical tumors was 111 Gy (for 7.6 MBq administered activity) and 128 Gy (for 58 MBq), respectively. For the clinical 3-dimensional geometries, on the basis of patient data, the mean doses delivered to the tumor were calculated to be in the range 102 to 113 Gy, with negligible dose to the pancreas for the smallest tumor volumes. The calculated dose distributions are highly non-uniform. For the largest tumor studied, the pancreas received approximately 6% of the tumor dose (5.7 Gy). Importantly, we found that because the smallest tumor studied exhibited the most dynamic changes in volume in response to the treatment, the dose to tumor and pancreas is significantly underestimated if a static tumor volume is assumed., Conclusions: These results demonstrate the dosimetry of 32 P microparticle localized internal radionuclide therapy for pancreatic cancer and the possibility of developing personalized treatment strategies. The results also highlight the importance of considering the effects of non-uniform dose distributions and dynamic change of tumor mass during treatment on the dosimetry of the tumor and critical organs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Methods: After injecting 25.6 ± 8.8 MBq (0.7 ± 0.2 mCi) of 18F-Fluoro-L-DOPA intravenously, three static PET scans were acquired at 20, 30, and 40 min post injection in 3-D mode on 10 patients (6 male, 4 female) with congenital hyperinsulinism. Regions of interest (ROIs) were drawn over several organs visible in the reconstructed PET/CT images and time activity curves (TACs) were generated. Residence times were calculated using the TAC data. The radiation absorbed dose for the whole body was calculated by entering the residence times in the OLINDA/EXM 1.0 software., Results: The mean residence times for the 18F-Fluoro-L-DOPA in the liver, lungs, kidneys, muscles, and pancreas were 11.54 ± 2.84, 1.25 ± 0.38, 4.65 ± 0.97, 17.13 ± 2.62, and 0.89 ± 0.34 min, respectively. The mean effective dose equivalent for 18F-Fluoro-L-DOPA was 0.40 ± 0.04 mSv/MBq. The CT scan used for attenuation correction delivered an additional radiation dose of 5.7 mSv. The organs receiving the highest radiation absorbed dose from 18F-Fluoro-L-DOPA were the urinary bladder wall (2.76 ± 0.95 mGy/MBq), pancreas (0.87 ± 0.30 mGy/MBq), liver (0.34 ± 0.07 mGy/MBq), and kidneys (0.61 ± 0.11 mGy/MBq). The renal system was the primary route for the radioactivity clearance and excretion., Conclusions: The estimated radiation dose burden from 18F-Fluoro-L-DOPA is relatively modest to newborns.

Pancreatic adenocarcinoma is the eighth leading cause of cancer deaths worldwide in men and ninth leading cause in women. Surgical resection offers the only chance of potential cure; however, only 9.4% of patients present at the localized, resectable stage, whereas the rest present at the locally advanced or metastatic, unresectable stages. Because of the guarded outcomes following systemic chemoradiation and the associated systemic toxicities, locoregional therapies have recently gained popularity. Various endoscopic techniques (endoscopic ultrasound [EUS]-guided ablative therapies, fine-needle instillation of antitumor agents, stereotactic body radiation therapy with EUS-guided fiducial marker placement, and EUS-guided brachytherapy) have been explored over the past several years. Endoscopic therapy plays a role in the treatment of unresectable pancreatic adenocarcinoma. Its minimal invasiveness and increased precision of delivering oncologic treatments under EUS guidance render it as a favorable option for patients who do not benefit from surgical resection. New endoscopic therapies are currently under investigation, and the emerging role of the endoscopist in the treatment of unresectable pancreatic cancer continues to grow.

