BACKGROUND:The prognostic value of conventional high-risk factors and the benefits of adjuvant chemotherapy (ACT) in stage II colon cancer with deficient mismatch repair (dMMR) remain controversial. The function of ACT in stage II dMMR colon cancer and survival results were assessed in this research. METHODS:273 patients with stage II dMMR colon cancer who had curative resection between August 2010 and October 2023 underwent a retrospective analysis. Clinicopathologic variables, postoperative treatment strategies, and survival endpoints were systematically assessed. Independent prognostic factors were identified using a multivariable Cox proportional hazards regression model. For subgroup analyses, a propensity score-matched (PSM) approach was used to minimize intergroup imbalances. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier approach. RESULTS:177 (64.8%) patients had at least one high-risk factor. With a median follow-up of 62.6 months, the estimated 5-year OS and DFS rates were 94.7% and 89.8%. Age ≥ 65 years and examination of fewer than 12 lymph nodes were independently associated with OS. For DFS, age ≥ 65 years, LNs < 12, and receipt of ACT were identified as independent prognostic factors. According to subgroup analyses, ACT was linked to better OS and DFS in patients with high-risk features or poorly differentiated histology. Results were similar after propensity score matching. CONCLUSION:Traditional high-risk features also exert prognostic impact on this population. ACT appeared to be associated with improved survival in selected high-risk patients, particularly those with poorly differentiated histology.

BACKGROUND Enterostomy is a routine procedure in colorectal surgery; however, stoma-related complications remain substantial. Variations in surgical performance, limited formal training, and insufficient collaboration between surgeons and enterostomal therapists contribute to inconsistent enterostomy management. Nevertheless, surgeons' attitudes and technical practices toward stoma creation remain poorly characterized. AIM To characterize Chinese surgeons' attitudes toward enterostomy and to describe their technical preferences in stoma creation. METHODS Through a comprehensive literature review, pilot testing, and expert consultation, a 37-item self-administered electronic questionnaire was developed. The survey was distributed through professional surgical networks and collaborative groups between June and July 2022, and eligible surgeons participated voluntarily. Following ethical approval in 2024, the data were retrospectively curated and analyzed. Descriptive analyses and subgroup comparisons were performed using the chi(2) test, Fisher's exact test, or Cram & eacute;r's V. RESULTS A total of 417 responses were received, and 16 duplicate questionnaires from the pilot phase were excluded. Among the 401 surgeons included, 60.4% reported having received formal training in stoma creation. Although 99.5% considered stoma-related complications to be related to surgical techniques, only 56.1% had participated in dedicated discussions or formal training programs. 37.2% reported that the adoption rate of preoperative stoma site marking was below 60%, and 44.6% considered the site selection performed by enterostomal therapists to be inaccurate. Substantial variability was observed in preoperative stoma site marking preferences and technical maneuvers during stoma creation, with no single approach predominant. No significant differences in self-reported attitudes toward enterostomy were observed between the junior and senior surgeons. Surgeons from secondary and lower-tier hospitals appeared to have less exposure to theoretical and practical training than those from tertiary hospitals. CONCLUSION Chinese surgeons demonstrate marked variability in the attitudes, concepts, and technical maneuvers in enterostomy creation. This heterogeneity may contribute to inconsistent clinical practices and variable patient outcomes. Future studies should focus on developing and validating a standardized training curriculum for enterostomy creation.

Cancer immunotherapies, such as programmed cell death protein 1 (PD-1) inhibitors, cancer vaccines, and chimeric antigen receptor T cells (CAR-T cells), have become first-line treatments for multiple tumors by eliciting antitumor immunity. However, their limited efficacy in immunosuppressive tumors, particularly Head and Neck Squamous Cell Carcinoma (HNSCC), underscores the urgent need for versatile therapeutics. Hereinto, we develop an injectable hydrogel incorporating Mg microparticles and Fe 3 O 4 magnetic nanoparticles (Mg/Fe 3 O 4 @Gel) to enhance antitumor immunotherapy, achieving potent vaccine-like tumor suppression against both distant and newly emerging tumors. Under an alternating magnetic field, Mg/Fe 3 O 4 @Gel induces HNSCC cell death via magnetic hyperthermia, while simultaneously triggering mitochondrial dysfunction and disrupting redox homeostasis, resulting in a 72% apoptosis rate. Meanwhile, the released corrosion products effectively neutralize the intracellular acidic environment, further enhancing the efficacy of systemic immunotherapy. Mechanistic studies induce Mg/Fe 3 O 4 @Gel immunogenic cell death via Ltf regulation, facilitating effective eradication of both primary and distant lesions. Moreover, vaccination with Mg/Fe 3 O 4 @Gel-killed tumor cells and adoptive CD3 + T cell transfer confer robust antitumor immunity, achieving 80% tumor growth suppression in immunodeficient models and surpassing typical clinical outcomes. Overall, our study highlights the potential of this metal-based hydrogel as a universal platform to enhance antitumor efficacy through a synergistic immunotherapeutic strategy.

