Introduction

Endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) is one of the most challenging endoscopic procedures due to the high risk of bleeding and fibrosis caused by prior treatment of varices. However, due to the small number of such cases, the clinical outcomes of ESD for ESCC with EVs have been reported in only a limited number of cases at single centers^​1-3.

Aims & Methods

We conducted a multicenter, retrospective, cohort study to clarify the safety and efficacy of ESD for ESCC with EVs.Eleven institutions in the Tohoku region of Japan participated in this multicenter, collaborative, retrospective study. We performed endoscopic resection for 3619 patients with esophageal carcinoma at the participating institutions during the period from January 2010 to April 2022. Among those, 30 patients who underwent ESD for ESCC with EVs were recruited for the present study.
Rates of en bloc resection and R0 resection, procedure time and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD.

Results

Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 minutes. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC.

Conclusion

This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

References

1. Sawaguchi M, Jin M, Matsuhashi T, et al. The feasibility of endoscopic submucosal dissection for superficial esophageal cancer in patients with cirrhosis (with video). Gastrointest Endosc 2014;79:681-5.
2. Choi YK, Noh JH, Kim DH, et al. Outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms in patients with liver cirrhosis. Clin Endosc 2022;55:381-9.
3. Zhang S, Liu YD, Chai NL, et al. Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper gastrointestinal tract in cirrhotic patients with esophagogastric varices: Ten-year experience from a large tertiary center in China. Gastrointest Endosc 2023 Online ahead of print.

Disclosure

The authors declare that they have no conflicts of interest.

Introduction

Colorectal cancer associated to chronic colitis (CAC) has a different pathogenesis compared to sporadic or familial colorectal cancer (CRC) and represents the major complication of inflammatory bowel disease (IBD). It is now well-established that IL-33 and its receptor, ST2, are important factors in the pathogenesis of IBD. Emerging evidence also suggests its critical role in epithelial proliferation and the potential contribution to inflammation-driven tumorigenesis that can lead to CRC.

Aims & Methods

The aim of our study was to characterize the precise contribution of IL-33/ST2 axis in the azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated CRC. C57/BL6 wild-type (WT), Il33^-/-, T1/St2^-/- and Nt5e^-/- mice were given a single dose of AOM (10 mg/kg) followed by two cycles of 3% DSS for 7d in drinking water. Vehicle-treated WT mice served as controls and were sacrificed at the same time points. Another group of WT followed the same protocol and received CD73 inhibitor i.p. treatment or vehicle. Disease Activity Index (DAI), as well as endoscopic, stereomicroscopic and histological evaluations of colons were performed. IHC, immunofluorescence (IF), qPCR, and ELISA were done on full-thickness colons of WT for IL-33 and ST2 localization and identification, as well as mRNA and protein expression, respectively. RNA-Seq was performed on whole tissues from AOM/DSS treated WT, Il33^-/- and T1/St2^-/-. qPCR analysis was done on isolated polyps from WT, Il33^-/- and T1/St2^-/- for Nt5e (CD73) and adenosine pathway targets.

Results

Il33, Ilrl1(ST2L), and Ilrl1(sST2) mRNA transcripts, as well as IL-33 and total ST2 proteins were dramatically elevated in AOM/DSS-treated WT mice vs. controls. IHC and IF of treated WT mice revealed localization of IL-33 to the colonic epithelium and to cells within the polyp LP morphologically consistent with stromal and mast cells. Little to no staining for IL-33 was present in controls. Using IF, IL-33 co-localized with sub-epithelial myofibroblast markers Actin and Vimentin, or with mast cell markers Tryptase and MCPT1. AOM/DSS treatment in Il33^-/- and T1/St2^-/- mice resulted in a significant decreased polyp number and size vs. WT, with colonoscopy revealing the development of protruding lesions with abnormal vascular patterns, suggesting tumorous lesions in WT mice, while all deficient mice showed their absence with a more impressive mucosal inflammation, likely due to reduced epithelial proliferation and repair caused by the deficiency of IL-33 signaling. RNA-Seq identified a significant reduction of Nt5e and adenosine pathway targets in Il33^-/- and T1/St2^-/- vs. WT. qPCR on isolated polyps confirmed this observation. AOM/DSS-treated Nt5e^-/- showed a significant decreased polyp number and size vs. controls. Therapeutic inhibition of CD73 produced similar results.

Conclusion

Our results suggest that the IL-33/ST2 axis promotes tumorigenesis in colitis-associated CRC through the activation of CD73. Further studies are underway to determine mechanisms of action that support these findings.

Introduction

Diverticular disease of the colon is one of the most common diseases in Western world. Despite in the natural history in most of cases diverticulosis remains asymptomatic or manifests with mild abdominal pain, complications may occur. Bleeding from diverticula is one of the most common complications and, despite it is usually a self-limiting event, it may lead to anemia or shock. Among the endoscopic interventions for active bleeding, direct or indirect clipping of the diverticulum is the most diffuse one. However, it has been hypothesized that endoscopic band ligation (EBL) may be more effective, since it may improve the chance to close the bleeding vessel, with a better outcome on long term. Therefore we performed a meta-analysis comparing clipping versus EBL for diverticular bleeding.

