145 Background: Given that Deficient Mismatch Repair (dMMR) colon cancer patients respond poorly to conventional chemotherapy but immunotherapy significantly improves pCR rates in this population, this study aims to explore whether neoadjuvant immunotherapy can increase the rate of R0 resection with preservation of adjacent organs in dMMR T4 colon cancer patients and investigate the optimal regimen of immunotherapy. Methods: This single-arm, open-label, phase II trial was conducted at Peking Union Medical College Hospital in China. Patients were eligible for enrollment if they had immunohistochemically confirmed colon adenocarcinoma with confirmation of dMMR and clinical T 4 stage (defined as a tumor has invaded the serosal surface [cT 4a ] or has invaded or adhered to adjacent organs or structures [cT 4b ]). All patients are planned to receive three cycles of camrelizumab (200mg intravenously administered at the beginning of each cycle every 3 weeks) followed by radical surgery. Surgery was scheduled 2–4 weeks after three cycles. The primary endpoint of this study was the R0 resection rate in all patients who received surgery (defined as resection with a microscopic negative margin). Secondary endpoints included the rate of pCR (defined as no residual viable tumor in either the tumor bed or the lymph nodes), tumor regression grade (TRG), the incidence of adverse event (AE) during neoadjuvant immunotherapy. Results: A total of 18 patients with clinical T 4 stage and dMMR colon cancers were deemed eligible for enrollment and 17 patients were included in per-protocol set analysis from April 2024 to July 2025. The primary endpoint was evaluable in 17 patients, with 16 patients having R0 resection of 94.1%. Pathological response was observed in 14 of 16 patients, including 11 with pathological complete response. The pCR associated with a decreased trend density of PD-L1+ cells [139.3 (99.0, 272.6) cells/mm 2 vs 323.1 (114.3, 528.2) cells/mm 2 , P =0.157]. All patients experienced treatment-related AEs (100%) during neoadjuvant immunotherapy. Sixteen patients (94.1%) had Grade 1-2 AEs, while 1 patients had Grade 3 AE. Conclusions: Three cycles of mono-immunotherapy appear to be a regimen for patients with dMMR T 4 colon cancer with acceptable surgical efficacy and safety. Clinical trial information: NCT06215677 .
BACKGROUND:The tumor microenvironment, particularly the tumor stroma, plays a critical role in tumor progression, immune evasion, and therapeutic resistance. However, its interaction with the immune landscape in rectal cancer (RC) remains incompletely understood. This study aimed to comprehensively characterize the stromal-immune ecosystem associated with the tumor stroma ratio (TSR) in RC and to evaluate its clinical and therapeutic relevance. METHODS:We analyzed a multicenter cohort of 498 patients with treatment-naïve RC in whom TSR was assessed on H&E-stained sections. Integrative multi-omics analyses were performed, including bulk RNA sequencing (n=118) and single-cell RNA/T-cell receptor (TCR) sequencing (n=10). Key findings were validated by immunohistochemistry (n=114) and multiplex immunofluorescence (n=20). Survival analyses and statistical comparisons were conducted to evaluate clinical associations and treatment responses. RESULTS:High TSR was an independent predictor of unfavorable disease-free survival and cancer-specific survival and was associated with aggressive clinicopathological features. Single-cell analyses revealed that TSR-high tumors exhibited a profoundly immunosuppressive microenvironment, characterized by clonally expanded terminally exhausted CD8+ T cells (CD8+ Tex-CXCL13) and activated CD4+ regulatory T cells (CD4+ Treg-TNFRSF4). Two LRRC15+ cancer-associated fibroblast (CAF) subsets (mCAF-CTHRC1 and mCAF-FAP) were enriched in TSR-high tumors. Among them, mCAF-CTHRC1 was associated with increased Treg abundance and activation features, with predicted interactions with CD4+ Treg-TNFRSF4 cells through the LGALS9-CD44 signaling axis. In addition, SPP1-expressing monocytes (Mon-SPP1) and malignant epithelial cells were prominent in TSR-high tumors and showed a predicted SPP1-CD44 interaction with T-cell subsets, suggesting potential involvement in immunosuppressive stromal-immune interactions. In patients receiving neoadjuvant therapy, pretreatment TSR-low tumors showed improved pathological response and survival outcomes compared with TSR-high tumors. In the neoadjuvant chemoradiotherapy plus immunotherapy cohort, TSR-low tumors were associated with a significantly higher major pathological response rate, whereas pathological complete response showed a non-significant trend in the same direction. CONCLUSIONS:High TSR identifies a clinically aggressive subtype of RC characterized by a profoundly immunosuppressive stromal-immune ecosystem enriched for exhausted T cells, immunosuppressive CAF programs, and SPP1-associated stromal-myeloid interactions. These findings highlight LGALS9-, LRRC15-, and SPP1-related stromal-immune pathways as candidate stromal-immune therapeutic vulnerabilities that warrant further mechanistic and preclinical validation.
