Feasibility, Indications, and Prognostic Significance of Selective Lateral Pelvic Lymph Node Dissection After Preoperative Chemoradiotherapy in Middle/Low Rectal Cancer: Results of a Multicenter Lateral Node Study in China.

BACKGROUND: Lateral pelvic lymph node dissection after preoperative chemoradiotherapy can decrease local recurrence to lateral compartments, thereby providing survival benefits. OBJECTIVE: The safety of lateral pelvic lymph node dissection after preoperative chemoradiotherapy was investigated, and the surgical indications and survival benefits of lateral pelvic lymph node dissection were established on the basis of preoperative characteristics. DESIGN: A multicenter retrospective study. SETTINGS: Three hospitals in China. PATIENTS: Four hundred nine patients with clinical evidence of lateral pelvic lymph node metastasis. INTERVENTIONS: Patients who received lateral pelvic lymph node dissection were divided into 2 groups depending on whether they received chemoradiotherapy (n = 139) or not (n = 270). MAIN OUTCOME MEASURES: The safety, indications, and survival benefits of lateral pelvic lymph node dissection after preoperative chemoradiotherapy were investigated. RESULTS: The surgery times were significantly prolonged by preoperative chemoradiotherapy (291.3 vs 265.5 min; p = 0.021). Multivariate analysis demonstrated that poor/mucinous/signet-ring adenocarcinoma (OR = 4.42, 95% CI, 2.24-11.27; p = 0.031) and postchemoradiotherapy lateral pelvic lymph node short-axis diameter ≥7 mm (OR = 15.2, 95% CI, 5.89-53.01; p < 0.001) were independent predictive factors for lateral pelvic lymph node metastasis. Multivariate prognostic analysis showed that swollen lateral pelvic lymph nodes beyond the obturator or internal iliac as well as the involvement of 3 or more lateral pelvic lymph nodes were independent adverse prognostic factors. LIMITATIONS: The retrospective nature of the study and the small sample size were the limitations of this study. CONCLUSIONS: Preoperative chemoradiotherapy combined with lateral pelvic lymph node dissection is a practicable procedure with acceptable morbidity. Postchemoradiotherapy lateral pelvic lymph node short-axis diameter ≥7 mm and poor/signet/mucinous adenocarcinoma could be used for predicting lateral pelvic lymph node metastasis after chemoradiotherapy. However, lateral pelvic lymph node dissection should be carefully considered in patients with swollen lateral pelvic lymph nodes beyond the obturator or internal iliac region or involvement of multiple lateral pelvic lymph nodes. See Video Abstract at http://links.lww.com/DCR/C133 . VIABILIDAD, INDICACIONES E IMPORTANCIA PRONSTICA DE LA DISECCIN SELECTIVA DE GANGLIOS LINFTICOS PLVICOS LATERALES DESPUS DE QUIMIORRADIOTERAPIA PREOPERATORIA EN CNCER DE RECTO MEDIO/INFERIOR RESULTADOS DE UN ESTUDIO MULTICNTRICO DE GANGLIOS LATERALES EN CHINA: ANTECEDENTES:La disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria puede disminuir la recurrencia local en los compartimentos laterales, lo que brinda beneficios de supervivencia.OBJETIVO:Se investigó la seguridad de la disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria, y se establecieron las indicaciones quirúrgicas y los beneficios de supervivencia de la disección de los ganglios linfáticos pélvicos laterales en función de las características preoperatorias.DISEÑO:Estudio retrospectivo multicéntrico.ESCENARIO:Tres hospitales en China.PACIENTES:Cuatrocientos nueve pacientes con evidencia clínica de metástasis en los ganglios linfáticos pélvicos laterales.INTERVENCIONES:Los pacientes que recibieron disección de ganglios linfáticos pélvicos laterales se dividieron en dos grupos dependiendo de si recibieron quimiorradioterapia (n = 139) o no (n = 270).PRINCIPALES MEDIDAS DE RESULTADO:Se investigaron la seguridad, las indicaciones y los beneficios de supervivencia de la disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria.RESULTADOS:Los tiempos de cirugía se prolongaron significativamente con la quimiorradioterapia preoperatoria (291,3 vs 265,5 min, p = 0,021). El análisis multivariable demostró que el adenocarcinoma mal diferenciado/mucinoso/en anillo de sello (odds ratio = 4,42, intervalo de confianza del 95%, 2,24-11,27; p = 0,031) y el diámetro del eje corto de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia ≥7 mm (odds ratio = 15,2, intervalo de confianza del 95%, 5,89-53,01; p < 0,001) fueron factores predictivos independientes de metástasis en los ganglios linfáticos pélvicos laterales. El análisis pronóstico multivariable mostró que la inflamación de los ganglios linfáticos pélvicos laterales más allá del obturador o la ilíaca interna, así como la afectación de tres o más ganglios linfáticos pélvicos laterales, eran factores pronósticos adversos independientes.LIMITACIONES:La naturaleza retrospectiva del estudio y el pequeño tamaño de la muestra.CONCLUSIONES:La quimiorradioterapia preoperatoria combinada con la disección de los ganglios linfáticos pélvicos laterales es un procedimiento practicable con una morbilidad aceptable. Posterior a la quimiorradioterapia, el diámetro del eje corto de los ganglios linfáticos pélvicos laterales ≥7 mm y el adenocarcinoma pobre/en sello/mucinoso podrían usarse para predecir la metástasis en los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia. Sin embargo, la disección de los ganglios linfáticos pélvicos laterales debe considerarse cuidadosamente en pacientes con ganglios linfáticos pélvicos laterales inflamados más allá del obturador o de la región ilíaca interna o compromiso de múltiples ganglios linfáticos pélvicos laterales. Consulte Video Resumen en http://links.lww.com/DCR/C133 . (Traducción-Dr. Felipe Bellolio ).

