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The clinical and pathological responses to multimodal neoadjuvant therapy in locally advanced rectal cancers (LARCs) remain unpredictable, and robust biomarkers are still lacking. Recent studies have shown that tumors present somatic molecular alterations related to better treatment response, and it is also clear that tumor-associated bacteria are modulators of chemotherapy and immunotherapy efficacy, therefore having implications for long-term survivorship and a good potential as the biomarkers of outcome. Here, we performed whole exome sequencing and 16S ribosomal RNA (rRNA) amplicon sequencing from 44 pre-treatment LARC biopsies from Argentinian and Brazilian patients, treated with neoadjuvant chemoradiotherapy or total neoadjuvant treatment, searching for predictive biomarkers of response (responders, n = 17; non-responders, n = 27). In general, the somatic landscape of LARC was not capable to predict a response; however, a significant enrichment in mutational signature SBS5 was observed in non-responders (p = 0.0021), as well as the co-occurrence of APC and FAT4 mutations (p < 0.05). Microbiota studies revealed a similar alpha and beta diversity of bacteria between response groups. Yet, the linear discriminant analysis (LDA) of effect size indicated an enrichment of Hungatella, Flavonifractor, and Methanosphaera (LDA score ≥3) in the pre-treatment biopsies of responders, while non-responders had a higher abundance of Enhydrobacter, Paraprevotella (LDA score ≥3) and Finegoldia (LDA score ≥4). Altogether, the evaluation of these biomarkers in pre-treatment biopsies could eventually predict a neoadjuvant treatment response, while in post-treatment samples, it could help in guiding non-operative treatment strategies.

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PURPOSE: To compare the influence of two metallic implants in the diagnosis of periprosthetic infection using 99m technetium-labeled ceftizoxime. METHODS: Twenty rats were randomly divided into four groups, which received sterile and contaminated titanium and stainless steel implants. After 3 weeks, scintilographic images were obtained using a gamma chamber. Radioactivity counts were obtained for the region of interest (ROI) on the operated and non-operated paws. RESULTS: Groups A, B, and C showed homogenous distribution of the radiopharmaceutical. Hyper uptake was observed in the operated paw from group D. The ROI target count was higher in the two groups with stainless steel implants. Among the control groups, the count was higher in the stainless steel group. Furthermore, among the contaminated groups, the uptake was higher in the stainless steel group, with a significant difference. The target: non-target ratio was significantly lower in the control and contaminated groups with both titanium and stainless steel, but the comparison between control groups and contaminated groups was only significant in the former. The cpm/g observed after a decay of 48h showed statistically significant differences between groups. CONCLUSION: Different biomaterials used in implants have an influence on the results of scintigraphy with 99mTc-CFT.

Assuntos

RESUMO

Abstract Purpose: To compare the influence of two metallic implants in the diagnosis of periprosthetic infection using 99m technetium-labeled ceftizoxime. Methods: Twenty rats were randomly divided into four groups, which received sterile and contaminated titanium and stainless steel implants. After 3 weeks, scintilographic images were obtained using a gamma chamber. Radioactivity counts were obtained for the region of interest (ROI) on the operated and non-operated paws. Results: Groups A, B, and C showed homogenous distribution of the radiopharmaceutical. Hyper uptake was observed in the operated paw from group D. The ROI target count was higher in the two groups with stainless steel implants. Among the control groups, the count was higher in the stainless steel group. Furthermore, among the contaminated groups, the uptake was higher in the stainless steel group, with a significant difference. The target: non-target ratio was significantly lower in the control and contaminated groups with both titanium and stainless steel, but the comparison between control groups and contaminated groups was only significant in the former. The cpm/g observed after a decay of 48h showed statistically significant differences between groups. Conclusion: Different biomaterials used in implants have an influence on the results of scintigraphy with 99mTc-CFT.

Assuntos

RESUMO

Purpose: To compare the influence of two metallic implants in the diagnosis of periprosthetic infection using 99m technetium-labeled ceftizoxime.Methods: Twenty rats were randomly divided into four groups, which received sterile and contaminated titanium and stainless steel implants. After 3 weeks, scintilographic images were obtained using a gamma chamber. Radioactivity counts were obtained for the region of interest (ROI) on the operated and non-operated paws.Results: Groups A, B, and C showed homogenous distribution of the radiopharmaceutical. Hyper uptake was observed in the operated paw from group D. The ROI target count was higher in the two groups with stainless steel implants. Among the control groups, the count was higher in the stainless steel group. Furthermore, among the contaminated groups, the uptake was higher in the stainless steel group, with a significant difference. The target: non-target ratio was significantly lower in the control and contaminated groups with both titanium and stainless steel, but the comparison between control groups and contaminated groups was only significant in the former. The cpm/g observed after a decay of 48h showed statistically significant differences between groups.Conclusion: Different biomaterials used in implants have an influence on the results of scintigraphy with 99mTc-CFT.(AU)

Assuntos

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BACKGROUND: Metal implants are used frequently in orthopedic procedures and the occurrence of subclinical low-virulence infection is difficult to diagnose. The objective of this study was to examine the hypothesis that peri-prosthetic subclinical infections may be diagnosed effectively in a murine model system using scintigraphic imaging with (99m)Tc-labeled ceftizoxime. METHODS: A sample population of 3-mo old Wistar rats (mean weight 327 g) was divided randomly into a control group (n=6), which received sterile implants, and an experimental group (n=6), which received implants contaminated with Staphylococcus aureus strain ATCC6538-P. Animals were anesthetized and femoral titanium implants were fixed beneath muscle tissue in left hind limbs. Three weeks after surgery, animals were injected with (99m)Tc-ceftizoxime solution (62.9 MBq) and scintigraphic images were obtained at 3.5 and 6.5 h after tracer injection. RESULTS: According to the scintigraphic images, the radiopharmaceutical showed affinity for the operated thigh areas of experimental animals but not for those of the control group. There was no difference between the control and experimental groups regarding the amount of radioactivity in the regions of interest measured at 3.5 h after injection of radiolabeled antibiotic, but the between-group difference determined at 6.5 h after treatment was statistically significant (p=0.026). Moreover, the level of radioactivity recorded in resected thigh tissues derived from experimental animals was greater than that of the control group (p=0.035). CONCLUSION: (99m)Tc-ceftizoxime scintigraphy can localize preferentially periprosthetic-infected areas adjacent to metal implants in a murine model. Furthermore, the radiolabeled antibiotic appears to be capable of detecting alterations in the micro-environment close to the implant and of reaching the bacteria attached to the implant surface.

Assuntos