Xiao Zhang

Locally advanced rectal cancer (LARC) staged as mrT3 could be further subdivided into mrT3a to T3d based on depth of tumor invasion through the muscularis propria. Limited evidence exists to compare the differences across subgroups. Clinical data from patients between January 2018 and 2022 were collected. The study included patients with mrT3 LARC who received neoadjuvant chemoradiotherapy (NCRT). Based on depth of invasion through muscularis propria, patients were categorized into three groups: mrT3a (< 5 mm), mrT3b (5~10 mm), mrT3c~d group (> 10 mm). The outcomes were disease-free survival (DFS), pathological complete response (pCR), tumor recurrence and metastasis. A total of 295 patients were identified, including 65 (22.0%) in mrT3a, 155 (52.5%) in mrT3b, and 75 (25.5%) in mrT3c~d group. The tumor vertical diameter was larger in mrT3c/d group (46.3 ± 13.7 mm), compared to mrT3a (39.4 ± 14.3 mm) and mrT3b (39.8 ± 12.1 mm) groups (P < 0.001). The positive rates of mesorectal fascia (61.3% vs. 30.3% vs. 7.7%, P < 0.001) and extramural vascular invasion (62.7% vs. 40.0% vs. 27.7%, P < 0.001) were significantly higher in mrT3c/d group compared to mrT3a and mrT3b groups. The estimated pCR rates were 33.9% for mrT3a, 32.3% for mrT3b, and 21.3% for mrT3c/d group (P = 0.172). The median follow-up time was 43 (29-58) months. The metastasis and local recurrence rates were 8.8% and 2.4%. The 3y-DFS rates were 92.2% for mrT3a, 87.7% for mrT3b, and 86.2% for mrT3c/d (P = 0.549). Despite mrT3c/d patients presenting with more aggressive baseline features, standardized NCRT followed by radical surgery effectively mitigated survival disparities across mrT3 substages. These findings suggest that mrT3 subclassification may not independently predict long-term survival outcomes when patients receive optimal multimodal therapy.

Purpose To evaluate the predictive value of MRI-determined variables for pathological complete response (pCR) in locally advanced rectal cancer (LARC) patients following neoadjuvant chemoradiotherapy (NCRT). Methods Clinical data were collected from patients who received NCRT between January 2019 and 2022. Patients with rectal adenocarcinoma, cT3-4N0, or TanyN1-2 were included. pCR was defined pT0N0. Patients were divided into pCR and non-pCR group. Logistic regression analysis was performed to identify factors associated with pCR. A nomogram model was constructed to validate its predictive ability and accuracy. Results A total of 585 patients were identified, with 144 (24.6%) in the pCR group and 441 (75.4%) in the non-pCR group. Patients with mrT2-3 (OR 6.41, P < 0.001), mrN0 (OR 2.17, P < 0.001), circumferential occupation range < 1/2 cycles (OR 2.11, P < 0.001), tumor vertical diameter < 36 mm (OR 2.10, P < 0.001), negative mesorectal fascia (OR 3.21, P < 0.001), and extramural vascular invasion (OR 5.68, P < 0.001) were more likely to achieve higher pCR rates. Logistic regression analysis revealed that mrT2-3 (OR 3.50, P < 0.001), tumor vertical diameter < 36 mm (OR 2.57, P < 0.001), and negative extramural vascular invasion (OR 4.03, P < 0.001) were independent protective factors for pCR. A nomogram was developed to predict pCR, achieving a C-index of 0.778. Conclusion Patients with mrT2-3, tumor vertical diameter < 36 mm, and negative extramural vascular invasion are more likely to achieve pCR after NCRT.

Background: The traditional neoadjuvant chemoradiotherapy (nCRT) combined with total mesorectal excision has been widely accepted as the standard treatment for patients with locally advanced rectal cancer (LARC). New strategies such as total neoadjuvant therapy (TNT) and neoadjuvant immunotherapy have shown great promise in certain patient populations. Currently, there is an urgent need to stratify patients before treatment to adopt the appropriate neoadjuvant strategies. Our previous study has shown that circulating tumour DNA (ctDNA) effectively reflects tumour burden and genetic characteristics and has significant predictive value for tumour recurrence, demonstrating great potential in guiding the choice of neoadjuvant strategies. Methods and analysis: The CINTS-R trial is a multicentre, open-label, randomised controlled trial designed to evaluate the efficacy and safety of a ctDNA-guided neoadjuvant treatment strategy compared with conventional neoadjuvant therapy regime in patients with LARC. The trial will enrol 470 patients diagnosed with LARC (staged cT3-4N0 or cTanyN1-2) with tumours located ≤12 cm from the anal verge across seven centres in China. Patients will be randomly assigned in a 2:1 ratio to the experimental group or the control group. Patients in the experimental group will receive different intensities of neoadjuvant chemoradiotherapy (TNT or modified nCRT) or neoadjuvant immunotherapy based on the molecular features of the tumour, baseline ctDNA concentration and changes in ctDNA status early in treatment. Patients in the control group will receive modified nCRT. The primary endpoint is the 2-year disease-related treatment failure rate. The secondary endpoints include time to recurrence, 2-year overall survival, 2-year disease-free survival, clinical complete response (cCR) rate, near cCR rate and pathologically complete response rate, pathological tumour regression grade and quality of life. Ethics and dissemination: This protocol has been approved by the ethics committee of Peking Union Medical College Hospital, with approval number I-23PJ157, and by the institutional review boards of all the participating centres. All data will be collected and stored in a specially designed database. The results of our trial will be disseminated through peer-reviewed publications and presented at national and international academic conferences. Trial registration number: This trial is registered on ClinicalTrials.gov and the registration ID is NCT05601505 .

