Introduction

Specialist guidelines recommend endoscopic surveillance for Barrett’s esophagus (BE) to reduce mortality related to esophageal adenocarcinoma (EAC), but the setting for optimal BE monitoring is unclear. Previous prospective BE surveillance studies showed rates of neoplastic progression between 0.78% and 1.2% (1-3).

Aims & Methods

We aimed to assess progression rate and disease-specific mortality in a large cohort of patients followed up in a single BE expert centre. Prospective longitudinal single centre study. The expert centre consisted of a dedicated BE service comprising endoscopists trained in BE surveillance standards and image-enhanced endoscopy, a centralised pathology review and a tracking system to reduce lost to follow up. We recruited patients referred for surveillance of BE. We excluded patients with single surveillance endoscopy, high-grade dysplasia (HGD) or OAC at or within 12 months from index endoscopy; no intestinal metaplasia (IM) or BE<1cm; <12 months follow-up. The primary outcome was progression to HGD/EAC. Secondary outcome measures included cancer stage and disease specific mortality (intention-to-treat analysis). Outcomes were compared with a cohort patients surveyed by non-expert endoscopists at the primary institution (non-expert cohort).

Results

A total of 1,929 patients referred to the BE service were prospectively recruited to the study between 2004 to 2022, of which 949 were excluded due to HGD/EAC at index endoscopy (n=492), BE <1cm or no IM (n=246), single endoscopy or follow up shorter than 12 months (n=157), miscellaneous reasons (n=54). Finally, 980 BE patients met the inclusion criteria (expert cohort) and were followed up for a median of 5.7 years. Of these, 869 had at most low-grade dysplasia at last follow-up and 111 developed HGD or OAC during the study period (progressors), which equalled to an annual progression rate of 1.98%. Overall, 49 patients received a OAC diagnosis, of which 39 (79.6%) had stage I, 5 (10.2%) had stage II, 3 (6.1%) had stage III, 2 (4.1%) had stage IV. In an intention-to-treat analysis, only 4 patients (0.4%) had disease-specific mortality, of which one declined surveillance and one was discharged as unfit for monitoring. In the non-expert cohort, we identified 213 patients from hospital records, of which 98 met the inclusion criteria and were followed up for a median of 4.1 years. The annual progression rate was 0,50%, with no HGD or stage I EAC diagnoses. Two patients were diagnosed with stage IV EAC and had disease specific mortality (2%).

Conclusion

Endoscopic surveillance in an expert BE centre leads to a high rate of early BE neoplasia detection and a low rate of disease specific mortality. Randomised-controlled trials are warranted to compare outcomes of surveillance in different clinical setting.

References

1. Development and Validation of a Model to Determine Risk of Progression of Barrett's Esophagus to Neoplasia. Parasa et al. Gastroenterology 2018, Apr;154(5):1282-1289
2. Barrett's esophagus surveillance in a prospective Dutch multi‐center community‐based cohort of 985 patients demonstrates low risk of neoplastic progression. Klaver et al United European Gastroenterol J 2021 Oct;9(8):929-937
3. Impact of surveillance for Barrett’s oesophagus on tumour stage and survival of patients with neoplastic progression. Kastelein et al. Gut 2016, Apr;65(4):548-54

