bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of congestive heart failure (CHF) with incidence rates of enteric infections and gram-negative sepsis (GNS) in patients with hepato-pancreatico-biliary cancers (HPBCs).
Authors: Mahadevia Himil , Modi Karnav , Vodnala Deepthi , Roth Marc Thomas 
Published: January 2024

567 Background: ChronicCHF leads to volume overload and can cause bowel wall edema. This may compromise local immune defense and promote increased translocation of gut bacteria into the blood.HPBCs can cause biliary tract obstruction which is also associated with bacteremia. Additionally, cancer treatments are associated with an increased risk of clostridium difficile infection (CDI), regardless of antibiotic exposure. While associations between cancer and increased infection rates are well-established, we questioned whether concomitant CHF increases this risk further in the HPBC population. We therefore investigated whether concomitant CHF and HPBC influenced CDI, other infectious gastroenteritis (IGE), GNS rates or all-cause-hospital mortality. Methods: A retrospective study was conducted by obtaining patients with HPBC through the application of specific ICD 10 codes from the National Inpatient Sample 2020, a large publicly available database of inpatient hospital stays incorporating data from hospitals across 48 U.S. states. Among this cohort, patients with chronic CHF were further identified by applying all CHF-specific ICD 10 codes. All patients with HPBC were divided into two groups, one with CHF (group A) and the other without CHF (group B). Outcomes were compared between the two groups using multivariate regression analysis (MVRA) adjusting for demographic factors, hospital-specific characteristics like location, bed size, etc., comorbidities including obesity, diabetes, hypertension, prior cardiovascular events, HIV, CKD, OSA, etc., prior coronary intervention/surgery as well as alcohol, smoking or substance use. Results: 211,790 patients were identified with HPBC. 40.55% were female. 18,955 patients (9.95%) were found to have chronic CHF. The incidence of GNS was higher in group A compared to group B in the MVRA (Adjusted (Ad) OR: 1.4, CI 1.07-1.95, p=0.015). However, there was no difference in the incidence rate of CDI between groups A and B (Ad OR: 1.0, CI 0.71-1.50, p=0.86). Similarly, the two groups had no difference in other IGE (Ad OR: 1.0, CI 0.71-1.37, p=0.96). All-cause hospital mortality was slightly higher in group A than group B but failed to reach statistical significance (Ad OR: 1.1, CI: 0.99-1.29, p=0.069). Conclusions: GNS was more common in patients with HPBC who also had comorbid chronic CHF. Future investigations may focus on the effect of increased GNS on outcomes beyond hospitalization, correlation between the severity of CHF and GNS as well as primary site of HPBC and infection risk. Based on this signal-finding analysis, it is postulated that early inter-disciplinary collaboration between oncology and cardio-oncology/cardiology may have special significance in the management of patients with chronic CHF and HPBCs, the latter of which already carries a dismal prognosis.
Repeat peptide receptor radionuclide therapy in neuroendocrine neoplasms: A NET Center of Excellence experience.
Authors: Grewal Udhayvir Singh , Paschke Alexander , Dillon Joseph S. , Chandrasekharan Chandrikha 
Published: January 2024

590 Background: Lu177 DOTATATE Peptide Receptor Radionucleotide Therapy (PRRT) was FDA approved in the United States in 2018 however this treatment modality has been widely available in European nations since early 2000s. Therefore, the data for the safety and efficacy of repeat PRRT are almost exclusively from European centers. We present a real-world experience with repeat PRRT in a cohort of US patients. Methods: We used our single-center longitudinal IRB approved neuroendocrine tumor (NET) registry to identify patients who had been previously treated with at least 1 dose of PRRT (PRRT 1, either Lu 177 DOTATATE or Y90 DOTATOC) and following disease progression were retreated with a second course of PRRT (PRRT 2). Patients who received alpha PRRT were not included. We reviewed patient, tumor and treatment characteristics, time to progression after PRRT 1 and PRRT 2 and toxicity. Results: A total of 153 patients received at least 1 dose of Lu-177 DOTATATE PRRT at our institution post FDA approval, out of which, 13/153 (8.5%) patients received repeat PRRT .2/13 patients were excluded due to lack of adequate follow up. All patients included were white (11/11, 100%). Median age of the participants was 65 years (IQR 63, 67) and 54.5% (6/11) patients were females. Most patients had grade 2 (9/11,81.8%) followed by grade 1 NET (2/11, 18.2%) and all except one patient included had a gastroenteropancreatic origin NET (10,11, 90.9%). 