Alterations of gut mycobiota profiles in intrahepatic cholangiocarcinoma

ObjectiveIntrahepatic cholangiocarcinoma (ICC) is a silent liver malignancy with an increasing incidence. Gut mycobiota plays a crucial role in benign liver diseases; however, its correlation with ICC remains elusive. This study aimed to elucidate fungal differences in patients with ICC compared to healthy controls.MethodsThe 40 fecal samples from 23 ICC patients and 17 healthy controls were collected and analyzed using ITS2 rDNA sequencing. Obtaining the OTUs and combining effective grouping, we carried out the biodiversity and composition of the fungi, as well as FUNGuild functional annotation.ResultsOur results revealed the presence of intestinal fungal dysbiosis with significant enrichment of opportunistic pathogenic fungi such as Candida and C. albicans, and significant depletion of the beneficial fungus Saccharomyces cerevisiae in ICC patients compared with healthy controls. Alpha-diversity analysis demonstrated that patients with ICC showed decreased fungal diversity compared to healthy controls. Beta diversity analysis indicated that the two groups exhibited significant segregated clustering. Besides, C. albicans was found to be significantly more abundant in the ICC patients with TNM stage III-IV than those with stage I-II. The FUNGuild functional classification predicted that pathotrophs were the most abundant taxon in the ICC group, well above their abundance in healthy controls.ConclusionThis study indicates that dysbiosis of the fecal mycobiome might be involved in ICC development. Further research into gut fungi may contribute to new therapeutic options for ICC patients

Artificial intelligence for diagnosis and Gleason grading of prostate cancer: The PANDA challenge

Through a community-driven competition, the PANDA challenge provides a curated diverse dataset and a catalog of models for prostate cancer pathology, and represents a blueprint for evaluating AI algorithms in digital pathology. Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge-the largest histopathology competition to date, joined by 1,290 developers-to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted kappa, 95% confidence interval (CI), 0.840-0.884) and 0.868 (95% CI, 0.835-0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.KWF Kankerbestrijding ; Netherlands Organization for Scientific Research (NWO) ; Swedish Research Council European Commission ; Swedish Cancer Society ; Swedish eScience Research Center ; Ake Wiberg Foundation ; Prostatacancerforbundet ; Academy of Finland ; Cancer Foundation Finland ; Google Incorporated ; MICCAI board challenge working group ; Verily Life Sciences ; EIT Health ; Karolinska Institutet ; MICCAI 2020 satellite event team ; ERAPerMe

Table_1_Alterations of gut mycobiota profiles in intrahepatic cholangiocarcinoma.XLSX

ObjectiveIntrahepatic cholangiocarcinoma (ICC) is a silent liver malignancy with an increasing incidence. Gut mycobiota plays a crucial role in benign liver diseases; however, its correlation with ICC remains elusive. This study aimed to elucidate fungal differences in patients with ICC compared to healthy controls.MethodsThe 40 fecal samples from 23 ICC patients and 17 healthy controls were collected and analyzed using ITS2 rDNA sequencing. Obtaining the OTUs and combining effective grouping, we carried out the biodiversity and composition of the fungi, as well as FUNGuild functional annotation.ResultsOur results revealed the presence of intestinal fungal dysbiosis with significant enrichment of opportunistic pathogenic fungi such as Candida and C. albicans, and significant depletion of the beneficial fungus Saccharomyces cerevisiae in ICC patients compared with healthy controls. Alpha-diversity analysis demonstrated that patients with ICC showed decreased fungal diversity compared to healthy controls. Beta diversity analysis indicated that the two groups exhibited significant segregated clustering. Besides, C. albicans was found to be significantly more abundant in the ICC patients with TNM stage III-IV than those with stage I-II. The FUNGuild functional classification predicted that pathotrophs were the most abundant taxon in the ICC group, well above their abundance in healthy controls.ConclusionThis study indicates that dysbiosis of the fecal mycobiome might be involved in ICC development. Further research into gut fungi may contribute to new therapeutic options for ICC patients.</p

