11532 Background: Reported median progression-free survival (mPFS) of Chondrosarcoma is less than 4 months for patients receiving first-line systemic therapy. Aponermin, a recombinant circularly permuted human Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), induces tumor cell apoptosis by activating the extrinsic apoptotic pathway. This study aimed to evaluate the efficacy of Aponermin in patients with advanced chondrosarcoma. Methods: This prospective, multicenter, single-arm study (Registration No: ChiCTR2500104488) was approved by an independent ethics committee. The planned enrollment was 32 patients aged 18-75 years with histologically confirmed advanced chondrosarcoma, documented evidence of disease progression within 6 months prior to enrollment, ECOG performance status ≤2, and measurable disease per RECIST 1.1. Patients received intravenous Aponermin 10 mg/kg (days 1-5, every 14 days as one cycle) until disease progression, unacceptable toxicity, or investigator's decision to discontinue. The primary endpoint was objective response rate (ORR). Secondary endpoints included 4-month PFS rate, disease control rate (DCR), overall survival (OS), and safety. Results: As of January 23, 2026, 21 patients were enrolled and treated. Median age was 51 years (range: 26-70), with a median of 2 prior surgeries (range: 1-6). Eight patients had received prior drug therapy. Histopathological subtypes included: conventional grade 1, 19% (4/21); conventional grade 2, 47.6% (10/21); conventional grade 3, 4.8% (1/21); mesenchymal, 9.5% (2/21); and one case each (4.8%) of myxoid, dedifferentiated, clear cell, and unknown subtype. Twenty patients were evaluable for efficacy. Median treatment duration was 3.6 months (range: 0.5-14.0), with 4 patients still on treatment. Although no objective responses were observed,80.0% (16/20) of DCR was achieved. Median PFS was 4.2 months (95% CI: 2.9-5.5), and the 4-month PFS rate was 57.9%. Median OS was not reached. Notably, Among patients achieving DCR, 50% maintained clinical benefit for over 4 months, including one patient with conventional grade 3 chondrosarcoma with SD lasting 7.4 months, two patients with conventional grade 2 with SD exceeding 10.0 months, and one patient with clear cell subtype with SD lasting 14 months. Aponermin demonstrated a favorable safety profile. Treatment-related adverse events occurred in approximately 9.5% (2/21) of patients, including one case (4.8%) of grade 1 allergic reaction and one case (4.8%) of hand-foot syndrome, both alleviated with symptomatic treatment. Conclusions: Aponermin monotherapy demonstrated promising disease control and a favorable safety and tolerability profile in advanced chondrosarcoma. Given the limited sample size and ongoing enrollment, final efficacy and safety assessments await study completion. Clinical trial information: ChiCTR2500104488.
Radiotherapy is a fundamental step in the combined treatment of glioblastoma (GBM), while radioresistance of GBM causes limitation of therapeutic efficacy. Natural killer (NK) cells, a potential target of immunotherapy, have attracted considerable attention due to the robust cancer cell-targeted cytotoxicity in combined treatment with radiotherapy, suggesting NK cell regulation might be a radiosensitization strategy. Here we show that a cytotoxic subset of NK cells could be stimulated by ionizing radiation (IR) and accumulate in the GBM tumor microenvironment (TME). Co-culturing with NK cells significantly enhances the GBM cell response to IR, and pharmaceutically depleting NK cells in mice elevates IR-induced tumor growth delay. Specifically, GZMB should be the radiosensitization effector secreted by NK cells. Suppressing GZMB activity remarkably impairs NK-mediated GBM radiosensitization. Meanwhile, administrating exogenous GZMB improves irradiation dose-survival response in vitro or in a xenograft model. Mechanically, GZMB blocks autophagosome-lysosome fusion in GBM cells by directly recognizing and cleaving SDC1, a key regulator of autophagosome maturation, at the valine 225 and aspartate 228 sites. Uncleavable mutation of SDC1 reverses GZMB-mediated radiosensitization in GBM. Further studies demonstrate that cleavage of SDC1 obstructs the localization of TGM2, a key MAP1LC3/LC3 recognizer, on the lysosome surface. Clinical data reveal GBM patients with an SDC1 valine 225 or aspartate 228 mutation display lower response to radiotherapy. In this study, we disclose the critical role of NK cells in tumor radiotherapy through secreting GZMB and impeding autophagosome maturation, as well as propose a potential strategy combining radiotherapy and NK-based immunotherapy against radioresistant GBM.Abbreviations: DEGs: differentially expressed genes; GBM: glioblastoma; GZMB: granzyme B; IL: interleukin; IR: ionizing radiation; IRS: immunoreactive score; LAMP: lysosomal associated membrane protein; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; mSDC1: mutant SDC1; NK: natural killer; PRF1: perforin 1; SDC1: syndecan 1; SNAP29: synaptosome associated protein 29; SQSTM1: sequestosome 1; STX17: syntaxin 17; TGM2: transglutaminase 2; TME: tumor microenvironment; TGD: tumor growth delay; VAMP8: vesicle associated membrane protein 8; WT: wild type.
