Impact of self-expanding metal stents on long-term survival outcomes as a bridge to surgery in patients with colon cancer obstruction: Current state and future prospects.

Since self-expanding metal stents (SEMS) were first introduced in acute colon cancer obstruction, the increased rate of primary anastomosis and improved quality of life following SEMS placement have been clearly shown. However, it was demonstrated that SEMS are associated with higher recurrence rates. Although several trials have shown that overall and disease-free survival in patients following SEMS placement is similar with patients undergoing emergency surgery, obstruction and a high incidence of recurrence imposed many concerns. The optimal time interval from SEMS to surgery is still a matter of debate. Some studies have recommended a time interval of ~2 weeks between SEMS insertion and elective surgery. A prolonged interval of time from SEMS insertion to elective surgery and the administration of neoadjuvant chemotherapy (NAC) has been proposed. SEMS-NAC might have advantages for improving the surgical and long-term survival outcomes of patients with acute colon cancer obstruction, which is an optional approach in the management of acute colon cancer obstruction.

Short-term outcomes of sleeve gastrectomy plus uncut jejunojejunal bypass (SG-uncut JJB) in patients with obesity: a preliminary prospective cohort study.

OBJECTIVE: To compare the safety, weight loss, and metabolic outcomes of patients with obesity with sleeve gastrectomy (SG) or sleeve gastrectomy plus uncut jejunojejunal bypass (SG-uncut JJB). METHODS: This prospective study included patients with BMIs ≥ 32.5 kg/m2 or refractory metabolic disorders undergoing SG or SG-uncut JJB between January and December 2020 in our hospital (NCT04534504). Weight loss, metabolic outcomes, surgical results, and complaints during 1-year follow-up were compared between two groups. RESULTS: Forty-seven patients were enrolled, 26 in the SG and 21 in the SG-uncut JJB groups. A longer operative time was observed in the SG-uncut JJB than in the SG group (140 (110-180) min vs. 90 (70-180) min, P = 0.001). No significant differences were found in complications. Total weight loss (TWL%) and excess weight loss (EWL%) in both groups increased with the duration of follow-up (P = 0.001). TWL% was greater at 1 month ((11.1 ± 2.4)% vs. (8.2 ± 4.4)%, P = 0.011] and 12 months [(29.7 ± 6.9)% vs. (20.3 ± 7.2)%, P = 0.001) with SG-uncut JJB than with SG. SG-uncut JJB and SG had similar metabolic outcomes and complaints during the 1-year follow-up, but less nausea was reported with SG-uncut JJB (9.2% vs. 46.2%, P = 0.006). CONCLUSION: In short-term follow-up, SG-uncut JJB was a safe and effective bariatric surgery procedure in patients with obesity.

Rationale and design of a prospective, multicenter, phase II clinical trial of safety and efficacy evaluation of long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorectal excision for locally advanced rectal cancer (NCRT-PD1-LARC trial).

BACKGROUND: Long course radiotherapy plus neoadjuvant chemotherapy followed by resection (total mesorectal excision, TME) has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1 humanized IgG4 monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China. However, the safety and efficacy of long course (neoadjuvant chemoradiotherapy, NCRT) plus tislelizumab followed by TME for LARC is still uncertain. METHODS: This NCRT-PD1-LARC trial will be a prospective, multicenter and phase II clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course NCRT plus tislelizumab followed by TME. This trial will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 7 cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by TME 6-8 weeks after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes. DISCUSSION: To our knowledge, this trial is the first multicenter clinical trial in China to assess the safety and efficacy of NCRT plus anti-PD1 therapy followed by TME to treat patients with LARC. NCRT followed by TME was recognized as the most recommended treatment against LARC while could not be completely satisfied in clinic. This study expects to provide a solid basis and encouraging outcomes for this promising combination of radiotherapy, chemotherapy and immunotherapy in LARC. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04911517. Date of registration: 23 May 2021. URL of trial registry record: https://www. CLINICALTRIALS: gov/ct2/show/NCT04911517?id=BFH-NCRTPD&draw=2&rank=1 .

Transcriptome of visceral adipose tissue identifies an inflammation-related ceRNA network that regulates obesity.

