Yun Liu

BACKGROUND: In laparoscopic anterior rectal resection with diverting loop ileostomy, specimen extraction through stoma incision avoids auxiliary incisions and contributes to a more minimally invasive postoperative outcome but enlarges the stoma site. The traditional suture method reduces incision size but creates peristomal incisions that are prone to stomal complications. The authors introduce the “dumpling suture method,” a skin-folding technique that reduces incision size without creating peristomal incisions. OBJECTIVE: This study aimed to assess the efficacy of the dumpling suture method in reducing stoma-related complications in patients undergoing specimen extraction through stoma incision surgery. DESIGN: Single-center, randomized, parallel-group controlled study. SETTINGS: This study was conducted at a tertiary referral center. PATIENTS: Seventy-two patients scheduled for laparoscopic anterior rectal resection surgery with specimen extraction through a stoma incision were enrolled and randomly assigned to the dumpling suture method or traditional suture method group. INTERVENTIONS: The experimental group received ileostomy creation using the dumpling suture method, whereas the control group underwent the traditional suture method. MAIN OUTCOME MEASURES: The primary end point was the rate of stoma-related complications. Secondary end points included peristomal skin lesions, pain scores, and quality-of-life scores. RESULTS: Patients in the dumpling suture method group had a significantly lower overall stomal complication rate compared to those in the traditional suture method group (11.1% vs 41.7%). The dumpling suture method reduced skin-related complications, including fecal dermatitis (8.3% vs 33.3%), skin erosion or infection (0% vs 25%), and mucocutaneous detachment (2.8% vs 13.9%). Peristomal skin infection scores for peristomal skin lesions were lower in the dumpling suture method group, and patients reported less stoma pain and improved quality of life. LIMITATIONS: Limitations include its single-center design and inability to blind participants. CONCLUSIONS: The dumpling suture method uses a skin-folding suture to reduce an enlarged stomal incision, effectively decreasing stoma-related complications. This procedure offers a novel suturing approach for loop ileostomy with enlarged incision, effectively eliminating postoperative incisions and minimizing surgical trauma. See Video Abstract. MÉTODO DE SUTURA CON NUDO VERSUS MÉTODO DE SUTURA TRADICIONAL PARA LA ILEOSTOMÍA EN ASA DESVIADA EN LA RESECCIÓN RECTAL ANTERIOR LAPAROSCÓPICA CON EXTRACCIÓN DE LA MUESTRA A TRAVÉS DE LA INCISIÓN DEL ESTOMA: ENSAYO ALEATORIZADO Y CONTROLADO EN PARALELO: ANTECEDENTES: En la resección rectal anterior laparoscópica con ileostomía en bucle de derivación, la extracción de la muestra a través de la incisión del estoma evita incisiones auxiliares y contribuye a un resultado postoperatorio menos invasivo, pero aumenta el tamaño del estoma. El método de sutura tradicional reduce el tamaño de la incisión, pero crea incisiones periestomales, propensas a complicaciones estomales. Presentamos el «método de sutura Dumpling», que utiliza una técnica de pliegue cutáneo para reducir el tamaño de la incisión sin crear incisiones peristomales. OBJETIVO: El objetivo de este estudio fue evaluar la eficacia del método de sutura Dumpling para reducir las complicaciones relacionadas con el estoma en pacientes sometidos a cirugía de extracción de muestras a través de la incisión del estoma. DISEÑO: Estudio controlado, aleatorizado, de grupos paralelos, realizado en un único centro. ENTORNO: Este estudio se llevó a cabo en un centro de referencia terciario. PACIENTES: Se inscribieron 72 pacientes programados para una cirugía de resección rectal anterior laparoscópica con extracción de muestras a través de una incisión estomal, que fueron asignados aleatoriamente al grupo del método de sutura Dumpling o al grupo del método de sutura tradicional. INTERVENCIONES: El grupo experimental se sometió a una ileostomía mediante el método de sutura Dumpling, mientras que el grupo de control se sometió al método de sutura tradicional. PRINCIPALES MEDIDAS DE RESULTADO: El criterio de valoración principal fue la tasa de complicaciones relacionadas con el estoma. Los criterios de valoración secundarios incluyeron lesiones cutáneas peristomales, puntuaciones de dolor y puntuaciones de calidad de vida. RESULTADOS: El grupo del método de sutura tipo dumpling tuvo una tasa global de complicaciones estomales significativamente menor en comparación con el método de sutura tradicional (11,1 % frente a 41,7 %). El método de sutura tipo dumpling redujo las complicaciones relacionadas con la piel, incluyendo la dermatitis fecal (8,3 % frente a 33,3 %), la erosión o infección de la piel (0 % frente a 25 %) y el desprendimiento mucocutáneo (2,8 % frente a 13,9 %). Las puntuaciones de infección cutánea peristomal para las lesiones cutáneas peristomales fueron más bajas en el grupo del método de sutura tipo dumpling, y los pacientes informaron de menos dolor en el estoma y una mejor calidad de vida. LIMITACIONES: Las limitaciones incluyen su diseño unicéntrico y la imposibilidad de cegar a los participantes. CONCLUSIONES: La técnica del método de sutura tipo dumpling emplea una sutura con pliegues cutáneos para reducir la incisión estomal agrandada, lo que disminuye eficazmente las complicaciones relacionadas con el estoma. Este procedimiento ofrece un nuevo enfoque de sutura para la ileostomía en bucle con incisión agrandada, lo que elimina eficazmente las incisiones postoperatorias y minimiza el trauma quirúrgico. (AI-generated translation )

