bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes on functional capacity after impact of oncological digestive surgery: Reality in Chilean patients at Clinical Oncology Institute Arturo López Pérez Foundation.
Authors: Hurtado Veronica , Brito Felipe , Carrera David , Penjean Marcela 
Published: May 2020

e16714 Background: Currently Chile does not have a database of functional capacity (FC) in cancer patients. Our purpose is to assess the impact of oncological digestive surgery in FC in Chilean patients at the Clinical Oncology Institute Foundation Arturo López Pérez (FALP) through the 6 minutes walking test (6MWT), which allows objectifying the FC based within the meters walked for 6 minutes by the patient. Methods: It’s a retrospective study of data analysis. The 6MWT was assessed on the day of admission to FALP and discharge. The FC was measured by the distance walked in 6 minutes. Inclusion criteria were male and female candidates for elective oncological digestive surgery from December 2018 - January 2020 and eligible for the 6MWD. We compared the result of the 6MWD baseline admission against an expected reference value according to age, weight and height, and were classified according to whether they were above or below the reference level; their change was also evaluated after surgery, estimated as a percentage of change. Digestive interventions were classified according to site. A P < 0.05 was considered significant. Results: 108 patients were included; the mean age was 57.8 years and the average body mass index (BMI) 26.6. Upon admission 40.7% (N = 44) were above the reference value and 59.3% (N = 64) below it. Regarding the length of hospital stay, we observed an average 8.97 days (Men = 9.96; women = 7.96; P = 0.008). At discharge in 6MWD an average decrease of 149.6 meters (admission = 502.2 mts; Discharge = 352.6 mts.) is seen. At admission, men with age < 40 years (P = 0.031) and subjects with BMI < 30 (P = 0.039) walked a greater distance. There are no significant differences by surgery classification. Regarding the percentage loss of FC, women are more affected (P < 0.001). Conclusions: Based on the results obtained in the 6MWT, we can conclude that the surgery has an impact on patient’s FC. Note that over 50% of patients had a lower value than the base reference. Therefore, we believe it is important to make a multidisciplinary approach at the time of cancer diagnosis to evaluate and optimize the FC baseline before surgery. Clear examples of this approach are the prehabilitation programs. More studies are required in Chilean patients for more conclusive data.
Identification of malignant ascites using MR-based T1 mapping.
Authors: Kuetting Fabian , Sprinkart Alois Martin , Faron Anton , Meffert Lisa , Jansen Christian , Luetkens Julian , Attenberger Ulrike , Kuetting Daniel 
Published: May 2020

e16719 Background: Non-invasive identification of malignant ascites is a challenge in clinical practice.Thus, we decided to assess if an MR-based T1 mapping approach allows non-invasive differentiation of malignant and non-malignant effusions. Methods: In-vitro and ex-vivo MR-examinations were performed on a clinical 1.5T MR-system. T1 mapping was performed with spectroscopy and an adapted modified Look-Locker inversion-recovery (MOLLI) acquisition. For in-vitro experiments 13 titrated solutions with varying albumin content (0 to 200 g/l) were examined. For ex-vivo evaluation 27 ascites/pleural effusion samples from patients with malignancy (19 with histologic tumor confirmation in effusion) and 18 samples from patients without malignancy were examined. All samples underwent histological and laboratory testing. Samples were classified as malignant-positive histology, malignant-negative histology and non-malignant negative histology. Lab values were correlated with T1 maps and receiver operating characteristic (ROC) analysis was used to determine the optimal T1-value threshold to differentiate malignant and non-malignant ascites. Results: In in-vitro analysis both methods showed a high correlation with albumin-content (MOLLI: r = -0.97; Spectroscopy: -0.98). T1-values derived from the reference standard (Spectroscopy) and the MOLLI technique had a high agreement (intraclass correlation single measures: 0,9889, 95% CI: 0,52 to 0,99; average measures: 9,994, 95% CI 0,69 to 0,99). Bland-Altman analysis showed a strong agreement between both methods: 62.5 ± 35 (95% CI: 41.2 to 83.8) Ex-vivo analysis revealed significant differences between T1 values from patients with malignant+ histology (median: 2237; IQR: 2132 to 2327.5) and patients with non malignant- negative histology (median: 2611; IQR: 2548 to 2803, p < 0.0001) as well as between malignant+ histology and all other included patients (median: 2585; IQR: 2503 to 2710, p < 0.0001) Multiple regression analysis of in-vivo results revealed that only albumin content correlated with MOLLI based T1 measurements (p < 0.0001; r = -0.65) ROC analysis for differentiation between malignant and non-malignant effusions (malignant+ histology vs. all other) showed an AUC of 0.897; 95% CI: 0.769 to 0.967). Malignant+ histology vs. non-malignant- histology showed an AUC of 1.000 (cut off Lolli > 2419; 95% CI: 0.905 to 1). Conclusions: T1 Mapping shows excellent correlation with protein content of fluids.MR- T1 mapping allows for non-invasive differentiation of malignant and non-malignant effusions in an ex-vivo set up.
Analysis of statistics of pancreatic cancer in Ukraine for a period of 10 years.
Authors: Zrielykh Liliia 
Published: May 2020