45.5% (5/11) patients received Lu-177 DOTATATE PRRT only both for PRRT1 and PRRT 2, while 54.5% (6/11) patients received Y90 DOTATOC PRRT for PRRT1. Median number of lines therapies before PRRT1 and PRRT were 2 (IQR 2,5) and 1 (IQR 1,2) respectively. Patients received a median of 3 (IQR 2, 4) and 3 (IQR 1,4) cycles for PRRT1 and PRRT2 respectively. At first restaging scan after PRRT1 (3-6 months), 54.5% and 45.5% patients had partial response (PR) and stable disease (SD) respectively. At first restaging scan after PRRT2 (3-6 months), 45.5%, 27.3% and 9.1% patients had SD, progressive disease (PD) and PR respectively; 2/11 patients (18.2%) died before first restaging scan. Median PFS for PRRT1 (n=11) was 22.5 months (IQR 12.7, 30.7). Median PFS (n=5) for PRRT2 was 10.9 months (IQR 10.05, 25.7). PFS was not reached for 1 patient after PRRT2. 1 (9.1%) patient each developed grade 2 nephrotoxicity and grade 3 thrombocytopenia after PRRT2. Conclusions: To our knowledge, this is the first of its kind analysis describing the safety and effectiveness of repeat PRRT in a US cohort. We show that repeat PRRT may benefit select patients and has an acceptable safety profile. Larger prospective clinical studies are required to identify patient groups that are more likely to benefit from repeat PRRT.
A novel early cancer detection approach for pancreatic cancer.
Authors: Bijlsma Maarten F. , Strasser Patrick Christian , Schneider Maximilian Christoph , Thumfart Norbert 
Published: January 2024

613 Background: Pancreatic adenocarcinoma (PDAC) is commonly diagnosed at advanced stages, leading to high mortality rates. Earlier detection of PDAC is associated with improved long-term survival, but effective population-level screening is not available. There is therefore an urgent need to improve early detection of PDAC. Wholomics has developed a PDAC-specific proprietary early detection test, using cancer-specific molecular signatures in peripheral blood. Methods: We conducted a retrospective analysis of serum samples from the Amsterdam UMC Liquid Biopsy Center. Three cohorts were included in this study: 1) A cohort of healthy control subjects, 2) patients with a histopathologically confirmed diagnosis of PDAC spanning stages I through IV, and 3) patients with a confirmed diagnosis of chronic pancreatitis. Peripheral blood samples of cancer patients were taken before treatment or surgery. Wholomics used its proprietary technology to quantitatively analyse all serum specimens. Disease-specific molecular signatures were identified and used to develop computational biomarkers specific to both pancreatic pathologies (chronic pancreatitis and pancreatic cancer) and to pancreatic cancer individually. A comparative analysis was conducted employing multiple machine learning algorithms, which were subjected to a 10-fold cross-validation procedure. The accuracy, specificity and sensitivity of the best-performing algorithm is reported. Results: This retrospective study included 50 healthy controls, 12 patients with chronic pancreatitis, and 42 patients with pancreatic cancer (12 stage I, 15 stage II, 9 stage III, 6 stage IV). Applying Wholomics´ technology, an accuracy of 99.1% in differentiating the chronic pancreatitis and pancreatic cancer patients from the healthy controls was achieved. A specificity of 98.0% and a sensitivity of 100.0% were reached. Furthermore, pancreatic cancer patients and chronic pancreatitis patients were differentiated with 95.2% accuracy. Wholomics was also capable of differentiating between early stage (stages I and II) and late-stage (stages III and IV) pancreatic cancer with an accuracy of 100%. Conclusions: Taken together, this study demonstrates that disease-specific molecular signatures in peripheral blood can distinguish patients with PDAC from healthy individuals and patients with pancreatitis with very high accuracy. If validated in additional cohorts, this method could be evaluated as a screening test for PDAC to allow for early detection and improve patient outcomes.
In-hospital outcomes of acute pulmonary embolism in patients with gastrointestinal cancer: A nationwide study.