Objectives: The role of radiotherapy (RT) in locally advanced pancreatic cancer (LAPC) is uncertain. This study examines patterns of care and survival outcomes of LAPC undergoing chemotherapy alone versus chemotherapy plus RT (C + RT)., Methods: The National Cancer Database was queried for nonmetastatic LAPC patients who received chemotherapy alone or C + RT., Results: Of the 13,695 patients included, 5306 underwent chemotherapy alone and 4971, C + RT. Use of C + RT declined from 2003 to 2011 (73%-53%), whereas chemotherapy alone increased. Of those receiving RT, rates of intensity-modulated radiotherapy (IMRT) increased (27%-72%), whereas 3-dimensional (3D) RT decreased (73%-28%). Unadjusted 1-year overall survival (OS) was longer for versus chemotherapy (45.6% vs 38.7%), as was 2-year OS (12.9% vs 11.9%) (hazard ratio, 0.88; 0.85-0.91; P < 0.001). Under multivariate analysis, C + RT was associated with improved OS (hazard ratio, 0.84; 0.81-0.87; P < 0.001). On subgroup analysis comparing C + IMRT, C + 3D RT, and chemotherapy alone, 1-year OS was 49.1%, 45.1%, and 38.7%, and 2-year OS was 13.1%, 11.6%, and 11.9% accordingly., Conclusions: Utilization of RT in LAPC is decreasing, whereas chemotherapy alone is increasing. Of patients undergoing RT, rates of IMRT are increasing. Whereas C + IMRT appeared to be associated with improved OS compared with chemotherapy alone, 3D RT was not.

Purpose: In an effort for early assessment of treatment response, we investigate radiation induced changes in quantitative CT features of tumor during the delivery of chemoradiation therapy (CRT) for pancreatic cancer., Methods: Diagnostic-quality CT data acquired daily during routine CT-guided CRT using a CT-on-rails for 20 pancreatic head cancer patients were analyzed. On each daily CT, the pancreatic head, the spinal cord and the aorta were delineated and the histograms of CT number (CTN) in these contours were extracted. Eight histogram-based radiomic metrics including the mean CTN (MCTN), peak position, volume, standard deviation (SD), skewness, kurtosis, energy and entropy were calculated for each fraction. Paired t-test was used to check the significance of the change of specific metric at specific time. GEE model was used to test the association between changes of metrics over time for different pathology responses., Results: In general, CTN histogram in the pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the 1st to the 26th fraction in MCTN ranged from -15.8 to 3.9 HU with an average of -4.7 HU (p<0.001). Meanwhile the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less peaked). The changes of MCTN, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response is associated with the changes of MCTN, SD, and skewness. In cases of good response, patients tend to have large reductions in MCTN and skewness, and large increases in SD and kurtosis., Conclusions: Significant changes in CT radiomic features, such as the MCTN, skewness, and kurtosis in tumor were observed during the course of CRT for pancreas cancer based on quantitative analysis of daily CTs. These changes may be potentially used for early assessment of treatment response and stratification for therapeutic intensification.

Purpose To compare overall survival between patients who received neoadjuvant therapy (NAT) followed by resection and those who received upfront resection (UR)-as well as a subgroup of UR patients who also received adjuvant therapy-for early-stage resectable pancreatic adenocarcinoma. Patients and Methods Adult patients with resected, clinical stage I or II adenocarcinoma of the head of the pancreas were identified in the National Cancer Database from 2006 to 2012. Patients who underwent NAT followed by curative-intent resection were matched by propensity score with patients whose tumors were resected upfront. Overall survival was compared by using a Cox proportional hazards regression model. Early postoperative and oncologic outcomes were evaluated. Results We identified 15,237 patients with clinical stage I or II resected pancreatic head adenocarcinoma. From the NAT group, 2,005 patients (95%) were matched with 6,015 patients who underwent UR. The NAT group was associated with improved survival compared with UR (median survival, 26 months v 21 months, respectively; stratified log-rank P < .01; hazard ratio, 0.72; 95% CI, 0.68 to 0.78). Patients in the UR group had higher pathologic T stage (pT3 and T4: 86% v 73%; P < .01), higher positive lymph nodes (73% v 48%; P < .01), and higher positive resection margin (24% v 17%; P < .01). Compared with a subset of UR patients who received adjuvant therapy, NAT patients had a better survival (adjusted hazard ratio, 0.83; 95% CI, 0.73 to 0.89). Conclusion NAT followed by resection has a significant survival benefit compared with UR in early-stage, resected pancreatic head adenocarcinoma. These findings support the use of NAT, particularly as a patient selection tool, in the management of resectable pancreatic adenocarcinoma.

