Clinical Case Summary

A 71-year-old female presented to the gastroenterology clinic following a two year history of dysphagia and sensation of food sticking in the oesophagus. Her dysphagia was limited to solid foods, and symptoms were not exacerbated by positional change. Pain was mostly localised around the sternal notch where she would have the sensation of a food bolus. Over the preceding 2 years, she had experienced about 7.5kg of weight loss with no constitutional symptoms of fevers or fatigue. Her past medical history included hypertension, dyslipidaemia, lower back pain, cold agglutinin disease, monoclonal B lymphocytosis and peripheral arterial disease. On examination, there were no signs of malnourishment or palpable lymph nodes in the axilla, neck or supraclavicular region. Her abdomen was soft and non-tender. Given largely non-illuminating blood results, an oesophageal-gastroduedonoscopy was performed. However, no findings were noted, specifically no oesophageal webs, Zenker diverticulum, gastroparesis, trachealisation of the oesophagus or corrosive pathology. H. pylori was also not isolated on histopathology. A barium swallow was then performed which showed extensive external compression of the proximal third of the oesophagus at the level of the arch of the aorta, most indicative of dysphagia lusoria (Fig 1). Computed tomography angiography (CTA) showed retroesophageal aberrant right subclavian artery bifurcating from the ascending aorta independent of a brachiocephalic artery and causing external oesophageal compression (Fig 2 & 3). Given this definitive diagnosis, the patient was then seen in clinic where management of dysphagia lusoria was explained. Despite ongoing symptoms, the patient decided to continue with conservative management and lifestyle modifications, which included eating smaller bites and increase in fluid intake. Although an extensive compression typically requires surgical intervention, our patient was stable at two-year follow-up (Fig 4 A-B).

References

Figure 1: Barium swallow examination showing extrinsic compression of the proximal third of the oesophagus at the level of the aortic arch (white arrow).
Figure 2: Axial view of computed tomography angiography (CTA) showing the posterior course of the retroesophageal aberrant right subclavian artery.
Figure 3: Axial view of computed tomography angiography (CTA) showing compression of oesophagus (white arrow) by the retroesophageal aberrant right subclavian artery (white arrowhead).
Figure 4: Computed tomography angiography (CTA) multi-planar reconstruction (MPR) showing the posterior course of the right subclavian artery (white arrow), crossing the mediastinum and compressing the oesophagus. A. coronal view B. Sagittal view

Disclosure

None.

Introduction

The role of inhaled and subsequently swallowed aeroallergens in treatment outcomes of adults with eosinophilic esophagitis (EoE) is unclear. We hypothesized that the pollen season contributes to the failure of dietary therapy in EoE. In this international two-centre study, we compared six-food elimination diet (SFED) outcomes of EoE patients assessed during versus outside the pollen season.

Aims & Methods

Consecutive adult patients (≥18 years) with EoE who underwent SFED and skin prick test (SPT) for birch and grass pollen were included. Demographics, atopy, SPT results, endoscopy findings (EREFS), and the date of the endoscopy following SFED were retrospectively extracted. Individual sensitization profiles and historical and location specific pollen count data were scrutinized to define whether each patient had been assessed during or outside the pollen season following SFED. For patients without pollen sensitization, Spring was considered as pollen season for comparison purposes. Patients were divided into group A (positive SPT for pollens) or B (negative SPT for pollens). All patients had active EoE before SFED (eosinophils ≥15/high-power field, HPF) and adhered to SFED under the supervision of a dietitian. Response to SFED (eos<15/HPF) was assessed after a minimum of 6 weeks. Data are described as median/interquartile range (Q1-Q3) or as counts/percent. Kruskal-Wallis Rank Sum Test, Pearson’s Chi-Square and Fisher’s exact test were used as appropriate. Significance threshold was p<0.05.

Results

Fifty-eight patients were included, 62.0% had positive SPT for grass and/or birch (group A), while in 37.9% SPT was negative (group B). Significantly more patients from group A also had positive SPT for dust mite, cat and/or dog dander (85.7% vs 31.8%, p<0.001). The two groups were comparable in sex, age, baseline symptoms, atopy, baseline EREFS, and duration of SFED (Table1). The overall SFED response was 56.9%, (95% CI, 44.1%-68.8%) regardless of SPT results and pollen season. When stratifying SFED response according to whether the assessment of the assessment had been performed during or outside the pollen season, patients sensitized to pollens showed significantly lower response to SFED when the assessment was performed during compared to outside the pollen season (21.4% vs 77.3%; p=0.003). Additionally, during the pollen season, patients with positive SPT for pollens had significantly lower response to SFED compared to those with negative SPT (21.4% vs 77.8%; p=0.01). Patients without pollen sensitization did not show seasonal variations in SFED response (66.7% vs 53.8%; p=0.67) (Table 2).

Conclusion

Pollens may have a role in sustaining esophageal eosinophilia in sensitized adults with EoE despite avoidance of trigger foods. SPT for pollens may have a clinical utility in the dietary management of EoE by identifying patients less likely to respond to SFED during pollen season. Further studies are needed to clarify if alternative/combined therapy during pollen season will improve outcomes in sensitized EoE patients undergoing SFED or if elimination diets need to be undertaken outside of the pollen season.