Obesity is becoming an epidemic of widespread concern, but the underlying causes remain elusive. In this study, whole transcriptome RNA sequencing revealed differential profiles of noncoding (nc) RNAs and mRNAs in visceral adipose tissue from obese (BMI > 32.5 kg/m2) and lean (BMI < 20 kg/m2) individuals, with 1920 differentially expressed genes, 1466 long noncoding (lnc) RNAs, 122 micro (mi) RNAs, and 52 circular (circ) RNAs identified. Gene Set Enrichment Analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis revealed that these ncRNAs were involved in inflammation-related pathways that included cytokine-cytokine receptor interaction, the tumor necrosis factor and nuclear factor kappa B signaling pathways. The results indicated a critical role of inflammation in the pathogenesis of obesity. The network interaction of lncRNA, circRNA, and miRNA revealed a competing endogenous (ce) RNA network that was associated with inflammation. The ceRNA network included circORC5/miR-197-5p/TNFRSF10D and circNTRK2/miR-760/LAT, which were dysregulated in obese patients. In conclusion, this whole transcriptome study provided a pool of data that will be useful for identifying biomarkers of obesity and identified an obesity-associated ceRNA network that is regulated by circORC5 and circNTRK2.

Impact of total neoadjuvant therapy consisting of consolidation chemotherapy on locally advanced rectal cancer survival.

PURPOSE: The objective was to compare disease-free survival (DFS) and distant metastasis in patients with neoadjuvant chemoradiotherapy (NCRT) and total neoadjuvant therapy (TNT) for locally advanced rectal cancer. METHODS: Patients with cT3-4N0M0 or cTxN1-2M0 rectal cancer were included in this retrospective study. Patients who received NCRT (radiotherapy with concurrent capecitabine) or TNT (radiotherapy with two concurrent cycles of capecitabine and oxaliplatin (CAPOX) followed by another two cycles of CAPOX) during January 2011 and November 2016 at Beijing Chaoyang Hospital, Capital Medical University were included. All patients had received radical surgery. Adverse events, pathological response and survival outcomes in the two groups were compared. RESULTS: One hundred eighty-two patients were enrolled, 120 in the TNT and 62 in the NCRT groups. No significant between-group differences in neoadjuvant therapy-associated adverse events or surgical complications were found. TNT achieved a higher pathological complete response (pCR) rate (25.8%) compared with NCRT (12.9%, P = 0.044). Patients in the TNT group had a higher 3-year DFS rate (82.8% versus 75.7%, P = 0.041) and lower distant metastasis rate (19.2% versus 33.1%, P = 0.049) than those in the NCRT group. Multivariate analysis showed that NCRT was an independent risk factor for DFS (95%CI 2.023-13.415, P = 0.001) and distant metastasis (95% CI 2.149-20.082, P = 0.001). CONCLUSION: With similar adverse events and a higher pCR rate when compared with NCRT, TNT might be considered as a safe and effective therapeutic strategy to improve prognosis in patients with locally advanced rectal cancer.

Long-term outcomes after extra-levator versus conventional abdominoperineal excision for low rectal cancer.

PURPOSE: Extralevator (ELAPE) and abdominoperineal excision (APE) are two major surgical approaches for low rectal cancer patients. Although excellent short-term efficacy is achieved in patients undergoing ELAPE, the long-term benefits have not been established. In this study we evaluated the safety, pathological and survival outcomes in rectal cancer patients who underwent ELAPE and APE. METHODS: One hundred fourteen patients were enrolled, including 68 in the ELAPE group and 46 in the APE group at the Beijing Chaoyang Hospital, Capital Medical University from January 2011 to November 2020. The baseline characteristics, overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were calculated and compared between the two groups. RESULTS: Demographics and tumor stage were comparable between the two groups. The 5-year PFS (67.2% versus 38.6%, log-rank P = 0.008) were significantly improved in the ELAPE group compared to the APE group, and the survival advantage was especially reflected in patients with pT3 tumors, positive lymph nodes or even those who have not received neoadjuvant chemoradiotherapy. Multivariate analysis showed that APE was an independent risk factor for OS (hazard ratio 3.000, 95% confidence interval 1.171 to 4.970, P = 0.004) and PFS (hazard ratio 2.730, 95% confidence interval 1.506 to 4.984, P = 0.001). CONCLUSION:  Compared with APE, ELAPE improved long-term outcomes for low rectal cancer patients, especially among patients with pT3 tumors, positive lymph nodes or those without neoadjuvant chemoradiotherapy.

Long-Term Outcomes of Ligation of the Inter-Sphincteric Fistula Tract Plus Bioprosthetic Anal Fistula Plug (LIFT-Plug) in the Treatment of Trans-Sphincteric Perianal Fistula.

