Gut microbiota-derived short-chain fatty acids (SCFAs) shape epithelial and immune homeostasis, yet systemic SCFA profiles may diverge from gut microbial composition due to absorption and host metabolism. We quantified fasting serum SCFAs in 36 surgically resected colorectal cancer (CRC) patients and 20 cancer-free controls using targeted high-performance liquid chromatography-triple quadrupole mass spectrometry, and integrated these data with fecal and serum bacterial DNA profiles generated by 16S ribosomal RNA sequencing and functional inference. CRC was associated with a distinct circulating SCFA pattern: total SCFAs and acetate were increased, branched SCFAs were higher, and butyrate and valerate were lower relative to controls. Despite this clear systemic signature, associations between serum SCFAs and the relative abundance (RA) of putative SCFA-producing genera were sparse and inconsistent across CRC and control groups, both when considering fecal producers and serum-detected taxa. Interestingly, the total RA of SCFA-producing genera was higher in controls in feces but higher in CRC in serum, further supporting compartment-specific decoupling. Finally, several circulating SCFAs showed inverse associations with indicators of tumor progression within CRC. These results motivate integrative microbiota-metabolite studies and validation in larger cohorts to clarify how circulating SCFAs relate to gastrointestinal disease biology and immune regulation.
BACKGROUND:Angiogenesis is essential for tumor progression, with vascular endothelial growth factor (VEGF) as a key regulator. A prior single-center study identified VEGF >370 pg/mL on postoperative day 4 (POD4) as a predictor of recurrence in colon cancer (CC). METHODS:We conducted a prospective study including 255 patients undergoing curative-intent CC surgery across seven Spanish institutions (NTC04851054). Serum VEGF was measured via ELISA on POD4. RESULTS:After a median follow-up of 34 months, recurrence occurred in 15.7 % of patients. The previously proposed VEGF cutoff was not validated. No significant differences in VEGF were observed between patients with and without recurrence. However, higher VEGF levels were associated with open surgery (p = 0.013) and postoperative complications (p < 0.001), with a trend in anastomotic leakage (p = 0.062). CONCLUSIONS:VEGF was not predictive of recurrence in this setting but remains a relevant marker of perioperative angiogenic activity, warranting further investigation.
Microbiota could be of interest in the diagnosis of colorectal and non-small cell lung cancer (CRC and NSCLC). However, how the microbial components of tissues and feces reflect each other remains unknown. In this work, our main objective is to discover the degree of correlation between the composition of the tissue microbiota and that of the feces of patients affected by CRC and NSCLC. Specifically, we investigated tumor and non-tumor tissues from 38 recruited patients with CRC and 19 with NSCLC. DNA from samples was submitted for 16S rDNA metagenomic sequencing, followed by data analysis through the QIIME2 pipeline and further statistical processing with STATA IC16. Tumor and non-tumor tissue selected genera were highly correlated in both CRC and NSCLC (100% and 81.25%). Following this, we established tissue-feces correlations, using selected genera from a LEfSe analysis previously published. In CRC, we found a strong correlation between the taxa detected in feces and those from colorectal tissues. However, our data do not demonstrate this correlation in NSCLC. In conclusion, our findings strongly reinforce the utility of fecal microbiota as a non-invasive biomarker for CRC diagnosis, while highlighting critical distinctions for NSCLC. Furthermore, our data demonstrate that the microbiota components of tumor and non-tumor tissues are similar, with only minor differences being detected.