Wound dressing is an important tool for wound management. Designing wound dressings by combining various novel materials and drugs to optimize the peri-wound environment and promote wound healing is a novel concept. Hydrogels feature good ductility, high water content, and favorable oxygen transport, which makes them become some of the most promising materials for wound dressings. In addition, nanomaterials exhibit superior biodegradability, biocompatibility, and colloidal stability in wound healing and can play a role in promoting healing through their nanoscale properties or as carriers of other drugs. By combining the advantages of both technologies, several outstanding and efficient wound dressings have been developed. In this paper, we classify nano-based hydrogel dressings into four categories: hydrogel dressings loaded with a nanoantibacterial drug; hydrogel dressings loaded with oxygen-delivering nanomedicines; hydrogel dressings loaded with nanonucleic acid drugs; and hydrogel dressings loaded with other nanodelivered drugs. The design ideas, advantages, and challenges of these nano-based hydrogel wound dressings are reviewed and analyzed. Finally, we envisaged possible future directions for wound dressings in the context of relevant scientific and technological advances, which we hope will inform further research in wound management.

Background: Prediction and management of short-term postoperative complications in patients with colorectal cancer are essential in postoperative rehabilitation. Through CT scan images, we can easily measure some parameters of abdomen anatomic characteristics. This study aimed to assess whether there is a relationship between the abdomen anatomic characteristics and short-term postoperative complications.Materials and methods: We conducted a retrospective study. Eighty patients in each complication group and non-complication group were recruited with propensity score match. Demographics, perioperative laboratory results and surgical information were collected and compared between groups with univariate analysis. Significant elements were brought into subsequent logistic regression analysis and ROC analysis for further identification.Results: Univariate analysis showed that preoperative white blood cells, preoperative neutrophil counts, rectus abdominis thickness (RAT), subcutaneous fat thickness (SFT), and abdomen depth (AD) were significantly different between the complication group and non-complication group. Logistic regression analysis demonstrated that higher RAT (p = 0.002), SFT (p < 0.001) and AD (p < 0.001) independently predicted the incidence of short-term postoperative complications.Conclusions: In this study on patients undergoing radical resection of colorectal cancer, abdomen anatomic characteristics including higher RAT, SFT and AD are associated with an increased risk of short-term postoperative complications.

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.

Background: Immunotherapy for colorectal cancer has developed rapidly in the past decade. Many high-quality clinical trials examining the application of PD-1/PD-L1 inhibitors in patients with metastatic colorectal cancer (mCRC) have been conducted in recent years. However, the clinical benefits, including the efficacy and safety of these treatments against mCRC, remain controversial. Hence, we conducted this meta-analysis on the clinical benefits of PD-1/PD-L1 inhibitors in patients with mCRC. Methods: We searched online databases including MEDLINE, Embase, Cochrane Library, and Web of Science, from inception to January 4, 2021. The outcomes related to efficacy and safety were extracted and analyzed. Subgroup analyses were conducted according to the categories of dMMR-MSI-H (tumors with mismatch repair deficiency and high levels of microsatellite instability) ≥ 5% vs. dMMR-MSI-H < 5%, monotherapy vs. combination therapy, PD-1 inhibitors vs. PD-L1 inhibitors, and nivolumab vs. pembrolizumab. Results: Fourteen studies including 1129 subjects were included in our systematic review. The overall complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD) rates were 0.01 (95% CI 0.00–0.04), 0.04 (95% CI 0.05–0.26), 0.27 (95% CI 0.22–0.32), and 0.44 (95% CI 0.30–0.58), respectively. The overall objective response rate (ORR) and disease control rate (DCR) were 0.16 (95%CI 0.06–0.31) and 0.50 (95%CI 0.35–0.65), respectively. The overall rate of adverse events (AEs) and severe adverse responses (SAEs) were 0.84 (95% CI 0.72–0.92) and 0.30 (95% CI 0.20–0.41), respectively. The ORRs of the dMMR-MSI-H ≥ 5% and dMMR-MSI-H < 5% subgroups were 0.40 (95% CI 0.30–0.51) and 0.04 (95% CI 0.00–0.09), respectively. Conclusions: PD-1/PD-L1 inhibitors produced encouraging clinical benefits including the response rate in the treatment of dMMR-MSI-H mCRC. They actually have been influenced by the present state of mCRC therapy including pMMR-MSI-L mCRC. Nevertheless, additional multi-center prospective studies are still expected. Trial registration: We have registered this study in the International Prospective Register of Systematic Reviews (PROSPERO), and the registration number is CRD42021249601.

Digestive tumours, a common kind of malignancy worldwide, have recently led to the most tumour-related deaths. Angiogenesis, the process of forming novel blood vessels from pre-existing vessels, is involved in various physiological and pathological processes in the body. Many studies suggest that abnormal angiogenesis plays an important role in the growth, progression, and metastasis of digestive tumours. Therefore, anti-angiogenic therapy is considered a promising target for improving therapeutic efficacy. Traditional strategies such as bevacizumab and regorafenib can target and block the activity of proangiogenic factors to treat digestive tumours. However, due to resistance and some limitations, such as poor pharmacokinetics, their efficacy is not always satisfactory. In recent years, nanotechnology-based anti-angiogenic therapies have emerged as a new way to treat digestive tumours. Compared with commonly used drugs, nanoparticles show great potential in tumour targeted delivery, controlled drug release, prolonged cycle time, and increased drug bioavailability. Therefore, anti-angiogenic nanoparticles may be an effective complementary therapy to treat digestive tumours. In this review, we outline the different mechanisms of angiogenesis, the effects of nanoparticles on angiogenesis, and their biomedical applications in various kinds of digestive tumours. In addition, the opportunities and challenges are briefly discussed.