Introduction

Patients with head and neck neoplasms (HNN) are at an increased risk of synchronous gastro-esophageal neoplasia (GEN) due to shared risk factors such as smoking, alcohol consumption, and HPV infection. Several scientific societies recommend screening HNN patients for synchronous esophageal neoplasms. Nevertheless, particularly in Western centers, few studies evaluated the impact of an organized screening program.

Aims & Methods

We conducted a prospective study that evaluated an organized GEN screening program in HNN patients diagnosed between 01/06/2020 and 31/12/2022, in a tertiary reference hospital. Patients were proposed to do an upper gastrointestinal endoscopy (UGE) with narrow-band imaging (NBI) and/or Lugol chromoendoscopy.

Results

We evaluated 34 patients, 82.4% male, with a median age of 64.5 (IQR: 57,5-70) years. 82.4% had a history of tobacco use, and 35.3% presented active alcohol consumption. The most common primary HNN sites were the larynx (50.0%) and the tonsil (14.7%), and the most frequent histological type was squamous cell carcinoma (SCC) (88.2%). The median time between HNN and UGE was 4.5 (IQR: 1.25-10) months, and 91.2% of the patients had already started treatment for HNN. The prevalence of synchronous GEN was 14.7% (Esophageal SCC n=4; Cardia adenocarcinoma n=1). One patient underwent ESD of two synchronous SCC (SCC pT1b), with adjuvant radiotherapy, other (T1/T2N0M0) underwent chemotherapy and radiotherapy, and two patients are waiting ESD. The patient with cardia adenocarcinoma underwent ESD (pT1b with lymphatic permeation) and total gastrectomy, with no evidence of residual lesion. All patients with synchronous GEN remain alive in the follow-up.

Conclusion

In our study the prevalence of synchronous GEN in HNN patients was significant and most lesions were detected in an early stage, still amenable for endoscopic resection. This study showed that the implementation of this screening strategy may potentially lead to a better prognosis for these patients and its cost-efficacy should be evaluated .

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

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

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

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.