BACKGROUND The ligation of the inter-sphincteric fistula tract plus bioprosthetic anal fistula plug (LIFT-plug) is a new procedure in the treatment of trans-sphincteric perianal fistulas. The aim of this study was to evaluate its long-term outcomes. MATERIAL AND METHODS Clinical data of 78 patients with trans-sphincteric perianal fistula who were managed by the LIFT-plug technique between March 2014 to October 2016 were analyzed retrospectively. The operation time, healing rate, postoperative complications, recurrences, and length of stay were reviewed. RESULTS No serious complications occurred during the operation in all patients. The median follow-up was 30 months (16 to 47 months), clinical healing of the anal fistula occurred in 75 patients (96.2%). The median operative time was 25 minutes (18 to 45 minutes). The mean complete healing time was 16 days (9 to 46 days). The median healing time for the external anal fistula opening was 2 weeks (range, 2 to 3 weeks), and the inter-sphincteric groove incision healing time was 4 weeks (range, 3 to 7 weeks). The median hospital stay after operation was 5 days. Fistula recurred in 2 patients because of spontaneous expulsion of the plug at 7 days post-surgery; perianal abscess occurred in 1 patient. The anal function was evaluated in 70 patients of the 78 patients. Perfect control of continence was recorded for 97.1% of the patients (68 out of 70 patients). Two patients were identified to a rare complication of gas incontinence (Wexner score 1). CONCLUSIONS LIFT-plug procedure for the treatment of trans-sphincteric fistulas is a simple procedure with a high healing rate, minimal invasiveness, quick healing, and without disturbance to anal function. LIFT-plug is an ideal procedure for trans-sphincteric fistula.

High Expression of Orai1 Enhances Cell Proliferation and is Associated with Poor Prognosis in Human Colorectal Cancer.

BACKGROUND: Store-operated Ca2+ entry (SOCE) is the predominant Ca2+ influx mechanism in non-excitable cells and regulates a variety of cellular functions. As the essential channel pore-forming protein of SOCE, Orai1 has recently been implicated in carcinogenesis and tumor progression in multiple malignancies. However, the role of Orai1 in colorectal cancer (CRC) has not been investigated. METHODS: The expression of Orai1 in 21 CRC specimens was examined by immunohistochemistry (IHC) staining, Western blot, and qRT-PCR. The results were compared with paired non-tumor tissues. The expression of Orai1 in additional specimens of 129 CRC patients was examined by IHC staining and the IHC scores were compared with clinicopathological features. After knock-down of the expression of Orai1 in LoVo cells, cell proliferation was examined using a MTT assay and colony formation assay. Flow cytometry was also used to detect apoptosis. RESULTS: The expression of Orai1 was upregulated in human CRC tissues, high expression of Orai1 was closely associated with depth of tumor invasion, lymph node metastasis, and perineural invasion, and patients with high expression of Orai1 had shorter overall survival. Moreover, the expression of Orai1 was also upregulated in CRC cell lines, knockdown of Orai1 inhibited cell proliferation, the effect of growth inhibition was not due to enhanced apoptosis, and stromal interaction molecule1 (STIM1) did not take part in the regulation of CRC cell proliferation. CONCLUSIONS: Orai1 is crucial to sustained CRC cell proliferation, high expression of Orai1 is associated with tumor progression and poor prognosis, and Orai1 may be a promising target for prognosis and treatment of CRC.

[Risk factors associated with incisional surgical site infection in colorectal cancer surgery with primary anastomosis].

OBJECTIVE: To investigate the incidence of surgical site infection (SSI) and risk factors in colorectal cancer surgery patients. METHODS: Between October 2003 and October 2013, 1 381 consecutive patients with colorectal cancer managed surgically with primary anastomosis were included in the study. There were 762 male and 619 female patients with mean body mass index (BMI) was (27.7 ± 3.7) kg/m², aged from 20 to 90 years with a median of 67 years. Patients undergoing emergency surgery and requiring stoma creation were excluded. The patients' characteristics, surgical conditions and prognosis were recorded. Univariate and multiple logistic regression analysis were used to identify any variable predictive factors of SSI. RESULTS: One hundred twenty-six (9.12%) cases developed incisional SSI. The occurrence time for SSI was from 2 to 20 days, mean (6.7 ± 2.9) days. According to multivariable logistic regression analysis, BMI (OR = 1.058, P = 0.030), intraoperative contamination (OR = 10.549, P = 0.000) and open operation as compared with a laparoscopic procedure (OR = 2.111, P = 0.001) were significant independent predictors of incisional SSI. There was a significant decrease in incisional SSI in wound protectors group (OR = 1.646, P = 0.012). CONCLUSION: BMI and intraoperative contamination are independent predictors of incisional SSI, and wound protectors and laparoscopic surgery are associated with a lower incidence of incisional SSI following colorectal cancer surgery.

