tbuckley/cabot-search huggingface dataset:
Abstract LT10: Recurrent <i>FBXW7</i> Mutations Bypass Wnt/β-catenin Addiction in Cancer
Authors: Zheng Zhong, David Virshup
Journal: Cancer Research (2024)

Abstract Inactivating mutations in RNF43 or gene fusions involving RSPO2/3 are potent activators of ligand-dependent Wnt signaling and drive multiple human cancers. Pharmacologically targeting the biogenesis of Wnt ligands, e.g., with PORCN inhibitors, is being investigated in clinical trials for treating RNF43-mutant/RSPO-fusion cancers. But, the therapeutic response is heterogeneous. Here we show that the tumor suppressor FBXW7 is frequently mutated in RNF43-mutant/RSPO-fusion tumors. Multiple RNF43-mutant/RSPO-fusion cancers harboring FBXW7 mutations show resistance to Wnt pathway blockade, while silencing FBXW7 by truncation or expressing a hotspot mutant in FBXW7-wildtype tumors leads to intrinsic drug resistance. Mechanistically, inactivation of FBXW7, the substrate recognition component of a SCF E3 ubiquitin ligase complex, stabilizes multiple oncoproteins especially Cyclin E and MYC, and antagonizes the cytostatic effect of Wnt inhibitors in these cancers. Moreover, although FBXW7 mutations do not mitigate β-catenin degradation upon Wnt inhibition, FBXW7 mutants instead lose dependence on β-catenin signaling, accompanied by dedifferentiation and loss of lineage specificity. These FBXW7-mutant Wnt/β-catenin-independent tumors are susceptible to multi-CDK inhibition by dinaciclib that targets both cell cycle and transcription. In summary, this study identifies FBXW7 mutations as a mechanism of Wnt independence and drug resistance in RNF43-mutant/RSPO-fusion cancers and reveals the potential of treating these cancers with multi-CDK inhibitors. Citation Format: Zheng Zhong, David Virshup. Recurrent FBXW7 Mutations Bypass Wnt/β-catenin Addiction in Cancer [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr LT10.
Switch of ELF3 and ATF4 transcriptional axis programs the amino acid insufficiency-linked epithelial-to-mesenchymal transition
Authors: Jianxiang Lin, Linjun Hou, Xin Zhao, Jingli Zhong, Yilv Lv, Xiaohua Jiang, Bo Ye, Yunbo Qiao
Journal: Molecular Therapy (2024)
Unique Advantages of Dendrimers‐Structured Mesoporous Silica Nanoparticles over Traditional Hollow Ones in Delivering Bcl2‐Functional Converting Peptide for Multidrug Resistant Cancer Treatment
Authors: Yuehuang Wu, Fangmei Ma, Lixue Yu, Ruimiao Lin, Sijin Lin, Zhihan Guo, Min Zhou, Mingyu Li, Yi Zhang, Jingjing Xie
Journal: Advanced Healthcare Materials (2024)

Abstract Innovative silica nanomaterials have made the significant advancements in curative therapy against cancers with multidrug resistance (MDR). The study on different‐nanostructured mesoporous silica nanoparticles (MSNs) with discrepant pore sizes affecting biomacromolecules in resisting cancer MDR hasn't been reported yet. In this study, a systematic comparison of 6 nm‐pore sized hollow‐structured MSNs (HMSNs) and 10 nm‐pore sized dendrimers‐structured MSNs (LMSNs) for delivering Bcl‐2‐functional converting peptide (N9) or doxorubicin (DOX) to overcome cancer MDR is comprehensively carried out both in in vitro and in vivo resistant tumor models. The results show that both LMSNs and HMSNs exert no significant difference in delivering DOX to treat drug‐resistant cancers. However, compared with N9@HMSNs, N9@LMSNs display the increased loading efficiency, the improved cell‐penetrative capability, the higher cancer cell apoptosis effect, the enhanced tumor accumulation and retention efficiency, and the final elevated tumor inhibition efficiency. Unexpectedly, naked LMSNs without surface modification especially at high dosage produce relatively more serious toxicity than HMSNs whatever in cells, zebrafish embryo or mice models. Collectively, the data provide the sufficient theoretical evidence that LMSNs might be a better choice for delivering biomacromolecules to treat resistant cancers after appropriate surface functionalization such as with PEGylation to weaken its intrinsic toxicity.
Safety and efficacy of salvage endoscopic submucosal dissection for Barrett’s neoplasia recurrence after radiofrequency ablation
Authors: Lauriane Mesureur, Pierre H. Deprez, Raf Bisschops, Roos E. Pouw, Bas L.A.M. Weusten, Maximilien Barret, Pieter Dewint, David Tate, Philippe Leclercq, Stefan Seewald, Federico Barbaro, Francisco Baldaque-Silva, Masami Omae, Mathieu Pioche, Mariana Figueiredo Ferreira, Michael J. Bourke, Rehan Haidry, Christophe Snauwaert, Pierre Eisendrath, Viviane De Maertelaer, Nicolas Rosewick, Jacques Devière, Arnaud Lemmers
Journal: Endoscopy (2024)