BackgroundPredicting occult lymph node metastasis in early-stage tongue squamous cell carcinoma remains a clinical challenge because traditional markers, such as depth of invasion, exhibit limited accuracy. This study aimed to identify spatial immunological biomarkers to improve risk stratification and clinical decision-making.MethodsOlink proteomic profiling was conducted to screen for metastasis-associated biomarkers. Subsequently, multiplex immunofluorescence coupled with artificial intelligence-powered spatial analysis was utilized to evaluate the microenvironment in primary lesions and paired cervical lymph nodes. A novel “Spatial Availability Index” was applied to map cellular distribution, and diagnostic performance was evaluated using receiver operating characteristic curve analysis.ResultsArginase-1 (ARG1) was identified as a top candidate biomarker, exhibiting a unique “tissue-low, serum-high” expression pattern in cases with occult metastasis. Spatial analysis revealed a significant depletion of ARG1+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in both primary tumors and paired lymph nodes during metastatic progression. Specifically, the reduction of these intact cells was most pronounced within a 35-μm proximal segment from the tumor boundary. This localized cellular loss inversely correlated with an accumulation of neutrophil extracellular traps (NETs) at the peritumoral interface, indicating that ARG1+ PMN-MDSC-associated spatial alterations coincide with NET-associated remodeling at the peritumoral interface. Integrating the intrastromal density of ARG1+ PMN-MDSCs with depth of invasion significantly enhanced the diagnostic accuracy for occult metastasis (Area Under the Curve = 0.8318) compared to using depth of invasion alone.ConclusionsEarly metastatic risk is driven by localized alterations within the myeloid compartment, characterized by the transition of intact ARG1+ PMN-MDSCs to NETs within a 35-μm peritumoral hotspot. This spatial biomarker provides a high-resolution tool to optimize patient selection for elective neck dissection.

This study compares the clinical efficacy of natural orifice specimen extraction surgery (NOSES) combined with enhanced recovery after surgery (ERAS) to that of conventional laparoscopic surgery for treatment of rectal cancer. This two-armed retrospective observational study without case-matched pairs included 100 patients with rectal cancer selected from the General Surgery Department of the Second Affiliated Hospital of Nanchang University from January 2019 to December 2021. The observation group comprised 49 patients treated with NOSES and ERAS, the control group 51 patients with laparoscopic surgery. Postoperative C‑reactive protein (CRP), procalcitonin (PCT), interleukin‑6 (IL-6), white blood cell count, percentage of neutrophils, K+ concentration, postoperative peristalsis recovery time, first time out-of-bed activity, first liquid feeding time, removal time of urinary and drainage tubes, hospital stay and intraoperative blood loss, number of lymph nodes detected, positive margin rate, incidence of complications, pain, and disease-free survival (DFS) were compared. The observation group had lower postoperative CRP, PCT, and IL-6 levels than controls (P < 0.05), but there was no significant difference in K+ (P > 0.05). Times of intestinal peristalsis recovery, first out-of-bed activity, first liquid feeding, urinary and drainage tube removal, and hospitalization were shorter in the observation group (P < 0.05), but the duration of surgery was longer (P < 0.05). There were no significant differences in intraoperative bleeding, number of lymph nodes detected, rate of positive resection margins, or incidence of complications (P > 0.05). The observation group had lower pain scores on the first, second, and third day after surgery (P < 0.05). There was no significant difference in DFS between the groups (P > 0.05). NOSES with ERAS for treatment of rectal cancer can reduce the surgical incision and alleviate the stress reaction and postoperative pain without increasing the recurrence rate. It is thus safe and feasible, improves therapeutic efficacy, reduces the complication rate, and is worthy of popularization and application.