Long-course chemoradiation plus concurrent/sequential PD-1 blockade as neoadjuvant treatment for MMR-status-unscreened locally advanced rectal cancer: protocol of a multicentre, phase 2, randomised controlled trial (the POLAR-STAR trial).

INTRODUCTION: Recent preclinical studies have discovered unique synergism between radiotherapy and immune checkpoint inhibitors, which has already brought significant survival benefit in lung cancer. In locally advanced rectal cancer (LARC), neoadjuvant radiotherapy plus immune checkpoint inhibitors have also achieved surprisingly high pathological complete response (pCR) rates even in proficient mismatch-repair patients. As existing researches are all phase 2, single-cohort trials, we aim to conduct a randomised, controlled trial to further clarify the efficacy and safety of this novel combination therapy. METHODS AND ANALYSIS: Eligible patients with LARC are randomised to three arms (two experiment arms, one control arm). Patients in all arms receive long-course radiotherapy plus concurrent capecitabine as neoadjuvant therapy, as well as radical surgery. Distinguishingly, patients in arm 1 also receive anti-PD-1 (Programmed Death 1) treatment starting at Day 8 of radiation (concurrent plan), and patients in arm 2 receive anti-PD-1 treatment starting 2 weeks after completion of radiation (sequential plan). Tislelizumab (anti-PD-1) is scheduled to be administered at 200 mg each time for three consecutive times, with 3-week intervals. Randomisation is stratified by different participating centres, with a block size of 6. The primary endpoint is pCR rate, and secondary endpoints include neoadjuvant-treatment-related adverse event rate, as well as disease-free and overall survival rates at 2, 3 and 5 years postoperation. Data will be analysed with an intention-to-treat approach. ETHICS AND DISSEMINATION: This protocol has been approved by the institutional ethical committee of Beijing Friendship Hospital (the primary centre) with an identifying serial number of 2022-P2-050-01. Before publication to peer-reviewed journals, data of this research will be stored in a specially developed clinical trial database. TRIAL REGISTRATION NUMBER: NCT05245474.

Inhibition of neuroactive ligand-receptor interaction pathway can enhance immunotherapy response in colon cancer: an in silico study.

BACKGROUND: The potential mechanism underlying the association between Homologous recombination deficiency (HRD) and immunotherapy in colon cancer has not been investigated. METHODS: The exon sequencing data and transcriptome data of 456 colon adenocarcinoma (COAD) patients were obtained from the TCGA database. Pathway activity score was calculated by GSVA methods and engaged in further survival analysis. The prognostic value of the candidate pathways was validated in an external GEO cohort and an immunotherapy cohort. RESULTS: Patients with high HRD were associated with poor prognosis, lower tumor mutation burden and microsatellite instability, higher fraction genome alteration, and less sensitivity to immunotherapy in COAD. And then, the neuroactive ligand-receptor interaction pathway was over-activated in high-HRD tumors and associated with immunosuppression in colon cancer with high HRD. Besides, the pathway was associated with prognosis and immunotherapy response in COAD. Moreover, genes in this pathway such as LTB4R2 can be used as a novel target for therapy development in colon cancer. CONCLUSION: Our study not only revealed the potential mechanism of HRD and the function of the neuroactive ligand-receptor interaction pathway in colon cancer but also provided new clues for the improvement of immunotherapy response in colon cancer.

A Prospective Long-Term Follow-Up Study: The Application of Circulating Tumor Cells Analysis to Guide Adjuvant Therapy in Stage II Colorectal Cancer.

BACKGROUND: The efficacy of circulating tumor cells (CTCs) in the selection of stage II colorectal cancer (CRC) patients for adjuvant chemotherapy remains inconclusive. OBJECTIVE: The aim of this study was to validate the necessity of adjuvant chemotherapy for stage II CRC patients with positive postoperative CTCs. METHODS: The clinicopathological features and overall survival (OS) of a cohort of 70 patients with confirmed CRC were collected and analyzed. RESULTS: The total rate of positive CTCs was 55.7%, while the average OS was 70.8 months and the OS rate was 75.7% (53/70). These 70 patients were divided into four subgroups, including a CTC-negative group with non-adjuvant chemotherapy (CHEMO-/CTC-) versus a CTC-positive group with non-adjuvant chemotherapy (CHEMO-/CTC+), CHEMO+/CTC- versus CHEMO+/CTC+, CHEMO-/CTC- versus CHEMO+/CTC-, and CHEMO+/CTC+ versus CHEMO-/CTC+; the total numbers in each subgroup were 25 versus 32, 6 versus 7, 25 versus 6, and 7 versus 32, respectively. The average OS of the CHEMO-/CTC- and CHEMO-/CTC+ groups was 82.0 and 68.1 months, respectively (p = 0.020); the average OS of the CHEMO+/CTC- and CHEMO+/CTC+ groups was 83.6 months and 76.4 months, respectively (p = 0.963); the average OS of the CHEMO-/CTC- and CHEMO+/CTC- groups was 82.0 months and 83.6 months, respectively (p = 0.999); and the average OS of the CHEMO+/CTC+ and CHEMO-/CTC+ groups was 76.4 months and 68.1 months, respectively (p = 0.247). CONCLUSIONS: Positive CTCs are a potential prognostic marker for stage II CRC.

