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.

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.

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.

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.

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.

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.

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.

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.

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 .

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.

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.

Serial Circulating Tumor DNA in Predicting and Monitoring the Effect of Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer: A Prospective Multicenter Study.

PURPOSE: We investigated the value of circulating tumor DNA (ctDNA) in predicting tumor response to neoadjuvant chemoradiotherapy (nCRT), monitoring tumor burden, and prognosing survival in patients with locally advanced rectal cancer (LARC). EXPERIMENTAL DESIGN: This prospective multicenter trial recruited 106 patients with LARC for treatment with nCRT followed by surgery. Serial ctDNAs were analyzed by next-generation sequencing at four timepoints: at baseline, during nCRT, presurgery, and postsurgery. RESULTS: In total, 1,098 mutations were identified in tumor tissues of the 104 patients being analyzed (median, seven mutations/patient). ctDNA was detected in 75%, 15.6%, 10.5%, and 6.7% of cases at the four timepoints, respectively. None of the 29 patients with pathologic complete response (ypCR) had preoperative ctDNA detected. The preoperative ctDNA-positive rate was significantly lower in the well-responded patients with pathologic tumor regression grade of ypCAP 0-1 than ypCAP 2-3 group (P < 0.001), lower in ypCR than non-ypCR group (P = 0.02), and lower in pathologic T stage (ypT) 0-2 than ypT 3-4 group (P = 0.002). With a median follow-up of 18.8 months, 13 patients (12.5%) experienced distant metastasis. ctDNA positivity at all four timepoints was associated with a shorter metastasis-free survival (MFS; P < 0.05). Multivariate analyses showed that the median variant allele frequency (VAF) of mutations in baseline ctDNA was a strong independent predictor of MFS (HR, 1.27; P < 0.001). CONCLUSIONS: We show that ctDNA is a real-time monitoring indicator that can accurately reflect the tumor burden. The median VAF of baseline ctDNA is a strong independent predictor of MFS.

Successful management of tubular colonic duplication using a laparoscopic approach: A case report and review of the literature.

BACKGROUND: Alimentary duplication is a rare congenital disease with a reported incidence of 1 per 4500 persons, although the exact incidence has been difficult to ascertain. According to previous reports, the most common site of duplication is the ileum, and colonic duplication is rare. Due to different types and locations of the duplication, the manifestations are varied, which makes establishing an accurate diagnosis before surgery a challenge. CASE SUMMARY: A 17-year-old female patient sought evaluation in our department with constipation and chronic abdominal pain for 12 years; she had difficulty defecating and had dry stools since she was a child. An abdominal computed tomography revealed two extremely enlarged loops of bowel full of stool-like intestinal contents in the left lower abdomen, which led us to consider the possibility of colonic duplication. A laparoscopic exploration was performed, which revealed a tubular duplicated colon that shared a common opening with the transverse colon. A left hemi-colectomy was performed with a side-to-side anastomosis. The pathologic results confirmed the diagnosis. At the 6-mo follow-up, the patient was doing well without constipation or abdominal pain. CONCLUSION: Colonic duplication is a rare alimentary abnormality in adults. Due to the non-specific manifestations and low incidence, it is usually difficult to make an accurate diagnosis pre-operatively. Surgery is the mainstay of treatment, even though some patients are asymptomatic.

Extralevator abdominoperineal excision for advanced low rectal cancer: Where to go.

Since its introduction, extralevator abdominoperineal excision (ELAPE) in the prone position has gained significant attention and recognition as an important surgical procedure for the treatment of advanced low rectal cancer. Most studies suggest that because of adequate resection and precise anatomy, ELAPE could decrease the rate of positive circumferential resection margins, intraoperative perforation, and may further decrease local recurrence rate and improve survival. Some studies show that extensive resection of pelvic floor tissue may increase the incidence of wound complications and urogenital dysfunction. Laparoscopic/robotic ELAPE and trans-perineal minimally invasive approach allow patients to be operated in the lithotomy position, which has advantages of excellent operative view, precise dissection and reduced postoperative complications. Pelvic floor reconstruction with biological mesh could significantly reduce wound complications and the duration of hospitalization. The proposal of individualized ELAPE could further reduce the occurrence of postoperative urogenital dysfunction and chronic perianal pain. The ELAPE procedure emphasizes precise anatomy and conforms to the principle of radical resection of tumors, which is a milestone operation for the treatment of advanced low rectal cancer.