Background:Alfentanil and ciprofol are used in combination for intravenous anesthesia, but the effective dose of alfentanil required to suppress movement during surgery when co-administered with ciprofol is not well-defined. This study aimed to determine the effective dose of alfentanil, combined with ciprofol, required to inhibit body movement responses in patients undergoing breast lumpectomy. Methods:Patients scheduled for elective breast lumpectomy uswere selected. Ciprofol was administered intravenously at anesthesia induction, and alfentanil was given using the sequential method with an initial dose of 10 μg/kg and a dose gradient of 1 μg/kg. The dosage of alfentanil, the incidence of intraoperative respiratory depression, hypotension requiring treatment, and bradycardia were recorded. Postoperative adverse reactions were assessed and recorded. Probit regression analysis was used to calculate the effective dose. Results:The median effective dose (ED₅₀) of alfentanil for inhibiting intraoperative body movement was calculated to be 13.396 μg/kg, with a corresponding 95% effective dose (ED95) of 15.752 μg/kg. During the surgical procedure, no patients required therapeutic intervention for either intraoperative hypotension or bradycardia. However, three patients developed respiratory depression. Notably, no postoperative adverse reactions were documented in any of the study participants. Conclusion:The ED50 of alfentanil combined with ciprofol for intravenous anesthesia to suppress movement during breast lumpectomy is 13.396 μg/kg, and the ED₉₅ is 15.752 μg/kg. Clinical trial registration:http://www.chictr.org.cn, ChiCTR2500109829.
6045 Background: Locally advanced head and neck squamous cell carcinoma (HNSCC) is characterized by high risks of local recurrence and distant metastasis, resulting in poor prognosis. Neoadjuvant therapy has the potential to improve survival outcomes in these patients. This study aimed to evaluate the safety and efficacy of benmelstobart in combination with anlotinib and chemotherapy as neoadjuvant therapy for resectable locally advanced HNSCC. Preliminary results were presented at the 2025 ESMO Congress (Abstract 1454eP), and updated consecutive results are reported herein. Methods: This single-center, phase II clinical trial enrolled patients with stage III/IVA HNSCC who met predefined eligibility criteria. Patients underwent neoadjuvant therapy with benmelstobart (1200mg), anlotinib (10mg), cisplatin (60mg/m²), and nab-paclitaxel (125mg/m², d1, d8) for three 21-day cycles. Surgical resection was performed within two weeks after neoadjuvant therapy completion, with tumor specimens collected for pathological evaluation. The primary endpoint was major pathological response (MPR) rate. Postoperative adjuvant therapy was administered based on risk assessment. Secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, 2-year disease-free survival (DFS), 2-year locoregional recurrence-free survival (LRFS), 2-year distant metastasis-free survival (DMFS), 2-year overall survival (OS), and safety assessment. Results: As of Jan 9, 2026, a total of 36 patients who met the inclusion and exclusion criteria were enrolled. The median age was 61 years (range: 38-77), with males accounted for 91.7%. ECOG performance status 0 was observed in 80.5% of patients, and hypopharyngeal carcinoma was the most common primary tumor site (50.0%). Stage III and IVA disease accounted for 25.0% and 75.0% of patients, respectively. At the data cut-off date, 32 patients completed neoadjuvant therapy, achieving an ORR of 96.9% and a disease control rate (DCR) of 100%. Among them, 27 patients underwent surgery and completed histopathological assessment. MPR was achieved in 23 cases (including 20 with pCR), resulting in an MPR rate of 85.2% (95%CI: 66.3%-95.8%). The incidence of all grade treatment-emergent adverse events (TEAEs) was 86.1% (31/36). The incidence of grade≥3 TEAEs was 8.3% (3/36), most commonly myelosuppression (5.6%) and renal impairment (2.8%). Conclusions: The combination of benmelstobart, anlotinib, and chemotherapy demonstrated promising efficacy as neoadjuvant therapy for resectable HNSCC, with high ORR and MPR rates, along with an acceptable safety profile. These updated results support further evaluation of this combination in randomized controlled trials. Clinical trial information: NCT0669949 .
