Introduction

Tobacco smoke is an established risk factor for Crohn’s disease (CD) postoperative recurrence (POR), however, the effect of e-cigarettes and heat-not-burn tobacco (HNBT) remains unknown. We aimed to evaluate the impact of e-cigarettes and HNBT on postoperative recurrence in CD patients.

Aims & Methods

We retrospectively included consecutive CD patients who underwent ileocolic resection and endoscopic evaluation between 6 and 12 months after surgery across 9 centers in Italy, Spain, and France. Based on smoking habits between surgery and endoscopy, patients were categorized as non-smokers, cigarette smokers, HNBT users, or e-cigarette users. To avoid confounding, the use of HNBT and e-cigarettes was confirmed by phone call, and patients smoking multiple products were excluded.
The primary outcome was endoscopic recurrence (Rutgeerts score ≥2) within the first year. Secondary analyses were conducted on the population receiving prophylactic treatment, using the modified Rutgeerts score (≥i2b), the mean Rutgeerts score, transmural disease activity, fecal calprotectin, time from diagnosis to surgery, and multivariable regression analysis.

Results

In total, 1157 patients were included, of which 860 (75%) were non-smokers, 220 (19%) conventional cigarette smokers, 37 (3%) HNBT users, and 33 (3%) e-cigarette users. Groups were homogeneous for most clinical and demographic variables, including a history of intestinal surgery for CD, use of biologics in the 12 months before surgery, and prescription of POR prophylaxis, but not age. HNBT users were younger than other groups.
Recurrence rates were significantly higher in all smoking groups compared to non-smokers: 70%, 69%, and 68% for e-cigarette, HNBT, and cigarette users, respectively, vs. 39% for non-smokers; all p<0.01. The association persisted in patients receiving pharmacological prophylaxis, with 75%, 69%, 70%, and 40% recurrence for the same groups, and all comparisons remaining significant (all p<0.005).
Using the modified Rutgeerts score cutoff of i2b to define POR overall rates decreased, with 57% recurrence for e-cigarette and HNBT users, 54% for conventional cigarette smokers, and 29% for non-smokers. However, the relative proportions remained consistent, and the differences between groups did not change.
When analyzing the Rutgeerts score as a continuous variable, traditional cigarette smoking, HNBT use, and e-cigarette use remained associated with significantly greater endoscopic disease activity compared to non-smokers (2.02, 2.09, and 1.7,4 respectively, vs. 1.12; all p<0.05). Interestingly, the mean Rutgeerts score among e-cigarette users was numerically lower than that of conventional tobacco cigarettes and HNBT, although the difference was not statistically significant (1.74 vs. 2.02 and 2.09, respectively, both p>0.05). When restricting the analysis to patients receiving prophylactic biologics, differences persisted (p<0.05).
The average fecal calprotectin levels and imaging assessments confirmed the trends observed in endoscopy. The mean calprotectin levels at the time of endoscopy were 221 μ/g, 206 μ/g and 174 μ/g for tobacco, HNBT, and e-cigarettes, respectively, vs. 124 μ/g in non-smokers. Rates of transmural remission were 35%, 48%, 56%, and 61% for the same groups, respectively. Nevertheless, in calprotectin and radiologic analyses, only the differences between conventional smokers and non-smokers reached statistical significance (p<0.05), possibly due to the limited availability of these data and the wide variability of calprotectin levels.
After accounting for potential confounders such as sex, location and behavior of disease at diagnosis, disease duration, type of anastomosis, and previous intestinal resections, all smoking groups remained significantly associated with an increased risk of endoscopic recurrence compared to nonsmokers, e-cigarette (OR 3.06, 95% CI 1.08-9.57, p=0.041), and HNBT (OR 4.47, 95% CI 2.00-10.77, p<0.001), and conventional tobacco (OR 4.66, 95% CI 3.07-7.20, p<0.001).
Finally, we compared disease duration at the time of surgery. Compared to those who never smoked, patients who smoked traditional cigarettes and used HNBT had a significantly shorter disease duration at the time of intervention (7.2 and 5.2 years vs 9.0; p=0.029 and p=0.046, respectively), suggestive of a more aggressive disease course. Instead, the difference with e-cigarettes was not significant (7.5 years vs 9.0, p=0.76).

Conclusion

E-cigarettes and heat-not-burn tobacco are associated with increased endoscopic recurrence of CD compared to non-smoking.