BRCA genes as candidates for colorectal cancer genetic testing panel: systematic review and meta-analysis.

BACKGROUND: Breast cancer susceptibility gene (BRCA) mutation carriers are at an increased risk for breast, ovarian, prostate and pancreatic cancers. However, the role of BRCA is unclear in colorectal cancer; the results regarding the association between BRCA gene mutations and colorectal cancer risk are inconsistent and even controversial. This study aimed to investigate whether BRCA1 and BRCA2 gene mutations are associated with colorectal cancer risk. METHODS: In this systematic review, we searched PubMed/MEDLINE, Embase and Cochrane Library databases, adhering to PRISMA guidelines. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Unadjusted odds ratios (ORs) were used to estimate the probability of Breast Cancer Type 1 Susceptibility gene (BRCA1) and Breast Cancer Type 2 Susceptibility gene (BRCA2) mutations in colorectal cancer patients. The associations were evaluated using fixed effect models. RESULTS: Fourteen studies were included in the systematic review. Twelve studies, including seven case-control and five cohort studies, were included in the meta-analysis. A significant increase in the frequency of BRCA1 and BRCA2 mutations was observed in patients with colorectal cancer [OR = 1.34, 95% confidence interval (CI) = 1.02-1.76, P = 0.04]. In subgroup analysis, colorectal cancer patients had an increased odds of BRCA1 (OR = 1.48, 95% CI = 1.10-2.01, P = 0.01) and BRCA2 (OR = 1.56, 95% CI = 1.06-2.30, P = 0.02) mutations. CONCLUSIONS: BRCA genes are one of the genes that may increase the risk of developing colorectal cancer. Thus, BRCA genes could be potential candidates that may be included in the colorectal cancer genetic testing panel.

Sarcobesity, but not visceral fat, is an independent risk factor for complications after radical resection of colorectal cancer.

Background: The influence of body composition on the outcome of colorectal cancer surgery is controversial. The aim of this study was to evaluate the effects of visceral obesity and sarcobesity on the incidence of total and surgical complications after radical resection of colorectal cancer. Methods: We collected a total of 426 patients who underwent elective radical resection of colorectal cancer at Beijing Friendship Hospital, Capital Medical University from January 2017 to May 2018. According to the inclusion and exclusion criteria, 387 patients were finally included. A CT scan at the level of the L3-L4 intervertebral disk was selected to measure the values of visceral fat area and skeletal muscle area. Multivariate analysis was used to explore the independent risk/protective factors affecting postoperative complications. Results: 128 (33.1%) patients developed complications, and 44 (11.4%) patients developed major complications. Among them, 111 patients developed surgical complications and 21 developed medical complications. Visceral fat area (Z = -3.271, p = 0.001), total fat area (Z = -2.613, p = 0.009), visceral fat area to subcutaneous fat area ratio (V/S, Z = -2.633, p = 0.008), and sarcobesity index (Z = -2.282, p = 0.023) were significantly associated with total complications. Visceral fat area (Z = -2.119, p = 0.034) and V/S (Z = -2.010, p = 0.044) were significantly associated with total surgical complications. Sarcobesity index, smoking, stoma, blood loss, surgery time, and American Society of Anesthesiology (ASA) score were selected as risk factors for total postoperative complications according to LASSO regression. Multivariate logistic regression analysis suggested that sarcobesity index was an independent risk factor for postoperative total complications and surgical complications. Subgroup analysis suggested that albumin level was an independent protective factor for postoperative total complications in male patients. Smoking, operative time, and sarcobesity index were independent risk factors, and cholesterol was an independent protective factor for total postoperative complications in female patients. Conclusion: Increased sarcobesity index is an independent risk factor for postoperative complications in patients with colorectal cancer, while visceral fat area is not. For female patients, smoking, operation time, and obesity index are independent risk factors for postoperative complications, while cholesterol is an independent protective factor. For male patients, serum albumin is an independent protective factor for postoperative complications.

Preservation of left colic artery in laparoscopic colorectal operation: The benefit challenge.