IntroductionThere is increasing evidence demonstrating the relationship between microbiota and colorectal cancer. Several studies have been published analyzing microbiota in tissues and feces from cancer patients; however, there are only a few publications investigating the clinical utility of serum microbiome from colorectal cancer patients. Our aim was to advance in the search for serum biomarkers for the diagnosis of colorectal cancer.MethodsWe conducted a cross-sectional study assessing bacterial DNA and metabolomic profiles in 64 serum samples from subjects affected by colorectal cancer and controls. A metagenomic analysis of the bacterial 16S rRNA gene in serum was established, and serum metabolites were detected through an untargeted metabolic study based on Gas Chromatography-Quadruple Time-Of-Flight Mass Spectrometry with accurate mass.Results and DiscussionAfter integrating the data resulting from the bioinformatics and statistical analyses, we obtained different profiles in colorectal cancer population and controls, regardless of the subjects' age, gender and body mass index. Serum levels of Firmicutes and threonic acid were the most relevant characteristics that could help differentiate both groups, achieving an excellent predictive accuracy in this discovery cohort (area under the ROC curve = 0.95). Although these results should be validated in other cohorts through multicenter studies, we consider that our data could be relevant and applicable to the early diagnosis of colorectal cancer.
The transcystic laparoscopic approach to manage choledocholithiasis using ultrathin flexible choledochoscopes is aimed at reducing complications linked to ERCP and transductal techniques when treating common bile duct stones with gallbladder in situ. Despite their advantages, transcystic techniques are not being widely adopted, highlighting the need for structured protocols, a multidisciplinary approach, and adequate resource allocation to optimize outcomes. This consensus document addresses key issues to standardize the approach, based on the responses to the 25 questions posed to the panel of experts. The recommendations issued, based on the evidence and expert opinion, cover the key factors for the success of the technique, including appropriate patient selection, technical characteristics of the approach, advanced equipment required, etc. This comprehensive guide aims to standardize the technique in order to improve patient outcomes and ensure safe, effective treatment of choledocholithiasis.
BackgroundDNA polymerase theta (POLQ) is a translesion synthesis polymerase essential for the repair of double strand breaks by the error-prone TMEJ (Theta Mediated End Joining) pathway. Although POLQ participates in maintaining genome stability, several studies have shown that its overexpression correlates with cancer progression and poor prognosis. Due to the fact that its role as a biomarker in pancreatic cancer remains unexplored, we aimed to study the usefulness of POLQ H-score as a prognostic factor in a pancreatic cancer patient cohort.MethodsWe evaluated POLQ gene expression using a web-based tool to deliver gene expression profiling and interactive analyses based on TCGA and GTEx (GEPIA) and we examined the POLQ immunostaining in 152 biliopancreatic cancer surgical specimens using tissue microarrays. Association with survival was evaluated by Kaplan Meier curves and uni-multivariate Cox regression.ResultsGEPIA analysis showed statistical differences according to POLQ mRNA levels in Disease Free Survival (DFS) (log rank 0.023, HR 2.8, p=0.029) and Overall Survival (OS) (log rank 0.011, HR 3.1, p=0.016). For immunohistochemistry (IHC) evaluation, POLQ H-score was calculated, and showed statistical differences for OS in Kaplan Meier curves (log rank 0.001) and uni-multivariate analysis (HR 2.27; 95% CI 1.24-4.15, p=0.008).ConclusionsOur results indicate that POLQ is an independent prognostic factor in pancreatic cancer when analyzed by immunostaining, which is in agreement with the results shown by the POLQ gene expression analysis (GEPIA).
Abstract Introduction Colorectal cancer (CRC) growth may be determined by various factors, with gut microbiota being one of them. The aim of this study is to Identify the microbiota differences in tumoral tissue (TT), non-tumoral tissue (NTT) and feces depending on CRC localization. Methods Prospective analysis was conducted on patients with CRC who underwent colorectal surgery in 2021 and 2022. Three samples were collected from each patient: feces, tissue from tumor (TT), and tissue from healthy colon (NTT). The study employed 16S rRNA massive sequencing techniques, followed by bioinformatics analyses. Results A total of 23 patients, comprising 18 males and 5 females, were included in the study. Tumor distribution revealed 12 cases in the right colon, 7 in the left colon, and 4 in the rectum. Significant differences were observed in beta diversity between the microbiota of feces and both types of tissue (TT and NTT). However, no differences in beta diversity were noted between TT and NTT. NTT exhibited a predominance of the phylum Actinobacteriota, while Bacteroidetes was the main phylum in feces. TT was characterized by a higher proportion of Fusobacteriota, with the genera Fusobacteria and Streptococcus being predominant compared to feces and the genus Fusobacteria compared to NTT. When considering tumor location, notable differences emerged. There was greater microbiota diversity in the right colon compared to the left colon and rectum. Phyla Clostridiales, Bifidobacteriales, Acidaminococcales, and Vibrionales were more abundant in the right colon, while Staphylococcales were more prevalent in the left colon. Conclusion The observed variations in microbiota based on tissue type and location imply its potential involvement in colorectal cancer (CRC) pathogenesis.