BACKGROUND Total mesorectal excision is the standard surgery for locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT), but it may lead to high complication rates and poor quality of life. This study evaluates whether transanal endoscopic microsurgery (TEM), as a partial resection procedure, can enhance quality of life for clinical complete response (cCR) or near-cCR patients without compromising survival. METHODS Between May 2017 to September 2021, 80 patients with T3-4N0M0 or TanyN+M0 mid-low rectal cancer achieving cCR or near-cCR post-nCRT were prospectively included at 6 Chinese centers. Patients underwent either TEM (Group A, n=38) or radical surgery (Group B, n=41). Clinicopathological, oncological, and functional outcomes were analyzed. RESULTS Postoperative histology revealed 22 ypT0 (57.9%), 5 ypT1 (13.2%), 10 ypT2 (26.3%), and 1 ypT3 (2.6%) cases in group A and 20 pCR (48.8%), 1 T0N1 (2.4%), 5 T1N0 (12.2%), 12 T2-3N0 (29.3%), 3 T2-3N1 (7.3%) cases in group B. After a 60-month median follow-up, local recurrence occurred in 2 patients (5.26%) in Group A and none in Group B. Distant metastases occurred in 8 patients (21.05%) in group A and 7 (17.07%) in group B. There was no significant difference between the two groups in 5-year disease-free survival (P=0.658) or 5-year overall survival (P=0.465). Group A showed significantly faster recovery (P<0.001) and better sphincter function per Wexner (1 vs. 4, P=0.001) and LARS (0 vs. 17, P<0.001) scores than Group B. CONCLUSION TEM may be an effective approach for assessing residual tumors in LARC patients with cCR or near-cCR. This approach offers an option for those requiring sphincter preservation, with no significant compromise in long-term oncological outcomes observed in our study.
OBJECTIVE:Current staging systems classify distant lymph node metastasis (DLM) in cervical cancer as stage IVB, typically treated with systemic therapy. We aim to assess if patients with DLM have different survival rates than those with other stage IVB cervical cancer forms. METHODS:This study included patients diagnosed with metastatic cervical cancer from 2000 to 2021, divided into three groups: para-aortic lymph node metastasis (PaLM), DLM, and distant organ metastasis (DM). Kaplan-Meier analyses estimated cervical cancer-specific (CCSS) and overall survival (OS). A 1:1 propensity-score match between DLM and PaLM patients used logistic regression. Univariate and multivariate Cox analyses identified prognostic risk factors. RESULTS:Of the included 6241 patients, 2079 (33.3 %) were diagnosed with PaLM only, 631 (10.1 %) with DLM only, and 3531 (56.6 %) had DM. Multivariate Cox regression analysis indicated that patients with DLM exhibited comparable CCSS (HR, 0.91; P = 0.28) and OS (HR, 0.93; P = 0.34) to those with PaLM. In contrast, compared to patients with DM, the DLM cohort demonstrated significantly improved CCSS (HR, 0.54; P < 0.001) and OS (HR, 0.58; P < 0.001). Following matching, the CCSS (HR, 0.96; P = 0.70) and OS (HR, 0.95; P = 0.61) of patients with DLM remained comparable to those with PaLM. Among the 632 patients with DLM, locoregional treatments such as total hysterectomy (HR, 0.46; P = 0.039) and radiotherapy (HR, 0.34; P = 0.046) were independently associated with improved OS. CONCLUSION:In cervical cancer, metastasis confined to distant lymph nodes indicates a locoregionally advanced stage, distinct from other stage IVB forms, and can be treated curatively with intensive locoregional therapy.
