Introduction

Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer-related death. Most colorectal cancers arise from benign polyps, especially dysplastic adenomas. Colonoscopy with polypectomy is the gold standard for preventing cancer by interrupting the adenoma-carcinoma sequence. This has led to the development of various techniques and devices for improved prevention and treatment. Hot snare endoscopic mucosal resection (HS-EMR), which combines submucosal injections with electrocautery, is commonly used for excising various colorectal polyps. However, it carries risks of diathermy-related complications, such as perforation, and bleeding. To address these issues, cold snare endoscopic mucosal resection (CS-EMR) has been proposed as an alternative. Concerns about residual adenoma/recurrence have been raised with CS-EMR. Therefore, we conducted this meta-analysis to compare the two techniques.

Aims & Methods

We searched electronic databases, including MEDLINE via PubMed, Scopus, Web of Science, and Cochrane, without restrictions on publication date or language. We included RCTs comparing CS-EMR and HS-EMR for colorectal polyp resection. Primary outcomes included the incidence of delayed bleeding and residual/recurrent adenoma (RRA).

Results

On Nov 5, 2024, our literature search across electronic databases retrieved a total of 1,888 records. Following a meticulous screening process, six studies met the eligibility criteria encompassing 1,449 patients and 1,947 polyps. Regarding safety, the overall effect estimates regarding delayed bleeding showed statistically significant results favoring CS-EMR group [OR 0.31, 95 % CI (0.12–0.76), P = 0.01] with no heterogeneity (P = 0.40; I² = 0 %). However, statistical superiority for CS-EMR could not be detected regarding early bleeding [OR 0.78, 95 % CI (0.31–1.97), P = 0.60]. Only two studies reported data on delayed perforation, showing a numerical difference favoring CS-EMR; however, statistical significance could not be obtained [OR 0.26, 95 % CI (0.03–2.41), P = 0.24]. Regarding efficacy, the overall effect estimates regarding complete resection and RRA did not favor either of the groups [OR 0.62, 95 % CI (0.25–1.53), P = 0.30], [OR 2.81, 95 % CI (0.43–18.47), P = 0.28] respectively.

Conclusion

Evidence obtained from this meta-analysis suggests that CS-EMR offers superior safety compared to HS-EMR for colorectal polyp resection. Current evidence remains limited due to the small number of studies included. Therefore, further high-quality randomized controlled trials with larger sample sizes are needed.

References

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

• Winawer SJ, Zauber AG, Ho MN, O'Brien MJ, Gottlieb LS, Sternberg SS, et al. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med. 1993;329(27):1977–81.

• Facciorusso A, Del Prete V, Antonino M, Buccino VR, Muscatiello N. Efficacy of endoscopic polypectomy techniques for colorectal polyps: a systematic review and network meta-analysis. Gastrointest Endosc. 2020;91(4):733–745.e9.

• Pohl H, Srivastava A, Bensen SP, Anderson P, Rothstein RI, Gordon SR, et al. Incomplete polyp resection during colonoscopy—results of the complete adenoma resection (CARE) study. Gastroenterology. 2013;144(1):74–80.e1.

• Tutticci N, Hewett DG. Cold snare polypectomy: A safe, effective technique for sessile polyps. Gastrointest Endosc Clin N Am. 2015;25(2):291–301.

• Kawamura T, Takeuchi Y, Asawa S, Yokota I, Matsuno T, Omori T, et al. A comparison of cold and hot snare polypectomy for small colorectal polyps: a randomized controlled trial. Am J Gastroenterol. 2018;113(3):403–411.

Introduction

Esophageal Squamous Cell Carcinoma (ESCC) remains a significant global health problem with few therapeutic options and poor prognosis. Camrelizumab, an anti-PD-1 immune checkpoint inhibitor, has been shown in clinical trials to be of potential value in the treatment of advanced or metastatic ESCC as monotherapy or in combination with chemotherapy or anti-angiogenic therapy.

Aims & Methods

The aim of this study is to evaluate the clinical efficacy and safety profile of Camrelizumab in patients with esophageal squamous cell carcinoma, with the main outcomes being progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events.
We conducted a comprehensive search of PubMed, Scopus, Web of Science, Embase, and Cochrane from their inception to April 2025, focusing on randomized controlled trials (RCTs) and observational studies evaluating Camrelizumab for the treatment of esophageal squamous cell carcinoma. Meta-analyses utilized a random-effects model to calculate odds ratios, mean differences, and 95% confidence intervals for adverse events and total patients.

Results

Out of 1,563 studies initially screened, 15 studies met the inclusion criteria for our meta-analysis, comprising adult patients. Meta-analysis established a median progression-free survival (PFS) of 7.60 months (95% CI: 6.00–9.19). The major pathological response rate (MPR) was 0.42 (95% CI: 0.37–0.48), and the objective response rate (ORR) was 0.53 (95% CI: 0.38–0.68). The R0 resection rate was also remarkably high at 0.98 (95% CI: 0.96–1), and the disease control rate (DCR) was 0.87 (95% CI: 0.64–1). The pathological complete response rate (pCR) was 0.31 (95% CI: 0.20–0.43).
Regarding safety, the most common treatment-related adverse events were leukopenia 0.45 (95% CI: 0.23–0.68), neutropenia 0.30 (95% CI: 0.19–0.41), anemia 0.14 (95% CI: 0.03–0.29), thrombocytopenia 0.09 (95% CI: 0.03–0.17), and elevated transaminases 0.06 (95% CI: 0.02–0.12). Pneumonia 0.17 (95% CI: 0.11-0.23) and hypertension 0.12 (95% CI: 0.06-0.19) were the other immune-related adverse events. The majority of these events were tolerable and within safe parameters.