Authors: POUDEL SAJANA , Ghimire Manoj , Ghimire Kalpana , Poudel Ayusha , Shrestha Karun , Subedi Prakriti , Karki Sandesh , Adhikari Anurag , Garzon_Siatoya Wendy Tatiana , Batool Humera , Elfert Khaled , Ibrahim Muhammad Bilal 
Published: January 2024

624 Background: Cancer is a well-established risk factor for the development of pulmonary embolism (PE), especially the. gastrointestinal (GI) cancers. While multiple studies have reported the burden of PE in cancer patients, recent data comparing in-hospital outcomes among different types of cancer patients are lacking. This study aimed to investigate the clinical and healthcare utilization outcomes of hospitalized patients with acute PE in the context of gastrointestinal (GI) cancers. Methods: A cross-sectional study was conducted using data from the National Inpatient Sample (2016-2020). International Statistical Classification of Diseases (ICD-10) codes were employed to identify hospitalized patients admitted with primary diagnosis acute PE. Data regarding GI cancer diagnosis along with demographic information, baseline clinical characteristics, and outcome variables, including mortality, hospital length of stay, total hospital charges, complications and risk factors were collected and analyzed. Statistical analysis was performed using the survey procedures function in STATA v.17, with statistical significance defined by the t-test at a significance level of p < 0.05. Results: Among the 181,060 patients admitted with primary diagnosis of acute pulmonary embolism, 550 (0.3%) had underlying gastric cancer, 1,790 (0.98%) had pancreatic cancer, 875 (0.48%) had hepatobiliary cancer, and 2,600 (1.61%) had small intestine and colorectal cancer. Mortality was found to be significantly higher in all types of GI cancer, with gastric cancer demonstrating the highest mortality rate (10%). After adjusting for age, sex, race, payment category, comorbidities, and risk factors of PE, gastric cancer (OR 2.6; 95% CI: 1.1-6.2) and pancreatic cancer (OR 2.2; 95% CI: 1.4-3.4) were found as independent risk factors for mortality. There was no significant difference in mean length of hospital stays and mean total hospital charges in patients with or without cancer. Similarly, no significant differences were observed in complications such as requirement for mechanical ventilation, arrhythmia, cardiac arrest, need for vasopressor and thrombolysis. Conclusions: In-hospital mortality in patients with acute pulmonary embolism is significantly higher in all types of GI cancer, however; there is no significant differences in hospital length of stay and total hospital charges in patients with or without cancer.
Frequency and oncologic outcomes of KRAS mutations in circulating tumor DNA of patients with pancreatic ductal adenocarcinoma.
Authors: Yousef Mahmoud M.G. , Hurd Mark W. , Yousef Abdelrahman M.G. , Snyder Rebecca A , Knafl Mark , Fanaeian Mohammad Mahdi , Chacko Ray , Peterson Jennifer , Smaglo Brandon George , Wolff Robert A. , Pant Shubham , Lee Michael Sangmin , Overman Michael J. , Tzeng Ching-Wei D. , Katz Matthew H. G. , Wang Huamin , Maitra Anirban , Ludmir Ethan B. , Shen John Paul Y.C. , Zhao Dan 
Published: January 2024

636 Background: KRAS genetic alterations have been reported in more than 90% of pancreatic ductal adenocarcinoma (PDAC). The association of KRAS mutation subtypes detected in circulating tumor DNA (ct-DNA) with survival remains unclear. We investigated the rate of liquid biopsy detected KRAS mutation subtypes, and their association with overall survival (OS) in patients with PDAC. Methods: The Foundry software platform was used to retrospectively query a single-institution Electronic Health Records to identify patients with PDAC who underwent ct-DNA liquid biopsy from 2018 to 2023 and extract their oncologic outcomes. Results: Liquid biopsies were performed for 313 patients with PDAC; 58% (n=181) were diagnosed with stage IV disease. The median follow-up was 25 months, with median OS 24 months (95%CI=21-29). Overall, 52% (n=162) tested positive for KRAS mutations. Among patients with metastatic disease at diagnosis (n=181), 66.7% (n= 120) tested positive for KRAS mutations. In contrast, only 31.8% (n= 42) of patients with stage I to III disease at diagnosis (n=132) tested positive. Among patients with metastatic disease, those with KRAS positive disease had significantly shorter OS (median OS 13 vs 27 months, HR=2.7, 95%CI=1.7-4.3, P<0.0001). In patients with non-metastatic disease, the median OS was 28 vs 43 months, respectively (HR=1.7, 95%CI=0.97-2.8, P=0.064). The most frequent KRAS mutation was G12D (n=66, 40.7% of KRAS mutations) followed by G12V (n=58, 35.8%), G12R (n=15, 9.3%), and Q61H (n=10, 6.2%). Among KRAS mutations allelic subtypes, KRAS G12D and Q61 mutations had significantly worse OS with median OS 13 and 10 months respectively (P <0.001). The most frequently co-occurring mutations detected in KRAS positive patients were TP53 (n=126, 77.8%), CDKN2A (n=34, 21%), SMAD4 (n=33, 20.4%), and ARID1A (n=12, 7.4%). Examining the prognostic significance of co-occurring mutations among patients with metastatic disease, only detection of co-occurring CDKN2A mutation was associated with worse OS as compared to patients with KRAS mutations without co-occurring CDKN2A mutations (median OS 8 vs 14 months, HR=2, 95%CI=1.1-3.5, P value=0.015). Conclusions: Detection of KRAS mutation in liquid biopsies of patients with metastatic PDAC is associated with worse OS. KRAS G12D/Q61 alterations detection is associated with worse OS compared to other KRAS mutation subtypes. Ct-DNA detection of co-occurring CDKN2A mutation is associated with worse OS in patients with KRAS positive metastatic disease.