Crohn's disease (CD) is frequently complicated by intestinal strictures, which substantially affect patients quality of life and long-term outcomes. Accurate classification of strictures-as inflammatory, fibrotic, or mixed-is critical for selecting optimal therapeutic strategies. In clinical practice, multidisciplinary team (MDT) consultation is often employed to assess stricture characteristics. However, the accuracy and inter-specialty consistency of stricture evaluation within MDTs remain inadequately characterized. This study aimed to assess the intra-disciplinary consistency and accuracy of decision-making for CD-related strictures, evaluate the accuracy of post MDT decisions, and propose recommendations for stricture nature assessment and MDT workflow optimization. A mixed-methods study was conducted at Peking Union Medical College Hospital involving 42 patients with CD and intestinal strictures. MDT participants-including specialists from gastroenterology, surgery, ultrasound, and MDT meeting chairs-were involved in evaluating intra-disciplinary decision consistency and accuracy. Semi-structured qualitative interviews were also conducted to explore factors influencing clinical decision-making. Gastroenterologists demonstrated the highest intra-team consistency (PABAK = 0.75) and diagnostic accuracy (89.3%). Ultrasound specialists showed improved consistency following targeted training (from 0.46 to 0.93). The overall accuracy of historical MDT decisions was 92.9%. Key factors influencing stricture nature judgment included clinical presentation, laboratory findings, imaging features, and endoscopic evaluation. Seven core components were identified to improve MDT workflow: expert selection, team building, training, pre-meeting preparation, in-meeting procedures, post-meeting actions, and continuous quality improvement. This study reveals variability in decision-making for CD-related strictures across different specialties. To improve diagnostic accuracy and treatment planning, we propose clear stricture classification criteria and a structured MDT workflow to standardize and enhance multidisciplinary management of CD.
To compare the overall survival (OS) and cancer-specific survival (CSS) of right-sided colon cancer patients undergoing CME versus D2 surgery after 5 years of follow-up, and to assess the heterogeneity of treatment effectiveness of CME between different subgroups. The 3-year result of the Radical Extent of lymphadenectomy of Laparoscopic Right Colectomy for colon cancer (RELARC) trial showed that standard D2 dissection should be performed in right-sided colon cancer patients. In patients with lymph node metastasis, complete mesocolic excision (CME) showed potentially favorable results. The parallel, open label, randomized controlled trial was conducted between January, 2016 to December, 2019 in 17 hospitals in China. Of a total of 1072 eligible patients enrolled, 995 patients were included in the modified intention-to-treat analysis. In the present study, the primary outcome was 5-year OS and the secondary outcome was 5-year CSS. The trial is registered with ClinicalTrials.gov (Identifier: NCT02619942). 995 patients were included in the final analysis. There was no significant difference between the 5-year OS (HR: 0.74, 95%CI: 0.51–1.07, P=0.105) or CSS (HR: 0.72, 95%CI: 0.49–1.06, P=0.091) in the CME and D2 groups. CME appears to improve 5-year outcomes in patients with stage III disease (OS: HR: 0.58, 95% CI: 0.37–0.93, P=0.023; CSS: HR: 0.59, 95% CI: 0.37–0.94, P=0.028), particularly in those with pN2 (OS: HR: 0.25, 95% CI: 0.11–0.57, P=0.001; CSS: HR: 0.25, 95% CI: 0.11–0.57, P=0.001), where a statistically significant interaction was identified. Patients with lymphovascular invasion also demonstrated favorable outcomes with CME with significant interaction effect (OS: HR: 0.34, 95% CI: 0.17–0.70; interaction P=0.009; CSS: HR: 0.32, 95% CI: 0.15–0.67, interaction P=0.008). The standard D2 dissection provides oncologic outcomes comparable to CME on the 5-year follow-up. However, CME seems to improve 5-year outcomes in patients with stage III, particularly those with pN2 status, and may confer benefit in patients with LVI.