BACKGROUND:To determine outcomes of MRI-assisted radiosurgery (MARS) for salvage brachytherapy using the radioisotope 103Pd after various upfront treatments including surgery, external beam radiotherapy, and brachytherapy. METHODS:We retrospectively reviewed data for patients who underwent salvage MARS for intraprostatic lesions or prostate bed recurrences from 2016 to 2022. Biochemical recurrence, prostate cancer-specific, and overall survival, and the cumulative incidences of toxicities, were determined by Kaplan-Meier estimates. Cox proportional hazards models were used to determine associations between clinical and treatment variables and risk of toxicity. RESULTS:Study included 31 patients with local recurrence after initial definitive treatment. Four (13%) were initially treated with prostatectomy and salvage radiation, twenty-four (77%) with external beam radiation, and three with brachytherapy. Most had intermediate- or high-risk prostate cancer at the time of diagnosis. Twenty-two patients (71%) had focal-gland and nine (29%) had whole-gland MARS LDR salvage brachytherapy. Median follow-up was 35-28 months. By last follow-up, 5 patients (16%) experienced recurrence and started ADT, 3 patients started ADT before experiencing recurrence due to physician discretion, and 23 patients (74%) remained without recurrence. No patients died of prostate cancer. Median PSA nadir for recurrence-free patients was 0.2 ng/mL (range, 0-0.9 ng/mL). Grade 3 toxicities occurred in 4 patients (13%) including 3 patients (13%) with genitourinary events only and 1 patient (3%) with both a grade 3 genitourinary and a grade 3 gastrointestinal event. CONCLUSIONS:In this modern series of patients undergoing salvage MARS with 103Pd, we observed acceptable toxicity and early, promising biochemical disease control. These findings highlight the broader applicability of salvage MARS regardless of upfront treatment modality.

Obesity is linked to an increased cancer risk, and probiotics show promise in weight management. Here, we elucidate the precise mechanisms through which the probiotic Bifidobacterium breve (B. breve) modulates the immune response in obesity-associated tumours utilizing a Hepa1-6 cell-bearing hepatocellular carcinoma (HCC) model sensitive to high-fat diet (HFD)-induced obesity. HFD-induced obesity expedited HCC progression and fostered an immunosuppressive microenvironment. Treatment with B. breve enhanced cancer control by rescuing the local infiltration of antitumour immune cells. Elevated serum taurocholic acid (TCA) levels were negatively correlated with B. breve levels in obese HCC mice. TCA hindered the infiltration of CD8+ T cells into the tumour microenvironment and diminished their antitumour efficacy by blocking ERK phosphorylation. B. breve deconjugated TCA via its type 4 bile salt hydrolase (BSH), and this effect was diminished upon BSH inhibition by AAA-10. These results highlight the potential application of the probiotic B. breve in the multidisciplinary treatment of cancer in obese individuals.

Neoadjuvant PD-1 inhibitor therapy has shown promise in locally advanced head and neck squamous cell carcinoma (HNSCC), but only a subset of patients achieves major pathological responses. Liquid biopsy, the analysis of tumor-derived biomarkers in readily accessible bodily fluids (primarily blood), offers significant advantages over traditional tissue biopsies for predicting cancer treatment outcomes. The aim of this study is to develop a predictive model for neoadjuvant PD-1 therapy response in HNSCC patients using exclusively liquid biopsy approaches-namely, peripheral blood immune profiling (CyTOF) and plasma cytokine panels (Olink). In a prospective trial involving 50 HNSCC patients treated with neoadjuvant tislelizumab plus chemotherapy, peripheral blood samples were collected pre- and post-treatment. Immune cell subsets were analyzed by mass cytometry (CyTOF), and circulating protein markers were quantified via a 92-plex targeted proteomics panel (Olink). Multimodal features were integrated into a predictive model using logistic regression. Baseline immune profiles differed significantly between responder (RD) and non-responder (NRD): RD showed higher frequencies of CD103−CD8+ central memory T cells (Tcm, c03) and elevated plasma interleukins (IL-5, IL-13), whereas NRD had more CD28−TIGIThighcPARP−CD8+ terminally differentiated effector memory CD45RA+ T cells (Temra, c17) and higher levels of chemokines (CCL3, CCL4) and MMP7. Neoadjuvant therapy reactivated both subsets, evidenced by downregulation of PD-1 and increased expression of activation markers (e.g., CD38) and cytotoxic mediators (e.g., granzyme B and interferon γ). A multimodal predictive model incorporating CD8+T cell subsets (c03, c17) and plasma biomarkers (IL-5, MMP7) demonstrated superior predictive accuracy (AUC = 0.9219). Integrated peripheral immune profiling enables robust, noninvasive prediction of neoadjuvant PD-1 blockade efficacy in HNSCC. The identified immune cell subsets and plasma biomarkers provide a clinically applicable framework for early response stratification and personalized immunotherapy, supporting liquid biopsy as a viable platform for clinical decision-making. Trial registration Chinese Clinical Trial Registry, clinical trial number CHiCTR2200056354, 04 February 2022, https://www.chictr.org.cn/showproj.html?proj=151364 .

