bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in US colorectal cancer mortality trends over the past 20 years.
Authors: Tan Jia Yi , Yeo Yong Hao , Ng Wern Lynn , Fong Zhi Ven , Brady Justin T. 
Published: June 2024

e15543 Background: In the last two decades, colorectal cancer (CRC) mortality has been decreasing in the United States (US). However, the mortality trends for the different subtypes of CRC, including different sides of colon, rectosigmoid, and rectal cancer remain unclear. Methods: We analyzed death certificate data from CDC WONDER from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals of CRC and its different subtypes and examined the trends over time by estimating the average annual percent change (AAPC) using the Joinpoint Regression Program. Results: From 1999 to 2020, 1,166,099 deaths were attributed to CRC, of which 957,182 deaths (82.08%) were due to colon cancer, 148,862 deaths (12.77%) from rectal cancer, and 60,055 deaths (5.15%) from rectosigmoid cancer. The overall CRC rates decreased significantly from 26.42 (95% CI, 26.20-26.64) to 15.98 (95% CI, 15.84-16.12) per 100,000 individuals, with AAPC of -2.41 (95% CI, -2.55, -2.27). However, the AAMR of rectosigmoid cancer increased significantly from 0.82 (95% CI, 0.78 -0.86) to 1.08 (95% CI, 1.04-1.11) per 100,000 individuals and the AAMR of right-sided colon cancer increased from 0.57 (95% CI, 0.54-0.60) to 0.70 (95% CI, 0.67-0.73) per 100,000 individuals, with AAPC of +1.10 (95%, 0.21-2.00) and +2.06 (95% CI, 0.85 - 3.27) respectively. Men had higher AAMR of CRC than women (23.90 [95% CI, 23.84-23.96] vs. 17.03 [95% CI, 16.99-17.08] per 100,000 individuals). African Americans had the highest AAMR of CRC (26.93 [95% CI, 26.79-27.07]), followed by Whites (19.60 [95%, 19.56-19.64] per 100,000 individuals), American Indians (14.53 [95%, 14.15-14.92] per 100,000 individuals), and Asians (13.04 [95%, 12.89-13.19] per 100,000 individuals). The overall AAMR of CRC decreased for those aged ≥ 50 years but increased significantly from 1.02 to 1.58 per 100,000 individuals for those aged 15-49 years, with an AAPC of +0.75. The AAMR from CRC was the highest in the Midwest (21.04 [95% CI, 20.96-21.12] per 100,000 individuals), followed by the South (20.51 [95% CI, 20.44-20.57]), the Northeast (20.30 [95% CI, 20.22-20.38] per 100,000 individuals), and the West (18.03 [95% CI, 17.95-18.10] per 100,000 individuals). Rural populations had higher AAMR than urban populations (22.40 [95% CI, 22.30-22.49] vs. 19.60 [95%, 19.56-19.64] per 100,000 individuals). Conclusions: Although overall CRC mortality declined, there were rising trends in young-onset CRC, rectosigmoid cancer, and right-sided colon cancer. Disparities persist in terms of sex, race, geographic region, and urbanization level, emphasizing the need for targeted public health measures.
Prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data.
Authors: Jafri Mohsin Saleet , Amniouel Soukaina 
Published: June 2024

e15548 Background: FOLFOX and FOLFIRI chemotherapy are considered standard first-line treatment options for colorectal cancer (CRC). However, the criteria for selecting the appropriate treatments have not been thoroughly analyzed. Here, we aim to use machine learning and genetic profiles to identify precise multi-gene panels that can predict the response to 5-Fluorouracil-based chemotherapy in colorectal cancer patients. Methods: The genetic profiling data, including drug response profiles, were retrieved from the Gene Expression Omnibus (GEO) database. These datasets were used to train and validate machine learning models. Feature selection methods, such as least absolute shrinkage and selection operator (LASSO) and variable selection from random forests (varSelRF) and various algorithms, such as Random Forest and Support Vector Machines, were applied to develop predictive models. Functional enrichment and network analyses were performed using Ingenuity Pathway Analysis (IPA). Results: This study identified relevant gene signatures at two stages of colorectal cancer: primary and metastasis using two different chemotherapy regimens, FOLFOX and FOLFIRI. The predictive models achieved an average prediction accuracy of 93% in identifying drug response outcomes across multiple chemotherapy regimens. The application of the machine learning model suggested that 28.6% of patients who failed the treatment therapy they received would benefit from the alternative treatment. Conclusions: The developed machine learning models demonstrate potential for guiding clinicians in selecting the most effective treatment options based on individual genetic profiles. With additional clinical validation, this approach could lead to improvements in treatment outcomes for patients with CRC and other cancers.
PIPAC in patients with peritoneal metastases from gastrointestinal tract (PIPOX): An open label, non-comparative phase 1/2 dose escalation and expansion trial.
Authors: Dumont Frederic , Kepenekian Vahan , Passot Christophe , Ezanno-Manasterki Anne-Cecile , Pocard Marc , Raoul Jean-Luc , Lelievre Benedicte , Hiret Sandrine , Senellart Hélène , Pein Francois J. L. , Raimbourg Judith , Thibaudeau Emilie , Paul Julie , Glehen Olivier 
Published: June 2024