[A prospective multicenter clinical trial of extralevator abdominoperineal excision for locally advanced low rectal cancer].

OBJECTIVE: To demonstrate the feasibility of extralevator abdominoperineal excision (ELAPE) for locally advanced low cancer in China. METHODS: A prospective multicenter clinical trial was carried out by 7 general hospitals across China from August 2008 to October 2011. A total of 102 patients underwent ELAPE for primary locally advanced low rectal cancer. There were 60 male and 42 female patients. The patients' characteristics, complications and prognosis were recorded. RESULTS: All patients underwent the ELAPE procedure successfully. The median operating time was 180 minutes (range 110-495 minutes) and median intraoperative blood loss was 200 ml (range 50-1000 ml). The rates of sexual dysfunction, perineal complications, urinary retention, and chronic perineal pain were 40.5%, 23.5%, 18.6% and 13.7%, respectively. Chronic perineal pain was associated with coccygectomy (12 months postoperatively, t = 8.06, P < 0.01), and the pain might gradually ease over time. Reconstruction of pelvic floor with biologic mesh was associated with lower rate of perineal dehiscence (χ(2) = 13.502, P = 0.006) and overall perineal wound complications (χ(2) = 5.836, P = 0.016) compared with primary closure. A positive circumferential margin (CRM) was demonstrated in 6 (5.9%) patients, and intraoperative perforations occurred in 4 (3.9%) patients. All CRM involvement and intraoperative perforation located at anteriorly and anterolaterally. The local recurrence was 4.9% at a median follow-up of 35 months (range, 18-58 months). CONCLUSIONS: ELAPE performed in the prone position for low rectal cancer leads to a reduction in CRM involvement, intraoperative perforations, and local recurrence, but it might result in a little high rate of perineal wound related complications. Reconstruction of pelvic floor with biologic mesh might lower the rate of perineal wound complications.

Gut microbiome model predicts response to neoadjuvant immunotherapy plus chemoradiotherapy in rectal cancer.

BACKGROUND: Accurate evaluation of the response to preoperative treatment enables the provision of a more appropriate personalized therapeutic schedule for locally advanced rectal cancer (LARC), which remains an enormous challenge, especially neoadjuvant immunotherapy plus chemoradiotherapy (nICRT). METHODS: This prospective, multicenter cohort study enrolled patients with LARC from 6 centers who received nICRT. The dynamic variation in the gut microbiome during nICRT was evaluated. A species-level gut microbiome prediction (SPEED) model was developed and validated to predict the pathological complete response (pCR) to nICRT. FINDINGS: A total of 50 patients were enrolled, 75 fecal samples were collected from 33 patients at different time points, and the pCR rate reached 42.4% (14/33). Lactobacillus and Eubacterium were observed to increase after nICRT. Additionally, significant differences in the gut microbiome were observed between responders and non-responders at baseline. Significantly higher abundances of Lachnospiraceae bacterium and Blautia wexlerae were found in responders, while Bacteroides, Prevotella, and Porphyromonas were found in non-responders. The SPEED model showcased a superior predictive performance with areas under the curve of 98.80% (95% confidence interval [CI]: 95.67%-100%) in the training cohort and 77.78% (95% CI: 65.42%-88.29%) in the validation cohort. CONCLUSIONS: Programmed death 1 (PD-1) blockade plus concurrent long-course CRT showed a favorable pCR rate and is well tolerated in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) patients with LARC. The SPEED model can be used to predict the pCR to nICRT based on the baseline gut microbiome with high robustness and accuracy, thereby assisting clinical physicians in providing individualized management for patients with LARC. FUNDING: This research was funded by the China National Natural Science Foundation (82202884).

Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer (NECTAR): a multi-center phase 2 study.