BACKGROUND:Stoma creation is a common procedure in colorectal cancer surgery, however, stoma-related complications remain a significant concern. AIM:To investigate the incidence, types, and risk factors of stoma-related complications in colorectal cancer patients who underwent stoma creation. METHODS:Patients with stoma was prospectively recorded in the established stoma system. Data was collected from this stoma management system from November 2021 through May 2024. The rates of stoma-related complications were assessed, and potential risk factors were analyzed using univariate and multivariate logistic regression models. RESULTS:A total of 734 patients were included in the analysis. The results showed that 12.3% of patients experienced stoma-related complications, with mucocutaneous separation, edema, and skin excoriation being the most common complications. The majority (90%) of complications were classified as grade 2 according to the Clavien-Dindo classification. Surgical factors, such as blood loss volume greater than 500 mL and open surgery, were significantly associated with stoma complications. Additionally, stoma features like location, shape, color, height, and edema were important factors in the association with complications. Body mass index over 30 kg/m² was also found to be a significant risk factor. CONCLUSION:These findings highlight the need for a holistic approach to preventing and managing stoma complications, considering both patient-related and surgical factors.

Cooking is one of the oldest and the most common human activities in daily life. Instructional cooking videos have also become one of the most common data sources for multi-modal visual understanding research, compared to general domains, cooking videos: (1) not only have a significantly stronger cross-modal dependency between the speech texts and their corresponding visual frames at each individual step, (2) but also have a significantly stronger cross-context dependency between sequential steps along their temporal dimensions, making it an ideal domain for contextualized multi-modal embedding and semantic understanding. This paper proposes CookingCLIP, which introduces the latest CLIP (Contrastive Language-Image Pre-training) embedding from the general domain into the specific domain of cooking understanding and makes two adaptions upon the original CLIP embedding for better customization to the cooking understanding problems: (1) from the upstream perspective, we extend the static multi-modal CLIP embedding with a temporal dimension, to facilitate context-aware semantic understanding; (2) from the downstream perspective, we introduce the concept of zero-shot embedding to sequence-to-sequence dense prediction domains, facilitating CLIP being not only capable of telling “ Which ” (cross-modal recipe generation), but also capable of telling “ When ” (cross-context recipe localization). Experiments conducted on two challenging cooking caption generation benchmarks, YouCook2 and CrossTask, demonstrate the effectiveness of the proposed embedding. The code will be released.

ObjectivesThe efficacy of treatments targeting recurrent or metastatic head and neck squamous cell carcinoma are unsatisfactory in practice for patients with a ECOG PS score ≥ 2. Thus, this study retrospectively evaluated the safety and efficacy of a programmed cell death 1 inhibitor (tislelizumab) combined with an epidermal growth factor receptor inhibitor (nimotuzumab) in treating patients with a PS score ≥ 2 who suffer from recurrent or metastatic oral squamous cell carcinoma (OSCC).Materials and methodsFifteen patients were treated with tislelizumab (200 mg IV Q3W) and nimotuzumab (200 mg IV Q3W). Programmed cell death-ligand 1 (PD-L1) expression in tumor biopsies was assessed with immunohistochemistry. Whole-exome sequencing was used to evaluate treatment efficacy based on PD-L1 expression and gene mutation.ResultsAt a median follow-up of 9.6 months, median overall survival was 10.1 months, and median progression-free survival was 4.0 months. Overall response rate was 40%, with 6/15 patients achieving partial response. Eight patients exhibited nine adverse events, eight out of nine being grade 2 and the remaining being grade 3. Whole-exome sequencing showed that DYNC1I2, THSD7A, and FAT1 mutations were associated with patient prognosis.ConclusionCombination therapy involving tislelizumab plus nimotuzumab is a promising, low-toxicity treatment for recurrent or metastatic OSCC in patients with a PS score ≥ 2.