PURPOSE:The clinical benefit of incorporating oxaliplatin into conventional neoadjuvant chemoradiotherapy (nCRT) for patients with high-risk locally advanced rectal cancer (LARC) remains controversial. METHODS AND MATERIALS:This multicenter, open-label, randomized controlled trial enrolled 505 patients with high-risk LARC, defined by the presence of at least 1 of the following adverse features: clinical T4 stage, clinical N2 stage, high tumor grade, extramural vascular invasion, involvement of the mesorectal fascia, or perianal musculature involvement. Enrollment took place between August 2017 and April 2022. Patients were randomly assigned to receive long-course radiation therapy combined with a 3-cycle chemotherapy regimen of capecitabine and oxaliplatin (CapeOX group; n = 248) or capecitabine alone (Cape group; n = 257). The primary endpoint was 3-year disease-free survival (3y-DFS). RESULTS:Following nCRT, radical surgery was performed in 91.5% of the CapeOX group and 92.2% in the Cape group (P = .778). Pathologic complete response rates were comparable between the CapeOX and Cape groups (25.5% vs 25.3%; P = .954). A significantly greater proportion of patients in the CapeOX group achieved marked tumor regression (College of American Pathologists (CAP 0-1)) compared with the Cape group (58.6% vs 46.8%; P = .011). The incidence of grade 3 to 4 treatment-related toxicities was similar between the groups (CapeOX: 14.1% vs Cape: 9.3%; P = .095). After a median follow-up of 37 months, 3y-DFS and 3-year overall survival rates were comparable between the groups (both P > .050). Overall, patients who achieved CAP 0 to 1 had significantly better 3y-DFS than those with CAP 2 to 3 (89.0% vs 80.9%; P = .018). CONCLUSIONS:The addition of oxaliplatin to conventional nCRT may enhance pathologic tumor regression in patients with high-risk LARC without a significant increase in severe adverse events. However, this intensified 3-cycle chemotherapy regimen did not translate into a long-term survival benefit.
BackgroundThe multifocal manifestation of high-grade glioma is a rare disease with an unfavorable prognosis. The pathogenesis of multifocal gliomas and pathophysiological differences in unifocal gliomas are not fully understood. The optimal treatment for patients with multifocal high-grade glioma is not defined in the current guidelines; therefore, individual case series may be helpful as guidance for clinical decision-making.MethodsPatients with multifocal high-grade glioma treated with simultaneous integrated boost intensity-modulated radiotherapy combined with temozolomide for postoperative treatment at our institution between January 2020 and December 2023 were retrospectively analyzed. Multifocality was neuroradiologically assessed and defined as at least two independent contrast-enhancing foci in the MRI T1 contrast-enhanced sequence. Overall and progression-free survival were calculated from the diagnosis until death and from the start of radiation therapy until the diagnosis of disease progression on MRI for all patients.ResultsA total of 42 patients with multifocal high-grade glioma were examined, of which 16 were female and 26 were male. The median age of all patients was 57 years (range: 23–77 years). The median KPS score was 80 (range: 50–100). Complete resection was performed in 10 cases, and partial resection was performed in 32 cases before the start of radiation therapy. The prescription schedule was 54 Gy (1.8 Gy × 30) with an SIB of 60 Gy (2 Gy × 30). Concomitant temozolomide chemotherapy was administered to 40 patients. Median survival was 19 months (95% CI 14.1–23.8 months) and median progression free survival after initiation of RT 13 months (95% CI 9.2–16.7 months). Five patients experienced grade 3 toxicity, none experienced grade 4 toxicity, and no treatment-related deaths occurred.ConclusionMultifocal high-grade gliomas can be treated safely and efficiently with simultaneous integrated boost intensity-modulated radiotherapy with concomitant and adjuvant TMZ chemotherapy.