The prognostic value of the advanced lung cancer inflammation index in patients with gastrointestinal malignancy

Abstract Background Systemic inflammation is crucial for the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is considered to be a better indicator of systemic inflammation than current biomarkers. However, the prognostic value of the ALI in gastrointestinal neoplasms remains unclear. We performed the first meta-analysis to explore the association between ALI and gastrointestinal oncologic outcomes to help physicians better evaluate the prognosis of those patients. Methods Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by December 29, 2022. Clinical outcomes were overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS). Results A total of 18 articles with 6898 patients were included in this meta-analysis. The pooled results demonstrated that a low ALI was correlated with poor OS (HR = 1.914, 95% CI: 1.514–2.419, P < 0.001), DFS (HR = 1.631, 95% CI: 1.197–2.224, P = 0.002), and PFS (HR = 1.679, 95% CI: 1.073–2.628, P = 0.023) of patients with gastrointestinal cancers. Subgroup analysis revealed that a low ALI was associated with shorter OS (HR = 2.279, 95% CI: 1.769–2.935, P < 0.001) and DFS (HR = 1.631, 95% CI: 1.197–2.224, P = 0.002), and PFS (HR = 1.911, 95% CI: 1.517–2.408, P = 0.002) of patients with colorectal cancer. However, the ALI was not related to CSS in the patients with gastrointestinal malignancy (HR = 1.121, 95% CI: 0.694–1.812, P = 0.640). Sensitivity analysis supported the stability and dependability of the above results. Conclusion The pre-treatment ALI was a useful predictor of prognosis in patients with gastrointestinal cancers

Image2_The correlation between probiotic use and outcomes of cancer patients treated with immune checkpoint inhibitors.TIF

Objective: Immune checkpoint inhibitors (ICIs) have recently demonstrated promising results in improving the prognosis of cancer patients. The goal of this meta-analysis was to determine the impact of probiotic use on the survival of cancer patients treated with ICIs.Methods: Before 3 March 2022, the eligible literature was searched using PubMed, EMBASE, Cochrane Library, Google Scholar, and Clinical trials.gov databases. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were the primary endpoints.Results: A total of 6 studies met the inclusion criteria, and 1,123 patients were included. Meta-analysis showed a trend for probiotic use to prolong PFS (HR: 0.585, 95% CI: 0.328–1.045, p = 0.070) and increase DCR (HR: 1.868, 95% CI: 0.890–3.922, p = 0.099), although it was of borderline statistical significance. We also found that probiotics significantly improved OS (HR: 0.526, 95% CI: 0.341–0.812, p = 0.004) and ORR (OR: 2.831, 95% CI: 1.578–5.076, p Conclusion: Current evidence reveals that probiotics can improve the efficacy of ICI treatment in NSCLC patients.Systematic Review Registeration:https://www.crd.york.ac.uk/prospero/, identifier CRD42022316104.</p

DataSheet1_Effects of PPIs use on clinical outcomes of urothelial cancer patients receiving immune checkpoint inhibitor therapy.docx

Objective: Immune checkpoint inhibitors (ICIs) have recently demonstrated promising performance in improving the prognosis of urological cancer patients. The goal of this meta-analysis was to determine the impact of PPI use on the clinical outcomes of urological cancer patients receiving ICI therapy.Methods: Before 6 May 2022, the eligible literature was searched using PubMed, EMBASE, Cochrane Library, and Google Scholar. The clinical outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).Results: A total of six articles met the inclusion criteria, and of the 1980 patients with advanced or metastatic urothelial cancers (UC) included. The meta-analysis displayed that PPI use could increase the risk of progression by 50.7% (HR: 1.507, 95% CI: 1.327–1.711, p Conclusion: The meta-analysis indicated that concomitant PPI use was significantly associated with low clinical benefit in UC patients.</p