e16721 Background: Pancreatic cancer (PC) is the 7th leading cause of cancer death in both sexes and 12th most common cancer worldwide. The estimated 5-year survival rate for it is nearly 5% both in developed and in developing countries. Methods: Analysis of data of National and regional cancer registries. Results: Number of new PC cases in 2003 in Ukraine was 4837 ( men – 2666, women – 2171), in 2013 – 5296 ( men – 2877, women – 2419). So the number of PC cases increased by 8,7% ( by 7,3% in men, by 10,3% in women) in 2013 in comparison to 2003. Number of deaths from PC in 2003 was 4115 (men – 2291, women – 1824), in 2013 – 4307 ( men – 2328, women – 1979). The number of PC deaths increased by 4,5% ( by 1,6% in men, by 7,8% in women). Incidence of PC in children population (age 0-17 years) in 2003 was 0, in 2013 – 4 ( men – 0, women – 4). Age-standardised incidence rate (world standard) of PC in 2003 was 5,9 ( 8,6 in men; 4,0 in women), in 2013 – 6,8 ( 9,8 in men; 4,7 in women). Age-standardised mortality rate (world standard) in 2003 was 5,0 ( men – 7,4; women – 3,4), in 2013 – 5,5 ( men – 7,9; women – 3,9). Patients diagnosed during the preventive medical examinations in 2003 were 3.8% ( men – 3,6%, women – 4,1%), in 2013 - 3.2% ( men – 3,2%, women – 3,3%). Newly diagnosed patients received the special treatment in 2003 were 27,6% (men – 28,7%, women – 26,1%), in 2013 - 26% (men – 25,5%, women – 26,6%). From among them surgical treatment only received 60.8% in 2003, 45.9% in 2013, Combined or complex scheme of treatment received 10.1% in 2003, 10.5% in 2013. The percentage of histologically verified PC in 2003 – 28,4%, in 2013 was 33,6%. Conclusions: There is a tendency of increase of incidence and mortality rates of PC in Ukraine. There have been cases of morbidity in children in 2013 compared with 2003. The number of patients revealed during preventive medical examinations remains low in 2013 and in 2003 due to low health financing, low coverage of preventive medical examinations. The number of patients who received special treatment remains low during 10 years. This is mainly due to lack of access to medical care, high cost of treatment, diagnosis of PC at an advanced stage.
Differentiation of liposomal irinotecan from dose-dense non-liposomal irinotecan in patient-derived pancreatic cancer xenograft tumor models.
Authors: Barbier Sandrine , Lezmi Stephane , Beaufils Benjamin , Lortie Adreanne , Hillairet de Boisferon Marc , Chaumeron Sophie , Espirito Anne , Klinz Stephan G , Thiagalingam Arunthathi , Meyer-Losic Florence 
Published: May 2020

