Total laparoscopic distal gastrectomy with natural orifice specimen extraction (TLDG-NOSES) avoids the auxiliary incision needed in laparoscopic-assisted distal gastrectomy (LADG), potentially improving recovery. However, high-quality evidence on its safety and efficacy for distal gastric cancer surgery remains limited. Our study addresses this evidence gap by presenting the first multi-center, prospective, randomized controlled trial whether TLDG-NOSES improves postoperative recovery and reduces complications compared with LADG for distal gastric cancer. From April 2023 to January 2026, 232 patients with cT1-3N0-2M0 distal gastric adenocarcinoma were randomly assigned to TLDG-NOSES (n = 116) or LADG (n = 116). Operative time, blood loss, and lymph node yield were comparable between two groups (all P > 0.05). The overall complication rate was similar (6.9% vs. 8.6%; P = 0.624). Interestingly, TLDG-NOSES significantly shortened postoperative hospital stay (6.86 ± 2.82 vs. 8.38 ± 3.59 days; P < 0.001), accelerated first flatus (2.65 ± 1.39 vs. 3.39 ± 1.17 days; P<0.001) and liquid diet resumption (2.58 ± 0.97 vs. 3.69 ± 1.37 days; P < 0.001), and reduced pain on postoperative days 1-3 (all P < 0.05). Quality of life and cosmetic satisfaction were significantly better with TLDG-NOSES (both P < 0.001), while disease-free survival did not differ (P = 0.570), with no deaths in either group. TLDG-NOSES thus provides superior postoperative recovery, reduced pain, shorter hospital stay, and better quality of life without increasing complications, representing a safe and effective minimally invasive alternative for selected patients with distal gastric cancer, pending long-term oncological follow-up.

The recovery of voluntary movement after complete spinal cord injury (SCI) remains a formidable clinical challenge, as it necessitates both the reconstruction of disrupted spinal cord neural pathways and the restoration of the excitatory/inhibitory balance in sensorimotor neural circuits. To tackle this dual challenge, we transplanted a biomimetic spinal cord tissueoid (SCToid) into the injury cavity to structurally reestablish neural pathways, while concurrently applying tail nerve electrical stimulation (TNES) to functionally reactivate silent sensorimotor neural circuits. The results showed that combined SCToid transplantation and TNES promoted the regeneration of corticospinal tract and sensory afferent axons, which formed functional synapses with SCToid neurons. Moreover, monosynaptic tracer assays revealed direct innervation of lumbar spinal cord central pattern generator (CPG) interneurons by SCToid neurons; some CPG interneurons and sensory afferent axons also exhibited synaptic connectivity with motor neurons. Compared with the control group, transplantation of SCToids combined with TNES increased the ratio of excitatory/inhibitory synaptic terminals on the soma surfaces of CPG interneurons and motor neurons toward the pattern observed in normal spinal cords. This change ultimately enhanced the excitability of sensorimotor neural circuits and restored weight-bearing hindlimb walking. Collectively, these findings establish that reconstructing neural pathways and restoring the excitatory/inhibitory balance within CPG-regulated sensorimotor neural circuits are both necessary and sufficient to enable voluntary movement recovery. This synergistic mechanism establishes a robust theoretical framework for integrating biological and physical therapeutic strategies in SCI treatment, with specific implications for the combined application of transplantable engineered organoids and neurostimulation-based rehabilitation approaches.

Objectives Fear of cancer recurrence (FCR) is a prevalent source of psychological distress among patients with gastrointestinal cancer, yet its underlying regulatory mechanisms remain elusive. Grounded in Leventhal's self-regulation theory of illness, this study aimed to investigate direct and indirect effects of illness perception on FCR, focusing on the sequential mediating roles of psychological flexibility and maladaptive cognitive emotion regulation (MCER). Methodology A two-wave questionnaire survey was administered to 243 patients with GI cancer, recruited from The Third Affiliated Hospital of Sun Yat-sen University. Validated instruments included the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Brief Illness Perception Questionnaire (BIPQ), Acceptance and Action Questionnaire-II (AAQ-II), and the maladaptive subscale of the Cognitive Emotion Regulation Questionnaire (CERQ). Results The mean score of FCR was 27.61 ± 8.50, with 26.7% of the participants reaching clinical significance (≥34 points). Illness perception exerted a direct positive effect on FCR (β = 0.532, p < 0.001) and three significant indirect effects through: (1) psychological flexibility (22.5% of the total effect, effect = 0.078), (2) MCER (12.1%, effect = 0.042), and (3) the sequential pathway of both the mediators (4.3%, effect = 0.015). Collectively, indirect effects explained 38.9% of the total variance. Implications Psychological flexibility and MCER sequentially mediate the relationship between illness perception and FCR. These findings underscore the need to integrate cognitive-restructuring and psychological flexibility-enhancing techniques into clinical interventions for FCR reduction. Longitudinal designs and multi-center samples are warranted to strengthen generalizability.

