Abstract Aim Growing evidence suggests that immune/inflammatory pathways play a crucial role in the persistence of symptoms in diverticular disease (DD). We hypothesize that chronic diverticulitis triggers a self‐sustained inflammatory status which can be detected by measuring the levels of tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). The aim of this study was to investigate the systemic levels of TNF‐α and IL‐6 before and after elective surgery in patients with DD, and their relationship with the gastrointestinal quality of life index (GIQLI) score. Method This prospective multicentric study enrolled patients from the Diverticular Disease Registry (DDR‐Trial, NCT04907383). All adult patients diagnosed with symptomatic uncomplicated diverticular disease (SUDD), uncomplicated recurrent diverticulitis (URD) and smouldering diverticulitis (SmD) between 1st December 2022 and 31st December 2023 were included in this study. Exclusion criteria were as follows: no surgery, a concurrent chronic immunomodulated systemic disease, a SARS‐CoV‐2‐positive test in the previous 12 months, a history of cancer in the previous 5 years, patients treated with immunomodulators, an American Society of Anesthesiologists category of class IV, and complicated acute diverticulitis. Results Seventy‐two patients were included: 52 (72%) with URD, 11 (15%) with SUDD, and nine (13%) with SmD. The median postsurgery – presurgery (Δ)IL‐6 and ΔTNF‐α levels were −16.8 and −17.3 pg/mL, respectively ( p < 0.001 for both; Wilcoxon test). Spearman correlation revealed a significant, negative association between the ΔGIQLI and the ΔIL‐6, as well as the ΔTNF‐α ( p < 0.001 for both). Greater reduction in the levels of IL‐6 and TNF‐α following surgery are associated with higher GIQLI scores postoperatively. Conclusion Patients with chronic diverticulitis may experience persistent systemic inflammation driven by a colonic trigger. Surgical removal of this trigger appears to enhance GIQLI outcomes reducing IL‐6 and TNF‐α across surgery.
Preoperative lateral lymph node features and impact on local recurrence after neoadjuvant chemoradiotherapy and total mesorectal excision for locally advanced rectal cancer: results from a multicentre international cohort study
AbstractAimLocally advanced rectal cancer (LARC) is commonly treated with neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME) to reduce local recurrence (LR) and improve survival. However, LR, particularly associated with lateral lymph node (LLN) involvement, remains a concern. The aim of this study was to investigate preoperative factors associated with LLN involvement and their impact on LR rates in LARC patients undergoing nCRT and curative surgery.MethodThis multicentre retrospective study, including four academic high‐volume institutions, involved 301 consecutive adult LARC patients treated with nCRT and curative surgery between January 2014 and December 2019 who did not undergo lateral lymph node dissection (LLND). Baseline and restaging pelvic MRIs were evaluated for suspicious LLNs based on institutional criteria. Patients were divided into two groups: cLLN+ (positive nodes) and cLLN– (no suspicious nodes). Primary outcome measures were LR and lateral local recurrence (LLR) rates at 3 years.ResultsAmong the cohort, 15.9% had suspicious LLNs on baseline MRI, and 9.3% had abnormal LLNs on restaging MRI. At 3 years, LR and LLR rates were 4.0% and 1.0%, respectively. Ten out of 12 (83.3%) patients with LR showed no suspicious LLNs at the baseline MRI. Abnormal LLNs on MRI were not independent risk factors for LR, distant recurrence or disease‐free survival.ConclusionAbnormal LLNs on baseline and restaging MRI assessment did not impact LR and LLR rates in this cohort of patients with LARC submitted to nCRT and curative TME surgery.
Modest agreement between magnetic resonance and pathological tumor regression after neoadjuvant therapy for rectal cancer in the real world
AbstractMagnetic resonance imaging (MRI) is routinely used for preoperative tumor staging and to assess response to therapy in rectal cancer patients. The aim of our study was to evaluate the accuracy of MRI based restaging after neoadjuvant chemoradiotherapy (CRT) in predicting pathologic response. This multicenter cohort study included adult patients with histologically confirmed locally advanced rectal adenocarcinoma treated with neoadjuvant CRT followed by curative intent elective surgery between January 2014 and December 2019 at four academic high‐volume institutions. Magnetic resonance tumor regression grade (mrTRG) and pathologic tumor regression grade (pTRG) were reviewed and compared for all the patients. The agreement between radiologist and pathologist was assessed with the weighted k test. Risk factors for poor agreement were investigated using logistic regression. A total of 309 patients were included. Modest agreement was found between mrTRG and pTRG when regression was classified according to standard five‐tier systems (k = 0.386). When only two categories were considered for each regression system, (pTRG 0‐3 vs pTRG 4; mrTRG 2‐5 vs mrTRG 1) an accuracy of 78% (95% confidence interval [CI] 0.73‐0.83) was found between radiologic and pathologic assessment with a k value of 0.185. The logistic regression model revealed that “T3 greater than 5 mm extent” was the only variable significantly impacting on disagreement (OR 0.33, 95% CI 0.15‐0.68, P = .0034). Modest agreement exists between mrTRG and pTRG. The chances of appropriate assessment of the regression grade after neoadjuvant CRT appear to be higher in case of a T3 tumor with at least 5 mm extension in the mesorectal fat at the pretreatment MRI.