e16724 Background: Liposomal irinotecan (ONIVYDE) is approved with 5-fluorouracil/leucovorin for metastatic pancreatic ductal adenocarcinoma (PDAC) post progression on gemcitabine-based therapy. The liposomal formulation prolongs payload residence time in the circulation and tumor lesions, where local conversion to the active metabolite SN-38 is thought to occur. The effect of the liposomal formulation on therapeutic index (TI) was assessed in patient-derived xenograft PDAC models (IM-PAN-001 [untreated tumor] and SA-PAN-077) in severe combined immunodeficiency mice. Methods: Liposomal (2.5, 10 or 50 mg/kg, intravenous [IV] 1 x weekly) and non-liposomal irinotecan (2, 5 or 10 mg/kg, IV 5 x weekly) were administered for 3 weeks (n = 8/group). Maximum tolerated dose (MTD) and clinically-relevant weekly doses (10 mg/kg, liposomal; 33 mg/kg, non-liposomal) of irinotecan were evaluated. TI was the ratio of MTD/lowest dose with anti-tumoral activity; time to reach tumor volume of 600 mm3 (TTV600) was a proxy for overall survival. Tumor, plasma, gut and bone marrow were sampled for pharmacokinetics and safety assessment; DNA damage was evaluated via pH2AX and 53BP1 IHC. Results: The Table reports results of the more sensitive IM-PAN-001 model: TI of weekly liposomal irinotecan was 4-fold higher than for 5 x weekly non-liposomal irinotecan (TI was narrower for SA-PAN-077). For liposomal vs non-liposomal irinotecan in IM-PAN-001, TTV600 was longer at both MTD and clinically equivalent doses, and tumoral irinotecan levels were higher at MTD. High levels of DNA damage were present in most cancer cells in IM-PAN-001 compared to SA-PAN-077 one week after the last liposomal treatment cycle. Conclusions: In both PDAC models, TI was higher for weekly liposomal vs 5 x weekly non-liposomal irinotecan, suggesting potential benefits of the liposomal formulation in a clinical setting. [Table: see text]
Utilization of imaging in pancreatic adenocarcinoma patients status post Whipple procedure.
Authors: Shah Neal , Podury Ruchika , Kikano Elias , Smith Daniel Arnold , Ramaiya Nikhil H. , Tirumani Sree Harsha 
Published: May 2020

e16725 Background: Pancreatic adenocarcinoma (PAC) remains the third leading cause of cancer death in the Western world. The 5-year survival of patients with PAC remains at 4%. Proper utilization of imaging to detect recurrence is necessary in patients who have undergone a Whipple procedure. Currently, Carbohydrate (CA) 19-9 is used for screening and is the only biomarker approved by the Food and Drug Administration (FDA). Sensitivity and specificity range from 79-81% and 82-90%. We intend to evaluate our single institute experience of imaging utilization, CA 19-9, and surgical specimen histopathologic features in the surveillance of PAC patients status post Whipple. Methods: Retrospective analysis of patients with a diagnosis of PAC who underwent imaging status post Whipple from 2008 - 2018 was completed. Cross-sectional imaging and clinical data was obtained from the electronic health record. Results: A total of 197 PAC patients status post Whipple were identified with mean age at diagnosis at 64.4 years and male to female ratio of 1.3. 85 patients were found to have died during treatment. The median survival for these patients was 68 years. Of the patients who died status post Whipple, postoperative CA 19-9 levels within 6 months of the procedure were elevated (p = 0.01). Patients who were found to have stage II to IV PAC at diagnosis were found to have a high CA 19-9 level within 6 months post-Whipple when compared to stage I patients (p < 0.05). Patients who were found to have less than 5 surveillance CTs status post Whipple were found to have higher CA 19-9 levels within 6 months status post Whipple (p < 0.01). There was no difference in number of CT scans between stages. Of those patients who died with stage I or II PAC at diagnosis, a large number were found to have less than 5 surveillance CT studies completed status post Whipple (p < 0.05). Furthermore, a higher cancer stage at diagnosis correlated with worse pathologic differentiation of the cancer (p < 0.001). Conclusions: Post Whipple CA 19-9 correlated with stage, recurrence, number of scans, and survival.
Morphological and biochemical heterogeneity in the tissue of pancreatic ductal adenocarcinoma (PDAC) according to structural and spectrometric MRI data.
Authors: Iozefi Dmitry Ya. , Vinidchenko Mikhail A. , Demchenko Nikolay S. , Kit Oleg I. , Fomenko Yuriy A. , Petrov Dmitry S. 
Published: May 2020