BACKGROUND: During laparoscopic resection for colorectal cancer, there is controversy regarding whether the left colic artery (LCA) should be preserved at its origin. AIM: To investigate the prognostic significance of preservation of the LCA in colorectal cancer surgery. METHODS: Patients were divided into two groups. The high ligation (H-L) technique (refers to ligation performed 1 cm from the beginning of the inferior mesenteric artery) group consisted of 46 patients, and the low ligation (L-L) technique (refers to ligation performed below the initiation of the LCA) group consisted of 148 patients. Operative time, blood loss, lymph nodes with tumor invasion, postoperative complications and recovery time, recurrence rate, and 5-year survival rate were compared between the two groups. RESULTS: The average number of lymph nodes detected in postoperative pathological specimens was 17.4/person in the H-L group and 15.9/person in the L-L group. There were 20 patients (43%) with positive lymph nodes (lymph node metastasis) in the H-L group and 60 patients (41%) in the L-L group. No statistical differences were found between the groups. Complications occurred in 12 cases (26%) in the H-L group and in 26 cases (18%) in the L-L group. The incidences of postoperative anastomotic complications and functional urinary complications were significantly lower in the L-L group. The 5-year survival rates in H-L and L-L groups were 81.7% and 81.6%, respectively, and relapse-free survival rates were 74.3% and 77.1%, respectively. The two groups were similar statistically. CONCLUSION: Complete mesenteric resection combined with lymph node dissection around the inferior mesenteric artery root while preserving the LCA is a beneficial surgical approach during laparoscopic resection for colorectal cancer.

Pathological and perioperative outcomes of extracorporeal versus intracorporeal anastomosis in laparoscopic transverse colon cancer resection: retrospective multicentre study.

BACKGROUND: The aim of this study was to compare the pathological and perioperative outcomes of extracorporeal versus intracorporeal anastomosis after laparoscopic transverse colon cancer resection. METHODS: In this retrospective study, patients from seven institutions in China who underwent laparoscopic resection of transverse colon cancer between 2019 and 2021 were selected and included. Either extended right hemicolectomy or transverse colectomy/extended left hemicolectomy was performed. The clinical characteristics and the pathological and perioperative outcomes were compared between patients undergoing extracorporeal or intracorporeal anastomosis. Resection margin lengths were measured on formalin-fixed specimens and an inadequate margin was defined as less than 4.2 cm between the division and the tumour. The outcome of interest was the prevalence of specimens with an inadequate margin. Length of incision, bowel function recovery, hospital stay, early postoperative pain (first day after surgery), 30-day complications, and nodal harvest were investigated as secondary outcomes. RESULTS: Of 411 patients treated during the study interval, 370 patients with transverse colon cancer were included (23.2 per cent treated with intracorporeal anastomosis and 76.8 per cent treated with extracorporeal anastomosis). The prevalence of specimens with inadequate margins was lower in the intracorporeal anastomosis group compared with the extracorporeal anastomosis group in patients undergoing extended right hemicolectomy (P = 0.045) and in patients undergoing transverse colectomy/extended left hemicolectomy (P = 0.030). In multivariate analysis, extracorporeal anastomosis (OR 2.94 (95 per cent c.i. 1.33 to 6.49), P = 0.008) and transverse colectomy/extended left hemicolectomy (OR 1.75 (95 per cent c.i. 1.03 to 2.96), P = 0.038) were independent risk factors for specimens with an inadequate margin. Intracorporeal anastomosis was associated with a shorter incision length (P < 0.001), an earlier recovery of bowel function (P = 0.035), a shorter postoperative hospital stay (P = 0.042), less early postoperative pain (P < 0.001), a longer specimen length (P = 0.042), a longer resection margin (P = 0.007), and a greater lymph node harvest (P = 0.036). There was no statistically significant difference in 30-day complications. CONCLUSION: Patients with transverse colon cancer have better perioperative outcomes, fewer margins of less than 4.2 cm, and larger lymph node harvests when the anastomosis is performed intracorporeally. Further studies are needed to confirm these findings. REGISTRATION NUMBER: NCT05061199 (www.clinicaltrials.gov).

A cuproptosis-related lncRNA signature to predict prognosis and immune microenvironment of colon adenocarcinoma.

Cuproptosis is a novel cell death modality but its regulatory role in the colon cancer remains obscure. This study is committed to establishing a cuproptosis-related lncRNA (CRL) signature to forecast the prognosis for colon adenocarcinoma (COAD). The Cancer Genome Atlas (TCGA) samples were randomly divided into training and validation cohorts. LASSO-COX analysis was performed to construct a prognostic signature consisting of five CRLs (AC015712.2, ZEB1-AS1, SNHG26, AP001619.1, and ZKSCAN2-DT). We found the patients with high-risk scores suffered from poor prognosis in training cohort (p < 0.001) and validation cohort (p = 0.004). Nomogram was created based on the 5-CRL signature. Calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) demonstrated the nomogram performed well in 1­, 3­, and 5­year overall survival (OS). Subsequently, we observed increased infiltration of multiple immune cells and upregulated expression of immune checkpoints and RNA methylation modification genes in high-risk patients. Additionally, gene set enrichment analysis (GSEA) revealed two tumor-related pathways, including MAPK and Wnt signaling pathways. Finally, we found AKT inhibitors, all-trans retinoic acid (ATRA), camptothecin, and thapsigargin had more sensitivity to antitumor therapy in high-risk patients. Collectively, this CRL signature is promising for the prognostic prediction and precise therapy of COAD.