Clinical Case Summary

A 39-year-old woman was admitted on June 20, 2024, with a right middle cerebral artery stroke, nine weeks after starting Upadacitinib for ulcerative colitis. She presented with dysarthria, dysphagia, and severe left-sided weakness. CT imaging revealed a wedge-shaped infarction without intracranial hemorrhage (CT head/ Brain MRI).
She was diagnosed with ulcerative colitis in November 2023, she initially responded to Mezavent and steroids but was hospitalized on March 31, 2024 for moderate UC flare, requiring infliximab rescue therapy. The patient presented with four bloody bowel movements and elevated inflammatory markers (CRP>100), confirmed by a Mayo score of 2 on flexible sigmoidoscopy and cytomegalovirus (CMV) infection was excluded. Clostridium difficile tests were negative twice and a CT scan revealed pancolitis. Despite minimal response to rescue therapy, she opted for medical treatment over colectomy.
On April 23, 2024, she began an eight-week induction of Upadacitinib 45 mg, which she tolerated well. However, on June 20, she developed sudden stroke symptoms while eating dinner, including difficulty swallowing, choking, left-sided weakness, and numbness. She had no vascular risk factors or family history of premature cardiovascular conditions. Lupus, and vasculitis work up were unremarkable and extensive thrombophilia screenings were all negative.
Discussion: Thrombosis in IBD patients can result from various potential causes. First of all, Inflammation and hypercoagulability, driven by elevated cytokines like TNF, interleukins, and CRP, activate the coagulation cascade, increasing thrombosis risk.
Conclusion: IBD is a known risk of thromboembolic disease, this risk increased during flare up will raise future research questions regarding extended anticoagulation prophylaxis during flare and uses of Jak stats inhibitor.

References

1. Ferro JM,Oliveira Santos M. Neurology of inflammatory bowel disease. J Neurol Sci. 2021 May 15;424:117426. doi: 10.1016/j.jns.2021.117426. Epub 2021 Mar 27.

2. Solitano V.Thrombosis in IBD in the Era of JAK Inhibition. Curr Drug Targets. 2021;22(1):126-136. doi: 10.2174/1389450121666200902164240.

3. Guiu A,a new opportunistic pathogen associated with cystic fibrosis?]Enferm Infecc Microbiol Clin. 2014 Oct;32(8):497-501. Spanish.DOI: 10.1016/j.eimc.2013.08.003

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5. Reddy VB.The burden of diverticular disease on patients and healthcare systems.Gastroenterol Hepatol (N Y). 2013 Jan;9(1):21-7.

6. Kim WJ.Major constituents and antimicrobial activity of Korean herb Acorus calamus.Nat Prod Res. 2011 Aug;25(13):1278-81.DOI: 10.1080/14786419.2010.513333

7. Lou JS, Effect of expectancy and personality on cortical excitability in Parkinson's disease.Mov Disord. 2013 Aug;28(9):1257-62.DOI: 10.1002/mds.25471PMID: 23630185

8. Parra-Izquierdo I,Janus kinase inhibitors ruxolitinib and baricitinib impair glycoprotein-VI mediated platelet function.Platelets. 2022 Apr 3;33(3):404-415.DOI: 10.1080/09537104.2021.1934665Epub 2021 Jun 7.

9. Kwak SH, Incidentally found resectable lung cancer with the usage of artificial intelligence on chest radiographs.PLoS One. 2023 Mar 10;18(3):e0281690.DOI: 10.1371/journal.pone.0281690PMID: 36897865;

10. Nguyen GC, et al. Consensus Statements on the Risk, Prevention, and Treatment of Venous Thromboembolism in Inflammatory Bowel Disease: Canadian Association of Gastroenterology. Gastroenterology. 2014;146(3):835–848. doi:10.1053/j.gastro.2014.01.042

Introduction

Ulcerative colitis (UC) is characterized by chronic immune mediated inflammation of the colon and rectum. Corticosteroid (CS) is a common treatment for patients with moderate to severe active UC, but its effect varies among patients, including resistance, response, and dependence. In addition, the longer CS therapy continues, the greater the concern regarding drug-related adverse effects. New immunomodulatory therapies are being developed for the treatment of UC drug showing promise in the treatment of patients with moderate UC refractory to aminosalicylic acid (5-ASA). Thus, the clinical benefit of being able to predict whether certain patients would benefit from CS therapy prior to administration cannot be overestimated.

Aims & Methods

We compared the clinical characteristics of patients with steroid-responder (SR) and steroid-non-responder (SNR) UC and retrospectively evaluated for biomarkers that could predict the efficacy of CS prior to administration in patients with moderate to severe active UC who failed to respond to 5-ASA.
We enrolled 100 UC patients presenting at Nippon Medical School Hospital with a history of CS administration prior to December 2023. The patients were divided into two groups, SR patients and SNR patients, and their clinical characteristics were determined according to medical records. Eosinophil counts were measured in the high-power field using Direct Fast Scarlet staining.