Aims & Methods

Literature search on main databases (PubMed, Web of science, SCOPUS, EMBASE) was performed in November 2022. Studies comparing clip versus EBL for acute diverticular bleeding were selected. We excluded case series, abstract and articles not written in English. The following outcomes were analysed: short term effectiveness, early rebleeding, tardive rebleeding and need for surgery or radiologic embolization. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculate according to Mantel-Haenszel method. Heterogeneity was estimated by I² statistic with chi square test, and, if present, a random effect model was used, otherwise a fixed one was adopted.

Results

Seven studies were selected, overall enrolling 2322 patients (979 in EBL and 1343 in clip groups). Immediate haemostasis was achieved in the EBL and clipping group respectively in the 96.8% and 96.5% (OR=0.94, 95% CI 0.59-4.19, p=0.79). Early rebleeding was observed more frequently in the clipping (25.0%) than in the EBL group (11.8%), with an OR=0.40 (95% CI 0.32-0.51, p<0.001). Similarly, tardive rebleeding was more common in the clipping arm (37.4%) than in the EBL (24.5%), OR=0.39, 95% CI 0.22-0.68, p=0.0001. Patients receiving clipping needed more frequently salvage surgery or embolization than EBL (1.48% versus 0.53%, OR=0.40, 95% CI 0.17-0.93, p=0.03).

Conclusion

Despite EBL and clip have similar effectiveness in achieving immediate haemostasis, EBL showed better effectiveness in maintaining it on longer interval times, with less probable need for major surgical/radiologic interventions.

Introduction

To prevent stent migration during EUS-HGS, intra-scope channel release technique is important, but are unfamiliar to non-expert hands. The self-expandable metal stent (SEMS) is an additional factor to prevent stent migration. However, no comparative studies of laser-cut and braided types during EUS-HGS have been reported.

Aims & Methods

The aim of this study was to compare the distance between the intrahepatic bile duct and stomach wall after EUS-HGS among laser-cut- and braided-type SEMS. To evaluate stent anchoring function, we measured the distance between the hepatic parenchyma and stomach wall before EUS-HGS, one day after EUS-HGS, and 7 days after EUS-HGS.　Also, propensity score matching was performed to create a propensity score for using Laser cut type group and Braided group with a logistic regression model.

Results

A total 144 patients were enrolled in this study. Among them, 24 patients underwent EUS-HGS using a laser-cut-type SEMS, and 118 patients underwent EUS-HGS using a braided-type SEMS. EUS-HGS using the laser-cut-type SEMS was mainly performed by non-expert endoscopists (n=21). However, EUS-HGS using braided-type SEMS was mainly performed by expert endoscopists (n=98), showing a significant difference. The distance after 1 day was significantly shorter with the laser-cut-type group (2.91 ± 1.88 mm) compared with the braided-type group (8.19 ± 6.07 mm). In addition, this distance remained significantly shorter in the laser-cut type group compared with the braided-type group after 7 days.　Although these results were similar after propensity score matching analysis, the distance between hepatic parenchyma and stomach after 7 days was increased 4mm compared with the distance after 1 day in Braided group. On the other hand, in Laser cut type group, the distance after 1 day and 7 days was almost same.

Conclusion

In conclusion, EUS-HGS using a laser-cut-type SEMS may be safe to prevent stent migration, even in non-expert hands, compared with a braided-type SEMS, although a randomized trial is warranted.

Disclosure

None

Introduction

Inflammatory Bowel Diseases (IBD) patients are associated to a higher risk of developing colonic dysplasia and colorectal cancer due to long-standing colonic inflammation and immunosuppressant therapies. They seem to have also a higher risk of developing extra-intestinal malignancies, such as cholangiocarcinoma, skin cancer, and others. Different studies have been conducted to assess whether a correlation exists between IBD, medical treatments and cancers, but the results are controversial.

Aims & Methods

Our study aimed to evaluate the risk factors of malignancies in our IBD patients, particularly considering the medication history.
In this single-center retrospective study, IBD patients with a history of at least one malignancy post-IBD diagnosis followed at the Gastroenterology Unit of Azienda Ospedale Università Padova were enrolled (cases). Demographics and clinical data, including medication information, were collected before and at the time of malignancy diagnosis. A group of IBD patients, matched by sex and age, without a malignancy history were also included (controls), considering the medications taken before and at the time of the last visit for comparison.