Peptide receptor radionuclide therapy (PRRT) is a form of systemic radiotherapy that allows targeted delivery of radionuclides to tumor cells expressing high levels of somatostatin receptors. The two radiopeptides most commonly used for PRRT, 90 Y-DOTATOC and 177 Lu-DOTATATE, have been successfully employed for more than a decade for the treatment of advanced neuroendocrine tumors (NETs). Recently, the phase III, randomized NETTER-1 trial has compared 177 Lu-DOTATATE versus high-dose octreotide LAR in patients with progressive, metastatic midgut NETs, demonstrating exceptional tolerability and efficacy. This review summarizes recent developments in the field of radionuclide therapy for gastroenteropancreatic and lung NETs and considers possible strategies to further enhance its clinical efficacy.

Background: To study the feasibility of down stage the borderline resectable pancreatic cancer (BRPC) to resectable disease, we reported our institutional results using an intensity-modulated radiation therapy (IMRT) simultaneous integrated boost (SIB) dose escalation approach to improve R0 resectability., Methods: We reviewed our past 7 years of experience of using neoadjuvant induction chemotherapy with Gemcitabine followed by concurrent chemoradiaiton for BRPC. During the concurrent, chemo was 5-FU and radiation were IMRT with SIB technique to target the key areas with dose escalation to 5600 in 28 fractions. The key areas were defined by PET positive area. This was followed by restaging imaging to rule out distant metastases before resection., Results: 25 finished dose escalation protocol. 2 of the 25 cases developed distant metastases, 23 (92%) patients without distant metastases underwent pancreatectomy. Among the those received pancreatectomy, 22 (95%) achieved negative margin (R0). The gastrointestinal toxicity > grade 2 was 8% and there was no grade 4 toxicity., Conclusion: Neoadjuvant Gemcitabine-based induction chemotherapy followed by 5-FU-based IMRT-SIB is a feasible option in improving the likelihood of R0 resection rate in BRPC without compromising the organs at risk for toxicity., Competing Interests: The authors have declared that no competing interests exist.

Pancreatic cancer (PC) is one of the most aggressive diseases. Only 10 % of all PC cases are thought to be due to genetic factors. Here, we analyzed the most recently published case-control association studies, meta-analyses, and cohort studies with the aim to summarize the main environmental factors that could have a role in PC. Among the most dangerous agents involved in the initiation phase, there are the inhalation of cigarette smoke, and the exposure to mutagenic nitrosamines, organ-chlorinated compounds, heavy metals, and ionizing radiations. Moreover, pancreatitis, high doses of alcohol drinking, the body microbial infections, obesity, diabetes, gallstones and/or cholecystectomy, and the accumulation of asbestos fibers seem to play a crucial role in the progression of the disease. However, some of these agents act both as initiators and promoters in pancreatic acinar cells. Protective agents include dietary flavonoids, marine omega-3, vitamin D, fruit, vegetables, and the habit of regular physical activity. The identification of the factors involved in PC initiation and progression could be of help in establishing novel therapeutic approaches by targeting the molecular signaling pathways responsive to these stimuli. Moreover, the identification of these factors could facilitate the development of strategies for an early diagnosis or measures of risk reduction for high-risk people.