Background:Tumor location affects rectal cancer management, but no consensus exists on criteria. The anterior peritoneal reflection (aPR), an anatomical landmark, shows potential for defining tumor location but requires clinical validation. This study evaluated the utility of aPR in guiding neoadjuvant chemoradiotherapy (nCRT) decisions and predicting lateral lymph node (LLN)/distant metastasis patterns. Methods:This single-center retrospective cohort analyzed data from Peking Union Medical College Hospital (Beijing, China) between January 2016 and August 2022. Magnetic resonance imaging (MRI)-measured aPR parameters were pathologically validated. Patients were stratified by aPR-based definition and tumor height (10 cm). Kaplan-Meier survival curves, log-rank tests, and Cox regression were used for prognostic analysis. Results:Among 588 patients (439 tumors ≥5 cm from the anal verge), MRI identified aPR with an accuracy of 95.4%. For tumors ≥5 cm, aPR-defined middle-to-low rectal cancer showed lower 3-year disease-free survival (DFS) rate than the upper rectal cancer (P = 0.010), while their 3-year overall survival (OS) rates were comparable. Conversely, 10-cm-defined classification showed no DFS or OS differences (both P > 0.2). Cox regression confirmed aPR-defined classification as an independent DFS predictor (HR = 3.19, P = 0.014), while 10-cm classification was non-predictive. nCRT with tumor regression grade (TRG) 0-1 trended toward improved DFS compared with direct surgery (HR = 0.56, P = 0.072). The independent protective effect of nCRT with TRG 0-1 for DFS was exclusive to the aPR-defined middle-to-low rectal cancer subgroup (HR = 0.45, P = 0.026) and not observed in the 10-cm subgroup. aPR-defined classification was independently associated with LLNs on MRI and postoperative pulmonary metastasis. Conclusion:aPR may guide nCRT decision-making and predict LLN metastasis and postoperative distant organ metastasis.
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.
OBJECTIVE:To compare the overall survival (OS) and cancer-specific survival (CSS) of right-sided colon cancer patients undergoing CME versus D2 surgery after 5 years of follow-up, and to assess the heterogeneity of treatment effectiveness of CME between different subgroups. SUMMARY BACKGROUND DATA:The 3-year result of the Radical Extent of lymphadenectomy of Laparoscopic Right Colectomy for colon cancer (RELARC) trial showed that standard D2 dissection should be performed in right-sided colon cancer patients. In patients with lymph node metastasis, complete mesocolic excision (CME) showed potentially favorable results. METHODS:The parallel, open label, randomized controlled trial was conducted between January, 2016 to December, 2019 in 17 hospitals in China. Of a total of 1072 eligible patients enrolled, 995 patients were included in the modified intention-to-treat analysis. In the present study, the primary outcome was 5-year OS and the secondary outcome was 5-year CSS. The trial is registered with ClinicalTrials.gov (Identifier: NCT02619942). RESULTS:995 patients were included in the final analysis. There was no significant difference between the 5-year OS (HR: 0.74, 95%CI: 0.51-1.07, P=0.105) or CSS (HR: 0.72, 95%CI: 0.49-1.06, P=0.091) in the CME and D2 groups. CME appears to improve 5-year outcomes in patients with stage III disease (OS: HR: 0.58, 95% CI: 0.37-0.93, P=0.023; CSS: HR: 0.59, 95% CI: 0.37-0.94, P=0.028), particularly in those with pN2 (OS: HR: 0.25, 95% CI: 0.11-0.57, P=0.001; CSS: HR: 0.25, 95% CI: 0.11-0.57, P=0.001), where a statistically significant interaction was identified. Patients with lymphovascular invasion also demonstrated favorable outcomes with CME with significant interaction effect (OS: HR: 0.34, 95% CI: 0.17-0.70; interaction P=0.009; CSS: HR: 0.32, 95% CI: 0.15-0.67, interaction P=0.008). CONCLUSION:The standard D2 dissection provides oncologic outcomes comparable to CME on the 5-year follow-up. However, CME seems to improve 5-year outcomes in patients with stage III, particularly those with pN2 status, and may confer benefit in patients with LVI.
Background:Rectal endometriosis is a complex condition requiring multidisciplinary treatment. Accurate preoperative assessment is critical for selecting the appropriate surgical technique, with transvaginal ultrasound (TVS) and endorectal ultrasound (ERUS) being key diagnostic tools. While TVS is effective in detecting ovarian endometriosis and pelvic deep infiltrating endometriosis, it has limitations in assessing bowel involvement. ERUS, however, provides detailed imaging of the rectal wall and depth of invasion. Materials and methods:A single-center prospective cohort study included 23 patients suspected of rectal endometriosis between August 2023 and September 2024. Perioperative findings and questionnaires, including Endometriosis Health Profile-30 and Gastrointestinal Quality of Life Index (GIQLI), were assessed. Results:Preoperative ERUS revealed that 82.6% of patients had a single rectal nodule, with a mean size of 2.1 ± 0.7 cm in length and 1.1 ± 0.6 cm in width. Luminal stenosis was found in two patients, and 100.0% of nodules extended into the muscular layer. TVS detected ovarian endometriosis and adenomyosis in 47.8% of patients and identified single rectal nodules in 60.9%, with a mean nodule length of 2.7 cm. Surgical approaches included rectal shaving (12 patients), disc excision (8 patients), and segmental resection (3 patients). Luminal stenosis was absent in the shaving and disc excision groups but present in 66.7% of segmental resection cases. The segmental resection group had significantly larger nodules (3.4 ± 0.5 cm length, 2.1 ± 0.8 cm width, 56.8 ± 0.4 cm2 area). Postoperative complications were generally mild, with only one patient experiencing Grade II rectal bleeding. Significant improvements were observed in pain (P = 0.004), control and powerlessness (P = 0.004), emotional well-being (P = 0.035), work-related issues (P = 0.030), and sexual relationship quality (P = 0.044). Conclusion:Our study highlights that combining preoperative ERUS with TVS improves the accuracy of assessments, enabling a more tailored surgical approach that enhances surgical outcomes and optimizes the management of rectal endometriosis.