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) / mismatch repair-proficient (pMMR) tumors is an attractive, but debatable strategy. This phase 2, multicenter, prospective, single-arm study enrolled patients from 6 centers from June 2021 to November 2022. Locally advanced rectal cancer (LARC, cT3-4aN0M0 and cT1-4aN1-2M0) patients aged ≥18 years with the distance from distal border of tumor to anal verge ≤10 cm (identified by Magnetic Resonance Imaging) were qualified for inclusion. The patients received long-course radiotherapy (50 Gy/25 fractions, 2 Gy/fraction, 5 days/week) and three 21-day cycles capecitabine (850-1000 mg/m2, bid, po, day1-14) and three 21-day cycles tislelizumab (200 mg, iv.gtt, day8) as neoadjuvant. Total mesorectal excision (TME) was 6-12 weeks after the end of radiotherapy to achieve radical resection. A total of 50 patients were enrolled in this study. The pathological complete response rate was 40.0% [20/50, 95% confidence interval (CI): 27.61-53.82%], while 15 (30.0%, 95% CI: 19.1-43.75%), 9 (18.0%, 95% CI: 9.77-30.8%), 2 (4.0%, 95% CI: 1.10-13.46%) patients respectively achieved grade 1, 2, and 3 tumor regression. Treatment-related adverse events (TRAEs) occurred in 28 (56.0%) LARC patients, including 26(52.0%) with grade I-II and 2 (4.0%) with grade III (1 with grade 3 immune-related colitis and 1 with grade 3 rash). PD-1 blockade plus long-course chemoradiotherapy (CRT) showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients. A larger randomized controlled study is desired to further validate the above findings.

[Surgical management of postoperative stricture of anastomosis after operation of intersphincteric resection for lower rectal cancer].

OBJECTIVE: To study surgical treatment of postoperative stricture of anastomosis for lower rectal cancer. METHODS: The data of 9 cases who were diagnosed as postoperative stricture of anastomosis after operation of intersphincteric resection for lower rectal cancer during January 2008 to June 2011 were analyzed retrospectively. Transanal excision of stricture were used in 3 cases diagnosed as membranous stricture. Transanal radial incision of stricture were used in 5 cases diagnosed as tubulous stricture. Biologic patch was used to repair the defect of the posterior wall of rectum after excision of severe stricture in 1 case. RESULTS: All 9 cases of postoperative stricture of anastomosis were cured by surgery. Anal dilation were performed every day by patients themselves after discharge. Digital examination showed that 1 to 2 fingers could pass through the anastomosis after operation. The patient whose rectal defect was repaired by biological patch underwent colonoscopy examination two weeks after operation. Colonoscopy showed that the biological patch had been filled with granulation and integrated into the surrounding intestinal tissue. All patients defecated without difficulty and the anal function of all patients was good after restoration of intestinal continuity. CONCLUSION: Aggressive surgery, combining with the use of biological patch if necessary is an effective therapy of postoperative stricture of anastomosis for lower rectal cancer.

[Technical improvements and results of individual cylindrical abdominoperineal resection for locally advanced low rectal cancer].

OBJECTIVE: To evaluate the safety and efficacy of individual cylindrical abdominoperineal resection (CAPR) for locally advanced low rectal cancer. METHODS: From June 2011 to February 2012, 11 patients with locally advanced low rectal cancer underwent individual CAPR. There were 7 male and 4 female patients, aged from 32 to 74 years with a median of 64 years. Forty-seven patients underwent classic CAPR from January 2008 to February 2012. Preoperative and postoperative parameters such as clinical information of patients, tissue morphometry and complications were compared. RESULTS: In the individual surgical group, 6 patients were treated with one side levator ani muscle totally or partially reserved, 3 patients with sacrococcyx reserved, and 2 patients with dissection close to the anterior rectal wall. Compared with classical surgery, the individual surgical specimens of horizontal section area ((2197 ± 501) mm(2)) and intrinsic muscle layer outer area ((1722 ± 414) mm(2)) were small, but the difference was not statistically significant (P = 0.150 and 0.167). The operative time, intraoperative blood loss, circumferential resection margin, total cross sectional tissue area, cross sectional tissue area outside the muscularis propria and bowel perforation rate between the two groups were not significantly different. Individual CAPR showed less incidence of chronic perineal pain (2/11, χ(2) = 6.116, P = 0.013) and sexual dysfunction (2/9, χ(2) = 4.412, P = 0.036) compared with classic CAPR. CONCLUSIONS: Individual CAPR has the potential to reduce the risk of chronic perineal pain and sexual dysfunction without influencing the radical effect when compare with classic CAPR for the treatment of low rectal cancer.