Results

Among 2213 IBD patients followed at our center (1212 males, 1040 CD, and 1173 UC), 153 cases (80 UC and 73 CD, 46.4% males, mean age at diagnosis: 38.4±14.7) and 50 sex and matched controls were included (30 UC and 20 CD, 52% males, mean age at diagnosis: 38.9±0.8). Twelve patients had two malignancies, and 2 had three. For the scope of our study, we considered only the first tumor. Results are shown in the Table 1. The mean time from IBD diagnosis to the first tumor was 15 years (SD 10.5). Considering malignancies, the most frequent in our population were breast cancer (27/1001 females, 2.7%), colorectal cancer (23/2213, 1%), melanoma (24/2213, 1.1%), and non-melanoma skin cancer (15/2213, 0.7%). Patients with colon cancer were younger at the time of IBD diagnosis (31.0±15.8 vs. 38.9±0.8), while patients with prostate and urinary cancer (11/2213, 0.5%) were older compared to controls (49.6±13.7 vs. 38.9±0.8). A lower percentage of patients with colon (13%), breast (4%), and prostate cancers (9.1%) had taken biological therapy before cancer occurrence, as compared to controls (44%, p<0.01). Finally, we observed a significantly higher number of melanoma and breast cancer patients taking azathioprine (AZA) at the time of cancer diagnosis for more than 4 years. No difference in terms of duration of AZA and biological therapies before cancer diagnosis was observed.

Table 1: Type and frequency of Malignancies and characteristics of the patients

Conclusion

Our study found that biological therapy was not associated to malignancies, while azathioprine use was associated with breast and melanoma cancers. A younger age at diagnosis was associated with colon cancer, while an older age with prostate and urinary cancers.

Introduction

Preoperative carbohydrate rich drink (CHO) is a component of the Enhanced Recovery After Surgery (ERAS) protocol and has been shown to improve patient discomfort during fasting. Evidence on its efficacy prior to endoscopic procedures such as oesophagogastroduodenoscopy (OGD) is limited.

Aims & Methods

We aimed to investigate whether CHO given prior to OGD can reduce fasting related discomfort and improve overall patient satisfaction. The primary objective was to evaluate if CHO given pre-OGD reduces fasting related discomfort and improves patient satisfaction compared to the other arms. The secondary objectives were to assess the effects of CHO consumed pre-OGD on procedural risks and gastric preparation quality.
This was a single centre, single-blinded randomised controlled trial. Patients undergoing elective outpatient OGD were randomised into 3 arms: CHO vs Water vs Fasting. All patients were instructed to fast 6 hours pre-OGD. Patients in the CHO and water arms consumed CHO (50g Nestle Preload^TM mixed with 400ml water) and 400ml of water only up to 2 hours pre-OGD. Exclusion criteria were: ASA (American Society of Anaesthesiologists), conditions and medication affecting gastrointestinal motility, pregnancy and diabetes. 30 minutes pre-OGD, patients completed a questionnaire consisting of 11 questions on a 9-point Likert scale pertaining to preprocedure discomfort and symptoms such as vomiting, abdominal pain and fatigue. Post-procedure, endoscopists blinded to the study arm, filled up a questionnaire recording complications and gastric preparation quality. One-way ANOVA test was used to compare the mean scores amongst the 3 groups for each question using SPSS version 27.

Results

262 out of 300 patients recruited were analysed. 52.3% were female and the mean age was 54 years. The predominant indication for OGD was dyspepsia. Our results (Figure 1) showed that patients in the CHO arm were significantly less hungry (4.68 vs 5.95; p=0.004) compared to the fasting arm and experienced less abdominal pain prior to OGD (1.74 vs 2.47; p=0.023). There was however no significant difference between the CHO arm vs water for hunger and pain.. Patients in both CHO (4.69 vs 5.86; p= 0.010) and Water arms (4.68 vs 5.86; p= 0.009) were less thirsty compared to those in the fasting arm. (Table 1). We observed a trend in reduction of depression and feeling weak in the CHO arm as compared to the fasting and Water arm, however these results did not reach statistical significance. There were no overall complications. 10.7% of patients had suboptimal gastric preparation with no significant difference amongst the 3 arms. Logistic regression analysis showed that younger age was associated with suboptimal gastric preparation(p=0.043).

Table 1: Mean Likert Scale Score for each variable. 1=strongly disagree, 3=disagree, 5=neutral, 7=agree, 9=strongly agree

Conclusion

CHO consumption pre-OGD reduces hunger, thirst and abdominal pain compared to fasting. Water consumption pre-OGD yielded similar results, with CHO appearing to suppress hunger better. Importantly, all the patients who consumed clear fluids pre-OGD had no significant residual gastric fluid. We propose that allowing consumption of water or CHO up to 2 hours pre-OGD may reduce discomfort during fasting. Larger studies are required to detect significant differences between CHO and Water and overall cost-effectiveness.

References

Hausel J, et al. A carbohydrate-rich drink reduces preoperative discomfort in elective surgery patients. Anesth Analg 2001 Nov