The prognosis for advanced colorectal cancer (CRC) remains poor, and 5-fluorouracil (5-FU)-based chemotherapy is the primary treatment option. Understanding the mechanisms that limit the effectiveness of this therapy is therefore clinically important. However, the molecular drivers of acquired chemotherapy resistance in advanced CRC are not fully understood. Here we show that expression of PDZ-LIM domain-containing protein 4 (PDLIM4) is significantly upregulated following neoadjuvant chemotherapy in patients with advanced CRC, and that its expression level is closely associated with patient prognosis. PDLIM4 promotes acquired resistance to 5-FU by enhancing the stemness, anti-apoptotic capacity, and drug efflux of colorectal cancer stem cells. Mechanistically, PDLIM4 facilitates the accumulation of sphingolipids, particularly sphingomyelin, and regulates the PI3K/Akt signaling pathway. These findings identify PDLIM4 as a potential biomarker and therapeutic target for overcoming chemoresistance in advanced colorectal cancer, opening new avenues for future treatment strategies.

Background: Chemotherapy resistance is a great challenge in the treatment of gastric cancer (GC), so it is urgent to explore the prognostic markers of chemoresistance. PUF60 (Poly (U)-binding splicing factor 60) is a nucleic acid-binding protein that has been shown to regulate transcription and link to tumorigenesis in various cancers. However, its biological role and function in chemotherapy resistance of GC is unclear. Methods: The expression and prognostic value of PUF60 in GC chemotherapy-resistant patients were analyzed by databases and K-M Plotter. The functional effect of PUF60 on chemoresistance in GC was studied by by RNA interference, CCK8 test, colony formation test and apoptosis detection. Moreover, further validation and mechanism exploration were conducted in clinical samples. Results: PUF60 was highly expressed in both GC and chemoresistant tissues, and was positively correlated with poor prognosis in GC patients treated with 5-fluorouracil (5-FU). In addition, the knockdown of PUF60 significantly reduced the proliferation of human gastric cancer cells and increased sensitivity to chemotherapy drugs, such as 5-FU and cisplatin (CDDP). Mechanistically, PUF60 enhances chemotherapy resistance in gastric cancer (GC) cells by actively excluding chemotherapy drugs via the recombinant ATP Binding Cassette Transporter A1 (ABCA1) and ATP Binding Cassette Subfamily C Member 1 (ABCC1). This process further affects the cell cycle, reduces cell apoptosis, and ultimately promotes resistance to chemotherapy in GC. Conclusion: PUF60 promotes chemoresistance in GC, resulting in poor prognosis of GC patients treated with 5-FU, and providing a new idea for overcoming the chemoresistance in GC.

BACKGROUND:Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is characterized by poor response to traditional chemotherapy but heightened sensitivity to immune checkpoint inhibitors (ICIs). However, it is unclear whether envafolimab, a subcutaneous programmed death-ligand 1 inhibitor, provides comparable efficacy and safety as a neoadjuvant treatment in these patients compared to programmed cell death-1 inhibitors. METHODS:This open-label, single-arm phase 2 trial enrolled patients with locally advanced dMMR CRC. Participants received subcutaneous envafolimab (300 mg every 3 weeks) for three to four cycles. Tumor response was assessed using computed tomography/magnetic resonance imaging and endoscopy, with pathological response evaluated postsurgery. The primary end point was the complete response rate (CR), including clinical complete response (cCR) and pathological complete response (pCR). The secondary end points included R0 resection rate, 3-year disease-free survival, 5-year overall survival, and treatment-related adverse events (AEs). RESULTS:Between August 22, 2022, to August 22, 2024, 15 patients were enrolled and received at least one dose of envafolimab. Two patients were excluded from efficacy analyses due to loss of follow-up or patient refusal. Of the remaining 13 patients, seven (53.8%) achieved a complete response (two, cCR; five, pCR). The median time to CR was 3.1 months. Eleven patients underwent radical surgery, with no disease recurrence observed during follow-up. Treatment-related AEs were mild and of low incidence (28.6%), with only one patient experiencing a grade 3 fever. Subcutaneous administration of envafolimab demonstrated high patient convenience and satisfaction. CONCLUSIONS:This preliminary study suggests that envafolimab is a promising effective and safe neoadjuvant option for locally advanced dMMR CRC; confirmation in larger cohorts is awaited.

