Wei Zhou

BACKGROUND Cap polyposis (CP) is a rare benign colorectal disorder characterized by polyps capped with fibrinopurulent exudate and is frequently misdiagnosed as inflammatory bowel disease because of overlapping clinical and histological features. No consensus exists regarding optimal management strategies. The aim of this study was to establish a standardized stepwise management algorithm for CP based on lesion distribution, number, size, and symptom severity, with the hypothesis that such an approach will optimize therapeutic outcomes while minimizing unnecessary interventions. AIM To clarify the clinical features, endoscopic findings, treatments and short-term outcomes of colorectal CP and provide clinical information for the diagnosis and treatment of this rare disease. METHODS We retrospectively collected data from seven consecutive patients with histologically confirmed CP who were treated at our center between January 2022 and January 2025. RESULTS The cohort comprised six males and one female (median age 36 years). Hematochezia was the main symptom (n = 3), and two patients had hypoalbuminemia. Five patients had solitary lesions and two patients had multiple lesions. All the polyps had a characteristic “cap-like” appearance with white fibrinous exudate covering the surface. Histology revealed elongated, dilated crypts and mucosal hyperplasia covered by granulation tissue. One patient with small, asymptomatic lesions was kept under surveillance. Three patients underwent endoscopic mucosal resection, and three underwent transanal excision. Symptoms resolved in all treated patients. During a median follow-up of 18 months (range 10-30 m), no recurrence was detected. CONCLUSION In this small series, CP affected mainly males and resulted in rectal bleeding. Both endoscopic and transanal resection relieved symptoms, but larger studies with longer follow-up periods are needed to confirm long-term efficacy.

Left-sided colorectal obstruction represents a formidable challenge in colorectal cancer management, often necessitating urgent intervention. Although self-expanding metal stents (SEMS) may act as a bridge to more controlled, elective surgery, the question remains whether this strategy confers measurable advantages over immediate emergency surgery (ES). We conducted a single-center, retrospective study comparing outcomes in patients with left-sided colorectal obstruction who underwent either SEMS placement followed by elective resection or direct ES. Between January 2018 and August 2023, 189 eligible patients were included. Perioperative variables, stoma formation, operative blood loss, and survival rates were documented. Kaplan–Meier analyses were performed to assess overall and disease-free survival in both groups. Of the 99 patients allocated to the SEMS group, 98 achieved successful stent deployment and 89 (91%) proceeded to elective surgery without stent-specific complications. Compared with the 100 patients in the ES group, the SEMS cohort exhibited significantly lower intraoperative blood loss (p < 0.001) and an increased rate of minimally invasive surgeries (p < 0.001). While all patients in the ES group underwent colostomy, only 80 in the SEMS group required ileostomy, and an additional 9 underwent primary anastomosis without a diversion. Ileostomy closure was completed more frequently (p = 0.002) and required less operative time (p < 0.001) than colostomy closure, resulting in reduced hospitalization. No significant differences in overall survival (p = 0.091) or disease-free survival (p = 0.22) were observed between the two treatment groups. In selected patients with obstructing left-sided colorectal cancers, SEMS placement as a bridge to elective surgery may reduce operative trauma, facilitate minimally invasive procedures, and lessen the burden of stoma formation, all without compromising long-term oncologic outcomes. Careful patient selection and strict procedural vigilance are fundamental to ensuring the safe adoption of this strategy.

Patients with colorectal cancer (CRC) harboring BRAF mutation have a poor prognosis. The median survival time for patients with advanced BRAFV600E-mutant CRC is only approximately one year. Owing to the insensitivity to standard chemotherapy, there are still no effective and highly specific treatment strategies available in clinical practice for CRC patients with BRAF mutation. Therefore, targeting the BRAFV600E mutation site, researching and exploring novel targeted therapies are essential to improve the survival rate of patients with this CRC subtype. This study aims to develop a precise therapeutic system for BRAFV600E CRC, based on the carrier properties of extracellular vesicles (EVs) and gene therapy targeting BRAFV600E. We first obtained engineered cells capable of stably producing EVs loaded with BRAFV600E nucleic acid drugs (siBRAFV600E). Next, BRAFV600E-mutant and wild-type CRC cell lines, as well as corresponding subcutaneous and metastasis models, were used to evaluate the therapeutic efficacy of EVs-siBRAFV600E and explored the mechanism. Notably, patient-derived xenograft (PDX) models, which share the same molecular characteristics, pathological features, and heterogeneity as patients do, were utilized to further explore the therapeutic efficacy and mechanisms. EVs-siBRAFV600E specifically inhibited BRAFV600E CRC but didn’t affect BRAF wild-type CRC in vitro and vivo. EVs-siBRAFV600E exerts its therapeutic effect by regulating the MEK1/2-ERK1/2 pathway, and it has demonstrated excellent therapeutic efficacy in PDX models. The therapeutic EVs we constructed are effective and specific for the BRAFV600E-mutant CRC. This study provides a novel strategy for the treatment of CRC patients with BRAFV600E mutation.