Introduction

The ability to achieve endoscopic R0 resection in colorectal T1 cancer depends on the submucosal (SM) invasion distance of the malignancy. In this study, we looked for correlations between the SM invasive distance and achievement of R0 resection.

Aims & Methods

We classified fibrosis of the SM layer as noncancerous (Type B) and cancerous (Type C) and further categorized each into three phases from mild (1) to severe (3). Measurements of SM invasion distances for each tumor were based on the criteria specified by the Japanese Society for Cancer of the Colon and Rectum (JSCCR). For 142 patients (70 male and 72 female, average age of 68.1 years), 143 lesions were diagnosed as cancerous fibrosis in subjects who underwent ESD and 1,813 lesions were scored as colorectal epithelial neoplasms, with T1 cancer being diagnosed by postoperative pathological diagnosis. We evaluated the diagnostic ability of cancerous fibrosis in 308 patients including 165 Type B cases. We also compared the degree of SM invasion in Type C-1, C-2, and C-3 malignancies in which we observed macroscopic typing of the 143 Type C lesions. We then scored the degree of SM invasion in R0 resected Type C lesions. Using an ROC curve and a 95% cutoff index, we calculated the maximal SM invasion distance for which R0 resection could be achieved.

Results

The macroscopic subtypes of Type C lesions were as follows: 0-Is+IIa (LST-G (nodular mixed type)): 55, 0-IIa (LST-NG (flat elevated typ)): 23, 0-IIc+IIa (LST-NG(pseudodepressed typ)): 19, 0-Is: 23, 0-IIa+IIc: 15, 0-IIc: 8. Perioperative endoscopy was able to accurately diagnose 83.9% Type C cases and 93.9% of Type B cases. With regard to diagnostic potential, perioperative endoscopy had 83.9% sensitivity, 93.9%, and specificity. Diagnostic precision was 92.3%, PPV was 92.3%, and NPV was 87.0%. Pathology was used to sub-classify the 143 Type C cases based on severity. Seventy-one patients were C-1, 34 were C-2, and 38 were C-3. The mean SM invasion distances in C-1, C-2 and C-3 cases were 801.2 ± 956.1 mm, 1,745 ± 891.6 mm, and 3063.5 ± 2008.4 mm, respectively; differences between each group were significant (p<0.01). We classified macroscopic types of Type C into Flat and Depressed (FD:0-IIa, 0-IIc+IIa, 0-IIa+IIc, 0-IIc) and Protruded (P: 0-Is+IIa, 0-Is ).Although the corresponding values in the P group were larger (C-1:970.6 mm, C-2:2292.3 mm, and C-3:3483.3 mm, respectively), this difference was not statistically significant. The R0 rate according to the invasive distance was 94.7% when SM was <1,500 mm, and 92.9% when SM was <1,000. For SM between 1,000 mm and 1,500 mm the R0 rate was 19/19 (100%).The percentage of cancer-positive cases in the vertical margin (VM (+)) increased proportionally with the degree of invasion. For SM values between 1,500 and 2,000, VM (+) was 79.2%, whereas for SM values of 2,000 or more, the R0 rate decreased to 45.5%. We identified a statistically significant difference (p=0.037) between less than 1,500 mm and 1,500-2,000 mm. The maximum Youden Index was 0.636 and the R0 rate was 95.4%, when the upper limit was less than 1,625 mm.

Conclusion

An SM of less than 1,625 mm (regardless of the macroscopic type) is predictive of an R0 resection for colorectal T1 cancer, and provided the possibility of curative treatment. Also, we infer that the quantitative and qualitative advantages of ESD can help endoscopists avoid the pitfalls associated with preoperative endoscopic diagnosis, which may be useful in clinical practice.

Introduction

Clostridioides difficile infection (CDI) is the most common cause of healthcare associated infectious diarrhea in hospitalized patients, affecting primarily elderly patients with comorbidities after antibiotic exposure. Despite introduction of novel antibiotic options, recurrent CDI (rCDI) remain a major clinical challenge. Bezlotoxumab, an anti-Toxin B monoclonal antibody used in conjunction with standard of care antibiotic therapy, has been shown to reduce the frequency of rCDI in registration trials. To date, there is limited post-marketing data on this compound concerning its clinical efficacy and safety outside trials. The aim of the BODEGA study was to assess the clinical efficacy, safety and logistics of administration of bezlotoxumab in a real-life setting.

Aims & Methods

In this observational, prospective and retrospective multicenter study, we collected data from 100 patients receiving bezlotoxumab in combination with standard of care for the prevention of rCDI. Follow-up with respect to response and safety was performed at days 10, 45 and 90. For each patient, variables with respect to demography, fitness, previous CDI treatments and CDI associated hospitalizations, diagnostic and outcome were documented. Documentation was performed by use of the online platform ClinicalSurveys.Net. For statistical analysis, SPSS version 29.0.0.0 (241) was used.