Interim result of phase II, prospective, single-arm trial of long-course chemoradiotherapy combined with concurrent tislelizumab in locally advanced rectal cancer.

Background: Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer, with modest benefits on tumor regression and survival. Since chemoradiotherapy combined with immune checkpoint inhibitors has been reported to have synergic effects. This study aims to explore the safety and efficacy of long-course chemoradiotherapy combined with concurrent tislelizumab as a neoadjuvant treatment regimen for patients with locally advanced rectal cancer. Methods: This manuscript reported the interim result of a prospective, multicenter, single-arm, phase II trial. Patients with mid-to-low locally advanced rectal cancer with clinical stages of cT3-4a N0M0 or cT1-4a N1-2M0 were included. The patients received long-course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles of capecitabine (1000 mg/m2, bid, day1-14) plus concurrent three 21-day cycles of tislelizumab (200 mg, day8), followed by a radical surgery 6-8 weeks after radiotherapy. The primary endpoint was the pathological complete response rate. (Clinical trial number: NCT04911517). Results: A total of 26 patients completed the treatment protocol between April 2021 and June 2022. All patients completed chemoradiotherapy, 24 patients received three cycles of tislelizumab, and 2 patients received two cycles. The pathological complete remission (ypT0N0) was achieved in 50% (13/26) of the patients with all proficient mismatch repair tumors. The immune-related adverse event occurred in 19.2% (5/26) of patients. Patients with no CEA elevation or age less than 50 were more likely to benefit from this treatment regimen. Conclusion: Long-course chemoradiotherapy combined with concurrent tislelizumab in patients with locally advanced low rectal cancer had favorable safety and efficacy, and does not increase the complication rate of surgery. Further study is needed to confirm these results.

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.

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.

Active surveillance in long period of total neoadjuvant therapy in rectal cancer: Early prediction of poor regression response.

Aim: To analyze locally advanced rectal cancer (LARC) patients and tumor characteristics during the period of total neoadjuvant therapy (TNT) and explore the risk factors that may predict poor tumor regression in response to TNT. Materials and methods: The data of 120 LARC patients who received TNT from December 2016 and September 2019 in our hospital were retrospectively analyzed. The clinicopathological characteristics of patients with different tumor regression responses were compared. Then we divided patients into two groups according to the carcinoembryonic antigen (CEA) clearance pattern after chemoradiation to explore risk factors that might predict the tumor regression response. Results: Of 120 LARC patients, 34 (28.3%) exhibited poor regression. Stratified analysis by tumor response showed that patients with poor response to TNT were more likely to obtain elevated CEA during the course of TNT (all P < 0.05). For those with elevated pretreatment CEA, fewer patients with poor response obtained normal CEA after chemoradiation (13.6% vs. 72.7%, P < 0.001). Besides, less patients' CEA levels in the poor response group decreased by greater than 50% after chemoradiation when compared with that in the good response group (18.2% vs. 60.6%, P = 0.002). Stratified analysis by CEA clearance pattern after chemoradiation showed patients who obtained an elevated pretreatment CEA and decreased by less than 50% after chemoradiation were more likely to have poor response to TNT compared to others (76.2% vs. 18.2%, P < 0.001). Logistic multivariate analysis revealed that cN2 (95% CI 1.553-16.448), larger tumors (95% CI 2.250-21.428) and CEA clearance pattern after chemoradiation (95% CI 1.062-66.992) were independent risk factors for poor tumor regression response. Conclusion: Approximately one-fourth of LARC patients with TNT achieved a poor regression response. Here, cN2, larger tumor size before treatment and elevated CEA levels were considered predictive features of a poor response. Active surveillance of CEA levels during the TNT course are potentially important, and CEA levels after chemoradiation might have important implications for the tumor response to TNT.

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.

Human acellular dermal matrix in the surgical management of rectal anastomotic stricture.

Anastomotic stricture after rectal resection is an intractable complication of rectal sugery. We present a case to introduce a new method to deal with rectal defect after dissecting anastomotic stricture by using biomaterial. The patient was diagnosed with rectal anastomotic stricture after radical resection for rectal carcinoma and was treated by reoperation. There was a defect in the posterior wall of the rectum after the anastomotic stenosis was dissected. We rapaired the defect successfully by using human acellular dermal matrix (HADM). The repair of rectal defect using HADM was easily and safely performed and provided long-term clinical success. It might be considered an innovative method for rectal defect repair.