BRAF ^V600E -mutant metastatic colorectal cancer (mCRC) is associated with poor prognosis. The combination of anti-BRAF/anti-EGFR (encorafenib/cetuximab) treatment for patients with BRAF ^V600E -mutant mCRC improves clinical benefits; unfortunately, inevitable acquired resistance limits the treatment outcome, and the mechanism has not been validated. Here, we discovered that monoacylglycerol O-acyltransferase 3–mediated (MOGAT3-mediated) diacylglycerol (DAG) accumulation contributed to acquired resistance to encorafenib/cetuximab by dissecting a BRAF ^V600E -mutant mCRC patient–derived xenograft (PDX) model exposed to encorafenib/cetuximab administration. Mechanistically, the upregulated MOGAT3 promoted DAG synthesis and reduced fatty acid oxidation–promoting DAG accumulation and activated PKCα/CRAF/MEK/ERK signaling, driving acquired resistance. Resistance-induced hypoxia promoted MOGAT3 transcriptional elevation; simultaneously, MOGAT3-mediated DAG accumulation increased HIF1A expression at the translation level through PKCα/CRAF/eIF4E activation, strengthening the resistance status. Intriguingly, reducing intratumoral DAG with fenofibrate or PF-06471553 restored the antitumor efficacy of encorafenib/cetuximab in resistant BRAF ^V600E -mutant mCRC, which interrupted PKCα/CRAF/MEK/ERK signaling. These findings reveal the critical role of the metabolite DAG as a modulator of encorafenib/cetuximab efficacy in BRAF ^V600E -mutant mCRC, suggesting that fenofibrate might prove beneficial for resistant BRAF ^V600E -mutant mCRC patients.

Background: Anastomotic stricture (AS) is a common complication following rectal cancer surgery with anastomosis, but its diagnosis and management pose significant challenges due to the lack of standardized diagnostic criteria. We present a case highlighting the complexities encountered in diagnosing and managing occult AS post-rectal cancer surgery.Case presentation: A 51-year-old male patient presented with symptoms suggestive of AS following robot-assisted laparoscopic low anterior resection for rectal adenocarcinoma. Despite conventional evaluations, including colonoscopy, digital rectal examination, and radiography, AS was not identified. Following prolonged and ineffective treatment for suspected conditions such as low anterior resection syndrome (LARS), the patient underwent anal dilatation, resulting in significant symptom improvement.Conclusions: This case underscores the challenges associated with diagnosing and managing occult AS following rectal cancer surgery. The absence of standardized diagnostic criteria and reliance on conventional modalities may lead to underdiagnosis and inadequate treatment. A comprehensive diagnostic approach considering intestinal diameter, elasticity, and symptoms related to difficult defecation may enhance diagnostic accuracy. Further research is needed to refine the diagnostic and therapeutic strategies for occult AS.

5-Fluorouracil (5-Fu) is the first-line chemotherapeutic option for colorectal cancer. However, its efficacy is inhibited by drug resistance. Cytokines play an important role in tumor drug resistance, even though their mechanisms are largely unknown. Using a cytokine array, we established that tissue inhibitor metalloproteinase 2 (TIMP-2) is highly expressed in 5-Fu resistant colorectal cancer patients. Analysis of samples from 84 patients showed that elevated TIMP-2 expression levels in colorectal patients were correlated with poor prognostic outcomes. In a 5-Fu-resistant patient-derived xenograft (PDX) model, TIMP-2 was also found to be highly expressed. We established an autocrine mechanism through which elevated TIMP-2 protein levels sustained colorectal cancer cell resistance to 5-Fu by constitutively activating the ERK/MAPK signaling pathway. Inhibition of TIMP-2 using an anti-TIMP-2 antibody or ERK/MAPK inhibition by U0126 suppressed TIMP-2 mediated 5-Fu-resistance in CRC patients. In conclusion, a novel TIMP-2-ERK/MAPK mediated 5-Fu resistance mechanism is involved in colorectal cancer. Therefore, targeting TIMP-2 or ERK/MAPK may provide a new strategy to overcome 5-Fu resistance in colorectal cancer chemotherapy.