Rhizoma Paridis total saponins alleviate H2O2­induced oxidative stress injury by upregulating the Nrf2 pathway.

Rhizoma Paridis total saponins (RPTS) is an active substance isolated from the traditional Chinese medicine Rhizoma Paridis, which possesses multiple biological activities. The aim of the present study was to explore the roles and mechanisms of RPTS in oxidative stress injury of ARPE­19 human retinal pigment epithelial cells. Cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP) and apoptosis were determined by Cell Counting kit­8 assay and flow cytometry, respectively. Enzyme­linked immunosorbent assay was performed to detect the expression of oxidative stress markers. Western blotting and reverse transcription­quantitative polymerase chain reaction were used to determine the expression levels of related genes and proteins. The results revealed that RPTS enhanced cell viability and reduced H2O2­induced oxidative stress of ARPE­19 human retinal pigment epithelial cells. RPTS increased the MMP of ARPE­19 cells compared with in H2O2­treated ARPE­19 cells. In addition, RPTS suppressed ROS production and apoptosis of H2O2­treated ARPE­19 cells. Additionally, RPTS modulated the expression levels of apoptosis­associated proteins and the nuclear factor 2­related factor 2 (Nrf2) pathway. In conclusion, RPTS alleviated H2O2­induced oxidative stress injury by upregulating the Nrf2 pathway. The potential effects of RPTS on protection against H2O2­induced apoptosis of ARPE­19 cells suggested that RPTS may be a potential therapeutic target for preventing age­related macular degeneration.

Replication and transcriptionomic analysis of human noroviruses in human intestinal enteroids.

Human noroviruses (HuNoVs) are a major cause of epidemic and sporadic cases of acute gastroenteritis worldwide. Recently, human intestinal enteroids (HIEs) have been shown to support the replication of HuNoVs, and be an excellent model to study HuNoV-host interactions. We implemented the HIE system in our laboratory and investigated the global molecular events associated with the mechanism of HuNoV-host interactions. Successful replication was observed for several norovirus GII genotypes, and totally 5,376 genes with different expression in HIEs were identified during infection. Bioinformatics analysis revealed that several important pathways, especially the "Signal transduction" and "Immune system" pathways, were involved in the HuNoV-host interaction. Quantitative PCR results validated that IFN-λ instead of IFN-ß was elevated in HIEs after infection. Our study showed the holistic understanding of the transcriptome events in the HIE model infected by HuNoVs, and highlighted the important role of IFN-λ signaling in the HuNoV-host interactions.

Successful treatment of obstructing colonic cancer by combining self-expandable stent and neoadjuvant chemotherapy: A case report.

BACKGROUND: Surgery 5-10 d after stent insertion was recommended by the European Society of Gastrointestinal Endoscopy for obstructing colonic cancer. For some obstructive patients, this may be not a good choice. Here, we report the successful treatment of obstructing colonic cancer by combining self-expandable stent and neoadjuvant chemotherapy. CASE SUMMARY: The patient was a 72-year-old man who was admitted with a chief complaint of abdominal pain for more than 1 mo. Computed tomography (CT) scanning revealed that there was a mass in the descending colon, which led to intestinal obstruction. On admission, a series of therapeutic measures, such as fasting and water deprivation, gastrointestinal decompression, total parenteral nutrition, and octreotide acetate, were taken to improve the obstructive symptoms. At the same time, a self-expandable metal stent was successfully placed across the stenosis, and a biopsy was obtained and diagnosed as adenocarcinoma. CT scanning 14 d after insertion of the stent revealed that the intestine was swollen significantly. Systemic chemotherapy with modified FOLFOX6 (mFOLFOX6) was administered. After two courses of mFOLFOX6, CT scanning showed clearly that swelling of the intestine was improved. Subsequently, the patient underwent left hemi-colectomy without stoma placement. The postoperative course was uneventful, and he has been disease-free for 6 mo after surgery. CONCLUSION: This modified treatment strategy may provide an alternative therapy for patients with obstructing colonic cancers.

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.