Hyperactivation of the YAP/TEAD transcriptional complex in cancers facilitates the development of an immunosuppressive tumor microenvironment. Herein, we observed that the transcription factor SP1 physically interacts with and stabilizes the YAP/TEAD complex at regulatory genomic loci in colorectal cancer (CRC). In response to serum stimulation, PKCζ (protein kinase C ζ) was found to phosphorylate SP1 and enhance its interaction with TEAD4. As a result, SP1 enhanced the transcriptional activity of YAP/TEAD and coregulated the expression of a group of YAP/TEAD target genes. The immune checkpoint V-domain Ig suppressor of T-cell activation (VISTA) was identified as a direct target of the SP1-YAP/TEAD4 complex and found to be widely expressed in CRC cells. Importantly, YAP-induced VISTA upregulation in human CRC cells was found to strongly suppress the antitumor function of CD8⁺ T cells. Consistently, elevated VISTA expression was found to be correlated with hyperactivation of the SP1-YAP/TEAD axis and associated with poor prognosis of CRC patients. In addition, we found by serendipity that enzymatic deglycosylation significantly improved the anti-VISTA antibody signal intensity, resulting in more accurate detection of VISTA in clinical tumor samples. Overall, our study identified SP1 as a positive modulator of YAP/TEAD for the transcriptional regulation of VISTA and developed a protein deglycosylation strategy to better detect VISTA expression in clinical samples. These findings revealed a new tumor cell-intrinsic mechanism of YAP/TAZ-mediated cancer immune evasion.

Objective: The plastic role of regulatory factor X1 (RFX1) in colon cancer progression and its impact on the tumor microenvironment remain poorly understood. The study aimed to clarify the molecular and clinical role of RFX1 in colon cancer. Methods: We classified colon cancers into subgroups with high and low RFX1 expression and characterized their immune profiles, mutational profiles, cancer immunotherapy and drug sensitivity. By combining RFX1 expression with persistent tumor mutational burden, we proposed a novel nomogram clinical prediction model and validated its predictive performance, and the correlation between high expression and poor prognosis. Results: Compared to tumor mutational burden (TMB), persistent tumor mutational burden (pTMB) is an independent predictor of prognosis in patients with colon cancer. The predictive efficacy of the combination of RFX1 expression and pTMB was superior to and sensitive than the combination of RFX1 expression with TMB. Among them, patients in the RFX1high/pTMBhigh subgroup had the worst quality of survival and prognosis, whereas those in the RFX1low/pTMBlow subgroup had a relatively better prognosis (p < 0.0001). Univariate Cox regression revealed a significant association between high RFX1 expression and increased risk in colon cancer patients (Hazard Ratio [HR] = 1.58, 95% Confidence Interval [CI]: 1.10–2.25, p = 0.012), which remained independently predictive in multivariate analysis after covariate adjustment (HR = 1.52, 95% CI: 1.04–2.22, p = 0.031). Conclusion: A nomogram model based on RFX1 combined with pTMB provides an alternative approach for the diagnosis and treatment of colon cancer.