Conclusion

Camrelizumab demonstrates promising efficacy in the treatment of esophageal squamous cell carcinoma with satisfactory rates of ORR, MPR, and R0 resection. The safety profile is acceptable with controllable adverse effects. These findings support the potential therapeutic value of camrelizumab as a significant treatment strategy in multimodal treatment of esophageal squamous cell carcinoma and the need for further research to optimize its clinical use.

Introduction

The safety and efficacy of endoscopic haemostasis in patients with upper gastrointestinal (UGI) bleeding has been widely assessed over the years. However, to date no study addressed the management of UGI bleeding specifically in the setting of patients with surgically altered anatomy.

Aims & Methods

Our study is focused on the evaluation of the endoscopic management of UGI bleeding in these patients with specific concern about the techniques used to achieve haemostasis, the management of technical failure and the rate of adverse events. We conducted a multicentre retrospective- prospective observational study in 13 endoscopy units in Italy. All consecutive patients with UGI bleeding and surgically altered anatomy managed endoscopically were collected from January 2023 to November 2024.

Results

We enrolled 162 patients (73% males) with a mean age of 69 years. 45% of patients had history of oncologic surgery while 20% underwent bariatric surgery. The most common clinical manifestations were melena (59%) followed by hematemesis (22%). At bleeding event patients were taking anticoagulants and antiplatelet in 32% and 16% of cases, respectively. In 43% of cases from 1 to 4 blood units were needed, in 15% more than 4 blood units, while in 42% of patients no transfusions ware required. 42% of endoscopic procedures were performed with anesthesiologist assistance. Bleeding was located at anastomotic site in 70% of cases and ulcer was the most common source of bleeding (54% of patients). The most frequently used treatments were adrenaline combined with TTSC (40 %) and TTSC alone (24%). Haemostatic powder or gel and adrenaline combined with thermal treatment were used only in 6 and 4% of cases respectively while OTSC was used in 1 patient alone after failure of adrenaline combined with TTSC. Bleeding control during endoscopy was achieved in 94% of patients. In 12 patients rebleeding occurred, which was managed with surgery in 2 patients, interventional radiology in 1 case and with new endoscopic treatment in 4 cases. No serious adverse events linked to endoscopy were reported.

Conclusion

Our preliminary results showed that patients with altered anatomy often had severe bleeding requiring a large amount of blood transfusions. The standard endoscopic homeostatic techniques seemed to be effective for the management of bleeding, although a not negligible rate of patients needed additional treatments. However, further data are needed to better assess clinical outcomes in this setting and to better define possible predictive predictors of clinical success and therefore which technique should be preferred to achieve haemostasis.

References

1. S. G. Lim et al., “Endoscopic Approach for Postoperative Complications Following Laparoscopic-Assisted Gastrectomy in Early Gastric Cancer: Literature Review,” Hepatogastroenterology., vol. 59, pp. 1308–1312, 2012.
2. J.-H. Park et al., “Safety and efficacy of post-anastomotic intraoperative endoscopy to avoid early anastomotic complications during gastrectomy for gastric cancer.,” Surg. Endosc., vol. 34, no. 12, pp. 5312–5319, Dec. 2020.
3. K.-H. Kim, M.-C. Kim, G.-J. Jung, J.-S. Jang, and S.-R. Choi, “Endoscopic treatment and risk factors of postoperative anastomotic bleeding after gastrectomy for gastric cancer.,” Int. J. Surg., vol. 10, no. 10, pp. 593–597, 2012.
4. Shen, Y.; Xiao, M.; Weng, J.; Yang, L.; Feng, Y.; Ye, Y.; Zheng, P. Diagnosis and treatment of postoperative bleeding in patients after gastrectomy: A retrospective case series study. J. Gastrointest. Oncol. 2023, 14, 110–118.
5. Wichmann, D.; Fusco, S.; Werner, C.R.; Voesch, S.; Duckworth-Mothes, B.; Schweizer, U.; Stüker, D.; Königsrainer, A.; Thiel, K.; Quante, M. Endoscopic Management for Post-Surgical Complications after Resection of Esophageal Cancer. Cancers 2022, 14, 980.