Objective: To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT). Methods: This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups. Results: Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion: Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Purpose As a rare subpopulation of colorectal cancer (CRC), signet ring cell carcinoma (SRCC) has poor prognosis. The prognostic role of DNA mismatch repair (MMR) has been seldom studied. Thus, to analyze the effect of MMR status on survival outcomes in colorectal SRCC patients, we conducted this retrospective study. Method DNA mismatch repair status was performed on 114 patients via IHC. Prognostic clinicopathologic parameters of deficient or proficient DNA mismatch repair status were compared by the chi-squared test. Survival outcomes (OS, DFS) were measured via the Kaplan-Meier LIFETEST and the log-rank test. The multivariate survival analysis was evaluated by the Cox proportional-hazards regression model, and the hazard ratio (HR) with 95% CI was provided. Results Among 7343 colorectal cancer patients from 2009 to 2020, there were 176 patients with SRCC, nearly one quarter (23.7%, 27/114) harbored dMMR. Besides, dMMR SRCC patients are more often located in the rectum (51.1%). No difference was found for metastatic disease while dMMR had relatively good prognosis for non-metastatic with a median follow-up of 71.9 months (13.9 to 155). The overall 3- and 5-year OS were 42.1% and 32.1%, respectively, while the 3- and 5-year DFS were 43.0% and 32.9%, respectively. Moreover, the multivariate survival analysis via Cox proportional-hazards model revealed MMR status was an independent prognostic for colorectal SRCC. Conclusion Nearly one quarter patients harbored dMMR and relatively better survival outcomes than pMMR in this colorectal SRCC cohort. Early identification of this subgroup may be of importance for the survival of SRCC patients.

Importance Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer, especially for patients with high-risk factors. However, the efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) rectal cancer is unknown. Objectives To evaluate the safety and efficacy of TNT with induction chemoimmunotherapy followed by long-course chemoradiation in patients with high-risk, pMMR rectal cancer and to identify potential molecular biomarkers associated with treatment efficacy. Design, Setting, and Participants This cohort study was a single-arm phase 2 trial conducted at Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, from June 2020 to October 2021. Biopsies and plasma were collected before treatment for whole-exome sequencing and cell-free DNA sequencing, respectively. Data were analyzed from May 2022 to September 2022. Interventions Participants received 3 cycles of induction oxaliplatin and capecitabine combined with camrelizumab and radiotherapy (50.6 Gy in 22 fractions) with concurrent capecitabine. Patients without disease progression received 2 cycles of consolidation oxaliplatin/capecitabine. Main Outcomes and Measures The primary end point was pathologic complete response rate. Results Of 25 patients enrolled (19 men [76%]; 6 women [24%]; median [IQR] age, 58 [48-64] years), 22 patients (88%) completed the TNT schedule. The pathologic complete response rate was 33.3% (7/21). Twelve patients (48%) achieved clinical complete response, and 4 patients (16%) chose to watch and wait. R0 resection was achieved in 21 of 21 patients, and the major pathologic response rate was 38.1% (8/21). The most common adverse event was nausea (80%, 20/25); grade 3 toxic effects occurred in 9 of 25 patients (36%). Patients with tumor shrinkage of 50% or greater after induction oxaliplatin/capecitabine and camrelizumab or clinical complete response had higher percentages of LRP1B mutation. Mutation of LRP1B was associated with high tumor mutation burden and tumor neoantigen burden. Patients with high tumor mutation burden all benefited from therapy. Conclusions and Relevance This study found that TNT with induction chemoimmunotherapy followed by long-course chemoradiation was safe and effective for patients with high-risk rectal cancer with pMMR status. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. There is also an urgent need to further validate the predictive value of LRP1B and discover other novel biomarkers with potential predictive value for rectal cancer.

