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PD-1 blockade has been recommended as first-line therapy for nonresectable or metastatic mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, the safety and efficacy of neoadjuvant PD-1 blockade immunotherapy for locally advanced dMMR/MSI-H CRC remain unclear.From June 2020 to June 2022, 11 locally advanced dMMR/MSI-H CRC patients treated at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were enrolled. All patients received 6 sintilimab (Innovent, LTD) injections (200 mg/injection, every 3 weeks) before radical laparoscopic resection. The patient clinical and pathological data were analyzed retrospectively.dMMR was confirmed by immunohistochemistry for all patients. However, polymerase chain reaction (PCR) or next-generation sequencing confirmed MSI-H for only 90.9% (10/11) of the patients, while 1 patient had microsatellite stable (MSS) disease. After 6 injections of neoadjuvant anti-PD-1 therapy, 90.9% (10/11) of the patients (those confirmed to have dMMR and MSI-H disease) achieved pathological complete response (pCR). The other patient, who achieved major pathological response with residual tumor1%, had dMMR but MSS disease. No grade 3 or above immunotherapy-related adverse events occurred [Common Terminology Criteria for Adverse Events ; version 5.0]. Overall, 72.7% (8/11) of the patients had grade 1-2 immunotherapy-related adverse events . No operational mortality or complications occurred within 30 days after surgery.Single-agent neoadjuvant PD-1 antibody immunotherapy was safe and effective in locally advanced dMMR/MSI-H CRC. Dual confirmation of MMR and MSI status by immunohistochemistry and next-generation sequencing or PCR is necessary for dMMR/MSI-H CRC patients before immunotherapy. The immunotherapy regimen used in this study deserves further validation in phase II and III clinical studies.

Introduction Although neoadjuvant chemo-radiotherapy (CRT) achieves low local recurrence rates in locally advanced rectal cancer (LARC), it raises a lot of concerns about long-term anal and sexual functions. We explored the efficacy of preoperative chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in patients with LARC. Patients and Methods Patients with LARC evaluated by pelvic magnetic resonance imaging (MRI) were enrolled in this trial. All received 4 to 6 cycles of mFOLFOXIRI. MRI was performed to assess clinical response after chemotherapy. Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive radiation before surgery, whereas responders would have immediate total mesorectal excision (TME). Adjuvant chemotherapy with mFOLFOX6 (folinic acid, 5-fluorouracil, and oxaliplatin) was recommended. The primary endpoint was the proportion of tumor downstaging to ypT0-2N0M0. The secondary endpoints were pathologic complete response rate (pCR), 3-year disease-free survival rate, and safety. Results Overall, 106 patients were enrolled and received neoadjuvant mFOLFOXIRI chemotherapy. A total of 103 participants underwent TME surgery. Among 103 patients who completed at least 4 cycles of preoperative chemotherapy, 2 received short-term radiation before TME, and 12 underwent long-term CRT after MRI evaluation. The pCR rate was 20.4%, and the tumor downstaging rate was 42.7%. Among patients without preoperative long-term radiotherapy, the pCR rate and tumor downstaging rate were 17.4% and 41.3%, respectively. Among the per-protocol population, the tumor downstaging rate was 48.1%, and the pCR rate was 20.3%. The chemotherapy-related toxicity was well-tolerated. Conclusion Neoadjuvant chemotherapy with mFOLFOXIRI and selective radiation does not seem to compromise outcomes in LARC. It could be a reasonable alternative to CRT in previously untreated patients with LARC.

The visualization of a three-dimensional (3D) distribution of high-density data for scientific computations with limited computing resources under a network environment is difficult. This paper describes the implementation of an interactive 3D display of air pollutants in a network environment using the open-source WebGL class library, Three. js. A kd-tree is used to find the nearest point data to interpolate the 3D grid data of pollutants because the source data are scattered, which helps locate the data conveniently at the client's end. The binary file format is used to save and transfer data to reduce the number of network transmissions and to improve the speed of the image display. The results show that the visual effects and rendering speed are significantly improved on the web with the use of the proposed technology.