Results

Clinical characteristics of UC patients were as follows: the median age, 48±17 years; height 167±9.2 cm, and weight, 58±14 kg; including 61 males to 39 females. The most common disease extent type was the total colitis (63%), followed by left-sided colitis (32%), and proctitis (5%). Complete SNR was observed in 15 patients (15%), with remaining 85 patients (85%) classified as SR. There was no significant difference found in Mayo Endoscopic Score, first dose of CS, number of hospitalizations, number of relapses, propotion of patients with total-colitis type, or duration of CS treatment between the SR group and the SNR group. The non-remission rate, defined as failure to achieve mucosal healing, was significantly higher in the SNR group (66%) than in the SR group (36%) (P=0.03). The proportion of patients treated with azathioprine was significantly higher in the SR group (40%) than in the SNR group (39%). The proportion of patients treated with biologics or small molecular compounds was significantly higher in the SNR group (40%) than in the SR group (22%) (P=0.03).
We then compared hematological biomarkers in blood samples obtained prior to CS administration between the two groups. There was no significant difference in WBC counts, hemoglobin values, serum albumin concentrations, CRP values, and ESR between the two groups. However, eosinophil profiles (both total count numbers and ratio to white blood cell counts) were significantly higher in the SR group than in the SNR group (P=0.02). Neutrophil-lymphocyte ratio tended to be higher in the SR group than in the SNR group (P=0.06). The number of infiltrated eosinophils in the inflamed rectal mucosal tissue was not significantly different between the two groups. The number of infiltrated eosinophils in the rectal mucosa tended to decrease in the steroid-response groups (p = 0.07). However, there was no difference in the number of infiltrated eosinophils in the steroid-non-response groups.

Conclusion

Both eosinophil in the blood and in the rectal mucosa, and neutrophil-lymphocyte ratio in the blood could be potential biomarkers for steroid responsiveness prior to administration.

References

・British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019; 68: s1–s106
・Severe ulcerative colitis: at what point should we define resistance to steroids? WJG 2008 Sep 28;14(36):5504-7.
・A reproducible grading scale for histological assessment of inflammation in ulcerative colitis: Gut 47：404－409，2000
・Mucosal Eosinophil Abundance in Non-Inflamed Colonic Tissue Is Associated with Response to Vedolizumab Induction Therapy in Inflammatory Bowel Disease：J Clin Med Res,2022

Introduction

Adequacy of bowel preparation (ABP) directly affects colonoscopy performance and adenoma detection rate. Studies attributed a role to the dosing regimen of the bowel cleansing agent, social and economic factors and comorbidities. However, data on the impact of kidney failure and renal replacement therapy (RRT) are lacking.

Aims & Methods

This study investigated how ABP compares between patients on RRT and age-matched subjects with normal kidney function.
All patients on RRT undergoing an elective colonoscopy between January 2016 and December 2021 were identified from the medical records of a university hospital, and matched to 2 closest age controls undergoing colonoscopy at the same date ± 7 days. Study subjects and controls were compared for demographics, comorbidities including history of abdominal surgery, use of bowel transit-influencing drugs, residential care stay and colonoscopy-related data (bowel preparation regimen, sedation type, colonoscopy findings, ABP defined as a cumulative Bristol Bowel Preparation Score >= 6 and a score of >= 2 for each colon segment). Statistical significant contributors to ABP were assessed by logistic regression.