The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed using the QIIME2 pipeline. We applied logistic regression to adjust for differences attributable to sex, age, and body mass index, and the diagnostic accuracy of our gut signatures was compared with other previously published results. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44), and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminococcaceae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1), were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application of two other published panels to our population. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis.
This work aims to investigate the expression levels of four preselected miRNAs previously linked to Cancer and/or Obesity, with the purpose of finding potential biomarkers in the clinical management of Colorectal Cancer (CRC) developed by obese and non-obese patients. We analyzed samples from a total of 65 subjects, 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were analyzed, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2-∆∆Ct) levels of 4 miRNAs (miR-181a-5p, miR-143-3p, miR-132-3p and miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC serum levels of miR-181a-5p, miR-143-3p and miR-23a-3p correlated with their levels in both SAT and OAT. Moreover, in the case of miR-181a-5p, these correlations were significantly influenced by the body mass index (BMI). From these data, we can conclude that both adiposity and CRC induce changes in the expression of the miRNAs investigated, demonstrating the potential utility of this panel of miRNAs in the diagnosis and prognosis of CRC patients.
This work aims to investigate the expression levels of four preselected miRNAs previously linked to cancer and/or obesity, with the purpose of finding potential biomarkers in the clinical management of CRC developed by patients showing different BMI values. We analyzed samples from a total of 65 subjects: 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were investigated, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2-∆∆Ct) levels of 4 miRNAs (hsa-miR-181a-5p, hsa-miR-143-3p, has-miR-132-3p and hsa-miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC, serum levels of hsa-miR-143-3p clearly correlated with their levels in both SAT and OAT, independently of the BMI group. Moreover, hsa-miR-181a-5p could be considered as a biomarker in CRC patients with BMI ≥ 25 Kg/m2 and emerges as a tumor location marker. We conclude that both adiposity and CRC induce changes in the expression of the miRNAs investigated, and hsa-miR-143-3p and hsa-miR-181a-5p expression analysis could be useful in the clinical management of CRC.
The reported high surgical morbidity and mortality in patients with SARS-CoV-2 prompted preoperative screening and modification of surgical protocols. Although vaccination and treatment of COVID-19 have resulted in lower hospitalization rates and infection severity, publications on postoperative results have not been updated. The aim of the study was to analyze the outcomes of patients undergoing surgery in two periods with high incidence of SARS-CoV-2 infection, before and after vaccination. This is a prospective cohort study of patients undergoing surgery in two periods: March–June 2020 (Group2020) and December 2021–February 2022 (Group2022) (after massive vaccination). In total, 618 patients who underwent surgery were included in the analysis (Group2020: 343 vs. Group2022: 275). Significantly more oncological procedures were performed in Group2020, and there were no differences in postoperative complications. Nosocomial SARS-CoV-2 infection occurred in 4 patients in Group2020 and 1 patient in Group2022. In Group 2022, 70 patients (25.4
Colorectal Cancer (CRC) and Obesity constitute two of the most common malignancies in the western world, and previously have been associated with intestinal microbial composition alterations. Our main aim in this study is to provide molecular data on intestinal microbiota patterns in subjects with CRC, as well as to establish possible associations with their Body Mass Index (BMI). A total of 113 samples from 45 subjects were collected and submitted to metagenomics analysis for gut microbiota. This study was performed by 16S ribosomal RNA bacterial gene amplification and sequencing using the Ion Torrent™ technology. The same dominant phyla were observed in feces and colorectal tissues, although a greater proportion of Fusobacteriota was found in tumor samples. Moreover, at the genus level, LEfSe analysis allowed us to detect a significant increase in Fusobacterium and Streptococcus in colorectal tissues with respect to fecal samples, with a significant preponderance of Fusobacterium in tumor tissues. Also, our data revealed relevant associations between gut microbiota composition and tumor location. When comparing bacterial profiles between right and left colon cancers, those from the left-sided colon showed a significant preponderance, among others, of the order Staphylococcales. Moreover, phyla Firmicutes and Spirochaetota were more abundant in the group of right-sided CRCs and phylum Proteobacteria was increased in rectal cancers. In relation to BMI of patients, we detected significant differences in beta diversity between the normal weight and the obese groups of cases. Microbiota from obese patients was significantly enriched, among others, in Bacteroidales. Therefore, our results are useful in the molecular characterization of CRC in obese and non-obese patients, with a clear impact on the establishment of diagnostic and prognosis of CRC.