Abstract Background This study evaluated the safety and efficacy of salvage endoscopic submucosal dissection (ESD) for Barrett’s neoplasia recurrence after radiofrequency ablation (RFA). Methods Data from patients at 16 centers were collected for a multicenter retrospective study. Patients who underwent at least one RFA treatment for Barrett’s esophagus and thereafter underwent further esophageal ESD for neoplasia recurrence were included. Results Data from 56 patients who underwent salvage ESD between April 2014 and November 2022 were collected. Immediate complications included one muscular tear (1.8%) treated with stent (Agree classification: grade IIIa). Two transmural perforations (3.6%; treated with clips) and five muscular tears (8.9%; two treated with clips) had no clinical impact and were not considered as adverse events. Seven patients (12.5%) developed strictures (grade IIIa), which were treated with balloon dilation. Histological analysis showed 36 adenocarcinoma, 17 high grade dysplasia, and 3 low grade dysplasia. En bloc and R0 resection rates were 89.3% and 66.1%, respectively. Resections were curative in 33 patients (58.9%), and noncurative in 22 patients (39.3%), including 11 “local risk” (19.6%) and 11 “high risk” (19.6%) resections. At the end of follow-up with a median time of 14 (0–75) months after salvage ESD, and with further endoscopic treatment if necessary (RFA, argon plasma coagulation, endoscopic mucosal resection, ESD), neoplasia remission ratio was 37/53 (69.8%) and the median remission time was 13 (1–75) months. Conclusion In expert hands, salvage ESD was a safe and effective treatment for recurrence of Barrett’s neoplasia after RFA treatment.
Clinical outcomes of on-pump versus off-pump coronary-artery bypass surgery: a meta-analysis
Authors: Liaoming He, Xieraili Tiemuerniyazi, Lianxin Chen, Ziang Yang, Shengkang Huang, Yifeng Nan, Yangwu Song, Wei Feng
Journal: International Journal of Surgery (2024)

The ongoing debate regarding off-pump coronary artery bypass grafting (CABG) and on-pump CABG has endured for over three decades. Although numerous randomized controlled trials (RCTs) and meta-analyses have been reported, new evidence has emerged. Therefore, an updated and comprehensive meta-analysis to guide clinical practice is essential.
Development and comprehensive validation of a predictive prognosis model for very early HCC recurrence within one year after curative resection: a multicenter cohort study
Authors: Lei Liu, Shangdong Qin, Kongying Lin, Qingguo Xu, Yuan Yang, Jinzhen Cai, Yongyi Zeng, Shengxian Yuan, Bangde Xiang, Wan Yee Lau, Weiping Zhou
Journal: International Journal of Surgery (2024)