Despite the progress of treatment in gastric cancer (GC), the overall outcomes remain poor in patients with advanced diseases, underscoring the urgency to develop more effective treatment strategies. BH3-mimetic drugs, which inhibit the pro-survival BCL2 family proteins, have demonstrated great therapeutic potential in cancer therapy. Although previous studies have implicated a role of targeting the cell survival pathway in GC, the contribution of different pro-survival BCL2 family proteins in promoting survival and mediating resistance to current standard therapies in GC remains unclear. A systematic study to elucidate the hierarchy of these proteins using clinically more relevant GC models is essential to identify the most effective therapeutic target(s) and rational combination strategies for improving GC therapy. Here, we provide evidence from both in vitro and in vivo studies using a broad panel of GC cell lines, tumoroids, and xenograft models to demonstrate that BCLXL and MCL1, but not other pro-survival BCL2 family proteins, are crucial for GC cells survival. While small molecular inhibitors of BCLXL or MCL1 exhibited some single-agent activity, their combination sufficed to cause maximum killing. However, due to the unsolved cardiotoxicity associated with direct MCL1 inhibitors, finding combinations of agents that indirectly target MCL1 and enable the reduction of doses of BCLXL inhibitors while maintaining their anti-neoplastic effects is potentially a feasible approach for the further development of these compounds. Importantly, inhibiting BCLXL synergized significantly with anti-mitotic and HER2-targeting drugs, leading to enhanced anti-tumour activity with tolerable toxicity in preclinical GC models. Mechanistically, anti-mitotic chemotherapies induced MCL1 degradation via the ubiquitin-proteasome pathway mainly through FBXW7, whereas HER2-targeting drugs suppressed MCL1 transcription via the STAT3/SRF axis. Moreover, co-targeting STAT3 and BCLXL also exhibited synergistic killing, extending beyond HER2-amplified GC. Collectively, our results provide mechanistic rationale and pre-clinical evidence for co-targeting BCLXL and MCL1 (both directly and indirectly) in GC.
Background The traditional neoadjuvant chemoradiotherapy (nCRT) combined with total mesorectal excision has been widely accepted as the standard treatment for patients with locally advanced rectal cancer (LARC). New strategies such as total neoadjuvant therapy (TNT) and neoadjuvant immunotherapy have shown great promise in certain patient populations. Currently, there is an urgent need to stratify patients before treatment to adopt the appropriate neoadjuvant strategies. Our previous study has shown that circulating tumour DNA (ctDNA) effectively reflects tumour burden and genetic characteristics and has significant predictive value for tumour recurrence, demonstrating great potential in guiding the choice of neoadjuvant strategies.Methods and analysis The CINTS-R trial is a multicentre, open-label, randomised controlled trial designed to evaluate the efficacy and safety of a ctDNA-guided neoadjuvant treatment strategy compared with conventional neoadjuvant therapy regime in patients with LARC. The trial will enrol 470 patients diagnosed with LARC (staged cT3-4N0 or cTanyN1-2) with tumours located ≤12 cm from the anal verge across seven centres in China. Patients will be randomly assigned in a 2:1 ratio to the experimental group or the control group. Patients in the experimental group will receive different intensities of neoadjuvant chemoradiotherapy (TNT or modified nCRT) or neoadjuvant immunotherapy based on the molecular features of the tumour, baseline ctDNA concentration and changes in ctDNA status early in treatment. Patients in the control group will receive modified nCRT. The primary endpoint is the 2-year disease-related treatment failure rate. The secondary endpoints include time to recurrence, 2-year overall survival, 2-year disease-free survival, clinical complete response (cCR) rate, near cCR rate and pathologically complete response rate, pathological tumour regression grade and quality of life.Ethics and dissemination This protocol has been approved by the ethics committee of Peking Union Medical College Hospital, with approval number I-23PJ157, and by the institutional review boards of all the participating centres. All data will be collected and stored in a specially designed database. The results of our trial will be disseminated through peer-reviewed publications and presented at national and international academic conferences.Trial registration number This trial is registered on ClinicalTrials.gov and the registration ID is NCT05601505.