e15561 Background: Withmodern systemic chemotherapy, survival remain poor for patient withadvanced isolated peritoneal metastases from gastrointestinal tract. We aimed to assess the safety and efficacy of PIPAC to oxaliplatin in combination or not with systemic chemotherapy. Methods: We did a phase 1/2, open label, non-comparative, dose escalation and expansion trial of PIPAC to oxaliplatin forpatients with peritoneal cancer index (PCI) more than 5, 13 and 15 for respectively a gastric, small bowell and colorectal cancer primary; who had received at least three months of systemic chemotherapy. PIPAC cycle lengths was 4 to 6 weeks with systemic chemotherapy allowed 15 days after each PIPAC. PCI and oxaliplatin concentration tumor was assessed every PIPAC cycles. Main endpoints were, tolerability, tumor response and survival. Results: Between2017 to 2020, 34 for patients were enrolled in three centers, in this phase 1/2 study of whom 25 were evaluable at recommanded dose of phase I of 90 mg/m2 plus systemic 5-FU. At this dose, safety profile showed acceptable tolerability. 8 patients (32%) had grade 3/4 treatment related adverse event. Minors (grade 1/2) adverse events were mainly abdominal pain (n = 19, 76%) and nausea (n = 16, 64%). Before inclusion patients received a median of 2 [1-4] chemotherapy lines and had a median PCI of 22.5 [7-29]. Median PFS was 6.1 months and median OS was 13 months. Conclusions: In patients with advanced and refractory peritoneal metastasis, PFS of 6.1 months is encouraging. A prospective randomized phase II study is required. Clinical trial information: NCT03294252 .
Stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer: Updated findings from a single-arm, prospective phase II trial (RIFLE).
Authors: Chen Yajie , Wang Kun , Zhiyuan Zhang , Zhang Hui , Yang Wang , Wu Ruiyan , Zhou Menglong , Zhang Zhen , Xia Fan 
Published: June 2024

e15570 Background: Stereotactic ablative radiotherapy (SABR) has been shown to sensitize immunotherapy through inducing immunogenic death and remodeling the tumor immune microenvironment. In addition, anti-angiogenic therapy exhibits synergistic antitumor effects with PD-1/PD-L1 antibodies through its immunomodulatory effects for metastatic colorectal cancer (mCRC) patients. Here, we report the updated results from RIFLE trial: the efficacy and safety of the combination of fruquintinib, PD-1 inhibitor tislelizumab and SABR in mCRC patients. Methods: This is a single-center, single-arm, prospective phase II clinical trial (NCT04948034). mCRC patients with at least 2 measurable lesions (≥1 of which can be targeted with radiation and ≥1 lesion outside the radiation field) who have failed ≥ 1L standard therapy will receive SABR followed by fruquintinib (5 mg, d1-14, qd) and tislelizumab (200 mg, d1, q3w) within two weeks from completion of radiation. The percentage change from baseline in the sum of longest diameter of target lesions, consist of specified radiated and non-radiated lesions, will be assessed after at least 2 cycles’ drug treatment. Primary endpoint is best objective response rate (ORR) of target lesions. Secondary endpoints include disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) rate, overall survival (OS) rate and toxicity. Results: From August 2021 to February 2024, 34 patients were included in the trial and 31 in the efficacy analysis. Median age was 62 years, 24 (77.4%) patients were male, 26 (83.9%) had ≥ 3 metastases, and 14 (45.2%) had received ≥ 3 prior lines of systemic therapy. The biological effective dose (BED) for irradiated lesions ranged from 37.5 to 105 Gy. Median study follow-up was 17.3 months (95%CI:13.841-20.759), 24 patients were alive and 13 remained on treatment. 1 patient achieved complete response (CR) for target lesions, 8 partial response (PR), 14 stable disease (SD), illustrating an ORR of 29% and a DCR of 74.2%. Median PFS was 8.8 months (95%CI:5.868-11.732). The most common treatment-related adverse events (TRAEs) were proteinuria (35.5%), hypertension (22.6%) and rash (19.4%). Grade 3-4 AEs occurred in 9 patients, including proteinuria and hypertension, and there were no treatment-related deaths. Conclusions: SABR combined with tislelizumab and fruquintinib shows promising effects and good safety in the treatment of metastatic colorectal cancer, which is expected to provide new therapeutic strategies and improve the prognosis for mCRC patients. Clinical trial information: NCT04948034 . [Table: see text]
Laparoscopic-assisted vs open surgery for low rectal cancer: 5-year outcomes of the LASRE randomized clinical trial.
Authors: Chi Pan , Jiang Weizhong , Su Xiangqian , Xu Jianmin , Qiu Huizhong , Kang Liang , Deng Haijun , Chen Weiping , Zhang Qingtong , Yang Chunkang , Guo Yincong , Zhong Ming , Ye Kai , You Jun , Xu Dongbo , Li Xinxiang , Ding Ke-Feng , Tao Kaixiong ,   LASRE Trial Investigators
Published: June 2024