Background: The high incidence of early recurrence after liver resection for hepatocellular carcinoma (HCC) is the main obstacle in achieving good long-term survival outcomes. The aim of the present study is to develop a prognostic model in predicting the risk of very early (1-year) recurrence. Material and Methods: Consecutive patients who underwent liver resection for HCC with curative intent at multi-centers in China were enrolled in this study. The VERM-pre (the Preoperative Very Early Recurrence Model of HCC) with good performance was derived and validated by internal and external cohorts retrospectively and by another two-center cohort prospectively. Results: 7401 patients were enrolled and divided randomly into 3 cohorts. Eight variables (tumor diameter, tumor number, macrovascular invasion, satellite nodule, alpha-fetoprotein, level of HBV-DNA, γ-GT and prothrombin time) were identified as independent risk factors for recurrence-free survival on uni- and multi-variate analyses. The VERM-pre model was developed which showed a high capacity of discrimination (C-index: 0.722; AUROC at 1 year: 0.722)) and was validated comprehensively by the internal, external and prospective cohorts, retrospectively. Calibration plots showed satisfactory fitting of probability of early HCC recurrence in the cohorts. Three risk strata were derived to have significantly different recurrence free survival rates (low-risk: 80.4%-85.4%; intermediate-risk: 59.7%-64.8%; high-risk: 32.6%-42.6%). In the prospective validation cohort, the swimming plot illustrated consistent outcomes with the beginning predictive score. Conclusion: The VERM-pre model accurately predicted the 1-year recurrence rates of HCC after liver resection with curative intent. The model was retrospectively and prospectively validated and then developed as the online tool.
The value of transitory protective stomas during primary debulking surgery for advanced epithelial ovarian cancer-- a retrospective cohort study
Authors: Sha Ni, Jiaqi He, Ling Ouyang
Journal: International Journal of Surgery (2024)

Objectives: Limited data are available on patients with advanced-stage epithelial ovarian cancer (OC) who require ostomy during primary cytoreductive surgery. This study aimed to investigate the application of postoperative and long-term oncological results from transitory protective stoma (TPS) formation during primary debulking surgery (PDS) for OC. Methods: This is a retrospective cohort study with a single center. We identified patients with stage III-IV OC who underwent colon resection and anastomosis. Depending on the methods used after colorectal anastomosis and the outcomes of surgical resection, the patients were stratified into three groups: resection and end-to-end anastomosis, resection and ostomy, or R1 resection. Demographic and clinical data were analyzed. Results: 84 patients underwent colorectal resection during cytoreduction for FIGO stage III-IV OC. Patients undergoing ostomy were more likely to have a longer mean operative time (266 vs. 283 vs. 236 min; P =0.003) and to undergo rectosigmoid resection at the time of cytoreductive surgery (56.0% vs. 22.7%, P =0.007). Their postoperative feeding (7 vs. 1 vs. 3 d, P &lt;0.001) and exhaustion (6 vs. 3 vs. 3, P &lt;0.001) times were similar to those of patients with R1 resection and much earlier than those of patients with intestinal anastomosis. The first normal time (35 d) and half-life (14.68 d) of CA125 after surgery were significantly better in patients with TPS group. The overall incidence of complications was the same, and there was no significant difference in the 30-day readmission rate. The overall quality of life assessment was significantly lower in the R1 resection group. Conclusions: TPSs can accelerate postoperative recovery and the initiation of postoperative chemotherapy, reduce the risk of mortality and disease progression and limit the incidence of complications.
3D auto-segmentation of biliary structure of living liver donors using magnetic resonance cholangiopancreatography for enhanced preoperative planning
Authors: Namkee Oh, Jae-Hun Kim, Jinsoo Rhu, Woo Kyoung Jeong, Gyu-Seong Choi, Jong Man Kim, Jae-Won Joh
Journal: International Journal of Surgery (2024)

Background: This study aimed to develop an automated segmentation system for biliary structures using a deep learning model, based on data from magnetic resonance cholangiopancreatography (MRCP). Materials and methods: Living liver donors who underwent MRCP using the gradient and spin echo technique followed by three-dimensional modeling were eligible for this study. A three-dimensional residual U-Net model was implemented for the deep learning process. Data were divided into training and test sets at a 9:1 ratio. Performance was assessed using the dice similarity coefficient to compare the model’s segmentation with the manually labeled ground truth. Results: The study incorporated 250 cases. There was no difference in the baseline characteristics between the train set ( n =225) and test set ( n =25). The overall mean Dice Similarity Coefficient was 0.80±0.20 between the ground truth and inference result. The qualitative assessment of the model showed relatively high accuracy especially for the common bile duct (88%), common hepatic duct (92%), hilum (96%), right hepatic duct (100%), and left hepatic duct (96%), while the third-order branch of the right hepatic duct (18.2%) showed low accuracy. Conclusion: The developed automated segmentation model for biliary structures, utilizing MRCP data and deep learning techniques, demonstrated robust performance and holds potential for further advancements in automation.
Letter to the Editor: The rise of ChatGPT: exploring its potential in vaccine hesitancy
Authors: Shidong Wang, Yujiao Wu
Journal: International Journal of Surgery (2024)