Background: Neoadjuvant chemoradiotherapy induced pathologic complete response (pCR) is associated with an excellent outcome for locally advanced rectal cancer (LARC) patients. However, it is unclear if patients achieving a pCR could further benefit from adjuvant chemotherapy (ACT). Methods: This retrospective study recruited consecutive LARC patients who received neoadjuvant therapy and total mesorectal excision from 2010 to 2018. The pCR patients who received different ACT cycles were compared by propensity score matching. Overall survival (OS), disease free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by the Kaplan-Meier method and log-rank test. Findings: In total, 1041 consecutive pCR patients (median age, 55.0 years; 56.9% male) were included. Of whom, 303 (29.1%) patients received non-ACT treatment, and 738 patients (70.9%) received fluoropyrimidine-based ACT (range, 1-12 cycles; median, 4 cycles). Specifically, 57.6% of patients (425/738) received 1-4 cycles of ACT, and 42.4% of patients (313/738) received 5 or more cycles of ACT. After 1:3 propensity matching, 712 patients who received ACT were matched to 297 patients who did not receive ACT. The 3-year outcomes (OS, DFS, LRFS, and DMFS) of the ACT and non-ACT subgroups were similar (all P > 0.05). Moreover, the subsets of patients who received different ACT cycle(s) (0 vs. 1-4 cycles and 0 vs. ≥ 5 cycles) also had similar 3-year OS, DFS, LRFS, and DMFS (all P > 0.05). In a stratified analysis, ACT treatment did not improve the survival outcomes (OS, DFS, LRFS and DMFS) of the high-risk patients who with baseline cT3-4 and/or cN1-2 (all P > 0.05). Interpretation: ACT administration could not provide additional survival benefits for neoadjuvant treatment-induced pCR LARC patients, even if is given much more cycles. Particularly, for the baseline high-risk subset patients, a pCR status is a guarantee of excellent outcome and ACT would be unnecessary. Funding Statement: This study was supported by Natural Science Foundation of China (No. 81872188), International Centre for Genetic Engineering and Biotechnology Research Grant (No. CRP/CHN16-04_EC), Guangdong Natural Science Foundation for Distinguished Young Scholar (No. 2014A030306016), the Science and Technology Planning Project of Guangdong Province (No. 2017B090901065). Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: This study was approved by the Clinical Ethics Review Committee at the Sixth Affiliated Hospital of Sun Yat-sen University.

Background Perioperative administration of dexamethasone may augment recurrence and mortality after tumor resection possibly by immunosuppression, which, unfortunately, has never been noted. We therefore carried out a retrospective study in rectal cancer to validate the hypothesis. Methods Five hundreds and fifteen patients with stage I to III rectal cancers who underwent a curative resection from June 2007 and June 2011 were enrolled in the current study. Patients who had been given intravenous (IV) dexamethasone (4–10 mg) postoperatively and/or intraoperatively were assigned to dexamethasone group. The outcome of dexamethasone group and non-dexamethasone group were compared. The primary outcome was disease-free survival (DFS) and overall survival (OS). Results dexamethasone group had significant lower three-year DFS (62.3% vs 71.8%, P = 0.026) and OS (74.1% vs 82.9%, P = 0.031) rate in comparison to non-dexamethasone group, the hazard ratios (HRs) of which were 1.59 (95% CI 1.05–2.39, P = 0.028) and 1.77 (95% CI 1.05–3.01, P = 0.034), respectively. Multivariate analysis revealed that administration of systemic dexamethasone were independently associated with DFS [adjusted HR 1.60 (95% CI 1.03–2.49, p = 0.039)], but for OS, dexamethasone didn't remain significant in this model. In the analyses of a subgroup of 428 patients (55/428 in dexamethasone group) without perioperative blood transfusion, dexamethasone had independently impact on both DFS and OS. Conclusion Patients not given dexamethasone had better three-year survival outcomes compared with patients given dexamethasone perioperatively. Our results indicate that rectal cancer patients treated with curative surgery may get survival benefit from avoiding low-dose perioperative dexamethasone.

Background: Zonulin is a newly discovered protein that has an important role in the regulation of intestinal permeability. Our previous study showed that probiotics can decrease the rate of infectious complications in patients undergoing colectomy for colorectal cancer.Objective: The objective was to determine the effects of the perioperative administration of probiotics on serum zonulin concentrations and the subsequent effect on postoperative infectious complications in patients undergoing colorectal surgery.Design: A total of 150 patients with colorectal carcinoma were randomly assigned to the control group (n = 75), which received placebo, or the probiotics group (n = 75). Both the probiotics and placebo were given orally for 6 d preoperatively and 10 d postoperatively. Outcomes were measured by assessing bacterial translocation, postoperative intestinal permeability, serum zonulin concentrations, duration of postoperative pyrexia, and cumulative duration of antibiotic therapy. The postoperative infection rate, the positive rate of blood microbial DNA, and the incidence of postoperative infectious complications—including septicemia, central line infection, pneumonia, urinary tract infection, and diarrhea—were also assessed.Results: The infection rate was lower in the probiotics group than in the control group (P < 0.05). Probiotics decreased the serum zonulin concentration (P < 0.001), duration of postoperative pyrexia, duration of antibiotic therapy, and rate of postoperative infectious complications (all P < 0.05). The p38 mitogen-activated protein kinase signaling pathway was inhibited by probiotics.Conclusions: Perioperative probiotic treatment can reduce the rate of postoperative septicemia and is associated with reduced serum zonulin concentrations in patients undergoing colectomy. We propose a clinical regulatory model that might explain this association. This trial was registered at http://www.chictr.org/en/ as ChiCTR-TRC-00000423.