BACKGROUND:Membrane anatomy (MA) has become pivotal in modern surgery, enabling surgeons to operate within avascular natural planes to minimize concomitant injury. However, intraoperative identification of membranous structures remains challenging. Poor membrane visualization compromises both radical resection and functional preservation, underscoring the need for innovative solutions. METHODS:In this study, we develop a innovative tool, DeepGuide, to help surgeon make membrane visualization during surgery. Moreover, we design a single-arm prospective study to validated its effectiveness. A total of 60 patients undergoing laparoscopic radical resection for gastrointestinal tumors at The Third Affiliated Hospital of Sun Yat-sen University were enrolled. Primary outcomes included signal-to-background ratio (SBR), mesenteric integrity, absorbance of membrane specimens, and immunofluorescence staining of collagen components. RESULTS:DeepGuide significantly improved mesenteric integrity rates from 75% (conventional laparoscopy) to 98%. SBR under DeepGuide (2.30 ± 0.15) surpassed conventional lighting (1.32 ± 0.16). Absorbance analysis revealed reduced light absorption at 385 nm. Immunofluorescence confirmed collagen I/III enrichment in mesenteric submucosa, aligning with 385 nm-excited autofluorescence properties. CONCLUSION:DeepGuide revolutionizes intraoperative membrane visualization without requiring contrast agents. It enhances surgical precision and supports MA principles. These findings highlight DeepGuide's potential to redefine standards in oncologic surgery.

Immunotherapy based on the PD-1/PD-L1 axis blockade has no benefit for patients diagnosed with colon cancer liver metastasis (CCLM) for the microsatellite stable/proficient mismatch repair (MSS/pMMR)) subtype, which is known as an immune-desert cancer featuring poor immunogenicity and insufficient CD8+ T cell infiltration in the tumor microenvironment. Here, a multifunctional nanodrug carrying a cyclin-dependent kinase (CDK)1/2/5/9 inhibitor and PD-L1 antibody is prepared to boost the immune checkpoint blockade (ICB)-based immunotherapy against MSS/pMMR CCLM via reversing the immunosuppressive tumor microenvironment. To enhance the MSS/pMMR CCLM-targeting efficacy, we modify the nanodrug with PD-L1 knockout cell membrane of this colon cancer subtype. First, CDKs inhibitor delivered by nanodrug down-regulates phosphorylated retinoblastoma and phosphorylated RNA polymerase II and meanwhile arrests the G2/M cell cycle in CCLM to promote immunogenic signal release, stimulate dendritic cell maturation, and enhance CD8+ T cell infiltration. Moreover, CDKi suppresses the secretion of immunosuppressive cytokines in tumor-associated myeloid cells sensitizing ICB therapy in CCLM. Notably, the great efficacy to activate immune responses is demonstrated in the patient-derived xenograft model and the patient-derived organoid model as well, revealing a clinical application potential. Overall, our study represents a promising therapeutic approach for targeting liver metastasis, remolding the tumor immune microenvironment (TIME), and enhancing the response of MSS/pMMR CCLM to boost ICB immunotherapy.