Results

Ninety-one patients on RRT (76 on haemodialysis and 15 on peritoneal dialysis) and 182 controls were identified. Patients on RRT were older (69±12 vs. 64±14y, p=.008) and less frequently women (34% vs. 50%, p=.013). They had more diabetes (40% vs. 24%, p=.008), more history of abdominal surgery (32% vs. 21%, p=.047) and took more bowel transit-influencing drugs (50% vs. 28%, p<.0001). Bowel preparation regimens were equally distributed between both groups. There was no difference in the rate of ABP between groups (87% vs. 81%, p=NS). Logistic regression analysis did not reveal an association between RRT and ABP. ABP was negatively influenced by residency in residential care, overnight stay in the hospital before colonoscopy, history of central nervous system disease, and positively by split-dose regimen (Nagelkerke R square 0.329, p=<.001).

Conclusion

Despite less favourable associated conditions, ABP in RRT patients remains comparable to controls. Split-dose regimen, neurological conditions and in-hospital stay are significant predictors of adequate bowel preparation.

References

Clark BT, Rustagi T, Laine L. What level of bowel prep quality requires early repeat colonoscopy: systematic review and meta-analysis of the impact of preparation quality on adenoma detection rate. Am J Gastroenterol. 2014;109(11):1714-23; quiz 24.
Hassan C, East J, Radaelli F, Spada C, Benamouzig R, Bisschops R, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019. Endoscopy. 2019;51(8):775-94.
Saumoy M, Jesudian AB, Aden B, Serur D, Sundararajan S, Sivananthan G, et al. High prevalence of colon adenomas in end-stage kidney disease patients on hemodialysis undergoing renal transplant evaluation. Clin Transplant. 2016;30(3):256-62.
24. Calderwood AH, Schroy PC, 3rd, Lieberman DA, Logan JR, Zurfluh M, Jacobson BC. Boston Bowel Preparation Scale scores provide a standardized definition of adequate for describing bowel cleanliness. Gastrointest Endosc. 2014;80(2):269-76.
25. Clark BT, Protiva P, Nagar A, Imaeda A, Ciarleglio MM, Deng Y, et al. Quantification of Adequate Bowel Preparation for Screening or Surveillance Colonoscopy in Men. Gastroenterology. 2016;150(2):396-405; quiz e14-5.
artel M, Barkun AN, Menard C, Restellini S, Kherad O, Vanasse A. Split-Dose Preparations Are Superior to Day-Before Bowel Cleansing Regimens: A Meta-analysis. Gastroenterology. 2015;149(1):79-88

Introduction

Esophageal reflux burden can be quantified using acid exposure time (AET), mean nocturnal baseline impedance (MNBI) and numbers of reflux episodes (RE), each of which has identified thresholds for physiologic, borderline and pathologic reflux evidence. Alternate parameters such as reflux-symptom association on ambulatory reflux monitoring, hiatus hernia on high resolution manometry, and advanced esophagitis grade on endoscopy escalate confidence for reflux. Each of these parameters has varying importance in determining conclusive evidence of gastroesophageal reflux disease (GERD).

Aims & Methods

Our aim was to determine if a novel reflux score (the Lyon Score) designed to quantify reflux burden can phenotype reflux syndromes and predict treatment outcome from medical or surgical anti-reflux therapy. Scores and ranges were assigned a priori to thresholds for each metric based on available research, the Lyon Consensus and ROME phenotypes (Table). An existing database of endoscopy-negative patients with typical reflux symptoms (heartburn, regurgitation, chest pain) evaluated off therapy for persisting reflux symptoms were reviewed from two centers (one each in Europe and US). Included patients were required to have completed high resolution manometry (Medtronic, Duluth, GA) and ambulatory pH-impedance monitoring (Diversatek, Boulder, CO) off antisecretory therapy. Symptom response was assessed using change in global symptom scores from validated symptom questionnaires over follow-up; a 50% reduction in global symptoms constituted a response to anti-reflux therapy, both medical management and anti-reflux surgery. Receiver operating characteristics (ROC) analysis determined performance of the scoring system in predicting overall response as well as within each distinct syndrome, and principal component analysis identified predictors of response within the scoring system.