BACKGROUND:While emergency laparoscopic cholecystectomy (ELC) is the standard treatment for acute cholecystitis (AC), optimal management of complex cases, particularly those with symptom duration ≥7 days or severe inflammation, remains controversial. OBJECTIVE:To assess the feasibility and safety of a proactive protocol for ELC in patients with complex AC, including high-risk cases defined by advanced age, prolonged symptoms, or severe inflammation (Tokyo Guidelines grade II/III). METHODS:From 1 August 2020 to 1 February 2024, the emergent surgical teams at Peking Union Medical College Hospital (National Emergent Surgery Center in North China) prospectively implemented proactive ELC for AC patients, irrespective of symptom duration and inflammatory severity. Intraoperative indocyanine green cholangiography (ICG-C) was selectively employed based on the surgeon's discretion. Clinicopathological data and perioperative outcomes were analyzed to assess safety and efficacy. Logistic regression and multi-way ANOVA were employed to assess the effects of multiple independent variables. RESULTS:Among 721 enrolled patients, 576 (79.9%) were interprovincial referrals, and 342 (47.7%) were transferred from external hospitals. More than half of the patients suffered from at least one comorbidity. The median age was 60 ± 16.7 years, with 11.5% aged >80 years. Symptom duration exceeded 3 days in 343 (47.6%) and 7 days in 190 (26.4%) of cases. Most patients had advanced disease (334 (46.3%) grade II, 199 (27.6%) grade III). Mean operative time was 64 ± 36.5 minutes, with intraoperative blood loss (IBL) of 65.0 ± 177.4 ml. Seven cases (1%) required conversion to open surgery, 39 (5.4%) underwent partial cholecystectomy, and 3 (0.4%) experienced iatrogenic colon injuries. Reoperation occurred in 2 cases (0.3%). The overall postoperative complication rate was 6.9%, with severe complications (Clavien-Dindo grade ≥III) at 1.2%. Patients older than 80 years did not have a higher rate of complications (P = 0.14). Patients with symptom duration ≥ 7 days had similar rates of partial resection and overall complications to those with 4-6 days. Although grade II/III had substantial adverse intraoperative and postoperative effects (all items, P ≤ 0.001), the overall rate of complications remains low (8.4%). ICGC correlated with reduced partial resection rates (0.7% vs. 6.3%, P = 0.005) and lower intraoperative blood loss (44.7 ± 82.8 mL vs. 69.4 ± 194.0 mL, P < 0.001). CONCLUSIONS:Proactive ELC could be safe and effective for complex AC, even in elderly patients (≥80 years), prolonged symptom duration (≥7 days), and severe disease (grade II/III), when performed in high-volume centers. ICGC enhances precision, mitigating incomplete resections and bleeding.
This study aimed to summarize the intestinal ultrasound (IUS) and computed tomography enterography (CTE) features of cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) and compare the performance of IUS and CTE in the evaluation of CMUSE in a single tertiary center. Clinically or pathologically confirmed CMUSE patients between December 2009 and April 2023 were recruited. Imaging features of CMUSE patients who underwent both IUS and CTE were summarized retrospectively. Twenty-nine patients were included. All patients were found to have ileum involvement, with the majority (96.6%, 28/29) showing superficial ulcers and stenosis at endoscopy. Nineteen patients who underwent both IUS and CTE during the same period were identified for image review. Intestinal lesions were present in 19 patients (100%) both on IUS and CTE. IUS features of CMUSE included minimal to moderate thickened small bowel wall with over half of the patients presenting with hypoechogenicity and vague stratification, over one-third of patients exhibiting proximal bowel dilation and increased bowel wall vascularity in most patients; on CTE, it presented as slight to moderate thickened bowel wall with mural enhancement, multiple short circumferential strictures and mild proximal bowel dilation in most patients. There was no statistically significant difference between IUS and CTE in detecting lesions (19/19 vs. 19/19), bowel wall thickening, bowel strictures (p = 0.727), and bowel wall vascularity (p = 0.375). IUS features of CMUSE were comparable with CTE in detecting lesions, bowel wall thickening, strictures and bowel wall vascularity, suggesting that IUS could serve as a radiation-free imaging modality for the diagnosis and surveillance of CMUSE. This pathology is relevant for gastroenterologists, radiologists, and the medical community, as well as for patients with small bowel disorders. Intestinal ultrasound could be of value and serve as a radiation-free imaging modality in assessing cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). More data are needed to characterize the intestinal ultrasound (IUS) findings of cryptogenic multifocal ulcerating stenosing enteritis (CMUSE). IUS features of CMUSE manifested as thickened bowel wall, with more than half of the patients presenting with hypoechogenicity with vague stratification. Computed tomography enterography (CTE) features of CMUSE included bowel wall thickening with mural enhancement, multiple short circumferential strictures, and mild small intestine dilation. IUS and CTE were comparable in detecting lesions, bowel wall thickening, bowel strictures, and bowel wall vascularity.