Survival of patients with microsatellite instability-high and Lynch syndrome-associated pancreatic ductal adenocarcinomas.
Authors: Nasar Naaz , Eikenboom Ellis , Seier Kenneth , Gonen Mithat , Wagner Anja , Jarnagin William R. , Drebin Jeffrey A. , D'Angelica Michael Ian , Kingham T. Peter , Balachandran Vinod P. , Soares Kevin , Spaander Manon C.W. , Wei Alice Chia-Chi 
Published: January 2024

640 Background: Pancreatic ductal adenocarcinoma (PDAC) remains a challenging disease due to its aggressive nature, late-stage diagnosis, and limited treatment options. There is an increased interest in cancers which harbor microsatellite instability (MSI) due to their susceptibility to immune checkpoint inhibitors. MSI in PDAC is rare, and little is known about survival in this subtype of pancreas cancers. Our aim was to assess overall survival in surgically resected high microsatellite instability (MSI-H), mismatch repair deficient (MMRd), and Lynch Syndrome (LS) associated PDACs treated in our center. Methods: Patients with surgically resected PDACs from 1990 to 2023 were identified. A total of 936 cases were sequenced utilizing MSK-IMPACT, a targeted next generation sequencing platform. Patients with germline or sporadic pathogenic variants or likely pathogenic variants in one of the DNA MMR genes MLH1, MSH2, MSH6, PMS2, or 3’ end of EpCAM were identified. MSI-H, MMRd, and LS-associated cases were matched to patients with microsatellite stable or MMR proficient, non-LS-associated PDAC in a 1:2 ratio with a direct match on age (±5 years), gender, and year of surgery (±3 years). Kaplan-Meier curves were used to visualize the data. A generalized estimating equation (GEE) cox model with robust sandwich estimator was used to compare matched cohorts. Results: 17 patients with MSI-H, MMRd or LS-associated surgically resected PDACs were identified. Five patients were classified as MSI-H, 3 patients were MSI-indeterminate, and 9 patients were microsatellite stable. Eight patients were found to have pathogenic germline variants in LS-associated genes. The remaining nine patients had sporadic pathogenic DNA MMR gene variants ( MLH1 n=3, MSH6 n=6). Median age at surgery was 66 (interquartile range (IQR) 60-77), 41% of the patients were female, and median year of surgery was 2014. MSI-H, MMRd or LS-associated PDACs were matched to 34 control patients. The median survival time of the cases was 12 years vs. 1.9 years in the control group. Five-year survival rate was 81% (IQR 60-100%) and 18% (7.4%-43%), respectively. LS-associated, MSI-H or MMRd status in resectable PDAC was a strong predictor of good prognosis (hazard ratio 0.17, 95% CI 0.07-0.38, p value <0.001). Conclusions: MSI-H, MMRd or LS-associated PDACs displayed significantly better survival compared to their MSI-stable, MMR proficient, non-LS-associated counterparts, in the era before routine use of immunotherapy. It is expected that survival will be increased further with more frequent availability of immunotherapy.
The interim analysis of a single-arm, open-label, phase II study investigating ALLEN regimen (durvalumab plus albumin paclitaxel and lenvatinib) in patients with metastatic pancreatic cancer (mPC).