BACKGROUND:The treatment strategy for recurrent or metastatic esophageal squamous cell carcinoma (ESCC) is immunotherapy-based systemic treatment. The effect of local radiotherapy on the survival of recurrent or metastatic ESCC patients is unclear. This work is aimed to investigate the efficacy of local radiotherapy in combination with immunotherapy-based systemic therapy. METHODS:In this retrospective observational study, data were collected from recurrent or metastatic ESCC patients treated at the Radiotherapy Department of Jiangsu Province Hospital between March 2019 and December 2022. This study enrolled a total of 73 patients with recurrent or metastatic ESCC. The overall survival (OS) of all patients and OS stratified by different treatment patterns were analyzed. Prognostic factors influencing OS were examined using uni- and multi-variate Cox tests. RESULTS:The median OS of the study population was 21.4 (95%CI: 13.7-29.1) months. The median OS of patients who received radiotherapy in additional to systemic therapy was 31.5 (13.5-49.5) months, while the patients who received systemic therapy alone had a significantly shorter median OS of 10.7 (95%CI: 8.0-13.4) months. OS was also significantly different among patients receiving different cycles of immunotherapy. The median OS of patients after 1-6 cycles of immunotherapy was 14.6 (95%CI: 11.3-18.0) months, that after 7-12 cycles was 21.1 (95%CI: 0-43.8) months, and that after more than 12 cycle was 52.1 (25.6-78.6) months. CONCLUSIONS:In the first-line therapy of recurrent or metastatic ESCC based on immunotherapy, the addition of local radiotherapy significantly improves patient survival. As the number of immunotherapy cycles increases, the survival benefits become more pronounced.
To evaluate the efficacy and safety of anlotinib plus temozolomide (TMZ) as a first-line treatment for recurrent/Residual glioma. Thirty eligible patients who either relapsed after the standard chemoradiotherapy regimen (TMZ plus radiotherapy) or had macroscopic residual tumors due to involvement of eloquent brain areas were enrolled between March 2018 and January 2021. Patients received anlotinib (12 mg once daily, 14 days on/7 days off) in combination with TMZ (200 mg/m², 5 days on/23 days off) until disease progression or unacceptable toxicity. The efficacy was evaluated using the Response Assessment in Neuro-Oncology(RANO) criteria for high-grade gliomas. Safety was assessed using the NCI-CTCAE 4.0. Survival outcomes were estimated with the Kaplan-Meier method and compared using the log-rank test. By April 2023, the median follow-up time was 28.1 ± 5.07 months(95
Introduction: Benign lymph node enlargement (BLNE) is common in colorectal cancer; however, few studies have investigated its influence on prognosis, clinicopathological features, and pathogenesis. Methods: A cohort study was conducted to analyze the clinicopathologic features and prognosis of colorectal cancer patients, categorized based on the presence or absence of BLNE. Given the correlation between lymph nodes and immune response, immunohistochemistry, transcriptome analysis, and exon sequencing were employed to further investigate the differences in the immune microenvironment of primary tumors. Results: Overall, 630 AJCC stage I/II patients were included in the study, with 131 in the BLNE group and 499 in the Non-BLNE (NBLNE) group. Patients in the BLNE group were found to have a significantly better disease-free survival (DFS) (hazard ratio [HR] 0.44, P = 0.016) and overall survival (OS) (HR 0.46, P = 0.011) than those in the NBLNE group. Pathologically, compared with the NBLNE group, the BLNE group had more mature tertiary lymphoid structures (66.7 % vs. 36.5 %, P = 0.002) and higher immunoscores (18.8 % vs. 2.1 %, P = 0.004) in primary tumor tissue. Also, transcriptome analysis showed that, compared with NBLNE, the genes upregulated in BLNE were enriched in immune-related pathways, such as adaptive immune response and immuno-regulatory interactions. Whole-exon sequencing analysis revealed a higher tumor mutation burden (TMB) in the BLNE group [6.03 (5.59, 7.59) vs. 5.33 (4.62, 6.34), P = 0.025]. Conclusion: BLNE is positively associated with the prognosis of colorectal cancer, possibly because patients with BLNE have a stronger anti-tumor immune response.