Clinical Case Summary

A 40-year-old female, known case of endometriosis, presented with a five-day history of diffuse abdominal pain and watery, non-bloody diarrhea. A similar episode three months earlier resolved spontaneously. CT imaging revealed inflammatory mural thickening of the terminal ileum with skip lesions, raising suspicion of inflammatory bowel disease (IBD), possibly Crohn’s disease. TB PCR results were intermediate, requiring repeat testing. Despite conservative management, the patient developed worsening symptoms with progressive small bowel obstruction and mesenteric lymphadenopathy.
Colonoscopy findings were unremarkable, and biopsies from the terminal ileum, colon, and rectum were within normal limits. Due to persistent abdominal pain and diagnostic uncertainty, diagnostic laparoscopy was performed.
Laparoscopy revealed a thickened, hard, and narrow tubular terminal ileum, densely adhered in the right lower abdomen. The ileocecal area was severely stuck, preventing safe mobilization. Due to extensive adhesions and a non-distensible ileum, conversion to laparotomy was required. Ileocecal resection (30 cm) with stapled side-to-side anastomosis was performed.
Postoperative Course: was complicated by anastomotic disruption with fecal spillage, requiring an exploratory laparotomy and ICU admission. She later developed right pneumothorax requiring chest tube insertion. Histopathological examination confirmed Crohn’s disease. TB QuantiFERON results returned negative, allowing initiation of infliximab therapy. The patient showed significant improvement and was discharged on 09/11/2023.
Discussion: This case highlights the role of laparoscopy in small bowel emergencies where imaging and endoscopy fail to provide a definitive diagnosis. Laparoscopy aids in assessing disease severity and guiding surgical decisions. However, in cases of extensive adhesions and severe strictures, conversion to laparotomy ensures safe and effective management.

References

• Figure 1: CT Scan of the Abdomen
  CT imaging revealed inflammatory mural thickening of the terminal ileum with skip lesions, suggestive of inflammatory bowel disease (IBD), likely Crohn’s disease. Additional findings included dilated small bowel loops with fat stranding and minimal free peritoneal fluid. No evidence of vascular occlusion or bowel ischemia was noted.
• Figure 2: Colonoscopy Images
  Colonoscopy demonstrated normal mucosal appearance from the rectum to the ascending colon. The ileocecal valve and terminal ileum were endoscopically unremarkable. Multiple biopsies were taken from the terminal ileum, right colon, left colon, and rectum, all reported as within normal limits.
• Figure 3: Laparotomy Image
  Intraoperative findings revealed a thickened, hard, and narrow tubular terminal ileum that was densely adhered in the right lower abdomen. Extensive adhesions and stricturing prevented safe laparoscopic mobilization, necessitating conversion to laparotomy. Ileocecal resection (30 cm) with stapled side-to-side anastomosis was performed.
• Figure 4: Histopathology Specimen Morphology
  The resected specimen demonstrated chronic transmural inflammation, granulomas, and fibrosis, consistent with Crohn’s disease. Morphological findings confirmed IBD with terminal ileum involvement, supporting the final diagnosis.

Introduction

Acetaminophen (APAP) is a major cause of drug-induced liver injury (DILI), once the latter evolves into liver failure, it significantly impacting clinical outcomes. Urokinase plasminogen activator receptor (uPAR) is a membrane protein that is distributed on various immune-active cell membranes, which is not only associated with cell adhesion, invasion and migration, but also can regulate the immune microenvironment. However, uPAR specific roles in the regulation of myeloid cell innate immunity and the maintenance of hepatic homeostasis during DILI remains unclear.

Aims & Methods

The expression pattern of uPAR in both mouse DILI models and DILI patients was determined. Multiplex Immunohistochemistry (mIHC), flow cytometry, spatial transcriptomics (ST), single-cell RNA sequencing (scRNA-seq), intravital 3D imaging, luciferase reporter gene assay and Cleavage Under Targets and Tagmentation (CUT&Tag) were used to explore molecular mechanisms. uPAR^-/-, Lyz2^creuPAR^f/f and AXL^-/- mice, various mouse primary cells, human liver and serum samples were used to verify the discoveries of bioinformatics analysis.

Results

We found that the expression level of uPAR in the liver of both mouse DILI models and DILI patients was significantly high, systemic and myeloid deficiency of uPAR could alleviate liver inflammation in mice after challenged with APAP. mIHC, flow cytometry, ST, scRNA-seq and intravital 3D imaging multidimensionally elucidated that macrophage efferocytosis in both uPAR^-/- and Lyz2^creuPAR^f/f mice was enhanced due to the upregulation of the AXL, leading to the accelerated clearance of senescent neutrophils and thereby promoting the resolution of liver inflammation. Luciferase reporter gene assay and CUT&Tag confirmed that transcription factor IRF7 directly bound to the promoter region of AXL in macrophages. Mechanistic studies showed that uPAR regulated AXL mediated efferocytosis through the STAT3/IRF7 pathway. Macrophage-specific overexpression of IRF7 in vivo enhanced macrophage efferocytosis and promoted the attenuation of liver inflammatory response in both mouse DILI and liver ischemia-reperfusion injury models. AXL^-/- mice had exacerbated phenotype, while AXL activator GAS-6 protein could alleviate liver injury.

Conclusion

uPAR/STAT3/IRF7/AXL signaling is critical to regulate macrophage efferocytosis and maintain hepatic tissue homeostasis in the progression of DILI. Its dual functionality as a liver homeostatic regulator and DILI therapeutic target warrants further investigation.