Authors: Chen Meixia , Li Zhifang , Ming Qianyi , Zhang Yan , Feng Kaichao , Mei Qian , Liu Yang , Han Weidong 
Published: January 2024

658 Background: Metastatic pancreatic cancer is a leading cause of cancer death worldwide with limited treatment options. Durvalumab, the anti- PD-L1 inhibitor has revealed remarkable efficacy in solid malignancies including hepatobiliary cancers. We conducted a study to evaluate the efficacy and safety of a combination therapy of Durvalumab, Albumin paclitaxel and Lenvatinib (ALLEN Regimen) in patients with mPC. Methods: This open-label, single-center, single-arm, phase Ⅱ clinical trial investigated patients with metastatic pancreatic cancer. Durvalumab (1000mg IV, q3w), albumin paclitaxel(180-220 mg/m2 IV q3w) and lenvatinib (8mg PO QD) were given regularly until disease progression. The primary endpoint was objective response rate (ORR) evaluated by investigators according to RECIST 1.1. The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Results: Between September 2021 and September 2023, seventeen patients with ECOG score 0-2 were enrolled, including 8 patients (47%) who were refractory to at least one systemic chemotherapy.The median follow-up was 6.0 months (95% CI 4.0, 8.4). 17 patients were evaluable, with a median age of 58 years. 9 patients (52.9%) were male. The ORR and DCR were 64.7% and 94.1%, respectively. The median PFS was 7.8 months (95% CI 3.1, 11.4), and the median OS was 8.1 months (95% CI 4.7, 13.5). TRAEs (all grades) occurred in 16 (94.1%) patients. The most common grade 1-2 TRAEs were nausea 8 (47.1%), diarrhoea 5(29.4%), peripheral sensory neuropathy 3 (17. 6% ) and hypertension 3(17.6% ). No grade 3 or higher TRAEs occurred. Conclusions: The ALLEN regimen demonstrated promising antitumor activity and well acceptable toxicity in metastatic pancreatic cancer. Further randomized controlled studies will be required in a larger patient population. Clinical trial information: NCT05327582 .
Does metformin use effect overall survival for patients with pancreatic cancer?
Authors: Ramjeesingh Ravi , Nazarali Samina , Sheridan Margaret , Sun Peiran , Popovacki Aimee 
Published: January 2024

660 Background: In Canada, the incidence of pancreatic cancer ranks 11th amongst all cancers but has resulted in the third highest mortality. Despite advancements in both diagnostics and therapeutics, the 5-year overall survival rate of pancreatic adenocarcinoma (PDAC) remains under 10%. Emerging studies have begun to examine the role of the hypoglycemic medication metformin, in improving outcomes of patients with PDAC. In cell cultures, metformin has been shown to have direct growth-inhibitory actions on malignant cells, and previous retrospective studies have suggested a potential association between metformin use and increased overall survival in breast and prostate cancer. To identify if metformin plays a role in improving PDAC outcomes, we have conducted a retrospective review of PDAC in Nova Scotia, Canada. Methods: We conduced a retrospective study of 630 patients diagnosed with PDAC treated at the Halifax Infirmary (Halifax, Nova Scotia). Records of patients were reviewed and information regarding patient demographics, cancer staging, metformin use, date of diagnosis, and date of death were collected. Statistical analysis using the log rank method was done to determine if there was a statistically significant difference in overall survival between groups. Results: Among the 630 patients identified, there were 337 males and 293 females. The average age at time of diagnosis was 74.02 years. There was no significant difference found in overall survival of patients on metformin (n=132, mean overall survival (mOS) 6.68 months), compared to those not on metformin (n=498, average survival 7.44 months), p=0.989. Further subgroup analysis based on cancer staging showed that patients with resectable pancreatic cancer (AJCC stage I-IIA, n=140), who did not use metformin (n=106) had a mOS of 12.98 months compared to 9.71 months for metformin users (n=34), p=0.438. For patients with locally advanced disease (AJCC stage IIB-III, n=125), the average mOS of non-metformin users (n=103) was 11.10 months compared to 10.73 months for metformin users (n=22), p=0.803. For patients with metastatic disease (AJCC stage IV, n=365), the average survival of non-metformin users (n=289) was 3.48 months compared to 4.26 months for metformin users (n=76), p=0.803. Diabetic patients (n=195) on metformin (n=132) compared to those not on metformin (n=63), did not show significant survival difference (mOS 6.68 months vs 6.61 months respectively, p =0.602). Conclusions: Despite suggestion that metformin use may improve survival in some cancers, we found no statistical improvement in mOS for metformin use in PDAC patients. Future research including a prospective study should be undertaken to confirm these results in a larger sample size.