Background: Nudix Hydrolase 21 (NUDT21) is crucial for the regulation of alternative polyadenylation, with its reduced expression frequently resulting in a shortened mRNA 3′ untranslated region (UTR), thereby enhancing the protein levels of downstream genes. Although NUDT21 is widely recognized for its tumor-suppressive function in various cancers, its involvement in colorectal cancer (CRC) remains poorly understood. Methods: The expression of NUDT21 in CRC and adjacent normal tissues was analyzed through qPCR, Western blot, and immunohistochemistry (IHC). Additionally, we investigated the correlation between NUDT21 expression and patient prognosis. With Cell Counting Kit-8 assay and Transwell assay, we detected the exact role of NUDT21 in the development and progress of CRC. We used RNA-Seq analysis to explore the downstream target gene of NUDT21. Meanwhile, DaPars analysis revealed the Hippo pathway as a critical pathway in CRC progress. Western blotting and luciferase assays were used to investigate the specific mechanisms by which NUDT21 regulates the Hippo pathway. In addition, the interaction between NUDT21 and TAZ was confirmed by co-immunoprecipitation and the correlation between the two expressions was verified by IHC. Results: In CRC, elevated NUDT21 expression has been identified as a predictor of poor prognosis, as well as a promoter of CRC cell proliferation and migration. Combined with RNA-seq and DaPars analyses, we identified the Hippo pathway as an important downstream target of NUDT21 in CRC. NUDT21 knockdown significantly downregulated the YAP, TAZ, and TEAD1 protein levels. Mechanistically, shortening of the 3′UTR of TAZ by NUDT21 knockdown suppressed TAZ protein expression. A positive correlation was observed between NUDT21 and TAZ proteins in CRC. Conclusion: NUDT21 plays a pro-tumorigenic role in CRC by upregulating TAZ protein expression, revealing a new regulatory mechanism of the Hippo pathway and providing insight into the biological effect of mRNA 3′UTR shortening.

Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the predominant serum tumour markers (STMs) for predicting the prognosis of colorectal cancer (CRC). The objective of this research is to develop clinical prediction models based on preoperative and postoperative CEA and CA19-9 levels.Methods: 1,452 consecutive participants with stage I-III colorectal cancer were included. Kaplan-Meier method, log-rank test, and multivariate COX regression were used to evaluate the significance of preoperative and postoperative STMs. Patients were grouped into a discovery cohort (70%) and a validation cohort (30%). Variables for the nomograms were selected according to the Akaike information criterion (AIC). Subsequently, two clinical predictive models were constructed, evaluated, validated, and then compared with the AJCC 8th TNM stage.Results: The overall survival (OS) rate and disease-free survival(DFS) rate declined progressively as the number of positive tumour markers(NPTMs) before and after surgery increased. For both OS and DFS, age, sex, pN stage, and NPTMs before and after surgery were independent prognostic factors, and then clinical prediction models were developed. The Concordance index (C-index), Receiver operating characteristic (ROC) curve, calibration curve, Decision curve analysis (DCA), and risk score stratification all indicated that the models possessed robust predictive efficacy and clinical applicability. The Net reclassification index (NRI) and Integrated discrimination improvement (IDI) indicated that the performance of models was significantly superior to the TNM stage.Conclusion: Nomograms based on pre-and postoperative CEA and CA19-9 can accurately predict survival and recurrence for stage I-III CRC patients after radical surgery, and were significantly better than the AJCC 8th TNM stage.

The role of processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P-body-related genes SAMD4A, AJUBA, and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P-body formation in colorectal cancer (CRC) cells. By reexpression of PNRC1 or knockdown of P-body core genes (DDX6, DCP1A, and LSM14A), we determined that disruption of P-bodies attenuates cell proliferation, cell migration, and tumor growth induced by overexpression of YAP^5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed co-dependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1, and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.

The role of Processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P- body-related genes SAMD4A, AJUBA, and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P- body formation in CRC cells. By reexpression of PNRC1 or knockdown of P-body core genes (DDX6, DCP1A, and LSM14A), we determined that disruption of P-bodies attenuates cell proliferation, cell migration and tumor growth induced by overexpression of YAP5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed codependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1 and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.