This article reports a diagnostically and therapeutically challenging case of small intestinal marginal zone lymphoma. The patient presented with recurrent abdominal pain as the chief complaint, and imaging revealed multifocal small bowel wall thickening with high uptake, multisegmental luminal stenosis, and proximal dilation. Initial diagnostic workup, including gastroscopy, colonoscopy, and enteroscopy with biopsy, failed to establish a definitive diagnosis. Empirical anti-tuberculosis therapy was ineffective. A repeat enteroscopic biopsy performed over eight months after symptom onset eventually confirmed the diagnosis of mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma. Despite three different chemotherapy regimens, the patient's intestinal obstruction symptoms persisted, with imaging still showing multifocal bowel wall thickening and hypermetabolic activity. A critical diagnostic dilemma arose regarding whether the PET/CT-positive lesions represented residual lymphoma or fibrotic scarring, whether further chemotherapy adjustments were warranted, and whether surgical resection was necessary. Multidisciplinary discussion concluded that imaging had limited discriminatory value in this scenario and that surgical intervention should be pursued if feasible. The patient successfully underwent partial small bowel resection, with postoperative pathology confirming no residual lymphoma but significant fibrotic changes. The patient has since resumed a normal diet, with body weight nearly restored to pre-illness levels. This case highlights that fibrotic transformation is a common sequela of treated marginal zone lymphoma and that PET/CT may misleadingly suggest residual disease, potentially leading to unnecessary chemotherapy. Timely surgical intervention is crucial in such scenarios.
PURPOSE Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. METHODS This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942 ) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). RESULTS Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group). CONCLUSION This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.
The pan-immune-inflammation value reflects the systemic inflammatory response, and tumor-infiltrating lymphocytes indicate a local immune response in rectal cancer. However, the association between systemic inflammatory response, as indicated by the pan-immune-inflammation value, and local immune responses in rectal cancer remains unclear. This study analyzed 915 treatment-naïve rectal cancer patients from the Peking Union Medical College Hospital and PLA General Hospital (PLAGH) cohorts who underwent radical surgery to investigate the relationship between the pan-immune-inflammation value and immune responses. Lower pan-immune-inflammation value was significantly associated with improved disease-free survival and cancer-specific survival. Multivariate Cox regression models identified the pan-immune-inflammation value as an independent prognostic factor. In the PLAGH cohort, patients with low pan-immune-inflammation values had higher immune cell levels, activated immune pathways, and increased expression of immune checkpoint genes according to RNA sequencing. Hematoxylin and eosin staining and immunohistochemical analysis revealed that lower pan-immune-inflammation value was associated with higher tumor-infiltrating lymphocyte density, more mature tertiary lymphoid structures, increased CD8+ T cells, and elevated human lymphocyte antigen class I expression. Conversely, patients with high pan-immune-inflammation values exhibited pathways linked to tumor progression, such as angiogenesis, epithelial-mesenchymal transition, hypoxia, KRAS signaling, and TGF-ß signaling. Among patients receiving anti-PD-1 therapy, responders had low pre- and post-treatment pan-immune-inflammation values. The pan-immune-inflammation value is a reliable marker associated with distinct immune microenvironment characteristics and can effectively predict disease-free survival, cancer-specific survival, and response to immunotherapy.
BACKGROUND:There is concern regarding the possibility of postoperative complications for laparoscopic right colectomy. OBJECTIVE:To evaluate the risk factors for postoperative complications for patients undergoing laparoscopic right colectomy. DESIGN:This was an observational study. SETTINGS:This was a post hoc analysis of a prospective, multicenter, randomized controlled trial (RELARC trial, NCT02619942). PATIENTS:Patients included in the modified intention-to-treat analysis in the RELARC trial were all enrolled in this study. MAIN OUTCOME MEASURES:Risk factors for postoperative complications were identified using univariate and multivariable logistic regression analysis. RESULTS:Of 995 patients, 206 (20.7%) had postoperative complications. Comorbidity ( p = 0.02; OR: 1.544; 95% CI, 1.077-2.212) and operative time >180 minutes ( p = 0.03; OR: 1.453; 95% CI, 1.032-2.044) were independent risk factors for postoperative complications, whereas female sex ( p = 0.04; OR: 0.704; 95% CI, 0.506-0.980) and extracorporeal anastomosis ( p < 0.001; OR: 0.251; 95% CI, 0.166-0.378) were protective factors. Eighty patients (8.0%) had