Results

At the time of this analysis, data from 88/100 unique patients with documented CDI was evaluable, as 12 had not yet completed follow-up. The evaluable study population consists of 62,5% (n=55) females with an average age of 59 years (range: 20-91). Overall, 94,3% (n=83) of patients presented with additional comorbidities. Gastrointestinal (n=33, 37,5,4%) and cardiovascular diseases (n=38, 43,2%) were most frequently documented. Patients experienced a median of 3 episodes (range=0-10) of CDI prior to the episode in which bezlotoxumab was administered. The most recent CDI episode was non-complicated in 90,9% (n=80) and community acquired in 52,9% (n=46). Patients received fidaxomicin standard (n=36, 40,9%), fidaxomicin extended (n=16, 18,2%), vancomycin standard (n=13, 14,8%), vancomycin tapered (n=13, 14,8%) and others (n=4, 4,5%) as antibiotic treatment for the episode during which bezlotoxumab was administered. In their CDI patient history, most patients received the following treatments sequentially: vancomycin and fidaxomicin (n=34, 38,6%) fidaxomicin only (n=25, 28,4%, multiple administrations possible) and vancomycin only (n=16, 18,2%, multiple administrations possible). In 76/88 patients (86,4%) and 67/83 (76,1%) there was no further recurrence on day 45 and 90, respectively.

Conclusion

Preliminary data from the BODEGA study demonstrates comparatively low recurrence rates at days 45 and 90 in a real-life setting. Our study population was characterized by cases of multiply recurrent CDI with an uncomplicated course of CDI, that was often acquired in an ambulatory care setting. In these aspects, the study population differs significantly from patients included in registration trials. Although follow-up is not yet complete for all study patients, we conclude that bezlotoxumab is a promising option for treating patients with multiply recurrent CDI.

References

N/A

Disclosure

Funded with an unrestricted grant from Merck/MSD

Introduction

Local resection of submucosally invasive rectal cancer (T1 stage) is increasingly used. For tumors that extend into or through the muscularis propria layer (T2+ stage), the risk of lymph node metastasis is too high to consider a local resection as the optimal oncological treatment. Discrimination between T1 and T2+ rectal cancer is thus important before embarking on a local procedure. However, there is no reliable imaging method to exclude deep infiltration. Advanced endoscopic imaging has a low sensitivity, MRI and radial (static) endoscopic ultrasound are often overstaging; in addition, for ultrasound there is a lot of intra-observer variation. Linear endoscopic ultrasound (L-EUS) can dynamically assess fixation of the tumor to the muscularis propria layer by testing shiftability. We hypothesize that impaired shiftability could be a predictor of T2+ stage.

Aims & Methods

In this single-center pilot study, L-EUS media, optical and pathological data were prospectively collected from patients referred for local resection of early rectal cancer. Fixation to the muscularis propria layer was visualized by moving the lesion with a biopsy forceps or with the tip of the echoendoscope (shiftability). Impaired shiftability was defined as joined and fixed movement of the tumor and the muscularis propria layer. Shiftability was considered unimpaired when the tumor moved freely over de muscularis propria layer.

Results

We included 91 patients. The sensitivity of advanced endoscopic imaging for T2+ stage tumor was 61.3% and the specificity 86.7%, with a false-negative (understaging) and false-positive (overstaging) rate of 18.8% and 29.6%, Shiftability was assessed in 66 patients; Post-hoc analysis showed no evidence of selection bias in patients in whom shiftability testing was not performed, except for deeply ulcerating lesions (n = 6) in which shiftability testing was often not done for obvious reasons (5 cases not tested).
The sensitivity of impaired shiftability for T2+ stage tumor was 94.4%, the specificity was 97.9%, with a false negative rate of 4.2% and a false-positive rate of 5.6% (p < 0.005). No optical feature or other ultrsonographic static feature (various forms of iso-echogenic extensions from the tumor to muscularis propria layer) could improve this prediction in multivariate logistic regression analysis.

Conclusion

We found excellent sensitivity and specificity of this feature for muscularis propria infiltration, with a sensitivity of 94.4 and a specificity of 97.9%.
Although this should be considered a pilot study, these results are promising and deserve further appraisal in other centers.

References

Beets-Tan RGH, Lambregts DMJ, Maas M, Bipat S, Barbaro B, Curvo-Semedo L et al. Magnetic resonance imaging for clinical management of rectal cancer: updated recommendations from the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting. Eur Radiol 2018; 28: 1465 – 1475.
Detering R, van Oostendorp SE, Meyer VM, van Dieren S, Bos ACRK, Dekker JWT, Reerink O, van Waesberghe JHTM, Marijnen CAM, Moons LMG, Beets-Tan RGH, Hompes R, van Westreenen HL, Tanis PJ and Tuynman JB, on behalf of the Dutch ColoRectal Audit Group: MRIcT1–2 rectal cancer staging accuracy: a population-based study. BJS 2020; 107: 1372–1382.