Establishing and validating predictive nomograms for lateral pelvic lymph node metastasis in patients with rectal cancer based on radiologic factors and clinicopathologic characteristics.

INTRODUCTION: It is critical to accurately predict the occurrence of lateral pelvic lymph node (LPN) metastasis. Currently, verified predictive tools are unavailable. This study aims to establish nomograms for predicting LPN metastasis in patients with rectal cancer who received or did not receive neoadjuvant chemoradiotherapy (nCRT). MATERIALS AND METHODS: We carried out a retrospective study of patients with rectal cancer and clinical LPN metastasis who underwent total mesorectal excision (TME) and LPN dissection (LPND) from January 2012 to December 2019 at 3 institutions. We collected and evaluated their clinicopathologic and radiologic features, and constructed nomograms based on the multivariable logistic regression models. RESULTS: A total of 472 eligible patients were enrolled into the non-nCRT cohort (n = 312) and the nCRT cohort (n = 160). We established nomograms using variables from the multivariable logistic regression models in both cohorts. In the non-nCRT cohort, the variables included LPN short diameter, cT stage, cN stage, histologic grade, and malignant features, and the C-index was 0.930 in the training cohort and 0.913 in the validation cohort. In the nCRT cohort, the variables included post-nCRT LPN short diameter, ycT stage, ycN stage, histologic grade, and post-nCRT malignant features, and the C-index was 0.836 in the training dataset and 0.827 in the validation dataset. The nomograms in both cohorts were moderately calibrated and well-validated. CONCLUSIONS: We established nomograms for patients with rectal cancer that accurately predict LPN metastasis. The performance of the nomograms in both cohorts was high and well-validated.

Feasibility and safety of lateral pelvic lymph node dissection for elderly patients with middle-low rectal cancer: results of a large multicenter lateral node collaborative group study in China.

BACKGROUND: Lateral pelvic lymph node (LPN) dissection can improve local control in certain rectal cancer patients with LPN metastasis. However, the effects of this technically complex procedure on perioperative safety and long-term survival of elderly patients (≥ 70 years) remain unclear. METHODS: Locally advanced middle-low rectal cancer patients diagnosed with LPN metastasis who underwent total mesorectal excision (TME) with LPN dissection at three institutions from January 2012 to December 2019 were included in this study. Additionally patients who had neoadjuvant chemoradiotherapy (nCRT) and those who did not were compared. RESULTS: In total there were 407 patients, including 49 elderly and 358 non-elderly patients, of which 249 were male, with a median age of 58 years (range:18-85 years). In the whole cohort, operation time (280.7 vs. 292.0 min, p = 0.498) and estimated blood loss (100 vs. 100 ml, p = 0.384) were comparable in the elderly and non-elderly groups. There was no significant difference in the incidences of overall complications (24.5% vs. 19.8%, p = 0.448) and severe (Clavien-Dindo grade 3-5) surgical complications (8.2% vs. 7.5%, p = 0.778) between the two groups. However, the incidence of urinary retention (14.3% vs. 5.6%, p = 0.032) and intensive care unit admission (16.3% vs. 6.1%, p = 0.018) was significantly higher in the elderly group compared with those in the non-elderly group. The 3-year overall survival (88.7% vs. 82.1%, p = 0.516) and disease-free survival (81.2% vs. 70.7%, p = 0.352) were comparable between the two groups. Moreover, results in the nCRT cohort were comparable to those in the overall cohort. CONCLUSIONS: Even with nCRT, TME combined with LPN dissection is safe and feasible for elderly patients, demonstrating low mortality and acceptable morbidity. Elderly and non-elderly patients with LPN metastasis who undergo LPN dissection can achieve comparable 3-year survival outcomes. TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT04850027.

Electroacupuncture vs Sham Electroacupuncture in the Treatment of Postoperative Ileus After Laparoscopic Surgery for Colorectal Cancer: A Multicenter, Randomized Clinical Trial.