Neurogenic erectile dysfunction, characterized by neurological repair disorders and progressive corpus cavernosum fibrosis (CCF), is an unbearable disease with limited treatment success. IL-17A exhibits a complex role in tissue remodelling. Nevertheless, the precise role and underlying mechanisms of IL-17A in CCF under denervation remain unclear. PCR array was employed to identified differentially expressed genes between neurogenic ED and normal rats. IL-17A expression and its main target cells were analyzed using Western blotting, immunofluorescence and immunohistochemistry. The phenotypic regulation of IL-17A on corpus cavernosum smooth muscle cells (CSMCs) was evaluated by cell cycle experiments and SA-β-Gal staining. The mechanism of IL-17A was elucidated using non-target metabolomics and siRNA technique. Finally, IL-17A antagonist and ABT-263 (an inhibitor of B-cell lymphoma 2/w/xL) were utilized to enhance the therapeutic effect in a rat model of neurogenic ED. IL-17A emerged as the most significantly upregulated gene in the corpus cavernosum of model rats. It augmented the senescence transformation and fibrotic response of CSMCs, and exhibited a strong correlation with CCF. Mechanistically, IL-17A facilitated CCF by activating the mTORC2-ACACA signalling pathway, upregulating of CSMCs lipid synthesis and senescence transition, and increasing the secretion of fibro-matrix proteins. In vivo, the blockade of IL-17A-senescence signalling improved erectile function and alleviated CCF in neurogenic ED. IL-17A assumes a pivotal role in denervated CCF by activating the mTORC2-ACACA signalling pathway, presenting itself as a potential therapeutic target for effectively overcoming CCF and erection rehabilitation in neurogenic ED. IL-17A is significantly upregulated in the corpus cavernosum under denervated conditions, promoting the senescence transformation and fibrotic response of corpus cavernosum smooth muscle cells, primarily through the activation of the mTORC2-ACACA signalling pathway. Blocking the IL-17A-senescence signalling axis can improve erectile function and alleviate corpus cavernosum fibrosis, suggesting that this pathway represents a potential therapeutic target for neurogenic erectile dysfunction.

Either extracorporeal anastomosis (EA) or intracorporeal anastomosis (IA) could be selected for digestive reconstruction in laparoscopic right hemicolectomy (LRH). However, whether LRH with IA is feasible and beneficial for overweight right-side colon cancer (RCC) is unclear. This study aims to investigate the feasibility and advantage of IA in LRH for overweight RCC. Forty-eight consecutive overweight RCC patients undergoing LRH with IA were matched with 48 consecutive cases undergoing LRH with EA. Both clinical and surgical data were collected and analyzed. The incidence of postoperative complications was 20.8

Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers’ fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.

Background Erectile dysfunction (ED) caused by intraoperative nerve injury is a major complication of pelvic surgery. Adipose-derived stem cells (ADSCs) have presented therapeutic potential in a rat model of bilateral cavernous nerve injury (BCNI), while inadequate in vivo viability has largely limited their application. Nuclear factor-E2-related Factor (Nrf2) is a key transcription factor that regulates cellular anti-oxidative stress. In this work, we investigated the effect of Nrf2 expression regulation on the viability of ADSCs, and explore its repair potential in a BCNI rat model. Results The survival time of tert-Butylhydroquinone (tBHQ)-ADSCs in BCNI model increased obviously. In addition, the tBHQ-ADSCs group presented better restoration of major pelvic ganglion (MPG) nerve contents and fibers, better improvement of erectile function, and less penile fibrosis than the other groups. Moreover, the expression of Nrf2 and superoxide dismutase 1 (SOD1) were higher than those of other groups. Conclusion Nrf2 could enhance the anti-oxidative stress ability of ADSCs, so as to improve the therapeutic effect of ADSCs on BCNI rat model.

Objectives: We aimed to explore reasonable lymph node classification strategies for left-sided colon cancer (LCC) patients.Methods: 48,425 LCC patients from 2010 to 2015 were identified in the US Surveillance, Epidemiology, and End Results database. We proposed an innovative revised nodal (rN) staging of the 8th American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) classification based on the cut-off value of retrieved lymph nodes and survival analyses in patients with LCC. Log odds of positive lymph nodes (LODDS) stage is a numerical classification strategy obtained by a formula that incorporates the numbers of retrieved and positive lymph nodes. To develop the TrN or TLODDS classification, patients with similar survival rates were grouped by combining T and rN or LODDS stage. The TrN or TLODDS classification was further evaluated in a validation set of 12,436 LCC patients from 2016 to 2017 in the same database and a Chinese application set of 958 LCC patients.Results: We developed novel TrN and TLODDS classifications for LCC patients that incorporated 7 stages with reference to the AJCC staging system. In comparison to the 8th AJCC TNM and TrN classifications, TLODDS classification demonstrated significantly better discrimination (area under the receiver operating characteristic curve, 0.650 vs. 0.656 vs. 0.661, p < 0.001), better model-fitting (Akaike information criteria, 309,287 vs. 308,767 vs. 308,467), and superior net benefits. The predictive performance of the TrN and TLODDS classifications was further verified in the validation and application sets.Conclusion: Both the TrN and TLODDS classifications have better discriminatory ability, model-fitting, and net benefits than the existing TNM classification, and represent an alternative to the current TNM classification for LCC patients.