Inflammatory responses, immune status, and nutritional conditions are critical determinants of tumor progression and treatment outcomes in rectal cancer. However, the prognostic value of integrated inflammatory-nutritional scores, including the modified Gustave Roussy Immune (mGRIm) score and modified Naples Prognostic Score (M-NPS), remains underexplored in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (nCRT). This study aimed to evaluate the prognostic significance of these scores and to develop a nomogram for identifying patient groups who may benefit from nCRT. A retrospective cohort study analyzed 157 rectal cancer patients who received nCRT, followed by total mesorectal excision (TME) and adjuvant chemotherapy at a single institution. The mGRIm score (based on lactate dehydrogenase [LDH], serum albumin, and neutrophil-to-lymphocyte ratio [NLR]) and M-NPS (incorporating albumin, total cholesterol, NLR, and lymphocyte-to-monocyte ratio [LMR]) were calculated. Patients were stratified into high- and low-score groups based on these prognostic scores. Kaplan–Meier analysis and Cox regression were used to assess associations with overall survival (OS) and progression-free survival (PFS). A nomogram integrating independent prognostic factors was developed and validated. High mGRIm and M-NPS scores were significantly associated with worse OS (p < 0.05, p < 0.01) and PFS (both p < 0.05). Multivariate Cox analysis identified tumor length > 5 cm, pre-radiotherapy metastasis, and high M-NPS as independent predictors of OS, while high mGRIm, advanced N stage, and metastasis predicted inferior PFS. The nomogram demonstrated robust predictive accuracy for 1-, 2-, and 3-year OS (AUC: 0.790, 0.739, 0.708) and PFS (AUC: 0.763, 0.727, 0.786), with excellent calibration. The mGRIm score and M-NPS are independent prognostic indicators for rectal cancer patients receiving nCRT. The novel nomogram, integrating these biomarker scores with clinical staging parameters, enables the quantification of individual prognosis before treatment initiation and facilitates the identification of optimal nCRT candidates through multivariable probability estimation.
Objective To determine the efficacy and tolerability of Anlotinib plus temozolomide (TMZ) as a first-line treatment for recurrent malignant glioma (rMG). Methods A total of 30 eligible patients who relapsed from the standard chemoradiotherapy regimen (TMZ and radiotherapy) or had macroscopic residual tumor after surgery because of tumor located in the eloquent brain areas were enrolled in this study between March 2018 and January 2021. Patients were subjected to a concurrent treatment of Anlotinib (12mg qd, 14 days on with 7 days off) and TMZ (200mg/m2, 5 days on with 23 days off) until disease progression or intolerable toxicity. Efficacy was evaluated using Response Assessment in Neuro-Oncology(RANO) criteria for high-grade glioma. Safety was assessed using NCI-CTCAE 4.0. Survival was estimated with the Kaplan-Meier curve and log-rank test. Results Until April 2023, our median follow-up time was 28.1 ± 5.07 months(95% CI:18.20-38.06m). The median OS(from recurrence to death or end of follow-up) was 17.87 ± 4.29 m(95%CI: 9.46-26.28m). 1-year, 1.5 year, 2-year OS rates were were 60.0%, 46.7% and 36.7% respectively. The median PFS(from the treatment of Anlotinib and TMZ to the endpoint) was 7.83 ± 0.82m(95%CI, 6.22-9.44m). 6-month, 1-year PFS rates were 63.3%, 36.7%, respectively. In the univariate analysis, patients of WHO Ⅱ group have a longer mOS and mPFS than that of WHO Ⅲ and Ⅳ group(Ⅱ: 30.45 ± 4.32m, Ⅲ: 15.07 ± 5.72m, Ⅳ: 9.21 ± 1.90m, P = 0.035). Patients ≤ 55 had a longer mPFS compared with those > 55 years old(12.97 ± 1.71m vs. 7.33 ± 1.95m. p = 0.010), but failed to reach statistical difference in OS(19.90 ± 6.29m vs. 10.53 ± 1.68m, p = 0.106). While their gender, 1p/19q and IDH mutation are not independent negative predictors on OS or PFS. In the multivariate analysis, age, pathological grade and IDH mutation all failed to serve as an independent negative predictor of PFS or OS in recurrent glioma. Conclusion Anlotinib combined with TMZ was effective for recurrent glioma in terms of OS and PFS, and was well tolerated in patients. Further randomized controlled clinical studies are needed to confirm the efficacy of Anlotinib combined with TMZ for the treatment of rMG.