Results

Data from 281 patients (median age 53 yr, 57.7% female) was analyzed, 71.9% with heartburn, 13.9% with regurgitation and 14.3% with chest pain. The median Lyon score was 4.0 (IQR 1.5-8.0, range 0.0-16.0). On ROC analysis, the Lyon score demonstrated an AUC of 0.816 in predicting 50% symptom improvement (p=0.026), with an optimal Lyon score threshold of 3.75 (sensitivity 81.2%, specificity 74.1%). The Lyon score performed better than any of the individual components of the score, and only AET (AUC 0.770, p=0.029), MNBI (AUC 0.747, p=0.030) and RE (AUC 0.728, p=0.030) approached the combined score. Using the Lyon score, patients were successfully phenotyped into distinct syndromes (Table), whereby proportions of patients with 50% response from anti-reflux therapy progressively increased across phenotypes with increasing reflux evidence: idiopathic heartburn: 6.1%, isolated permeability defect: 18.2%, reflux hypersensitivity: 27.7%, borderline GERD: 55.9%, conclusive GERD 76.6%, severe GERD 76.9% (Table, p<0.001 across groups). On principal component analysis, AET, MNBI and RE all demonstrated high values within the component matrix (≥0.80 for each), suggesting that each of these primary metrics carries independent weight in driving response to anti-reflux therapy.

Phenotype, score range	No GERD* (0-0.5)	Isolated permeability defect (0.5-2.0)	Reflux hypersensitivity (1.0-3.0)	Inconclusive or borderline GERD (≥3.0)	Conclusive GERD (≥5.0)	Severe GERD (≥10.0)
EGD	Normal: 0 LA A: 0.5	Normal-0 LA A: 0.5	Normal-0 LA A: 0.5	Normal- 0 LA A: 0.5	LA B: 5	LA C/D: 10
AET	< 4.0%: 0	< 4.0%: 0	< 4.0%: 0	4-6%: 2	>6.0%: 5	>10%: 10
RE (number)	<40: 0	<40: 0 40-80: 1	<40: 0 40-80:1	<40: 0 40-80: 1 >80: 2	<40: 0 40-80: 1 >80: 2	<40: 0 40-80: 1 >80: 2
MNBI (ohms)	>2500: 0	<1500: 1	<1500:1 1500-2499: 0.5 >2500: 0	<1500: 1 1500-2499 0.5 >2500- 0	< 1500: 1 1500-2499: 0.5 >2500: 0	<1500: 1 1500-2499: 0.5 >2500: 0
RSA	Negative: 0	Negative: 0	Positive:1	NA	Negative: 0 Positive: 1	Negative:0 Positive: 1
Hiatus Hernia	Negative: 0	Negative: 0	Negative: 0 <3 cm: 1 ≥3 cm: 2	Negative-0 <3 cm: 1 ≥3 cm: 2	Negative: 0 <3 cm: 1 ≥3 cm: 2	Negative: 0 <3 cm: 1 ≥3 cm: 2
Median score (IQR)	0.0 (0.0-0.0)	2.0 (1.0-2.0)	1.4 (0.5-2.3)	4.3 (2.8-4.7)	6.5 (5.5-8.0)	14.0 (12.0-15.0)
50% response**	3/49 (6.1%)	4/22 (18.2%)	13/47 (27.7%)	19/34 (55.9%)	59/77 (76.6%)	40/52 (76.9%)

GERD: gastroesophageal reflux disease; EGD: esophagogastroduodenoscopy; LA: Los Angeles grades (A/B/C/D); AET: acid exposure time; RE: reflux episodes: MNBI: mean nocturnal baseline impedance: RSA: reflux symptom association; IQR: interquartile range
*idiopathic heartburn, presumed esophageal chest pain; **improvement with medical or surgical anti-reflux therapy;

Conclusion

The novel Lyon score segregates reflux phenotypes, and identifies likelihood of symptom response from anti-reflux therapy. Prospective validation of the Lyon score is warranted.

Introduction

Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult.

Aims & Methods

We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for superficial pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT.

Results

Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI: 6.9 – 22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining.

Conclusion

Endoscopic surveillance for pharyngeal sublesions with lugol staining during ER for superficial pharyngeal SCC is feasible and useful.