Multiple anticancer drugs have been proposed to cause cell death, in part, by increasing the steady-state levels of cellular reactive oxygen species (ROS). However, for most of these drugs, exactly how the resultant ROS function and are sensed is poorly understood. It remains unclear which proteins the ROS modify and their roles in drug sensitivity/resistance. To answer these questions, we examined 11 anticancer drugs with an integrated proteogenomic approach identifying not only many unique targets but also shared ones-including ribosomal components, suggesting common mechanisms by which drugs regulate translation. We focus on CHK1 that we find is a nuclear H2O2 sensor that launches a cellular program to dampen ROS. CHK1 phosphorylates the mitochondrial DNA-binding protein SSBP1 to prevent its mitochondrial localization, which in turn decreases nuclear H2O2 . Our results reveal a druggable nucleus-to-mitochondria ROS-sensing pathway-required to resolve nuclear H2O2 accumulation and mediate resistance to platinum-based agents in ovarian cancers.

Aim The incidence and risk factors of low anterior resection syndrome (LARS) largely variate in different studies. In addition, there is lack of study on how patients evaluate the therapeutic effect of LARS. This single-center retrospective study aims to investigate the status of LARS in Chinese patients undergoing laparoscopic low anterior resection (LAR). Methods Consequent patients undergoing laparoscopic LAR and free from disease recurrence from January 2015 to May 2021 were issued with both LARS questionnaire and satisfaction survey. Related data were collected and analyzed. Results Both LARS questionnaires and self-made satisfaction survey were received from 261 eligible patients. The overall incidence of LARS was 47.1% (minor in 19.5%, major in 27.6%), decreased with the passage of postoperative time (64.7% within 12 months, and 41.7% within 12–36 months), and became stable 36 months later (39.7%). The most common symptoms were defecation clustering (n = 107/261, 41.0%) and defecation urgency (n = 101/261, 38.7%). According to the multivariable regression analysis, risk factors of major LARS were: 1 year increase in age (OR 1.035, 95% CI 1.004–1.068), protective stoma (OR 2.656, 95% CI 1.233–5.724) and T 3 − 4 stage (OR 2.449, 95% CI 1.137–5.273). Most patients complained defecation disorder (87.3%) to doctors and 84.5% got suggestions or treatments for it. However, only 36.8% patients thought the treatments worked for them. Conclusions LARS frequently occurs after laparoscopic LAR, while the therapeutic effect is not satisfying. Elder, advanced T-stage and protective stoma were risk factors for postoperative major LARS.

IntroductionThe Like-Smith (LSM) family plays a critical role in the progression of several cancers. However, the function of LSMs in chemoresistance of gastric cancer (GC) is still elusive.MethodsThe Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database and Tumor Immune Estimation Resource Analysis (TIMER) were utilized to analyze the expression, prognostic value and immune infiltration of LSMs in GC patients. Moreover, qPCR and immunohistochemistry (IHC) experiment were conducted with clinical samples.ResultsThe expression of LSMs was upregulated in GC tissues and most of LSMs were negatively correlated with overall survival of GC patients with 5-fluorouracil (5-FU) treatment. We further revealed that LSM5, 7 and 8 were hub genes of GEO (GSE14210). Besides, the qPCR results demonstrated that a higher level of LSM5 and LSM8 was associated with 5-FU chemoresistance in GC. Moreover, both TIMER and IHC revealed that a lower expression of LSM5 and LSM8 was correlated with high infiltration of T cells, regulatory T cells, B cells, macrophages, and neutrophils.DiscussionOur study systematically investigated the expression pattern and biological features of LSM family members in GC, and identified LSM5 and LSM8 as potential biomarkers in GC with 5-FU chemotherapy.