e15630 Background: The long-term efficacy of laparoscopic versus open surgery for low rectal cancer has not yet been established. The primary outcome of 3-year disease free survival (DFS) have been published (Chi et al., ASCO GI 2024). Here, we presented the data of 5-year outcomes, including DFS and overall survival (OS) and locoregional recurrence. Methods: This is a multicenter, noninferiority trial. A total of 1070 patients scheduled for curative-intent resection of low rectal cancer were randomized at a 2:1 ratio to undergo laparoscopic or open surgery from November 2013 to June 2018. All analyses were performed on an modified intention-to-treat (mITT) basis. Results: The final analysis included 1039 patients (median age: 57 years, 620 men; 685 and 354 in laparoscopic and open groups, respectively). Clinical TNM stage was II/III in 659 patients, and I in the remaining 380 patients. The 5-year DFS rate was 76.4% in the laparoscopic group versus 75.6% in the open group (log-rank P = 0.766). The 5-year OS rate was 84.6% in the laparoscopic group versus 86.6% in the open group (log-rank P = 0.405). The 5-year locoregional recurrence rate was 5.5% and 3.1%, respectively (log-rank P = 0.079). Conclusions: The findings of the LASRE trial demonstrate that the noninferiority of laparoscopic surgery compared to open surgery for low rectal cancer, as evidenced by the 3-year outcomes, is sustained over a 5-year period when conducted by skilled surgeons. These results affirm laparoscopic surgery as a secure and minimally invasive option for the treatment of low rectal cancer. Clinical trial information: NCT01899547 .
AI-assisted colonoscopy in gastroenterology fellowship training: An interim analysis of a randomized controlled trial.
Authors: Kong Niwen , Chang Patrick , Nguyen Denis , Wang Sarah , Sharma Nisha , Amini Maziar , Ong Justin , Wang Daniel , Dodge Jennifer , Bruce Dara , Bui Aileen , Bakr Omar , Kim John , Buxbaum James 
Published: June 2024