Dear Editor, A series of successful SARS-CoV-2 vaccines have played a huge role in the efforts to control the COVID-19 pandemic, and saved at least tens of millions of lives. However, during the immunisation procedure for COVID-19, vaccine hesitancy has surfaced, especially in vulnerable populations like patients and pregnant women1. We have read recent articles published by Nazir et al.2 and Suvvari et al.3 in International Journal of Surgery. They note that vaccine hesitancy among pregnant women and infants may be prevalent in respiratory syncytial virus (RSV) vaccinations, and that one of the major reasons for the Measles virus (MeV) outbreak is vaccine hesitancy. It is striking that vaccine hesitancy is such a widespread phenomenon. Recent breakthroughs in artificial intelligence have resulted in the development of highly complex chatbot technologies, particularly ChatGPT, developed by OpenAI, which has garnered a lot of attention. The field of large language models (LLMs) is experiencing rapid development, especially in the field of global health4. Some views suggest that chatGPT has the potential to alleviate vaccine hesitancy by effectively addressing widespread concerns surrounding vaccines, including but not limited to adverse reactions, long-term safety implications, and the duration of vaccine development. By providing individuals with comprehensive information and instructions, chatGPT can effectively dispel doubts and facilitate the formation of informed decisions. However, ChatGPT currently also has certain issues. The most serious problem is that compared to search engines, we are unable to find the source of information for ChatGPT. This means that the accuracy of the answers provided by ChatGPT may be questionable5. Therefore, ChatGPT can serve as a helpful friend providing suggestions, rather than assuming the role of a medical authority in decision-making for the user. Clinicians do not have enough energy or time to educate patients about vaccine-related concerns in clinical practice due to limited medical resources and other factors. ChatGPT can help in this area. This is particularly significant in developing countries, where medical resources may be scarce. ChatGPT provides not just answers to questions, but also provides a portion of emotional value. While there are certain limitations, the LLMs represented by ChatGPT may add a new dimension to the resolution of vaccine apprehension. This study was supported by the Science and Technology Project of Changzhou (Grant No. CJ20239024). Ethical approval Not applicable. Consent Not applicable. Sources of funding Not applicable. Author contribution S.W.: writing; Y.W.: study design. Conflicts of interest disclosure There are no conflicts of interest. Research registration unique identifying number (UIN) Not applicable. Guarantor Yujiao Wu. Data availability statement Not applicable. Provenance and peer review Not commissioned, externally peer-reviewed.
Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study
Authors: Xue-Lei Li, Zhi-Peng Liu, Xing-Xing Su, Yi Gong, Yi-Shi Yang, Xiao-Lin Zhao, Zi-Mu Li, Jun-Jie Ding, Yi Zhu, Da-Long Yin, Chao Yu, Jin-Xue Zhou, Dong Zhang, Rui Ding, Wei Chen, Yao Cheng, Ping Yue, Zi-Ran Wang, Yan-Qi Zhang, Yan Jiang, Xian-Yu Yin, Jie Bai, Hai-Su Dai, Wan Yee Lau, Zhi-Yu Chen
Journal: International Journal of Surgery (2024)

The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients.
The efficacy of extracorporeal shock wave therapy for knee osteoarthritis : an umbrella review
Authors: Peiyuan Tang, Ting Wen, Wenhao Lu, Hongfu Jin, Linyuan Pan, Hengzhen Li, Biyun Zeng, Yang Zhou, Wenfeng Xiao, Yusheng Li
Journal: International Journal of Surgery (2024)