Objectives: The purpose of the retrospective study was to evaluate the additional value of dual-phase multidetector computed tomography (MDCT) protocols over a single-phase protocol on initial MDCT in patients with acute pancreatitis using three CT-based pancreatitis severity scores with regard to radiation dose., Methods: In this retrospective, IRB approved study MDCT was performed in 102 consecutive patients (73 males; 55years, IQR48-64) with acute pancreatitis. Inclusion criteria were CT findings of interstitial edematous pancreatitis (IP) or necrotizing pancreatitis (NP) and a contrast-enhanced dual-phase (arterial phase and portal-venous phase) abdominal CT performed at ≥72h after onset of symptoms. The severity of pancreatic and extrapancreatic changes was independently assessed by 2 observers using 3 validated CT-based scoring systems (CTSI, mCTSI, EPIC). All scores were applied to arterial phase and portal venous phase scans and compared to score results of portal venous phase scans, assessed ≥14days after initial evaluation. For effective dose estimation, volume CT dose index (CTDIvol) and dose length product (DLP) were recorded in all examinations., Results: In neither of the CT severity scores a significant difference was observed after application of a dual-phase protocol compared with a single-phase protocol (IP: CTSI: 2.7 vs. 2.5, p=0.25; mCTSI: 4.0 vs. 4.0, p=0.10; EPIC: 2.0 vs. 2.0, p=0.41; NP: CTSI: 8.0 vs. 7.0, p=0.64; mCTSI: 8.0 vs. 8.0, p=0.10; EPIC: 3.0 vs. 3.0, p=0.06). The application of a single-phase CT protocol was associated with a median effective dose reduction of 36% (mean dose reduction 31%) compared to a dual-phase CT scan., Conclusions: An initial dual-phase abdominal CT after ≥72h after onset of symptoms of acute pancreatitis was not superior to a single-phase protocol for evaluation of the severity of pancreatic and extrapancreatic changes. However, the effective radiation dose may be reduced by 36% using a single-phase protocol., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Objectives: Late abdominal irradiation toxicity during childhood included renal damage, hepatic toxicity and secondary diabetes mellitus. We compared the potential of conformal radiotherapy (CRT), helical tomotherapy (HT) and proton beam therapy (PBT) to spare the abdominal organs at risk (pancreas, kidneys and liver- OAR) in children undergoing abdominal irradiation., Methods: We selected children with abdominal tumors who received more than 10 Gy to the abdomen. Treatment plans were calculated in order to keep the dose to abdominal OAR as low as possible while maintaining the same planned target volume (PTV) coverage. Dosimetric values were compared using the Wilcoxon signed-rank test., Results: The dose distribution of 20 clinical cases with a median age of 8 years (range 1-14) were calculated with different doses to the PTV: 5 medulloblastomas (36 Gy), 3 left-sided and 2 right-sided nephroblastomas (14.4 Gy to the tumor + 10.8 Gy boost to para-aortic lymphnodes), 1 left-sided and 4 right-sided or midline neuroblastomas (21 Gy) and 5 Hodgkin lymphomas (19.8 Gy to the para-aortic lymphnodes and spleen). HT significantly reduced the mean dose to the whole pancreas (WP), the pancreatic tail (PT) and to the ipsilateral kidney compared to CRT. PBT reduced the mean dose to the WP and PT compared to both CRT and HT especially in midline and right-sided tumors. PBT decreased the mean dose to the ispilateral kidney but also to the contralateral kidney and the liver compared to CRT. Low dose to normal tissue was similar or increased with HT whereas integral dose and the volume of normal tissue receiving at least 5 and 10 Gy were reduced with PBT compared to CRT and HT., Conclusion: In children undergoing abdominal irradiation therapy, proton beam therapy reduces the dose to abdominal OAR while sparing normal tissue by limiting low dose irradiation., Competing Interests: The authors have declared that no competing interests exist.

