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

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.

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-beta/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.

BACKGROUND:The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. METHODS:Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. RESULTS:Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P <0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P <0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P <0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. CONCLUSIONS:Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.

PURPOSE:This study aimed to compare the oncological and functional outcomes following intersphincteric resection (ISR) with transverse coloplasty pouch (TCP) or straight coloanal anastomosis (SCAA) for low rectal cancer.METHODS:A single-center retrospective analysis was performed on patients with low rectal cancer who received ISR between January 2016 and June 2021. The primary endpoint was to compare the outcomes of bowel function within 1 year, 1 to 2 years, and 2 years after ileostomy closure in patients undergoing two different bowel reconstruction procedures (TCP or SCAA). The postoperative complications and oncological results were also compared between the two groups.RESULTS:A total of 235 patients were enrolled in this study (SCAA group: 166; TCP group: 69). There was no significant difference in complications, including grades A-C anastomotic leakage (9.6% vs 15.9%), 3-year local recurrence rates (6.1% vs 3.9%), disease-free survival (82.4%vs 83.8%), or overall survival (94.1% vs 94.7%) between the two groups. Two years after ileostomy closure, 52.7% of patients in the SCAA group were assessed as having major low anterior resection syndrome (LARS), which was significantly higher than the 25.9% of patients in the TCP group (P = 0.014), but no difference was found prior to 2 years. Similar differences were seen in Wexner scores 2 years after surgery (P = 0.032). Additionally, TCP was an independent protective factor for postoperative bowel function as measured by both the LARS (OR, 0.28; 95% CI, 0.10-0.82; p = 0.020) and Wexner scoring (OR, 0.28; 95% CI, 0.09-0.84; p = 0.023).CONCLUSION:This study suggests that TCP is a safe technique that may decrease bowel dysfunction after ISR for low rectal cancer compared with SCAA 2 years after ileostomy closure.

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.

[文献来源]PIOZZI G N, KHOBRAGADE K, ALIYEV V, et al. International standardization and optimization group for intersphincteric resection (ISOG-ISR): modified Delphi consensus on anatomy, definition, indication, surgical tech-nique, specimen description and functional outcome[J]. Colorectal disease: the official journal of the Association of Coloproctology of Great Britain and Ireland, 2023, 25(9):1896-1909.

Purpose The incidence of early-onset colorectal cancer (EO-CRC), which occurs in people under age 50, has been increasing annually. The aim of this study was to provide an up-to-date estimate of the global EO-CRC burden. Methods We used Global Burden of Disease Study data and methodologies to describe changes in the EO-CRC burden from 1990 to 2019, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs). The driving factors for cancer burden variation were further analyzed using decomposition analysis. Frontier analysis was used to visually demonstrate the potential for burden reduction in each country or region based on their development levels. Results The global EO-CRC incidence more than doubled, increasing from 95,737 (95% uncertainty interval (UI): 90,838-101.042) /100,000 in 1990 to 226,782 (95% UI: 207,495-248,604) /100,000 in 2019. Additionally, related deaths increased from 50,997 (95% UI: 47,692-54,410) /100,000 to 87,014 (95% UI: 80,259-94,339) /100,000, and DALYs increased from 256,1842 (95% UI: 239,4962-2,735,823) /100,000 to 4,297,573 (95% UI: 3,965,485-4,650,790) /100,000. Regarding age-standardized rates, incidence and prevalence increased significantly, while mortality and DALYs rate were basically unchanged. Decomposition analysis showed a significant increase in DALYs in the middle sociodemographic index (SDI) quintile region, in which aging and population growth played a major driving role. Frontier analysis showed that countries or regions with a higher SDI quintile tend to have greater improvement potential. Conclusion The current EO-CRC burden was found to be the greatest in the high-middle SDI quintile region and East Asia, which may need to adjust screening guidelines accordingly and introduce more effective interventions.