Introduction

Post endoscopy upper gastrointestinal cancers (PEUGIC) are often missed opportunities to diagnose earlier or even prevent cancer. Up to 71% of PEUGIC are potentially avoidable, but identifying and investigating them can be challenging. A national process for identifying all PEUGIC in the English National Health Service and performing root cause analysis was developed.

Aims & Methods

Potential PEUGIC between 2017 and 2023 occurring 3-36 months after an index endoscopy which did not result in a cancer diagnosis were identified from National Cancer Registration Dataset and Hospital Episode Statistics held by the National Cancer Registration and Analysis Service. Data from local root cause analysis were uploaded onto a secure portal for national analysis. PEUGIC following surveillance endoscopies were excluded from this analysis. Logistic regression analysis was used to identify associations with outcomes of interest.

Results

3151 potential PEUGIC were examined by local reviewers in 144 English hospitals. 635 (20%) were excluded on local review and data were available for 2516 PEUGIC. 1897 (75.4%) PEUGIC followed diagnostic, follow-up or screening endoscopies. PEUGIC sites were oesophagus 61%, stomach 34% and duodenum 5%.
Table 1 shows the summary PEUGIC root cause results analysis based on the World Endoscopy Organisation categorisation. Categories C and D were associated with poor outcomes with 29% and 23% of cases receiving curative treatment, respectively. Compared to categories A and B receiving curative treatment in 53% and 37% of cases, respectively. Squamous cell cancers accounted for 37.5% of oesophageal PEUGIC and were associated with no lesion being detected (category C or D) in the PEUGIC segment OR 1.71 (95% CI 1.21-2.43).
Findings on index endoscopy (category A or B) at later oesophageal PEUGIC: pre-malignant lesion 23% (e.g. Barrett’s), cancer associated lesion 20% (e.g. ulcer) and other oesophageal focal lesions 15%. Findings on index endoscopy in gastric PEUGIC: cancer associated lesion 26%, pre-malignant lesion 7% and other gastric focal lesions 18%. 45% of the index endoscopies were classified as inadequate. Patient harm and adverse treatment outcomes were associated with an inadequate index endoscopy OR 1.56 (95% CI 1.28-1.91). The most common reason for inadequate endoscopy was inadequate management of lesions identified, which were most likely to be cancer associated lesions OR 1.43 (95% CI 1.11-1.69), specifically oesophageal strictures (24%) and gastric ulcers (23%).
Gastric diagnostic PEUGIC were diagnosed with more advanced cancer (40% stage 4 at diagnosis vs 30% oesophageal PEUGIC). Treatment following cancer diagnosis was adversely affected in 42% of PEUGIC. Reviewers considered that 57% of PEUGIC were at least possibly avoidable and 9% led to premature death.

Table 1 Root causes of all diagnostic PEUGIC

Conclusion

Abnormalities in the area of the later cancer were detected at index endoscopy in 59% of PEUGIC. Inadequate lesion assessment, endoscopy and/or decision making was noted in 45% of PEUGIC, which adversely affected treatment outcome. Oesophageal squamous cell cancer was a common cause of PEUGIC, suggesting issues with lesion recognition in this cancer. Many patients had incurable disease when diagnosed and treatment was adversely affected in 42%.

Clinical Case Summary

Introduction: This case describes a rare complication, triggered by SARS-CoV2 infection in a patient with Crohn’s disease (CD) and a long history of gastrointestinal and extraintestinal manifestations but otherwise stable at the infection onset.
Case Presentation: 25-year old male,non smoker, unvaccinated against COVID-19,with fistulizing and stricturing CD diagnosed at age 12 with multiple extraintestinal complications (articular,ocular, thrombotic, malnutrition). Therapeutic history is marked of various failed attempts over the years, ranging from many courses of steroids, anti-TNFalfa drugs, immunosupresives to holistic approaches until the age of 24 when he presented at our clinic and we initiated treatment with ustekinumab with a good response. During his previous visit,he presented with fever and COVID-19 infection. Radiologic image of the lung was normal but a computed tomography scan was performed to rule out a complication of CD. Both clinical and imaging evaluations confirmed a stable condition with colo-cutaneous fistula in partial remission. Four days later he presented with signs of acute abdomen, extremely distressed, hypotensive,tachycardic.
Tests revealed: leukocytosis, rised inflammatory markers, thrombocytopenia, high D-dimer. The scan suggested a perforation and was taken to surgery where the laparotomy confirmed it, at the level of the transverse colon. He suffered a cardiopulmonary arrest during the surgery and died despite resuscitative efforts.
Discussion: SARS-CoV2 virus binds to the human angiotensin-converting enzyme 2 receptors and triggers direct endothelial lesions and activation of prothrombotic factors resulting in a cascade of microvascular injury and ultimately ischemic tissue damage. Ischemia weakens the bowel wall, increasing risk of ulceration, necrosis,and perforation, especially in Crohn’s patients with fragile mucosa.
Conclusion: The case highlights the potential for fatal outcomes and the importance of close observation in CD patients during SARS CoV2 infection.