Background: An umbrella review was conducted to compare the effectiveness of extracorporeal shock wave therapy (ESWT) versus non-ESWT in the treatment of knee osteoarthritis (KOA). Materials and methods: Three databases including PubMed, Embase and Web of science were searched up to September 2023. Literature screening, quality evaluation, and data extraction were performed according to inclusion and exclusion criteria. Meta-analysis of outcome indicators was performed using Revman 5.4 software. Results: A total of eight meta-analysis were included in this umbrella review. All meta-analysis were graded against a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and scored between 8 and 11. Compared to the sham group, the ESWT group showed better results in WOMAC (Western Ontario and McMaster Universities Arthritis Index) [mean difference (MD)=−2.94, 95% CI: −5.52, −0.37, P =0.03, I²=60%], Visual Analog Scale (VAS) (MD=−2.0, 95% CI: −2.5, −1.5, P &lt;0.01, I²=0%), range of motion (ROM) (MD=17.55, 95% CI: 13.49, 21.61, P &lt;0.00001, I²=0%), and Lequesne index (MD=−2.85, 95% CI: −3.64, −2.07, P &lt;0.00001, I²=48%). Conclusion: Based on the results of our analysis, ESWT is now an effective therapy for improving pain and function in patients with KOA.
A commentary on “Complex causal association between genetically predicted 731 immunocyte phenotype and osteonecrosis: A bidirectional Two-sample mendelian randomization analysis” (Int J Surg. 2024 Mar 18.)
Authors: Guolin Zhang, Zhen Wang, Yanchun Ding
Journal: International Journal of Surgery (2024)

aDepartment of Cardiology, The Second Hospital of Dalian Medical University, Dalian 116021, Liaoning, China bDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, China Guolin Zhang and Zhen Wang: These authors have contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding Author. Address: Department of Cardiology, The Second Hospital of Dalian Medical University, Dalian 116021, Liaoning, China. E-mail address: [email protected] (Y. Ding). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Colosplenic fistula diagnosis and management: a case series and review of literature
Authors: Oscar Hernandez Dominguez, Eddy P. Lincango, Rebecca Spivak, Federico Almonacid-Cardenas, Christopher Prien, Tairin Uchino, Anna Spivak, Tracy L. Hull, Scott R. Steele, Stefan D. Holubar
Journal: International Journal of Surgery (2024)

Background: A colosplenic fistula (CsF) is an extremely rare complication. Its diagnosis and management remain poorly understood, owing to its infrequent incidence. Our objective was to systematically review the etiology, clinical features, diagnosis, management, and prognosis to help clinicians gain a better understanding of this unusual complication and provide aid if it is to be encountered. Methods: A systematic review of studies reporting CsF diagnosis in Ovid MEDLINE, Ovid EMBASE, Scopus, Web of Science, and Wiley Cochrane Library from 1946 to June 2022. Additionally, a retrospective review of four cases at our institution were included. Cases were evaluated for patient characteristics (age, sex, and comorbidities), CsF characteristics including causes, symptoms at presentation, diagnosis approach, management approach, pathology findings, intraoperative complications, postoperative complications, 30-day mortality, and prognosis were collected. Results: Thirty patients with colosplenic fistulas were analyzed, including four cases at our institution and 26 single-case reports. Most of the patients were male (70%), with a median age of 56 years. The most common etiologies were colonic lymphoma (30%) and colorectal carcinoma (17%). Computed tomography (CT) was commonly used for diagnosis (90%). Approximately 87% of patients underwent a surgical intervention, most commonly segmental resection (81%) of the affected colon and splenectomy (77%). Nineteen patients were initially managed surgically, and twelve patients were initially managed non-operatively. However, eleven of the non-operative patients ultimately required surgery due to unresolved symptoms. The rate of postoperative complications was (17%). Symptoms resolved with surgical intervention in 25 (83%) patients. Only one patient (3%) had had postoperative mortality. Conclusions: Our review of 30 cases worldwide is the largest in literature. Colosplenic fistulas are predominantly complications of neoplastic processes. Colosplenic fistula may be successfully and safely treated with splenectomy and resection of the affected colon, with a low rate of postoperative complications.