We aimed to develop a clinical predictive model for predicting the overall survival (OS) in stage I–III CRC patients after radical resection with normal preoperative CEA. This study included 1082 consecutive patients. They were further divided into a training set (70%) and a validation set (30%). The selection of variables for the model was informed by the Akaike information criterion. After that, the clinical predictive model was constructed, evaluated, and validated. The net reclassification index (NRI) and integrated discrimination improvement (IDI) were employed to compare the models. Age, histologic type, pT stage, pN stage, carbohydrate antigen 242 (CA242), and carbohydrate antigen 125 (CA125) were selected to establish a clinical prediction model for OS. The concordance index (C-index) (0.748 for the training set and 0.702 for the validation set) indicated that the nomogram had good discrimination ability. The decision curve analysis highlighted that the model has superior efficiency in clinical decision-making. NRI and IDI showed that the established nomogram markedly outperformed the TNM stage. The new clinical prediction model was notably superior to the AJCC 8th TNM stage, and it can be used to accurately assess the OS of stage I–III CRC patients undergoing radical resection with normal preoperative CEA.

With the emergence of novel variants, there have been widespread COVID-19 infections in the Chinese mainland recently. Compared to ancestral COVID-19 variants, Omicron variants become more infectious, but less virulent. Previous studies have recommended postponing non-emergency surgery for at least 4–8 weeks after COVID-19 infection. However, delayed surgery has been shown to be associated with tumor progression and worse overall survival for cancer patients. Here, we examined surgery risk and optimal timing for colorectal cancer patients with perioperative COVID-19 infection. A total of 211 patients who underwent colorectal cancer surgery from 1 October 2022 to 20 January 2023 at Xinhua Hospital were included. In addition, COVID-19-infected patients were further categorized into three groups based on infected time (early post-COVID-19 group, late post-COVID-19 group and postoperative COVID-19 group). The complication rate in patients with COVID-19 infection was 26.3%, which was significantly higher than in control patients (8.4%). The most common complications in COVID-19-infected patients were pneumonia, ileus and sepsis. Patients who underwent surgery close to the time of infection had increased surgery risks, whereas surgery performed over 1 week after recovery from COVID-19 did not increase the risk of postoperative complications. In conclusion, surgery performed during or near the time of COVID-19 infection is associated with an increased risk of developing postoperative complications. We recommend that the safe period for patients with recent COVID-19 infection in colorectal cancer surgery be at least 1 week after recovery from COVID-19.

Background: Microsatellite stable (MSS) colorectal cancer (CRC) has been referred to as the “cold tumor” because of almost no response to anti–programmed death-1 (PD-1) antibody. A recent REGONIVO trial showed that regorafenib plus nivolumab had an encouraging efficacy in MSS metastatic CRC (mCRC). However, only a small subset of patients may benefit from the combination therapy. We aim to evaluate the efficacy and safety data of immune checkpoint inhibitors combined with regorafenib in refractory MSS mCRC and to discover biomarkers that can effectively stratify the beneficial patient population.Methods: We retrospectively analyzed patients with MSS mCRC who received regorafenib combined with anti–PD-1 antibody therapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and status of gene mutation were reviewed and evaluated.Results: Twenty-one patients received combination treatment. At a median treatment duration of 4 months, one patient achieved complete response, three patients achieved partial response, and two patients achieved stable disease as the best response. The ORR and DCR were 19% and 28.5% in the overall population, respectively. The median PFS was 4 months, and the median OS was 25 months. Only erbb2 receptor tyrosine kinase 2/erbb3 receptor tyrosine kinase 3 (ERBB2/ERBB3) mutation status was confirmed to be a potential predictive factor for effective treatment. In patients with ERBB2/ERBB3 mutation, ORR, DCR, and PFS exhibited significant improvements in comparison with that in wild-type patients. Grade 3 or higher treatment-related adverse events occurred in three patients (14.3%).Conclusions: Regorafenib in combination with PD-1 inhibitor provides a feasible treatment regimen for refractory MSS mCRC with tolerated toxicity. Patients with ERBB2/ERBB3 mutation may be the preferred population for this combination regimen.