e16727 Background: Comparing the MRI characteristics of pancreatic tissue in normal, solid adenocarcinomas and chronic pancreatitis in a multiparametric study, the radiologist needs tools that reduce the subjective component in making a diagnostic decision. The study is devoted to the assessment of structural heterogeneity, diffusion coefficient, lipid and lactate concentration according to MR spectroscopy in vivo. PDAС cells are proliferating and surviving within a particularly severe microenvironment characterized by relative hypovascularity, hypoxia, and nutrient deprivation. In this case cells have to show biochemical flexibility (survival phenotype) in order to adapt to unusual conditions. Methods: 20 patients with pancreatic adenocarcinomas (PDAC), 10 patients with chronic pancreatitis and 10 patients with unchanged pancreas were examined MRI using Signa HD 1.5 t General Electric. The results of their multiparametric imaging and NMR spectroscopy were investigated and compared.The heterogeneity coefficients (HC) were measured as ratio standard deviation in small region of interest to signal intensity in T1FS and T2. Lipid concentration was measured by Dixon method as the pancreatic -to-splenic attenuation ratio. Results: In a small sample, we observed a significant increase in HC in chronic pancreatitis, and in solid tissue in adenocarcinomas in comparison with normal tissue, depending on the main source of the MR signal (hydrogen in the macromolecules or hydrogen of water and fat). In adenocarcinomas, an increase in the signal from lipids (lip13a) peak was revealed, with a decrease in the total lipid concentration. A decrease in lipid concentration in the tumor in the presence of diffusion restriction (ADC 0,001-0,0016 мм2/s) and the appearance of a peak of lactate may be a biochemical marker of adenocarcinoma. In chronic pancreatitis, an increase in the mass fraction of lipids was revealed. Conclusions: The results obtained in current and future in-depth studies are promising for creation of a metabolically oriented diagnostic model of pancreatic cancer.
Association of fatty pancreas with increased risk of pancreatic adenocarcinoma.
Authors: El Kurdi Bara , Bataineh Adam , Babar Sumbal , El Iskandarani Mahmoud , Alomari Mohammad , Albawaliz Anas , Sanaka Madhusudhan 
Published: May 2020

e16729 Background: Pancreatic adenocarcinoma (PADC) remains one of the most fatal malignancies with poor outcomes and prognosis. Several risk factors have been associated with its development such as smoking, age, obesity, chronic pancreatitis, diabetes mellitus and a family history of PADC. Furthermore, recent pathologic studies demonstrated that fatty infiltration of the pancreas (FP) is positively correlated with PADC development. We sought to systematically review the literature and perform the first meta-analysis to study the risk of PADC among patients with FP. Methods: We conducted a systematic search of the Pubmed, EMBASE, and Cochrane databases from inception through November-2019 for studies correlating FP with PADC. Relevant data was extracted and analyzed using comprehensive meta-analysis software. Random-effects model was used for all variables. Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic. Publication bias was assessed using Egger’s test. Meta regression models accounting for independent variables such as age, sex, smoking, family history of PADC, chronic pancreatitis and method of FP diagnosis were constructed to explain heterogeneity. Results: Five observational case-control studies published between 2014 and 2019 including a total of 761 patients (320 PADC patients and 441 controls) were included. FP was associated with increased PADC with an OR 4.6 (CI 2.4-8.9) compared to controls with a considerable heterogeneity (I2= 69%). Meta regression analysis accounting for modality used to diagnose FP was able to explain 100% of the noted heterogeneity. Conclusions: While we noted FP to be significantly associated with increased PADC, heterogeneity in FP diagnostic approach resulted in significant inter-study variation. A consensus on a clear definition of FP with a standardized diagnostic approach is needed to better appraise literature on this emerging disease entity. Further prospective studies are needed to validate our results and explore the possible role for PADC screening in FP in addition to known factors such as family history and new-onset diabetes mellitus.
Endoscopic retrograde cholangiopancreatography (ERCP) findings to predict survival in patients with metastatic pancreatic adenocarcinoma.
Authors: Sridharan Vishwajith , Shafique Neha , Darnell Elijah , Wang Thomas , Hernandez-Barco Yasmin , Weniger Maximilian , Qadan Motaz , Fernandez Del-Castillo Carlos , Casey Brenna , Krishnan Kumar 
Published: May 2020