Importance: Despite the adoption of the optimized Enhanced Recovery After Surgery (ERAS) protocol, postoperative ileus (POI) severely impairs recovery after colorectal resection and increases the burden on the health care system. Objective: To assess the efficacy of electroacupuncture (EA) in reducing the duration of POI with the ERAS protocol. Design, Setting, and Participants: This multicenter, randomized, sham-controlled trial was conducted in China from October 12, 2020, through October 17, 2021. There was a 1:1 allocation using the dynamic block random method, and analyses were by intention to treat. Patients 18 years or older undergoing laparoscopic resection of colorectal cancer for the first time were randomly assigned to treatment group by a central system. Interventions: Patients were randomly assigned to 4 sessions of EA or sham electroacupuncture (SA) after surgery. All patients were treated within the ERAS protocol. Main Outcomes and Measures: The primary outcome was the time to first defecation. Secondary outcomes included other patient-reported outcome measures, length of postoperative hospital stay, readmission rate within 30 days, and incidence of postoperative complications and adverse events. Results: A total of 249 patients were randomly assigned to treatment groups. After the exclusion of 1 patient because of a diagnosis of intestinal tuberculosis, 248 patients (mean [SD] age, 60.2 [11.4] years; 153 men [61.7%]) were included in the analyses. The median (IQR) time to first defecation was 76.4 (67.6-96.8) hours in the EA group and 90.0 (73.6-100.3) hours in the SA group (mean difference, -8.76; 95% CI, -15.80 to -1.73; P = .003). In the EA group compared with the SA group, the time to first flatus (median [IQR], 44.3 [37.0-58.2] hours vs 58.9 [48.2-67.4] hours; P < .001) and the tolerability of semiliquid diet (median [IQR], 105.8 [87.0-120.3] hours vs 116.5 [92.0-137.0] hours; P = .01) and solid food (median [IQR], 181.8 [149.5-211.4] hours vs 190.3 [165.0-228.5] hours; P = .01) were significantly decreased. Prolonged POI occurred in 13 of 125 patients (10%) in the EA group vs 25 of 123 patients (20%) in the SA group (risk ratio [RR], 0.51; 95% CI, 0.27-0.95; P = .03). Other secondary outcomes were not different between groups. There were no severe adverse events. Conclusions and Relevance: Results of this randomized clinical trial demonstrated that in patients undergoing laparoscopic surgery for colorectal cancer with the ERAS protocol, EA shortened the duration of POI and decreased the risk for prolonged POI compared with SA. EA may be considered as an adjunct to the ERAS protocol to promote gastrointestinal function recovery and prevent prolonged POI after surgery. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000038444.

Mesorectal excision with or without lateral lymph node dissection for elderly patients with mid-low rectal cancer: safety and feasibility analysis.

OBJECTIVE: The perioperative safety and survival benefits of lateral lymph node dissection in elderly patients have been less reported. This study aimed to compare short-term and survival outcomes of total mesorectal excision and total mesorectal excision + lateral lymph node dissection in elderly patients. METHODS: A total of 444 elderly patients (≥65 years) with middle-low rectal cancer were enrolled in three institutions and divided into the total mesorectal excision + lateral lymph node dissection group (n = 110) and the total mesorectal excision group (n = 334). Eighty-three matched pairs were selected for evaluation after propensity matching. Data of 297 patients (age <65 years) with middle-low rectal cancer who underwent total mesorectal excision + lateral lymph node dissection were also collected and reviewed. Clinical and pathological features, postoperative outcomes and survival data were collected and analyzed. RESULTS: Compared with the total mesorectal excision group, the operation time of patients in the total mesorectal excision + lateral lymph node dissection group was significantly longer (277.6 vs. 171.4 min, P < 0.001), and the estimated blood loss was significantly more (119.6 vs. 57.5 ml, P = 0.014). Although there was no significant difference in overall complications (24.1% vs. 14.4%, P = 0.115) and grade 3-5 complications (9.6% vs. 7.2%, P = 0.576) between the two groups, the incidence of urinary retention (10.8% vs. 2.4%, P = 0.029) was higher in the total mesorectal excision + lateral lymph node dissection group. Two groups of patients achieve a similar 3-year overall survival (92.8% vs. 85.4%, P = 0.195) and 3-year disease-free survival (81.5% vs. 73.0%, P = 0.625). In addition, we compared long-term outcomes in 110 elderly patients with total mesorectal excision + lateral lymph node dissection and 297 non-elderly patients with total mesorectal excision + lateral lymph node dissection, and the results showed that 3-year (89.2% vs. 80.9%, P = 0.546) and disease-free survival (76.4% vs. 70.4%, P = 0.346) were similar between elderly and non-elderly patients. CONCLUSIONS: Although urinary retention is closely related to the implementation of lateral lymph node dissection in elderly patients, total mesorectal excision with lateral lymph node dissection could be performed safely with accepted overall and grade 3-5 postoperative complications in elderly patients with rectal cancer. Moreover, elderly patients with clinical lateral lymph node metastasis can also benefit from lateral lymph node dissection as well as younger patients. Prospective studies with large sample sizes are needed to verify our results further.

Impact of Pre-Operative Right Ventricular Response to Hemodynamic Optimization on Outcomes in Patients with LVADs.

Background: Right ventricular failure (RVF) continues to affect patients supported with durable left ventricular assist devices (LVAD) and results in increased morbidity and mortality. Information regarding the impact of right ventricular response to pre-operative optimization on outcomes is scarce. Methods: Single-center retrospective analysis of consecutive patients who underwent first continuous flow LVAD implantation between 2006 and 2020. Patients with bi-ventricular support before LVAD or without hemodynamic data were excluded. Invasive hemodynamics at baseline and after pre-operative medical and/or temporary circulatory support were recorded. Patients were grouped in the following categories: A: No Hemodynamic RV dysfunction (RVD) at baseline; B: RVD with achievement of RV hemodynamic optimization goals; C: RVD without achievement of RV optimization goals. The main outcomes were right ventricular failure defined as inotropes >14 days after implantation, or postoperative right ventricular mechanical support, and all-cause mortality. Results: Overall, 128 patients were included in the study. The mean age was 58 ±12.5 years, 74.2% were males and, 68.7% had non-ischemic cardiomyopathy. Hemodynamic RVD was present in 70 (54.7%) of the patients at baseline. RV hemodynamic goals were achieved in 46 (79.31%) patients with RVD and in all the patients without RVD at baseline. Failure to achieve hemodynamic optimization goals was associated with a significantly higher risk of RVF after LVAD implantation (adjusted OR 4.37, 95% CI 1.14−16.76, p = 0.031) compared with no RVD at baseline and increased 1-year mortality compared with no RVD (adjusted HR 4.1, 95% CI 1.24−13.2, p = 0.02) and optimized RVD (adjusted HR 6.4, 95% CI 1.6−25.2, p = 0.008).Conclusion: Among patients with RVD, the inability to achieve hemodynamic optimization goals was associated with higher rates of RV failure and increased 1-year all-cause mortality post LVAD implantation.