Background:Simultaneous or delayed surgery for synchronous colorectal liver metastases is performed in the clinic; which method is better is still up for debate. In particular, infectious complications are rarely compared. This study aims to investigate the differences between simultaneous and delayed surgery for synchronous colorectal liver metastases by comparing infectious complications and prognosis.Methods:Firstly, the patients' information from a single institution's database was retrospectively analyzed. Then the patients were divided into a simultaneous group and a delayed group according to synchronous colorectal liver metastases. Analyzing the postoperative complications within 30 days, the progression-free survival, and the overall survival in the two groups.Results:The simultaneous group had a higher neo-adjuvant chemotherapy rate (42.0% VS. 16.0% in the delayed group, P < 0.05) and laparoscopic surgery rate (89.8% VS. 72.0% in the delayed group, P < 0.05) than the delayed group. Moreover, the simultaneous group had a higher liver-related infection rate (17.0 VS. 0.0% in the delayed group, P < 0.05).Conclusion:Although there was no difference in survival rate between delayed and simultaneous surgeries, the delayed surgery have fewer liver-related infections compared with the simultaneous surgery in synchronous colorectal liver metastases patients. Delayed surgery could be a better treatment method for synchronous colorectal liver metastases patients.

In recent years，the concept of membrane anatomy has been widely applied in colorectal cancer surgery. The concept of "membrane" is associated with organ resection，radical tumor treatment，neurovascular anatomy and functional protection，which significantly promotes the further development of minimally invasive surgery for colorectal cancer. However，the definition of membrane structure，the establishment of membrane and surgical plane，especially for rectal cancer surgery，are still largely controversial.This study aims to investigate the concept and structure of low rectal cancer surgery related fascia，containing the fascia of low rectal cancer surgery，including proper fascia of rectum，pelvic fascia，Denonvilliers fascia，Waldeyer fascia and pelvicfascia，and discuss the principle of surgical plane for rectal cancer basing on fascia anatomy，to further standardize and improve the effect of minimally invasive surgery for low rectal cancer，and achieve the result of "radical tumor resection" and "function protection".

Urinary and sexual dysfunctions due to intraoperative pelvic autonomic nerve injury have become the most common complications of rectal cancer surgery, seriously affecting postoperative quality of life. How to protect the nerve and urogenital function while ensuring radical resection for rectal cancer has become the focus of research. We previously carried out a series of systematic studies on Denonvilliers fascia, an important anatomical structure closely related to protection of pelvic autonomic nerve, and demonstrated the importance of Denonvilliers fascia in preservation of intraoperative pelvic autonomic nerve and protection of postoperative urogenital function from aspects of anatomy, physiology, tissue, operation practice and so on. Meanwhile, based on the interim results of our multicenter randomized controlled study, we confirmed that total mesorectal excision with preservation of Denonvilliers fascia (innovative TME, iTME) could effectively reduce the incidence of postoperative urinary and sexual dysfunctions in male patients with mid-low rectal cancer, without sacrificing oncologic outcome. In this article, combined with our research results, we review the literature on anatomy research progress of Denonvilliers fascia to demonstrate the significance and research prospect of Denonvilliers fascia in the pelvic autonomic nerve preservation surgery for rectal cancer.

Gastrointestinal (GI) cancers are among the most lethal malignancies. The treatment of advanced­ stage GI cancer involves standard chemotherapeutic drugs, such as docetaxel, as well as targeted therapeutics and immunomodulatory agents, all of which are only moderately effective. We here show that Π electron-stabilized polymeric micelles based on PEG-b-p(HPMAm-Bz) can be loaded highly efficiently with docetaxel (loading capacity up to 23 wt%) and potentiate chemotherapy responses in multiple advanced-stage GI cancer mouse models. Complete cures and full tumor regression were achieved upon intravenously administering micellar docetaxel in subcutaneous gastric cancer cell line-derived xenografts (CDX), as well as in CDX models with intraperitoneal and lung metastases. Nanoformulated docetaxel also outperformed conventional docetaxel in a patient-derived xenograft (PDX) model, doubling the extent of tumor growth inhibition. Mechanistically, micellar docetaxel modulated the tumor immune microenvironment in CDX and PDX tumors, increasing the ratio between M1- and M2-like macrophages, and toxicologically, it was found to be very well-tolerated. These findings demonstrate that Π -conjugated polymeric micelles loaded with docetaxel hold significant potential for the treatment of advanced-stage GI cancers.