overall surgical site infection, 53 (5.3%) had incisional surgical site infection, and 33 (3.3%) had organ/space surgical site infection. Side-to-side anastomosis was a risk factor for overall surgical site infection ( p < 0.001; OR: 1.912; 95% CI, 1.118-3.268) and organ/space surgical site infection ( p = 0.005; OR: 3.579; 95% CI, 1.455-8.805). The extracorporeal anastomosis was associated with a reduced risk of overall surgical site infection ( p < 0.001; OR: 0.239; 95% CI, 0.138-0.413), organ/space surgical site infection ( p = 0.002; OR: 0.296; 95% CI, 0.136-0.646), and incisional surgical site infection ( p < 0.001; OR: 0.179; 95% CI, 0.099-0.322). Diabetes ( p = 0.039; OR: 2.090; 95% CI, 1.039-4.205) and conversion to open surgery ( p = 0.013; OR: 5.403; 95% CI, 1.437-20.319) were risk factors for incisional surgical site infection. LIMITATIONS:Due to the retrospective nature, the key limitation is the lack of prospective documentation and standardization regarding the perioperative management of these patients, such as preoperative optimization, bowel preparation regimens, and antibiotic regimens, which may be confounder factors of complications. All surgeries were performed by experienced surgeons, and the patients enrolled were relatively young, generally healthy, and without obesity. It is unclear whether the results will be generalizable to obese and other populations worldwide. CONCLUSIONS:Male sex, comorbidity, prolonged operative time, and intracorporeal anastomosis were independent risk factors for postoperative complications of laparoscopic right colectomy. Side-to-side anastomosis was associated with an increased risk of organ/space surgical site infection. Extracorporeal anastomosis could reduce the incidence of overall surgical site infection. Diabetes and conversion to open surgery were associated with an increased risk of incisional surgical site infection. See Video Abstract . CLINICALTRIALSGOV IDENTIFIER:NCT02619942. FACTORES DE RIESGO DE COMPLICACIONES POSOPERATORIAS EN COLECTOMA DERECHA LAPAROSCPICA UN ANLISIS POST HOC DEL ENSAYO RELARC:ANTECEDENTES:Existe preocupación con respecto a la posibilidad de complicaciones postoperatorias en colectomía derecha laparoscópica.OBJETIVO:Evaluar los factores de riesgo de complicaciones postoperatorias en pacientes sometidos a colectomía derecha laparoscópica.DISEÑO:Este fue un estudio observacional.ENTORNO CLINICO:Este fue un análisis post hoc de un ensayo controlado aleatorio, multicéntrico y prospectivo: ensayo RELARC (NCT02619942).PACIENTES:Todos los pacientes incluidos en el análisis de intención de tratar modificado en el ensayo RELARC fueron inscritos en este estudio.PRINCIPALES MEDIDAS DE RESULTADO:Los factores de riesgo de complicaciones posoperatorias se identificaron mediante análisis de regresión logística univariante y multivariable.RESULTADOS:De 995 pacientes, 206 (20,7%) tuvieron complicaciones postoperatorias. La comorbilidad ( p = 0,02, OR: 1,544, IC 95%: 1,077-2,212) y el tiempo operatorio >180 min ( p = 0,03, OR: 1,453, IC 95%: 1,032-2,044) fueron factores de riesgo independientes de complicaciones postoperatorias. Mientras que el sexo femenino ( p = 0,04, OR: 0,704, IC 95%: 0,506-0,980) y la anastomosis extracorpórea ( p < 0,001, OR: 0,251, IC 95%: 0,166-0,378) fueron factores protectores. 80 (8,0%) tenían infección general del sitio quirúrgico (ISQ), 53 (5,3%) tenían ISQ incisional y 33 (3,3%) tenían ISQ de órgano/espacio. Anastomosis latero-lateral fue un factor de riesgo para la ISQ general ( p < 0,001, OR: 1,912, IC 95%: 1,118-3,268) y ISQ órgano/espacio ( p = 0,005, OR: 3,579, IC 95%: 1,455-8.805). La anastomosis extracorpórea se asoció con un riesgo reducido de ISQ general ( p < 0,001, OR: 0,239, IC 95%: 0,138-0,413), ISQ órgano/espacio ( p = 0,002, OR: 0,296, IC 95%: 0,136-0,646), e ISQ incisional ( p < 0,001, OR: 0,179, IC 95%: 0,099-0,322). Diabetes ( p = 0,039, OR: 2,090, IC 95%: 1,039-4,205) y la conversión a cirugía abierta ( p = 0,013, OR: 5,403, IC 95%: 1,437-20,319) fueron factores de riesgo para ISQ incisional.LIMITACIONES:Debido a la naturaleza retrospectiva, la limitación clave es la falta de documentación prospectiva y estandarización sobre el manejo perioperatorio de estos pacientes, como la optimización preoperatoria, los regímenes de preparación intestinal y los regímenes de antibióticos, que pueden ser factores de confusión de las complicaciones. Todas las cirugías fueron realizadas por cirujanos experimentados y los pacientes inscritos eran relativamente jóvenes, generalmente sanos y no obesos. No está claro si los resultados serán generalizables a las poblaciones obesas y de otro tipo en todo el mundo.CONCLUSIONES:Sexo masculino, comorbilidad, el tiempo operatorio prolongado y anastomosis intracorpórea fueron factores de riesgo independientes de complicaciones postoperatorias de la colectomía derecha laparoscópica. Anastomosis latero-lateral se asoció con un mayor riesgo de SSI de órgano/espacio. La anastomosis extracorpórea podría reducir la incidencia de ISQ general. La diabetes y la conversión a cirugía abierta se asociaron con un mayor riesgo de ISQ incisional. (Traducción- Dr. Francisco M. Abarca-Rendon ).