Functional constipation (FC), a common functional gastrointestinal disorder, is usually overlapping with upper gastrointestinal symptoms (UGS). We aimed to explore the clinical characteristics of patients with FC overlapping UGS along with the related risk factors. The differences in the severity of constipation symptoms, psychological state, quality of life (QoL), anorectal motility and perception function, autonomic function, and the effect of biofeedback therapy (BFT) among patients with FC in different groups were analyzed, along with the risk factors of overlapping UGS. Compared with patients with FC alone, those with FC overlapping UGS had higher scores in the Patient Assessment of Constipation Symptoms and Self-Rating Anxiety Scale and lower scores in the Short Form-36 health survey ( P < 0.05). Patients with FC overlapping UGS also had lower rectal propulsion, more negative autonomic nervous function, and worse BFT efficacy ( P < 0.05). Overlapping UGS, especially overlapping functional dyspepsia, considerably affected the severity of FC. Logistic regression model showed that age, body mass index (BMI), anxiety, exercise, and sleep quality were independent factors influencing overlapping UGS in patients with FC. Overlapping UGS reduces the physical and mental health and the QoL of patients with FC. It also increases the difficulty in the treatment of FC. Patient's age, BMI, anxiety, physical exercise, and sleep quality might be predictors for FC overlapping UGS.
Colonoscopy is critical in colorectal cancer screening and the effect of intestinal preparation affects the accuracy of diagnosis, especially in elderly patients. The commonly used Polyethylene Glycol Electrolyte, PEG, is found inadequate in bowel cleansing for the elderly patients.
Capecitabine-based neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer. The objective of this study is to analyze overall survival (OS), disease-free survival (DFS) and prognostic factors of patients with stage II to III rectal cancer treated with nCRT in our institution. Between March 2014 to June 2020, 121 locally advanced rectal cancer patients were retrospectively reviewed and analyzed. All of the enrolled patients were treated with capecitabine-based nCRT (pelvic radiotherapy: 45–50.4 Gy, 1.8 Gy/d plus concomitant capecitabine-based chemotherapy), total mesorectal excision surgery (surgery was carried out 8–12 weeks after the end of CRT), and capecitabine-based adjuvant chemotherapy. We examined the pathological complete response rate, 3-year OS, 3-year DFS and the other prognostic factors. Kaplan–Meier method and Log-rank test were used to estimate and compare survival rate. With a median follow-up of 36 months, 3-year DFS and 3-year OS was 74.4% and 83.2%, respectively. Among the 121 patients, 24 achieved pathological complete remission (19.8%). After multivariate analysis, ypTNM stage (TNM stage after neoadjuvant therapy) was significantly associated with DFS. Positive mesorectal fasciae (MRF) status on magnetic resonance imaging and ypTNM stage were significantly related to OS. CRT with capecitabine based regimen provides high rates of survival and sphincter preservation with acceptable toxicity. YpTNM stage was significantly associated with DFS; magnetic resonance imaging MRF status and ypTNM stage were significant factors for OS after multivariate analysis. Distant metastasis is the dominant mode of treatment failure, and it is crucial to optimize systemic treatment for newly diagnosed patients.
