Oncological outcomes of cervical esophageal cancer treated primarily with surgery: a systematic review and meta-analysis.

PURPOSE: To determine the oncological outcomes of cervical esophageal cancer (CEC) treated primarily with surgery. METHODS: A systematic review and meta-analysis was performed according to the PRISMA guidelines. RESULTS: A total of 868 patients were included from 18 studies. Estimated pooled Overall Survival (OS) rates (95% Confidence Interval, CI) at 1 and 5 years were 74.4% (66.5-83.3), and 26.6% (20.3-34.7), respectively. Larynx non-preserving surgery (n = 229) showed an estimated pooled OS rates (95% CI) at 1 and 5 years of 59.3% (51.5-68.2) and 14.6% (8.8-24.3), respectively. On the other hand, larynx preserving surgery (n = 213) showed an estimated pooled OS rates (95% CI) at 1 and 5 years of 83.6% (78.2-89.4) and 35.1% (24.9-49.6), respectively. CONCLUSIONS: Primary larynx-preserving surgery remains a valuable option for the management of CEC, with similar survival outcomes compared to primary chemoradiotherapy (CRT). On the other hand, larynx non-preserving surgery showed a significantly reduced survival, that may reflect the more advanced T classification of these tumors. Further studies are mandatory to directly compare primary surgery and primary CRT, distinguishing larynx preserving and non-preserving surgery.

Impaired Mucosal Integrity in Proximal Esophagus Is Involved in Development of Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease.

BACKGROUND AND OBJECTIVE: Weakly acidic reflux reaching to the proximal esophagus is closely related to the perception of gastroesophageal reflux in patients with nonerosive reflux disease despite treatment with a proton pump inhibitor (PPI). However, little is known about the involvement of the patients' mucosal integrity of the proximal esophagus. METHODS: We recruited 15 symptomatic nonerosive gastroesophageal reflux disease (GERD) patients with a positive symptom index despite PPI treatment and 11 healthy asymptomatic volunteers as controls. The biopsy specimens obtained from the proximal and distal esophagus were applied to a mini-Ussing chamber system to measure transepithelial electrical resistance (TEER) against a pH 4 weak acid. The esophageal biopsy samples were subjected to quantitative real-time PCR and immunohistochemical analysis. RESULTS: In the proximal esophagus, the weak acid exposure reduced the TEER in the PPI-refractory patients compared to that in the controls. The frequency of the reflux extending to the proximal esophagus had a significant correlation with the reduction in the proximal esophageal TEER in the patients. The reduced TEER in the proximal esophagus was accompanied by an increase in IL-8 and IL-1ß mRNA and a decrease in occludin mRNA levels. The proximal esophageal mucosa in the patients presented infiltration of CD3-positive lymphocytes and an increased expression of solute carrier organic anion transporter family member 2A1 (SLCO2A1), a passage gate of reflux symptom-evoking molecules. CONCLUSIONS: The reflux perception is related to an impairment of the proximal esophageal mucosal integrity in patients with nonerosive reflux disease despite PPI.

Improved submucosal tunneling endoscopic resection with slant tunnel for submucosal tumors in proximal esophagus.

BACKGROUND: The improved submucosal tunneling endoscopic resection (STER) with slant tunnel was created by our group innovatively for submucosal tumors (SMTs) in the proximal esophagus. This study aimed to provide the preliminary results of the improved STER from our center. METHODS: The key step of the improved STER is establishing a slant tunnel instead of a vertical tunnel. After a longitudinal incision was made proximally in the inclined top to the tumor, a submucosal tunnel was established from the incision to the SMT slantingly. 28 patients undergoing STER with slant tunnel were enrolled in the retrospective study. Clinical results including en bloc resection, curative resection and complication were collected. RESULTS: All the submucous tumors located at proximal esophagus originated from muscularis propria were successfully resected by the innovative STER. Tumor size ranged from 18-43 mm, with 96.4% (27/28) en bloc resection rate and 92.9% (26/28) curative rate. Three patients suffered complication, 1 patient with mild pleural effusion and another 2 patients with fever for one day. All of the complications were cured by conservative treatment. CONCLUSIONS: STER with slant tunnel seems to provide an optional treatment for tumors in proximal esophagus.

Cervical Esophageal Cancers: Challenges and Opportunities.

PURPOSE OF THE REVIEW: Cervical esophageal cancers (CECs) are a rare subset of esophageal cancers that are distinct in their management and outcomes. This review explores current data on the optimal management of this disease. RECENT FINDINGS: While outcomes for CEC have been suboptimal, several strategies have been proven beneficial in recent years. These include selective surgical resection or salvage surgery, chemoradiation (CRT) vs. radiation (RT) alone, dose escalation, IMRT, and induction chemotherapy. The optimal management of CEC to achieve the best oncological outcomes and minimize morbidity appears to be definitive chemoradiation with surgery reserved for selective salvage. While the benefit of dose escalated vs. standard dosing for radiation is unclear, most appear to use doses in excess of 50.4 Gy, even in the United States. IMRT might provide a benefit independent of allowing for dose escalation. Induction chemotherapy might allow for "chemoselection", but the benefit is unclear.