Effective dissecting range and prognostic significance of lateral pelvic lymph node dissection for middle-low rectal cancer patients with lateral pelvic lymph node metastasis: Results of a large multicenter lateral node collaborative group in China.

Background: Lateral pelvic lymph node (LPN) metastasis causes increased lateral local recurrence and poor prognosis. We aimed to investigate the prognostic significance and effective range of dissection for the LPN dissection (LPND) in rectal cancer patients with LPN metastasis. Materials and methods: Through this large, multicenter retrospective cohort study, we evaluated the therapeutic effect of LPND. From January 2012 to December 2019, 387 rectal cancer patients with clinical evidence of LPN metastasis who underwent total mesorectal excision with LPND were included in the study. According to pathological findings, they were divided into negative (n = 296) and positive (n = 91) LPN groups. Primary endpoints were 3-year overall survival (OS), recurrence-free survival (RFS), and local recurrence-free survival (LRFS). Results: The OS, RFS, and LRFS in the positive group were significantly worse than those in the negative group; However, LPN metastases were not independent prognostic risk factors for LRFS (hazard ratio [HR]: 2.42; 95% confidence interval [CI], 0.77-7.64; P=0.132). Among patients with pathological LPN metastases, LPN metastases to the common and external iliac arteries were independent prognostic risk factors both for OS (HR: 4.74; 95% CI, 1.74-12.90; P=0.002) and RFS (HR: 2.70; 95% CI, 1.16-6.29; P=0.021). No significant difference was observed in the 3-year OS (72.3% vs. 70.2%, P=0.775) and RFS rates (60.9% vs. 52.6%, P=0.408) between patients with metastases to the obturator or internal iliac arteries and patients at N2b stage. Conclusions: LPND may be effective in controlling local recurrence in patients with LPN metastasis but not systemic metastases. Patients with LPN metastasis limited to the internal iliac and obturator regions achieve a long-term survival benefit from LPND, and their prognoses may be comparable to those at the N2b stage. Further metastasis to the external iliac or common iliac region should be considered systemic disease, and LPND should be avoided. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04850027.

Risk factors and prognostic significance of postoperative complications following lateral pelvic lymph node dissection for rectal cancer: results of the multicenter lateral node study in China.

OBJECTIVE: Total mesorectal excision (TME) plus lateral pelvic lymph node (LPN) dissection (LPND) is a technically complex and challenging procedure with higher morbidity than TME alone. We aimed to investigate the risk factors for postoperative complications after TME + LPND, and the impact of complications on patient prognosis. METHODS: A total of 387 rectal cancer patients with clinical LPN metastasis (LPNM) who underwent TME + LPND at three institutions affiliated with the Chinese Lateral Node Collaborative Group were included. Logistic regression models were used to identify the risk factors for post-surgical complications, and the log-rank test was used to compare the prognosis. Severe complications were described as grade III-V. RESULTS: The incidence rates of overall complications and severe complications after TME + LPND were 15.2% (59/387) and 7.8% (30/387), respectively. Multivariate analysis showed that a duration of operation ≥260 min was an independent risk factor for both overall (odds ratio [OR] = 3.03, 95% confidence interval [CI] = 1.57-5.85, P = 0.001) and severe postoperative complications (OR = 2.67, 95% CI = 1.06-6.73, P = 0.037). The development of overall postoperative complications (P = 0.114) and severe postoperative complications (P = 0.298) had no significant impact on the overall survival. However, patients with overall complications (P = 0.015) or severe complications (P = 0.031) with a postoperative hospital stay >30 days had significantly an overall worse survival. CONCLUSION: A surgical duration of ≥260 min is a significant risk factor for both overall and severe postoperative complications after TME + LPND for middle-low rectal cancer. Furthermore, the development of overall complications or severe complications that require a postoperative hospital stay >30 days significantly worsens the prognosis.

Short- and long-term outcomes of laparoscopic versus open selective lateral pelvic lymph node dissection for locally advanced middle-low rectal cancer: Results of a multicentre lateral node study in China.