Objective:To evaluate the safety and efficacy of neoadjuvant chemotherapy(NCT)in mid-low locally advanced rectal cancer with negative mesorectal fascia(MRF). Methods:This prospective,single-arm phase Ⅱ trial was designed and conducted at Peking University Cancer Hospital.The patients who provided consent received 3 months of NCT(capecitabine and oxaliplatin,CapOX)followed by total mesorectal excision(TME).The primary endpoint was the rate of pathological complete response(pCR). Results:From January 2019 through December 2021,a total of 53 patients were enrolled,7.5％of whom experienced grade 3-4 adverse events during NCT.The pCR rate was 17.0％for the entire cohort,and the overall rate of postoperative complications was 37.7％(1.9％of grade Ⅲa patients).The 3-year disease-free survival rate was 91.4％,and 23.5％(12/51)of the patients suffered from major low anterior resection syndrome(LARS).Postoperative complications were independently associated with major LARS. Conclusions:For patients with mid-low rectal cancer with negative MRF,3 months of NCT were found to yield a favorable tumor response with acceptable toxicity.With fair long-term survival,the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.

BACKGROUND:Rectal cancer has become one of the leading malignancies threatening people's health. For locally advanced rectal cancer (LARC), the comprehensive strategy combining neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant chemotherapy has emerged as a standard treatment regimen, leading to favorable local control and long-term survival. However, in recent years, an increasing attention has been paid on the exploration of organ preservation strategies, aiming to enhance quality of life while maintaining optimal oncological treatment outcomes. Local excision (LE), compared with low anterior resection (LAR) or abdominal-perineal resection (APR) was introduced dating back to 1970's. LE has historically been linked to a heightened risk of recurrence compared to TME, potentially due to occult lymph node metastasis and intraluminal recurrence. Recent evidence has demonstrated that LE might be an alternative approach, instead of LAR or APR, in cases with favorable tumor regression after NCRT with potentially better quality of life. Therefore, a retrospective analysis of clinicopathological data from mid-low LARC patients who underwent LE after NCRT was conducted, aiming to evaluate the treatment's efficacy, safety, and oncologic prognosis. AIM:To explore the safety, efficacy, and long-term prognosis of LE in patients with mid-low rectal cancer who had a good response to NCRT. METHODS:Patients with LE between 2012 to 2021 were retrospectively collected from the rectal cancer database from Gastro-intestinal Ward III in Peking University Cancer Hospital. The clinicopathological features, postoperative complications, and long-term prognosis of these patients were analyzed. The Kaplan-Meier method was used to create cancer-specific survival curve, and the log-rank test was used to compare the differences regarding outcomes. RESULTS:A total of 33 patients were included in this study. The median interval between NCRT and surgery was 25.4 (range: 8.7-164.4) weeks. The median operation time was 57 (20.0-137.0) minutes. The initial clinical T staging (cT): 9 (27.3%) patients were cT2, 19 (57.6%) patients were cT3, and 5 (15.2%) patients were cT4; The initial N staging (cN): 8 patients (24.2%) were cN negative, 25 patients (75.8%) were cN positive; The initial M stage (cM): 2 patients (6.1%) had distant metastasis (ycM1), 31 (93.9%) patients had no distant metastasis (cM0). The pathological results: 18 (54.5%) patients were pathological T0 stage (ypT0), 6 (18.2%) patients were ypT1, 7 (21.2%) patients were ypT2, and 2 (6.1%) patients were ypT3. For 9 cT2 patients, 5 (5/9, 55.6%) had a postoperative pathological result of ypT0. For 19 cT3 patients, 11 (57.9%) patients were ypT0, and 2 (40%) were ypT0 in 5 cT4 patients. The most common complication was chronic perineal pain (71.4%, 5/7), followed by bleeding (43%, 3/7), stenosis (14.3%, 1/7), and fecal incontinence (14.3%, 1/7). The median follow-up time was 42.0 (4.0-93.5) months. For 31 patients with cM0, the 5-year disease-free survival (DFS) rate, 5-year local recurrence-free survival (LRFS) rate, and 5-year overall survival (OS) rate were 88.4%, 96.7%, and 92.9%, respectively. There were significant differences between the ycT groups concerning either DFS (P = 0.042) or OS (P = 0.002) in the Kaplan-Meier analysis. The LRFS curve of ycT ≤ T1 patients was better than that of ycT ≥ T2 patients, and the P value was very close to 0.05 (P = 0.070). The DFS curve of patients with ypT ≤ T1 was better than that of patients with ypT ≥ T2, but the P value was not statistically significant (P = 0.560). There was a significant difference between the ypT groups concerning OS (P = 0.014) in the Kaplan-Meier analysis. The LRFS curve of ypT ≤ T1 patients was better than that of ypT ≥ T2 patients, and the P value was very close to 0.05 (P = 0.070). Two patients with initial cM1 were alive at the last follow-up. CONCLUSION:LE for rectal cancer with significant tumor regression after NCRT can obtain better safety, efficiency, and oncological outcome. Minimally invasive or nonsurgical treatment with patient participation in decision-making can be performed for highly selected patients. Further investigation from multiple centers will bring better understanding of potential advantages regarding local resection.

