IDDF2022-ABS-0260 Targeting GUT microbiota to prevent anastomotic tumors and distant metastasis in colorectal cancer surgery
Bibliographic record
Abstract
Background Despite major advances in treatment and early detection, colorectal cancer (CRC) remains a leading cause of mortality worldwide. This is mainly due to cancer recurrence following surgical resection, which is the main CRC treatment. Colorectal resections involve an anastomosis to rejoin the remaining bowel ends to restore gastrointestinal continuity. It has been suggested that poor anastomotic healing and leakage (AL) allows cancer cells to implant at the anastomotic site thereby increasing the risk of local cancer recurrence and metastatic spread. In previous studies, we showed that inulin, a well-known prebiotic improves anastomotic healing by strengthening the gut barrier. Here we further investigated the relationship between the promotion of postoperative intestinal healing using prebiotics and anastomotic cancer local implantation and dissemination. Methods A 10 year’s retrospective review of AL and non-AL cases after CRC surgery was performed. To experimentally assess the effect of poor anastomotic healing on local tumor implantation, we subjected mice to colonic surgery and modulated wound repair by varying the number of sutures. The effect of dietary supplementation with inulin on the occurrence of local anastomotic tumors was assessed in a mouse model inoculated with tumor cells directly in the gut lumen after surgery. Finally, we investigated in mice whether inulin may prevent metastatic spread and growth of tumor cells in the liver by transplanting CRC cells surgically into the spleen. Results Patients experiencing AL (N = 135) displayed significantly lower overall survival and more cancer recurrence and progression compared to non-AL patients (N = 360) (IDDF2022-ABS-0260 Figure 1A Overall and oncological survival after colorectal cancer surgery, IDDF2022-ABS-0260 Figure 1B Overall and oncological survival after colorectal cancer surgery). Poor anastomotic healing in mice led to larger anastomotic tumors and peritoneal cancer dissemination. Inulin supplementation significantly inhibited local tumor implantation and metastatic spread, increased butyrate production, and decreased bacterial translocation. Conclusions AL was associated with worse oncological outcomes in patients and mice. Inulin was shown to reinforce the gut barrier function, decrease the implantation of cancer cells at the anastomosis site, and to prevent tumor dissemination and progression of liver metastasis. Our data suggest that improving anastomotic healing after CRC surgery through gut microbiota modulation not only prevents AL but may additionally inhibit anastomotic cancer recurrence and metastatic spread.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.011 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".