Background: Left colic artery (LCA) preservation or non-preservation in radical resection for colorectal cancer is still under debate. This study aimed to compare the perioperative and oncological outcomes between the two procedures.Methods: Systematic search was performed in PubMed, Medline, Embase, Web of Science, and China National Knowledge Infrastructure databases for relevant randomized and non-randomized clinical trials published between 2011 and 2019. The primary endpoints were 5-year overall survival (OS), 5-year disease-free survival (DFS), total lymph nodes harvested, and anastomotic leakage. Secondary endpoints included the number of metastatic lymph nodes, intraoperative blood loss, urinary dysfunction, bowel obstruction, and operation time. Results: Twenty-eight studies with 10545 patients (LCA non-preservation surgery, 4920; LCA preservation surgery, 5625) were included. Data of 7142 rectal cancer patients (LCA non-preservation surgery, 3468; LCA preservation surgery, 3674) were extracted for subgroup analysis. There was significantly lower incidence of anastomotic leakage (odds ratio=1.21; 95% confidence interval |1.04, 1.41|; P=0.015) in colorectal cancer patients with LCA preservation. When rectal cancer was independently analyzed, no significant difference was found in anastomotic leakage between the groups. There were significantly more metastatic lymph nodes and significantly shorter operation time in colorectal cancer and rectal cancer patients with LCA non-preservation. No significant difference was found regarding 5-year OS, 5-year DFS, total lymph nodes harvested, intraoperative blood loss, urinary dysfunction, and bowel obstruction for colorectal and rectal cancer.Conclusions: LCA non-preservation was not proved to increase anastomotic leakage in rectal cancer surgery and was associated with more harvested metastatic lymph nodes and shorter operation time. Trial registration: A review protocol was registered on PROSPERO (registration number: CRD42020183906) and http://www.researchregistry.com (registration number: reviewregistry841).
Fatty acid binding protein 5 (FABP5) has been reported to play an important role in various cancers. We found that high FABP5 expression was associated with poor histological differentiation and vascular invasion. High FABP5 expression indicated a poor prognosis. Downregulation of FABP5 suppressed cell proliferation, cell migration and invasion, and induced cell apoptosis. Bioinformatic analysis revealed that the Hippo signaling pathway was related to FABP5. We found that overexpression of yes-associated protein 1 (YAP1) could partially reverse the effect of FABP5 knockdown on growth and apoptosis. The FABP5 inhibitor SBFI-26 suppressed the proliferation and promoted the apoptosis of gastric cancer (GC) cells and interfered with the Hippo signaling pathway by inhibiting YAP1. Our data suggested that FABP5 might act as a potential target associated with the Hippo signaling pathway for GC treatment.
Abstract PurposeNeoadjuvant chemoradiotherapy (nCRT) has been recommended as a standard treatment for locally advanced rectal cancer. In our study, we retrospectively analyzed the oncological outcomes of patients with stage II-III rectal cancer who were treated in our department.Patients and MethodsDuring March 2014 to June 2020, total 139 patients were retrospectively reviewed, of whom 121 were analyzable. All of our enrolled patients with stage II to III rectal cancer were treated with nCRT with a capecitabine-based regimen, total mesorectal excision surgery, and an adjuvant capecitabine-based chemotherapy regimen. We examined the pathologic complete response (pCR) rate after neoadjuvant chemoradiotherapy, 3-year overall survival (OS), and disease-free survival (DFS) and investigated adverse factors related to the survival of this group of patients. We used the Kaplane-Meier method and Cox modeling to estimate and compare survival in our populations.ResultsWith a median follow-up of 36 months, overall survival at 3 years was 83.2%, and disease-free survival at 3 years was 74.4% in this arm. After multivariate adjustment, ypTNM stage(TNM stage after neoadjuvant therapy) was significantly associated with disease-free survival (DFS). A positive circumferential resection margin (CRM) status on MRI and ypTNM stage were significantly related to a worse overall survival (OS). Among the 121 patients, 24 achieved a pCR (19.8%); two patients did not complete radiation therapy. Eighteen patients died due to a cancer-related cause.ConclusionThe oncological outcomes of nCRT at our institution are comparable with those of other clinical studies on rectal cancer in which patients were treated with neoadjuvant therapy. Among the 121 patients, 24 had a pCR (19.8%). ypTNM stage was significantly associated with DFS; CRM status and ypTNM stage were were significantly related to overall survival (OS) after multivariate analysis.