e15642 Background: Artificial intelligence (AI) assisted colonoscopy may increase adenoma detection rates (ADR) for endoscopists, but its role for trainees in learning endoscopy has not been delineated. This randomized control trial explores the impact of AI on ADR by year of fellowship and anatomical location. Methods: In a registered randomized controlled trial (NCT05423964), gastroenterology fellows were assigned to AI (GI Genius, Medtronic; Minneapolis, MN) vs. conventional colonoscopy(CC). We included all symptomatic or screening colonoscopies with adequate bowel prep by trainees (postgraduate year 4-6). Baseline demographics, polyp pathology, size in 5mm increments, and location, and ADR was collected and compared for AI versus CC arms. A multivariate regression was used to identify factors influencing ADR of the right colon. Results: Of 685 colonoscopies between March 15th to July 28th, 2023, a total of 381 procedures performed by 17 fellows met criteria. Patient characteristics were similar between arms. In the CC arm, there was no difference in ADR among fellow years (1st 39% vs. 2nd 33% vs. 3rd 36%, p = 0.63; Right colon: 1st 31% vs 2nd 21% vs 3rd 30%, P = 0.21). Within 2nd year fellows, there was higher ADR using AI vs. CC for screening colonoscopies (52% vs 17%, p = 0.025). In the right colon, ADR was significantly higher using AI vs. CC for screening alone colonoscopies within 1st and 2nd year fellows (1st 50% vs 13%, p = 0.04; 2nd 57% vs 9%, p < 0.001). 2nd year fellows also increased ADR in the right colon using AI vs CC for symptomatic and screening colonoscopies (44% vs 21%, p = 0.001). There was no difference in procedural time with addition of AI, but a trend to longer withdrawal time. Multivariable logistic regression analysis also showed AI assisted colonoscopies was associated with enhanced ADR in right colon for trainees performing colonoscopy for symptomatic and screening (OR [95%CI]: 2 [1.3-3.3]) and screening alone (OR [95%CI]: 8.3 [2.5-26.6]). Conclusions: This randomized control trial shows AI assisted colonoscopies improve ADR, particularly in the right colon for postgraduate trainees. We propose a use case for AI assisted colonoscopy guiding targeted improvement of ADR in in the right colon which has been highlighted by the American Gastroenterology Association as an area of need. Clinical trial information: NCT05423964 . [Table: see text]
Acute cardiac complications in colorectal cancer compared to other gastrointestinal malignancies: A 10-year retrospective study.
Authors: Olafimihan Ayobami Gbenga , Turk Ekrem , Jackson Inimfon , Bello Jeremiah , Olatunji Gbolahan , Kokori Emmanuel , Aderinto Nicholas , Oh Youjin , Fawehinmi Praise , Mullane Michael Russell 
Published: June 2024

e15652 Background: Patients diagnosed with gastrointestinal (GI) cancers have long-term risks of cardiovascular disease and mortality. However, research comparing patients with colorectal cancer (CRC) to other GI cancers to assess their risk of acute cardiac complications is lacking. We evaluated the risk of hospitalization with acute cardiac complications (acute myocardial infarction [MI], arrhythmias and heart failure [HF]) among patients with CRC versus other GI cancers. Methods: A ten-year retrospective study using the Nationwide Inpatient Sample (NIS) database (2010-2019) was conducted. Using ICD-9 and ICD-10 codes, patients with diagnoses of GI cancers were identified. Multivariate logistic regression analysis was used to evaluate the odds of admission with an acute cardiac complication among patients with a diagnosis of CRC when compared to other GI cancers (esophageal, gastric, intestinal, hepatobiliary, and pancreatic cancers). Results: Among 4,408,321 GI cancer hospitalizations, 82,592 (0.18%) were for acute cardiac complications. Of these, 43.1% were in CRC patients and 56.9% were in those with other GI malignancies (P < 0.001). Multivariate analyses revealed that patients with CRC had more than two-fold higher odds of acute MI compared to other GI cancer patients (Adjusted Odds Ratio (AOR): 2.47; 95% Confidence interval ( CI): 2.30-2.65), 1.8 times higher risk of arrhythmia (AOR: 1.78; 95% CI: 1.69-1.87) and 2.2 times higher risk of HF (AOR: 2.23; 95% CI:2.11-2.36). Overall, in comparison to other GI cancers, CRC patients were twice as likely to be admitted for acute cardiac complications (AOR: 2.09; 95% CI:2.02-2.16). Conclusions: Colorectal cancer patients have significantly higher odds of hospitalizations with acute cardiac complications relative to other GI malignancies. Older age and pre-existing comorbidities of CRC patients are unlikely to sufficiently explain these findings. CRC patients would benefit from active surveillance for cardiac diseases as well as further research on the long-term survival impact of acute cardiac complications on CRC patients. [Table: see text]
Soluble guanylate cyclase activator vericiguat prevents anthracycline-mediated cardiotoxicity and sarcopenia through cGMP-NLRP3-cytokine pathway: Potential application in patients with cancer.
Authors: Iovine Martina , Quagliariello Vincenzo , Giacobbe Ilaria , Barbato Matteo , Giordano Vienna , Arianna Raffaele , Izzo Francesca , Berretta Massimiliano , Inno Alessandro , De Laurentiis Michelino , Maurea Nicola 
Published: June 2024