To investigate the molecular mechanisms that link obesity and colorectal cancer (CRC), we analyzed parameters related to telomere function in subcutaneous and visceral adipose tissues (SAT and VAT), including subjects with and without CRC, who were classified according to their body mass index (BMI). Adipose tissues were obtained from 147 patients who had undergone surgery. A total of 66 cases corresponded to CRC patients, and 81 subjects were not affected by cancer. Relative telomere length was established by qPCR, and telomerase activity was determined by a method based on the telomeric repeat amplification protocol. Our results indicated longer telomeres in patients affected by CRC, both in SAT and VAT, when compared to the group of subjects without CRC. Tumor local invasion was associated with telomere length (TL) in SAT. Considering the BMI values, significant differences were found in the TL of both adipose tissues between subjects affected by CRC and those without cancer. Overweight subjects showed the greatest differences, with longer telomeres in the group of CRC patients, and a higher number of cases with telomerase reactivation in the VAT of subjects without cancer. In conclusion, parameters related to telomere function in adipose tissue could be considered as potential biomarkers in the evaluation of CRC and obesity.
Hepatic reactive lymphoid hyperplasia (HRLH) is an uncommon lesion. We present the case of a 58-year-old patient with a liver nodule incidentally found by abdominal ultrasonography (US). Liver function, tumor markers, viral serology and immunology were normal. Magnetic resonance imaging (MRI) showed a 16 mm nodule in segment VI-VII, with hypervascular enhancement in the arterial phase, wash-out in late phases, without contrast-retention in the hepatobiliary phase and restriction on diffusion-weighted imaging, suggestive of hepatocellular carcinoma (HCC).
Background: Considering that the risk of colorectal cancer (CRC) development has been related to telomere dysfunction and obesity. However, these parameters have not clearly investigated in relation to the clinical evolution of CRC patients. The aim of this study was to evaluate the impact of obesity and telomere status in the prognosis of patients affected by CRC and submitted to curative surgical treatment.Methods: We performed a prospective study including 162 CRC patients submitted to curative surgical treatment. Subjects were classified according to their Body Mass Index (BMI). Telomere status was established through telomere length and telomerase evaluation. Statistical analyses were performed using the SPSS software package version 22.Results: Patients with shorter telomeres, both in the tumor (median telomere length < 6.5 kb) and their non-tumor paired tissues (median telomere length < 7.1 kb), had the best clinical evolution, independently of the Dukes' stage of cancers (P = 0.025, for tumor samples; P = 0.003, for non-tumor samples).Telomere shortening was inversely associated with BMI in CRC patients. Also, subjects with a BMI > 31.85kg/m2 showed the worse clinical outcomes. Of interest, the impact of BMI showed gender dependence, since only the group of men showed significant differences in CRC prognosis in relation to obesity status (P = 0.037).Conclusions: Telomere length constitutes a useful biomarker to predict prognosis in CRC. Independently of BMI values, the better clinical evolution was associated with shorter telomeres. The impact of BMI seems to be related to other factors such as gender.