AIM: Lateral pelvic lymph node dissection (LPND) is a technically challenging procedure, and the safety and feasibility of laparoscopic LPND remains undetermined. Here, we compared the short- and long-term survival outcomes of laparoscopic LPND with those of open LPND. METHODS: From January 2012 to December 2019, locally advanced middle-low rectal cancer patients with clinical evidence of lateral pelvic lymph node metastasis (LPNM) who underwent total mesorectal excision with LPND at three institutions were included. Propensity score matching was used to minimize selection bias. The short-term and oncological outcomes of open and laparoscopic LPND were compared. RESULTS: Overall, 384 patients were enrolled into the study including 277 and 107 patients who underwent laparoscopic and open LPND, respectively. After matching, patients were stratified into laparoscopic (n = 100) and open (n = 100) LPND groups. Patients in the laparoscopic LPND group had a shorter operation time (255 vs. 300 min, p = 0.001), less intraoperative blood loss (50 vs. 300 ml, p < 0.001), lower incidence of postoperative complications (32.0% vs. 15.0%, p = 0.005), shorter postoperative hospital stay (8 vs. 14 days, p < 0.001), and excision of more lateral pelvic lymph nodes (9 vs. 7, p = 0.025) than those in the open LPND group. The 3-year overall survival (p = 0.581) and 3-year disease-free survival (p = 0.745) rates were similar between the groups, and LPNM was an independent predictor of survival. CONCLUSION: Laparoscopic LPND is technically safe and feasible with favourable short-term results and similar oncological outcomes as open surgery in selected patients.

Electroacupuncture versus sham electroacupuncture in the treatment of postoperative ileus after laparoscopic surgery for colorectal cancer: study protocol for a multicentre, randomised, sham-controlled trial.

INTRODUCTION: Postoperative ileus (POI) is an inevitable complication of almost all abdominal surgeries, which results in prolonged hospitalisation and increased healthcare costs. Various treatment strategies have been developed for POI but with limited success. Electroacupuncture (EA) might be a potential therapy for POI. However, evidence from rigorous trials that evaluated the effectiveness of EA for POI is limited. Thus, the aim of this study was to examine whether EA can safely reduce the time to the first defecation after laparoscopic surgery in patients with POI. METHODS AND ANALYSIS: This multicentre randomised sham-controlled trial will be conducted in four hospitals in China. A total of 248 eligible participants with colorectal cancer who will undergo laparoscopic surgery will be randomly allocated to an EA group and a sham EA group in a 1:1 ratio. Treatment will be performed starting on postoperative day 1 and continued for four consecutive days, once per day. If the participant is discharged within 4 days after surgery, the treatment will cease on the day of discharge. The primary outcome will be the time to first defecation. The secondary outcome measures will include time to first flatus, tolerability of semiliquid and solid food, length of postoperative hospital stay, postoperative nausea and vomiting, abdominal distension, postoperative pain, postoperative analgesic, time to first ambulation, blinding assessment, credibility and expectancy and readmission rate. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of Beijing University of Chinese Medicine (number 2020BZHYLL0116) and the institutional review board of each hospital. The results will be disseminated through peer-reviewed publications. This study protocol (V.3.0, 6 March 2020) involves human participants and was approved by the ethics committees of Beijing University of Chinese Medicine (number 2020BZHYLL0116), Beijing Friendship Hospital Affiliated to Capital Medical University (number 2020-P2-069-01), Beijing Chao-Yang Hospital Affiliated to Capital Medical University (number 2020-3-11-2), National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (number 20/163-2359), and the Affiliated Hospital of Qingdao University (number QYFYKYLL711311920). The participants gave informed consent to participate in the study before taking part. TRIAL REGISTRATION NUMBER: ChiCTR2000038444.

Ring finger protein 128 promotes, rather than inhibits, colorectal cancer progression by regulating the Hippo signaling pathway.

Background: Colorectal cancer is a common malignancy of the gastrointestinal tract, and its incidence and mortality rates have increased in recent years. RNF128 is an E3 ubiquitin ligase that plays an important role as a suppressor gene or oncogene in various cancers, but its mechanism in colorectal cancer is not yet clear. The aim of this study was to investigate the role and mechanism of RNF128 in colorectal cancer. Methods: The expression of RNF128 in colorectal cancer tissues was assessed by immunohistochemistry and western blotting. The proliferation ability of colorectal cancer cells was measured by colony formation assay and CCK-8 assay, the migration and invasion ability of colorectal cancer cells was measured by wound healing assay and transwell assay, and the protein expression levels of the Hippo signaling pathway and its target gene were examined by western blotting. Immunoprecipitation was used to assess the interaction of RNF128 with MST. In vivo, a xenograft tumor model was used to detect the effect of RNF128 on tumor growth. Results: At the tissue level, the expression level of RNF128 was significantly higher in colorectal cancer tissues than in adjacent normal tissues. In LoVo cells and HCT116 cells, the proliferation, migration and invasion abilities were significantly reduced with RNF128 knockdown. At the protein level, knockdown of RNF128 resulted in significant activation of the Hippo signaling pathway. In vivo experiments, the volume and weight of xenograft tumors in nude mice were significantly decreased compared with those in the normal control group with RNF128 knockdown. Conclusion: RNF128 promotes the malignant behaviors of colorectal cancer cells by inhibiting the Hippo signaling pathway, which may provide a new target for colorectal cancer prevention and treatment.