References

Images with the colo-cutaneous fistula before and after the treatment with ustekinumab
Ragiologic and computed tomography imaging from his previous visit with the first SARS-CoV2 positive test
Radiologic and computed tomography imaging from his last visit when he presented with acute abdomen

Introduction

Gastrointestinal (GI) hemorrhage accounts for 30% of acute decompensations in cirrhotic patients, with 60% originating from variceal bleeding. Each decompensation episode carries an in-hospital mortality rate of 13%, and a 6-week mortality rate of 20%, commonly assed using Child Pugh (CP) and MELD scores. The ALBI (Albumin-Bilirubin) score, which includes only two variables, offers a simplified evaluation of liver function. However, there is limited data on its utility in predicting short-term mortality in cirrhotic patients with GI hemorrhage.

Aims & Methods

This study aimed to evaluate the association between ALBI Score with short-term mortality in cirrhotic patients with GI hemorrhage. We conducted a prospective, cross-sectional study between January and December of 2023 at Hospital Roosevelt, Guatemala, including cirrhotic patients admitted for GI hemorrhage. Informed consent was obtained from all participants. Categorical variables were analyzed using the chi-square test, normally distributed continuous variables with Student’s t-test, and non-normally distributed variables with the Mann-Whitney U test. Logistic binary regression and AUROC analysis were used to assess associations with short-term mortality. Statistical analyses were performed using SPSS.

Results

A total of 187 patients were included: 50.8% female and 49.2% male, with a mean age of 56 among survivors and 58 among non-survivors. Of these, 52.9% had a prior diagnosis of cirrhosis, while 47.1% were newly diagnosed. Cirrhosis etiology was metabolic in 50.2%, alcoholic in 42.7%, autoimmune in 4.3%, HCV in 1.6%, and HBV in 1.1%. At admission, 80.8% had no ascites and 97.3% had no hepatic encephalopathy. he causes of GI hemorrhage were 86.1% esophageal varices, 3.2% gastric varices, 9.1% gastric ulcers, and 1.6% esophagitis.
Non-survivors had significantly lower systolic blood pressure (93.90 ± 16.3 mmHg vs. 107.92 ± 17.4 mmHg; p = 0.002) and mean arterial pressure (69.50 ± 14.5 mmHg vs. 79.67 ± 11.7 mmHg; p = 0.005) compared to survivors. Non-survivors exhibited significantly higher INR (1.79 ± 0.56 vs. 1.52 ± 0.41; p = 0.026) and total bilirubin (5.85 ± 8.73 mg/dL vs. 2.02 ± 2.82 mg/dL; p = 0.031), and lower serum albumin levels (2.40 ± 0.43 g/dL vs. 3.10 ± 0.54 g/dL; p < 0.001).

Prognostic scores were significantly higher among non-survivors: MELD (19.25 ± 10.09 vs. 13.57 ± 5.47; p = 0.002), MELD-Na (20.35 ± 9.76 vs. 14.44 ± 6.42; p = 0.002), Child-Pugh (9.15 ± 2.21 vs. 7.18 ± 1.90; p < 0.001), and ALBI score (-0.96 ± 0.51 vs. -1.76 ± 0.58; p < 0.001). Additionally, the length of hospital stay was significantly shorter among non-survivors (3.90 ± 3.82 days) compared to survivors (6.59 ± 5.58 days; p = 0.001).

• Higher ALBI score was significantly associated with mortality (Risk Ratio 25.80; 95% CI: 6.75–98.67; p < 0.001),
• Hospital stay <5 days (RR 9.91; 95% CI: 2.07–47.47; p = 0.004),
• Endoscopy performed within 12 hours (RR 7.53; 95% CI: 2.01–28.15; p = 0.003).

Conclusion

The ALBI score outperforms CP and MELD scores in predicting short-term mortality (in-hospital, 4 weeks, and 6 weeks) in cirrhotic patients with GI hemorrhage. Observed mortality was 10% in-hospital, 13% at 4 weeks, and 16% at 6 weeks.