Robotic intersphincteric resection for low rectal cancer: a cumulative sum analysis for the learning curve.

PURPOSE: This study aimed to assess the learning curve of robot-assisted intersphincteric resection for low rectal cancer. METHODS: We retrospectively analyzed the clinical data of 89 patients who underwent robot-assisted intersphincteric resection. All surgeries were performed by the same group of surgeons at our institution between June 2016 and April 2021. The learning curve was evaluated using a cumulative sum analysis and the best-fit curve. The different stages of the learning curve were compared based on patient characteristics and short-term clinical outcomes to evaluate their impact on clinical efficacy. RESULTS: The minimum number of cases required to overcome the learning curve was 47. The learning curve was divided into the learning improvement and proficiency stages. Significant differences were observed in the operation time and the number of lymph nodes between the two stages (P < 0.05), whereas no significant differences were found in intraoperative blood loss, first postoperative exhaust time, postoperative complications, 3-year progression-free survival, overall survival, and local recurrence-free survival (P > 0.05). CONCLUSION: Robotic-assisted intersphincteric resection for low rectal cancer exhibits a learning curve that can be divided into two stages: namely, learning improvement and proficiency. Achieving proficiency requires a minimum of 47 surgical cases.

Textbook anastomotic success in patients with low rectal cancer treated by intersphincteric resection: reappraising surgical, oncological, and functional outcomes.

Previous studies on successful anastomosis after intersphincteric resection (ISR) for low rectal cancer (LRC) primarily focused on anastomotic complications rather than functional outcomes. Here, we improved the anastomotic success criteria by considering surgical, oncological, and functional outcomes and proposed a new composite outcome, "textbook anastomotic success" (TASS). This retrospective single-center study included patients with LRC treated with ISR from January 2014 to April 2020. TASS was defined as (1) no anastomotic complications occurring after ISR; (2) ileostomy was closed and there was no severe intestinal dysfunction 2 years after ISR; and (3) no local recurrence within 2 years of surgery. TASS was achieved upon meeting all indicators. We analyzed 259 patients with LRC, with 125 (48.3%) achieving TASS. Multivariate analysis showed that male sex (OR 0.47; 95% CI 0.27-0.81; p = 0.007), hypertension (OR 0.48; 95% CI 0.24-0.97; p = 0.041), ASA score ≥ 3 (OR 0.28; 95% CI 0.10-0.81; p = 0.018), pre-treatment major low anterior resection syndrome (OR 0.37; 95% CI 0.15-0.94; p = 0.037), and preoperative neoadjuvant chemoradiotherapy (OR 0.41; 95% CI 0.22-0.77; p = 0.006) were independent risk factors for not achieving TASS. Conversely, transverse coloplasty pouch (OR 2.13; 95% CI 1.07-4.25; p = 0.032) and higher anastomosis level (OR 1.56; 95% CI 1.05-2.30; p = 0.026) were independent protective factors for achieving TASS. The nomogram constructed to evaluate the probability of achieving TASS demonstrated good accuracy in the dataset (area under curve, 0.737). TASS provides a comprehensive quality assessment for ISR in patients with LRC. The nomogram predicting TASS may assist surgeons in decision-making for managing LRC.

Combining proteomics and Phosphoproteomics to investigate radiation-induced rectal fibrosis in rats and the effects of pSTAT3 inhibitor S3I-201 on human intestinal fibroblasts.

OBJECTIVE: To investigate the regulatory mechanisms of radiation-induced rectal fibrosis (RIRF) and assess the therapeutic potential of S3I-201. METHODS: Sprague-Dawley rats were divided into control and radiation groups, with the latter exposed to 20 Gray pelvic X-rays. After 10 weeks, rectal tissues were analyzed using tandem mass tag (TMT) proteomics and phosphoproteomics. Pathway enrichment was performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, with secondary annotation using Cluego. Representative proteins and their phosphorylated counterparts were validated through immunoblotting in another cohort. STAT3 levels in rectal tissues from irradiated and non-irradiated colorectal cancer patients were examined, and the effects of S3I-201 on human rectal fibroblasts were evaluated. RESULTS: The radiation group showed significant inflammatory responses and collagen deposition in the rat rectal walls. Enrichment analysis revealed that radiation-induced proteins and phosphoproteins were primarily involved in extracellular matrix-receptor interaction and the MAPK signaling pathway. Immunoblotting indicated increased expression of p-CAMKII, p-MRACKS, p-Cfl1, p-Myl9, and p-STAT3 in the radiation group compared to the control, while p-AKT1 expression decreased. Elevated phosphorylation of STAT3 was observed in submucosal fibroblasts of the post-radiation human rectum. S3I-201 specifically inhibited STAT3 phosphorylation and suppressed activation of human rectal fibroblasts, also inhibiting the pro-fibrotic effects of the classical TGF-ß/Smad/CTGF pathway. CONCLUSION: By integrating phosphoproteomics and proteomics, this study elucidated the protein regulatory network of RIRF and identified the potential therapeutic targets, including phosphoproteins such as STAT3 in managing RIRF. SIGNIFICANCE: In our research, we employed TMT labeling alongside LC-MS/MS techniques to comprehensively explore the proteomic and phosphoproteomic landscapes in rat models of radiation-induced intestinal fibrosis (RIRF). Our analysis revealed the function and pathways of proteins and phosphorylated proteins triggered by radiation, as well as those with protective roles. We mapped a network of interactions among these proteins and validated key protein expression levels using quantitative methods. Furthermore, we investigated STAT3 as a potential therapeutic target, assessing the efficacy of the inhibitor S3I-201 in laboratory settings, and highlighting its potential for RIRF treatment. Overall, our findings provide groundbreaking insights into the mechanisms underlying RIRF, paving the way for the development of future antifibrotic therapies.

Transanal local excision versus intersphincteric resection for low rectal cancer with stage ypT0-1ycN0 after neoadjuvant chemoradiotherapy: an inverse probability weighting analysis for oncological and functional outcomes.

OBJECTIVES: This study aimed to compare the efficacy of local excision (LE) and intersphincteric resection (ISR) in patients with locally advanced rectal cancer who achieved a significant or complete pathological response following neoadjuvant chemoradiotherapy. METHODS: We performed a retrospective analysis of data from patients with stage ypT0-1ycN0 low rectal cancer after neoadjuvant chemoradiotherapy who underwent LE or ISR between June 2016 and June 2021. Baseline characteristics, short-term outcomes, long-term oncological outcomes, and functional outcomes, were compared between the two groups. To reduce the selection bias, inverse probability of treatment weighting (IPTW) was performed. RESULTS: This study included 106 patients (LE group: n = 51, ISR group: n = 55). There were significant differences in baseline characteristics between the two groups (P < 0.05). After IPTW, there were almost no significant differences in baseline data between the two groups. The LE group showed less postoperative complications and better function outcomes compared to the ISR group. The LE group had significantly lower rates of complications (13.7% vs. 36.4%, P = 0.014). There were no significant differences between the two groups in terms of long-term oncological outcomes. CONCLUSIONS: For patients with locally advanced low rectal cancer achieving significant or complete pathological response after neoadjuvant therapy, both LE and ISR present comparable oncological outcomes. Yet, LE seems to show more advantages in terms of postoperative complications and functional outcomes. These findings offer important insights for surgical decision-making, emphasizing the necessity to consider both oncological and functional outcomes in selecting the optimal surgical approach.