Introduction

Squamous dysplasia is the histopathological precursor of esophageal squamous cell carcinoma (ESCC). The optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. In this study, we aimed to assess the ESCC risk in patients with esophageal squamous dysplasia in a Western country.

Aims & Methods

This nationwide cohort study included all patients with esophageal squamous dysplasia, diagnosed between 1991 and 2020 in the Dutch nationwide histopathology registry (PALGA). Squamous dysplasia was divided in mild-to-moderate dysplasia (consisting of mild, low-grade, and moderate dysplasia) and higher-grade dysplasia (high-grade dysplasia, severe dysplasia, and carcinoma in situ). The primary endpoint was diagnosis of prevalent (within 6 months) and incident (after more than 6 months after squamous dysplasia) ESCC, identified in PALGA and the Netherlands Cancer Registry.

Results

873 patients (55% male, mean age of 68 years SD±13.2) were diagnosed with esophageal squamous dysplasia, comprising mild-to-moderate dysplasia (n=456), higher-grade dysplasia (n=393) and dysplasia not specified (n=24). 57% of the patients with mild-to-moderate dysplasia received endoscopic re-assessment after 12 weeks (IQR 6-29). During first endoscopic-reassessment, ESCC was detected in 5.1%, 1.8% and 12.8% of patients with baseline mild, low-grade, and moderate dysplasia, respectively. In total, ESCC was diagnosed in 77 (17%) patients with mild-to-moderate dysplasia (49 prevalent, 28 incident ESCC) and in 162 (41%) patients with higher-grade dysplasia (128 prevalent, 34 incident ESCC) (Table 1). After excluding prevalent ESCC, the annual risk of ESCC was 4.0% (95% CI: 2.7-5.7%) in patients with mild-to-moderate and 8.5% (95% CI: 5.9-11.7%) per patient-years and higher-grade dysplasia.

Table 1. The proportion of patients with distinct grades of baseline squamous dysplasia diagnosed with prevalent and incident ESCC.

Baseline grade of dysplasia	No. of patients	No. of patients diagnosed with ESCC	Prevalent ESCC	Incident ESCC1	Annual ESCC risk per PY1	PY at risk1
Mild dysplasia	179	15 (8.4%)	9 (5.0%)	6 (3.5%)	2.1%	279.7
Low-grade dysplasia	80	13 (16.3%)	8 (10.0%)	5 (6.9%)	5.1%	97.3
Moderate dysplasia	197	49 (24.9%)	32 (16.2%)	17 (10.3%)	5.2%	324.4
High-grade dysplasia	77	24 (31.2%)	18 (23.4%)	6 (10.2%)	8.9%	67.5
Severe dysplasia	244	110 (45.1%)	92 (37.7%)	18 (11.8%)	7.5%	239.7
Carcinoma in situ	72	28 (38.9%)	18 (25.0%)	10 (18.5%)	10.6%	94.6
Dysplasia NOS2	24	9 (37.5%)	4 (16.7%)	5 (25.0%)	10.1%	49.6
Total cohort	873	248 (28.4%)	181 (20.7%)	67 (9.7%)	5.8%	1152.7
Data presented as n with (%). ESCC were divided in prevalent (≤ 6 months) and incident (>6 months) after baseline diagnosis of squamous dysplasia. 1 Calculated for patients at risk of ESCC at 6 months after baseline squamous dysplasia (n=692). 2Grading of squamous dysplasia was not possible, due to biopsy size or orientation. ESCC, esophageal squamous cell carcinoma; NOS, not otherwise specified, PY, patient-years.

Conclusion

All patients with squamous dysplasia, including those with mild, low-grade, and moderate dysplasia, have a substantial risk of developing ESCC. Consequently, endoscopic surveillance of the esophageal mucosa is recommended for patients with mild-to-moderate dysplasia in Western countries.

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.

Introduction

Radiofrequency ablation is considered the standard therapy for flat dysplastic BE. Hybrid APC is a newer under evaluation, less expensive technique, but with the need of a special injection device and catheter. Aim of the study: To evaluate the efficacy of a standard APC catheter after submucosal injection for BE ablation.

Aims & Methods

To evaluate the efficacy of a standard APC catheter after submucosal injection for BE ablation. Naïve or after previous treatments patients with BE and low - grade dysplasia (LGD) were prospectively evaluated. Sodium chloride solution 0.9% was injected submucosally with a 23 G needle followed by APC application with a standard catheter (ERBE APC 300, 45Watts) on the created cushion. The same procedure was repeated for most of BE surface to be cauterized, with special attention not to ablate large circumferential areas. Patients were under high dose PPIs. Biopsies were taken according to the Seattle protocol during the follow-up.

Results

31 patients, 28 males (90.3%), 56.7±12.5 years old. Their initial diagnosis was: 19 patients with LGD (61.3%), 7 with high grade dysplasia (22.6%), and 5 with intramucosal cancer (16.1%). Eleven patients (35.5%) had previous endoscopic mucosal resection (EMR) while 7 (22.6%) had received radiofrequency ablation (RFA). Median BE length with LGD at the beginning of APC was 4cm (25th-75th:2-7, min-max:1-10). Median follow-up:10.1(1-108) months. In total 20 (64.5%) patients completely eradicated BE. For the remaining 11 patients APC led to a substantial reduction of BE length [Initial Median: C3M6 (Min: C0M1, Max: C6M8) to a final median: C0M2 (Min:C0M1, Max:C2M5] but the study is ongoing. Initial BE length was correlated to APC sessions needed (r= 0.54, p<0.01) but was not a limiting factor for complete BE eradication. Instead, smoking was an aggravating factor for BE complete eradication (HR=3.12, 95%CI.: 1.2-8.12, p=0.02). No death, hospitalization, severe hemorrhage, or perforation were observed. In 7 patients moderate pain requiring paracetamol, resolved after a few hours of in hospital supervision while 11 patients had mild dysphagia the following days without permanent stenosis.

Conclusion

Conclusions: 1) Standard APC after submucosal injection is safe and tolerable for BE ablation. 2) It may be applied in naïve patients or if other techniques were previously used. 3) Length increases the number of sessions needed but does not seem to be a limiting factor for APC application.

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

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

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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

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