e24015 Background: Anthracycline-induced cardiomyopathies and sarcopenia are frequently seen in cancer patients, affecting their overall survival and quality of life; therefore, new cardioprotective strategies are needed in cardioncology. Vericiguat is a new oral guanylate cyclase activator that reduces heart failure hospitalizations or cardiovascular death through improvement of smooth muscle cell relaxation and reduction of myocardial fibrosis and inflammation. In this study, we highlight on the potential cardioprotective properties of vericiguat against anthracycline.mediated cardiotoxicity and sarcopenia. Methods: Human cardiomyocytes (AC-16 cells) and Primary Skeletal Muscle Cells (HSkMC cells) were exposed for 24h h to doxorubicin (DOXO) at 0,3 and 1 µM with or withour a pre-treatment with Vericiguat at 0.1 or 1 or 10 µM for 1h. Mithocondrial cell viability, LDH and Citocrome C release were performed to study cytoprotective properties. TUNEL assay, cGMP and NLRP-3, Myd-88 intracellular levels were quantified through colorimetric and selective ELISA methods. IL-1β, IL-6, IL-8, CXCL-2, TGF-β and IL-18 were also analyzed in cardiac and muscle cell lysates after treatments. Results: Vericiguat exerts a significant cytoprotective and anti-apoptotic effect in cardiac and muscle cell lines during exposure to DOXO. A drastic increase in cGMP expression and reduction in NLRP-3, Myd-88 levels were also seen in Vericiguat-DOXO groups vs DOXO groups ( p < 0.001). Pro-inflammatory and cytotoxic cytokines were also downregulated after Vericiguat treatment during DOXO exposure. Conclusions: Vericiguat significantly reduced cardiotoxic effects and sarcopenia induced by DOXO therapy though enhancement of cGMP levels and reduction of NLRP-3/Myd-88/cytokines pathways. These findings provide a framework for future studies aiming to assess vericiguat for the primary prevention of anthracycline-mediated cardiotoxicity and sarcopenia.
Outcomes among hospitalized patients with colorectal cancer and comorbid congestive heart failure: A United States population-based cohort study.
Authors: Syal Arshi , Arya Yajur , Casipit Carlo , Wattanachayakul Phuuwadith , Casipit Bruce Adrian , Eidbo Sarah , Leighton John Charles , Dourado Claudia M. 
Published: June 2024

e24019 Background: Colorectal cancer is one of the leading causes of cancer related deaths in the United States. Advances in chemotherapeutics have improved survival in these patients, although with the potential for more adverse effects. Congestive heart failure continues to be an important comorbidity in patients with colorectal cancer. However, its impact on outcomes in this subgroup needs further exploration. Methods: We utilized the 2020 National Inpatient Sample (NIS) Database in conducting this retrospective cohort study. We identified patients with colorectal cancer and congestive heart failure using appropriate ICD-10 diagnostic codes. We stratified patients with colorectal cancer based on the presence or absence of congestive heart failure. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of < 0.05 was considered statistically significant. The aim of this study was to investigate the impact of congestive heart failure on in-hospital mortality, hospital length of stay (LOS), and total hospitalization charge among hospitalized patients with colorectal cancer. Results: We identified a total of 77130 hospitalized patients with colorectal cancer, of which 10.08% (7755/77130) had comorbid congestive heart failure. The overall in-hospital mortality among patients with colorectal cancer was 2.74% (2115/77130). Among those with comorbid congestive heart failure, the mortality rate was significantly higher at 6.5% (504/7755, p < 0.001). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, congestive heart failure was found to be an independent predictor of increased in-hospital mortality (adjusted OR 1.79; 95% (confidence interval [CI], 1.33-2.41; p < 0.001), longer LOS (coefficient 2.42; CI 1.91-2.92; p < 0.001), and higher total hospitalization charge (coefficient $22464; CI $15132- $29795; p < 0.001). Conclusions: Our analysis demonstrated that congestive heart failure is widely prevalent in patients with colorectal cancer, and significantly worsens outcomes including increased in-hospital mortality, LOS, and cost of healthcare utilization. Early diagnosis and management of heart failure using guideline directed medical therapy along with close follow up may improve outcomes. Further prospective multicentric studies are warranted to better describe these associations.