Introduction

Colorectal cancer (CRC) is considered to develop through interaction of driver mutations such as APC and KRAS mutations with tumor microenvironment (TME) and inflammatory factors. Although chronic inflammation is widely recognized as a risk factor for CRC, the effect of transient and mild inflammation on tumorigenesis remains unclear. This study aimed to evaluate the effects of mild inflammation on colorectal tumorigenesis using a genetically modified mouse model.

Aims & Methods

Three genetically engineered mouse models were used: CDX2P9.5-CreER^T2;Kras^LSL-G12D/+ （KRAS mut）, CDX2P9.5-CreER^T2;Apc^flox/+（APC mut）, and CDX2P9.5-CreER^T2;Apc^flox/+;Kras^LSL-G12D/+（APCKRAS mut）. Each model was examined with and without a 5-day administration of 1.5% Dextran Sulfate Sodium (DSS). All the mice were treated with tamoxifen at 6 weeks of age, and DSS-treated groups were administered DSS at 8 weeks; subsequently, all the mice were sacrificed at 20 weeks. Location, number, size, and histological features of the tumors were analyzed. Immunofluorescence staining (F4/80, CD163, CD4, FoxP3, CD8, and Ki67) was performed to investigate changes in the TME.

Results

In the absence of DSS, no tumors were observed in either KRAS mut or APC mut mice. However, in APCKRAS mut mice, small tumors developed in the proximal colon. Upon DSS administration, no tumors were detected in KRAS mut mice, whereas APC mut and APCKRAS mut mice exhibited multiple tumors throughout the colon. Moreover, in APCKRAS mut mice, the tumors in the proximal colon were significantly more numerous and larger than those in DSS-untreated mice (number: 6.83±1.33 vs 2.14±1.21 [P<0.01], size: 2.14±0.38mm vs 2.83±0.41mm [P=0.01] ).Immunofluorescence staining revealed no substantial differences in the proximal colon tumors of APCKRAS mut mice between DSS-treated and -untreated groups. However, when APCKRAS mut and APC mut mice were compared, the former exhibited an increase in Tregs and M2 macrophages, indicating the formation of an immunosuppressive TME.

Conclusion

This study demonstrates that even mild inflammation can promote colorectal tumorigenesis in APC muttation mice.

Introduction

Anastomotic leaks and fistulae following upper gastrointestinal (GI) surgery remain a serious clinical challenge, carrying high morbidity and mortality. Endoscopic vacuum therapy (EVT) has emerged as a promising minimally invasive treatment option for managing these complications. This study aimed to assess the efficacy and safety of EVT for postoperative anastomotic leaks in a high-volume tertiary referral center.

Aims & Methods

We conducted a retrospective analysis of all patients treated with EVT for anastomotic leakage following upper GI surgery between January 2022 and January 2025. The primary outcome was EVT success, defined as complete leak closure confirmed through both endoscopic and radiologic assessment. Secondary outcomes included procedure-related adverse events and all-cause mortality.

Results

Twenty-four patients were included (79.2% male; mean age: 64 ± 12 years). Of these, 16 patients underwent oesophagectomy and 8 total gastrectomy; only two surgeries were performed for benign conditions. EVT achieved leak closure in 20 patients (87%). One patient died due to hemorrhagic shock from a hepatic artery pseudoaneurysm, unrelated to EVT.
Among successful cases, the mean duration of EVT was 30 ± 19 days, with a median of four sponge exchanges (IQR = 5). Median hospital stay was 52 days (IQR = 41). EVT failure occurred in three patients, all of whom had cancer-related surgeries and defect sizes exceeding 30 mm. In these cases, adjunctive endoscopic treatment with self-expanding metallic stents led to successful leak closure.
A larger defect size was associated with a lower likelihood of closure (p = 0.067), suggesting a trend toward reduced efficacy in extensive leaks. Importantly, no EVT-related complications were observed throughout the study period.

Conclusion

EVT demonstrated a high success rate (87%) and an excellent safety profile for managing postoperative anastomotic leaks following upper GI surgery. Larger leak sizes showed a trend toward lower closure rates, highlighting the importance of early diagnosis and timely initiation of EVT when defects are smaller. Given its effectiveness and minimal risk, EVT should be considered a first-line endoscopic treatment for anastomotic leaks. Further studies are warranted to refine treatment protocols and establish standardized indications based on leak characteristics.