BACKGROUND A growing body of research indicates significant differences between left-sided colon cancers (LCC) and right-sided colon cancers (RCC). Pan-immune-inflammation value (PIV) is a systemic immune response marker that can predict the prognosis of patients with colon cancer. However, the specific distinction between PIV of LCC and RCC remains unclear. AIM To investigate the prognostic and clinical significance of PIV in LCC and RCC patients. METHODS This multicenter retrospective cohort study included 1510 patients with colon cancer, comprising 801 with LCC and 709 with RCC. We used generalized lifting regression analysis to evaluate the relative impact of PIV on disease-free survival (DFS) in these patients. Kaplan-Meier analysis, as well as univariate and multivariate analyses, were used to examine the risk factors for DFS. The correlation between PIV and the clinical characteristics was statistically analyzed in these patients. RESULTS A total of 1510 patients {872 female patients (58%); median age 63 years [interquartile ranges (IQR): 54-71]; patients with LCC 801 (53%); median follow-up 44.17 months (IQR 29.67-62.32)} were identified. PIV was significantly higher in patients with RCC [median (IQR): 214.34 (121.78-386.72) vs 175.87 (111.92-286.84), P < 0.001]. After propensity score matching, no difference in PIV was observed between patients with LCC and RCC [median (IQR): 182.42 (111.88-297.65) vs 189.45 (109.44-316.02); P = 0.987]. PIV thresholds for DFS were 227.84 in LCC and 145.99 in RCC. High PIV (> 227.84) was associated with worse DFS in LCC [PIV-high: Adjusted hazard ratio (aHR) = 2.39; 95% confidence interval: 1.70-3.38; P < 0.001] but not in RCC (PIV-high: aHR = 0.72; 95% confidence interval: 0.48-1.08; P = 0.114). CONCLUSION These findings suggest that PIV may predict recurrence in patients with LCC but not RCC, underscoring the importance of tumor location when using PIV as a colon cancer biomarker.
IntroductionThe mid-transverse colon cancer is relatively uncommon in all colon cancers and the optimal surgical approach of mid-transverse colon cancer remains debatable.Aim and ObjectivesOur study aimed to depict the techniques and outcomes of laparoscopic transverse colectomy in one single clinical center and compare this surgical approach to traditional laparoscopic right hemicolectomy and laparoscopic left hemicolectomy.MethodThis was a retrospective cohort study of patients with mid-transverse colon cancer in one single clinical center from February 2012 to October 2020. The enrolled patients were divided into two groups undergoing laparoscopic transverse colectomy and laparoscopic right/left hemicolectomy, respectively. The intraoperative, postoperative complications, oncological outcomes and functional outcomes were compared between the two groups. The primary endpoint was disease free survival (DFS).ResultsThe study enrolled 70 patients with 40 patients undergoing laparoscopic transverse colectomy and 30 patients undergoing laparoscopic hemicolectomy. The intraoperative accidental hemorrhage and multiple organ resection occurred similarly in the two groups. In transverse colectomy, caudal-to-cephalic approach was likely to harvest more lymph nodes although require more operation time than cephalic-to-caudal approach (23.1 ± 14.3 vs. 13.4 ± 5.4 lymph nodes, P = 0.004; 184.3 ± 37.1 min vs. 146.3 ± 44.4 min, P = 0.012). The laparoscopic transverse colectomy was marginally associated with lower incidence of overall postoperative complications and shorter postoperative hospital stay although without statistical significance (8(20.0%) vs. 12(40.0%), P = 0.067; 7(5–12) vs. 7(5–18), P = 0.060). The 3-year DFS showed no significant difference (3-year DFS 89.7% in transverse colectomy vs. 89.9% in hemicolectomy, P = 0.688) between the two groups. The alternating consistency of defecation occurred significantly less after laparoscopic transverse colectomy than laparoscopic hemicolectomy (15(51.7%) vs. 20(80.0%), P = 0.030).ConclusionThe laparoscopic transverse colectomy is technically feasible with satisfactory oncological and functional outcomes for mid-transverse colon cancer. Performing the caudal-to-cephalic approach might be more advantageous in lymphadenectomy.
BACKGROUND:Owing to the special features of biologics, deficient mismatch repair (dMMR) in patients with colon cancer has achieved little treatment efficacy from chemoradiotherapy. Immunotherapy has shown promising results for the treatment of colon cancer. The high response rate observed suggests a great option for patients presenting with unresectable tumors, as it allows for better oncological resection. Here, we aimed to highlight the significant effects of immunotherapy on dMMR in colon cancer.CASE SUMMARY:A 54-year-old man diagnosed with locally unresectable dMMR colon cancer received preoperative immunotherapy (three cycles of pembrolizumab) and achieved a pathological complete response after surgery.CONCLUSION:Immunotherapy can be used as a conversion treatment for locally unresectable colon cancer with dMMR.