Background: Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear., Methods: Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs)., Results: Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trend<0.001), with an OR of 4.6 (95% CI 1.9-11.0) for ⩾25 Gy vs <25 Gy. Radiation-related risks remained elevated ⩾20 years after TC diagnosis (P=0.020). The risk increased with the number of cycles of chemotherapy with alkylating or platinum agents (P=0.057), although only one case was exposed to platinum., Conclusions: A dose-response relationship exists between radiation to the pancreas and subsequent cancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.

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 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., Methods: 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., 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 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., Conclusions: Radiation treatment causes macrophages murine PDA to acquire an immune-suppressive phenotype and disabled T-cell-mediated anti-tumor responses. MCSF blockade negates this effect, allowing radiation to have increased efficacy in slowing tumor growth., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to clarify whether pretreatment human equilibrative nucleoside transporter (hENT1) expressions in endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) specimens obtained from resectable, borderline resectable, and locally advanced unresectable pancreatic ductal adenocarcinoma (PDAC) are concordant with those in the resected specimen after gemcitabine-based chemoradiotherapy (Gem-CRT) and to validate the utility of hENT1 expression using EUS-FNAB samples as a prognostic marker., Methods: We evaluated the relationship between hENT1 expressions assessed by immunohistochemical staining and clinical outcomes in 51 of 76 patients with PDAC who were diagnosed by EUS-FNAB and received preoperative Gem-CRT., Results: The concordance rate of hENT1 expressions was 89.2% (K = 0.681). Median survival time (month) in the 51 whole patients and 37 patients with resection was significantly longer in hENT1 positive than in hENT1 negative: 25.0 and 30.0 versus 9.0 and 9.0, respectively. A multivariate analysis confirmed that hENT1 expression was an independent prognostic factor in both whole patients and those with resection. Regardless of T3 and T4, hENT1-positive patients with resection had significantly better prognosis than hENT1-negative patients, whose prognosis was similar to those without resection., Conclusions: The assessment of hENT1 expression using EUS-FNAB samples before Gem-CRT provides important information on patients with PDAC who can benefit from curative-intent resection.

Intratumoral radiation therapy - 'brachytherapy' - is a highly effective treatment for solid tumors, particularly prostate cancer. Current titanium seed implants, however, are permanent and are limited in clinical application to indolent malignancies of low- to intermediate-risk. Attempts to develop polymeric alternatives, however, have been plagued by poor retention and off-target toxicity due to degradation. Herein, we report on a new approach whereby thermally sensitive micelles composed of an elastin-like polypeptide (ELP) are labeled with the radionuclide (131)I to form an in situ hydrogel that is stabilized by two independent mechanisms: first, body heat triggers the radioactive ELP micelles to rapidly phase transition into an insoluble, viscous coacervate in under 2 min; second, the high energy β-emissions of (131)I further stabilize the depot by introducing crosslinks within the ELP depot over 24h. These injectable brachytherapy hydrogels were used to treat two aggressive orthotopic tumor models in athymic nude mice: a human PC-3 M-luc-C6 prostate tumor and a human BxPc3-luc2 pancreatic tumor model. The ELP depots retained greater than 52% and 70% of their radioactivity through 60 days in the prostate and pancreatic tumors with no appreciable radioactive accumulation (≤ 0.1% ID) in off-target tissues after 72h. The (131)I-ELP depots achieved >95% tumor regression in the prostate tumors (n=8); with a median survival of more than 60 days compared to 12 days for control mice. For the pancreatic tumors, ELP brachytherapy (n=6) induced significant growth inhibition (p=0.001, ANOVA) and enhanced median survival to 27 days over controls., (Published by Elsevier B.V.)

The purpose of this study was a comparison of the X-ray density in certain organs and anatomical structures and the determination of the radiation exposure during venous-arterial MSCT scanning and classical two-phase CT of organs of the abdominal cavity. It has been established that the technique of venous-arterial MSCT scanning provided a significant reduction of radiation dose during CT of organs of the abdominal cavity and could be used as an alternative to two-phase examination in the process of dynamic monitoring of cancer patients.