e16734 Background: Chemotherapy is the primary therapy for patients with metastatic pancreatic ductal adenocarcinoma (PDAC), but response to therapy is variable. Patients with PDAC often develop jaundice and cholangitis and require endoscopic biliary stenting. Here, we investigate the association between ERCP findings, cholangitis, chemotherapy use, and survival in PDAC patients. Methods: We conducted a retrospective chart review of all patients who received metal stents for biliary obstruction with PDAC over a five-year period at the Massachusetts General Hospital. Only patients with metastatic cancer were included. Patients were stratified by whether or not they received chemotherapy, as well as the presence or absence of cholangitis. Associations between chemotherapy use and ERCP findings were investigated. Survival analyses were performed to compare patients by chemotherapy use, presence of cholangitis, and findings at ERCP. Results: A total of 126 patients were included; the average age of patients in our study was 69.9 ± 11.8. The average size of the primary lesion was 38.7 ± 14.4 mm. Sixty-nine percent of patients completed chemotherapy. The average number of stents for all patients was 2.5 ± 2.5, but was significantly higher in patients who experienced cholangitis (3.3 ± 2.8) as expected (p < 0.001). The majority of ERCP reports noted debris or sludge (44%), followed by presence of infiltrating or obstructing tumor (27%), stone (13%), pus or purulence (11%), and blood clot (5%). Patients who did not receive chemotherapy were more likely to have tumor obstruction noted on ERCP compared to those who received chemotherapy (p = 0.024). Patients undergoing chemotherapy were also more likely to have sludge noted on ERCP (p = 0.009) compared to those who did not have chemotherapy. There was no association between chemotherapy use and presence of stones (p = 0.94) or presence of purulence (p = 0.44) noted on ERCP. Among patients who received chemotherapy, those who had sludge or debris noted on their ERCP tended to have better survival compared to those where sludge was not noted on endoscopy (p = 0.038). Conversely, among patients who received chemotherapy, identification of an obstructing tumor on ERCP was prognostic of poorer survival (p = 0.037). Among patients who did not get chemotherapy, there was no survival difference between patients who had sludge or tumor and those who did not. Conclusions: Findings on ERCP may serve as a surrogate for chemotherapy response and be prognostic of survival in metastatic PDAC.
Use of a real-world data approach to rapidly generate outcomes data following a case study of a novel treatment combination in pancreatic adenocarcinoma.
Authors: Rahib Lola , Chen Karen , Ocean Allyson J. , Xie Changqing , Duffy Austin , Manji Gulam Abbas , Greten Tim F. , Shapiro Mark , Shrager Jeff , Hoos William , Federowicz Bryan , Kinsey Conan Grant 
Published: May 2020

e16735 Background: We use a real-world data approach to report on safety and benefits on metastatic pancreatic cancer pts who were treated with a MEK inhibitor plus hydroxychloroquine (HCQ) after exhausting all other treatment options. MEK inhibition acts on the KRAS pathway, which in turn increases autophagy as a resistance mechanism, furthermore, HCQ inhibits autophagy causing a cytotoxic effect. This combination was shown to diminish tumor volume in xenograft mouse models and a partial response in one heavily pre-treated patients was reported. Methods: XCELSIOR is an IRB approved, patient-centric, real-world data and outcomes registry for developing operational and analytic methods in precision oncology. Searching the XCELSIOR database, we identified 14 pts for whom this regimen had been considered. As part of their participation in XCELSIOR, these patients shared access to their full medical records, which were collected, processed, and abstracted into a 21 CFR 11 compliant database for analysis. We additionally collected de-identified data on 12 pts treated with this combination from five academic centers. Three more patients are expected to start treatment soon. Results: Between March 2018 and January 2020, 15 patients treated with the trametinib/HCQ combination and 3 patients treated with cobimetinib/HCQ were identified in XCELSIOR and five academic institutions. The median age at diagnosis was 64 (range 43-74) and 56% were male. For patients treated with trametinib/HCQ, the median time on treatment was 67 days (range 5-172 days), 11 patients were treated for more than 30 days (median time 97 days). The median PFS for this group was 2.9 months and the median OS was 7.4 months. The clinical benefit rate was 60% for the 10 evaluable patients treated with trametinib/HCQ, 1 patient had a partial response (previously published), 5 had stable disease (for at least 8 weeks) and 4 had progressive disease (physician reported). 2/3 patients treated with cobimetinib/HCQ were on treatment for more than 30 days and all three had progressive disease within 7 weeks. The most common side effects were Grade 1 fatigue and Grade 1/2 rash for both combinations. An additional 3 patients will start treatment soon and will be included in the analysis. Conclusions: Combinatorial MEK and autophagy inhibition was well tolerated in heavily treated metastatic pancreatic cancer patients. Trametinib/HCQ demonstrates some clinical benefit for this group. We demonstrate the feasibility of utilizing real-world data in precision oncology. Clinical trial information: NCT03793088 .