ObjectivesThe treatment of locally advanced oral or oropharyngeal squamous cell carcinoma (LAOOPSCC) is surgery and radiotherapy or chemoradiotherapy but with unsatisfactory survival rate. Neoadjuvant programmed death-1 (PD-1) therapy are being used in several clinical trials. Therefore, in this retrospective study we aimed to determine the feasibility of neoadjuvant tislelizumab plus chemotherapy followed by surgery for LAOOPSCC.Materials and methodsThe clinical data of 33 patients with LAOOPSCC who received neoadjuvant PD-1 inhibitors and chemotherapy between April 2021 and October 2022 were retrospectively analyzed. Patients with stage III-IV LAOOPSCC received tislelizumab, albumin-bound paclitaxel, and cisplatin every 3 weeks (Q3W) for two cycles, followed by surgery and adjuvant radiotherapy or concurrent chemoradiotherapy. A median follow-up period was 20 months.ResultsThe objective response rate (ORR) was 66.7%, with the major pathological response (MPR) rate at 54.5%, and the pathological complete response (pCR) rate was 33.3%. Sixteen patients underwent limited surgeries, and 15 patients were remitted from undergoing mandibulectomy and 9 patients were remitted from undergoing near total glossectomy or total glossectomy. A significant difference in the overall survival (OS) and disease-free survival (DFS) was observed in patients who achieved major pathological response (MPR) than who did not. The most common adverse events in neoadjuvant therapy were alopecia, decreased appetite or anorexia, leukopenia, and fatigue.ConclusionNeoadjuvant PD-1 inhibitors combined with chemotherapy are feasible and safe, with a high pathological response and possible organ preservation in oral or oropharyngeal squamous cell carcinoma. However, further studies with a larger cohort of patients and longer follow-up period is required to strengthen our findings and evaluate the survival benefits of the treatment.

Purpose To assess the prognostic value of three novel biomarkers, DNA ploidy, stroma-tumor fraction, and nucleotyping, seeking for more accurate stratification in stage II colon cancer.Methods A total of 417 patients with complete follow up information were enrolled in this study and divided into three clinical risk groups. IHC was performed to examine MSI status. DNA ploidy, stroma and nucleotyping were estimated using automated digital imaging system. Kaplan-Meier survival curves, Cox proportional hazards regression models, and correlation analyses were carried out to process our data.Results In the whole cohort of stage II colon cancer, nucleotyping and DNA ploidy were significant prognostic factors on OS in univariate analyses. The combination of nucleotyping and DNA ploidy signified superior OS and DFS. Difference was not significant between low-stroma and high-stroma patients. In multivariable analyses, nucleotyping and the combination of nucleotyping and DNA ploidy were proven the dominant contributory factors for OS. In the low-risk group, we found the combination of nucleotyping and DNA ploidy as the independent prognostic factor statistically significant in both univariate and multivariable, while in the high-risk group, the nucleotyping.Conclusions Our study has proven nucleotyping and the combination of DNA ploidy and nucleotyping as independent prognostic indicators, thus expanding the application of nucleotyping as a predictor from high risk stage II colon cancer to whole risks.