References

1. de Moura DTH, et al. Role of endoscopic vacuum therapy in the management of gastrointestinal transmural defects. World JGastrointestEndosc. 2019 May 16;
2. Mastoridis S, et al. Endoscopic vacuum therapy (EVT) in the management of oesophageal perforations and post-operative leaks. Minim Invasive TherAllied Technol. 2022 Mar;
3. Livingstone I, et al. Current Status of Endoscopic Vacuum Therapy in the Management of Esophageal Perforations and Post-Operative Leaks. Clin Endosc. 2021 Nov;
4. Panneerselvam K,et al. Endoscopic vacuum therapy for treatment of spontaneous and iatrogenic upper gastrointestinal defects. Clin Endosc. 2023 Nov.

Introduction

Acute kidney injury (AKI) in cirrhosis manifests as pre-renal azotemia (PRA), hepatorenal syndrome (HRS), or acute tubular necrosis (ATN), each with distinct prognosis ⁽¹⁾. Early subtype classification and outcome prediction are critical. In Decompensated Cirrhosis patients with AKI, urine NGAL (UNGAL) and urine IL-18 (UIL-18) have been evaluated for differentiating between ATN and non-ATN AKI (PRA and HRS) with conflicting results ^(2,3). The present study compared the diagnostic accuracy of UNGAL and UIL-18 for predicting ATN AKI, AKI resolution and in-hospital mortality.

Aims & Methods

Present study was conducted at a tertiary care hospital (GIPMER, India) from July 1, 2023 to December 31, 2024. Patients with Decompensated Cirrhosis having AKI stage IB or higher were included, while advanced chronic kidney disease, Hepatocellular carcinoma prior liver transplant were excluded. The AKI was diagnosed as per International Club of Ascites Consensus (2015) and classified as per clinical adjudication after volume expansion with injection Human Albumin (20%, 1 g/kg body weight) on day 3 ⁽⁴⁾. Urine NGAL (sandwich ELISA) and IL-18 (sandwich ELISA) were measured after 48 hours of volume expansion, that is on day 3 of AKI diagnosis. The primary outcome was prediction of ATN-AKI on day 3 and secondary outcomes were prediction of AKI resolution at discharge and in-hospital mortality. The Receiver-operator curve (ROC) and multivariate logistic regression were used for analysis and p value <0.05 considered statistically significant.

Results

Total of 81 Decompensated Cirrhosis patients with AKI were enrolled in study. The aetiology of AKI was 24 (29.5%) PRA, 37 (45.7%) HRS and 20 (24.7%) ATN respectively. Mean MELD Na score was 28.4+7.3 and majority (82.7%) were CTP-C. Mean Serum Creatinine was 2.85+0.95 mg/dl. Mean UNGAL was 109.7 (PRA), 206.6 (HRS) and 396.4 (ATN) ug/g Creatinine (p<0.001). Mean UIL-18 was 39.8 (PRA), 85.6 (HRS) and 139.3 (ATN) pg/ml (p<0.001). AUROC for differentiation of ATN from non-ATN for urine NGAL was 0.9 (best cut-off 236.3 ug/g Creat) and urine IL-18 was 0.88 (best cut-off 108.75 pg/ml). AKI resolution occurred in 95.8% (PRA), 81% (HRS), and 40% (ATN). Mortality was highest in ATN (50%), vs PRA (16.7%) and HRS (8.1%). AUROC of UNGAL was 0.211 and UIL-18 was 0.185 for predicting AKI resolution. AUROC of UNGAL was 0.654 and UIL-18 was 0.641 for predicting in-hospital mortality (AUROC: NGAL 0.654, IL-18 0.641). Urine NGAL ( and urine IL-18 failed to predict AKI resolution (p 0.14 and 0.27) and in-hospital mortality (p 0.06 and 0.07) in multivariate regression analysis.

Conclusion

Urine NGAL and IL-18 had good diagnostic accuracy in predicting ATN-AKI in patients with Decompensated Cirrhosis, however do not independently predict resolution of AKI and in-hospital mortality.

References

1. Tariq R, Hadi Y, Chahal K, Reddy S, Salameh H, Singal AK. Incidence, mortality and predictors of acute kidney injury in patients with cirrhosis: A systematic review and meta-analysis. J Clin Transl Hepatol. 2020;8(2):135.
2. Puthumana J, Ariza X, Belcher JM, Graupera I, Ginès P, Parikh CR. Urine interleukin 18 and lipocalin 2 are biomarkers of acute tubular necrosis in patients with cirrhosis: a systematic review and meta-analysis. Clinical Gastroenterology and Hepatology. 2017;15(7):1003-13.
3. Huelin P, Solà E, Elia C, Solé C, Risso A, Moreira R, et al. Neutrophil gelatinase-associated lipocalin for assessment of acute kidney injury in cirrhosis: a prospective study. Hepatology.2019;70(1):319–33.
4. Angeli P, Ginès P, Wong F, Bernardi M, Boyer TD, Gerbes A, et al. Diagnosis and
management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut. 2015;64(4):531–7.