Oncological outcomes of squamous cell carcinoma of the cervical esophagus treated with definitive (chemo-)radiotherapy: a systematic review and meta-analysis.

PURPOSE: To determine the oncological outcomes of cervical esophageal squamous cell carcinoma (CESCC) treated with definitive chemoradiotherapy (CRT). METHODS: A systematic review and meta-analysis was performed according to the PRISMA guidelines. RESULTS: A total of 1222 patients (median age: 63.0 years, 95% CI 61.0-65.0) were included from 22 studies. The median follow-up time was 34.0 months (n = 1181, 95% CI 26.4-36.0). Estimated pooled OS rates (95% CI) at 1, 3, and 5 years were 77.9% (73.9-82.2), 48.4% (43.2-54.3), and 35.3% (29.7-41.9), respectively. The median OS (95% CI) was 33.4 months (25.8-42.2). Estimated pooled PFS rates (n = 595; 95% CI) at 1, 3, and 5 years were 64.1% (57.9-71.0), 38.0% (33.3-45.5), and 29.8% (23.9-37.1), respectively. The median PFS (95% CI) was 19.8 months (14.9-26.6). CONCLUSIONS: Definitive CRT is a valuable first-line treatment for the management of CESCC. Further studies should focus on survival predictors able to define stage-based clinical guidelines.

Reply to Letter to the Editor regarding "Oncological outcomes of squamous cell carcinoma of the cervical esophagus treated with definitive (chemo-)radiotherapy: a systematic review and meta-analysis".

In a previous study, we performed a meta-analysis of the oncological outcomes of patients suffering from cervical esophageal squamous cell carcinoma treated with definitive chemoradiotherapy. Further analysis was performed, and a random effect modeling showed a pooled local-regional failure rate of 41.4% (95% CI 32.2-50.8), and a pooled distant failure rate of 21.6% (95% CI 17.0-26.5). The included studies used a median radiotherapy (RT) dose of 61.2 Gy (95% CI 60.0-62.0, range 56.0-66.0), but we measured a non-significant impact of the RT dose on the pooled overall survival (OS), suggesting that an increased RT dose might not be related to an improved OS (p = 0.23). Further research should be conducted to define predictors and prognostic categories that may select the best treatment option for each patient.

Changes in the esophagogastric junction outflow obstruction manometric feature based on the Chicago Classification updates.

BACKGROUND: The critical diagnostic criteria for esophagogastric junction outflow obstruction (EGJOO) were published in the latest Chicago Classification version 4.0 (CCv4.0). In addition to the previous criterion [elevated integrated relaxation pressure (IRP) in supine position], manometric diagnosis of EGJOO requires meeting the criteria of elevated median-IRP during upright wet swallows and elevated intrabolus pressure. However, with the diagnostic criteria modification, the change in manometric features of EGJOO remained unclear. AIM: To evaluate the esophageal motility characteristics of patients with EGJOO and select valuable parameters for confirming the diagnosis of EGJOO. METHODS: We performed a retrospective analysis of 370 patients who underwent high-resolution manometry with 5 mL water swallows × 10 in supine, × 5 in upright position and the rapid drink challenge (RDC) with 200 mL water from November 2016 to November 2021 at Peking University First Hospital. Fifty-one patients with elevated integrated supine IRP and evidence of peristalsis were enrolled, with 24 patients meeting the updated manometric EGJOO diagnosis (CCv4.0) as the EGJOO group and 27 patients not meeting the updated EGJOO criteria as the isolated supine IRP elevated group (either normal median IRP in upright position or less than 20% of supine swallows with elevated IBP). Forty-six patients with normal manometric features were collected as the normal high-resolution manometry (HRM) group. Upper esophageal sphincter (UES), esophageal body, and lower esophageal sphincter (LES) parameters were compared between groups. RESULTS: Compared with the normal HRM group, patients with EGJOO (CCv4.0) had significantly lower proximal esophageal contractile integral (PECI) and proximal esophageal length (PEL), with elevated IRP on RDC (P < 0.05 for each comparison), while isolated supine IRP elevated patients had no such feature. Patients with EGJOO also had more significant abnormalities in the esophagogastric junction than isolated supine IRP elevated patients, including higher LES resting pressure (LESP), intrabolus pressure, median supine IRP, median upright IRP, and IRP on RDC (P < 0.05 for each comparison). Patients with dysphagia had significantly lower PECI and PEL than patients without dysphagia among the fifty-one with elevated supine IRP. Further multivariate analysis revealed that PEL, LESP, and IRP on RDC are factors associated with EGJOO. The receiver-operating characteristic analysis showed UES nadir pressure, PEL, PECI, LESP, and IRP on RDC are parameters supportive for confirming the diagnosis of EGJOO. CONCLUSION: Based on CCv4.0, patients with EGJOO have more severe esophagogastric junction dysfunction and are implicated in the proximal esophagus. Additionally, several parameters are supportive for confirming the diagnosis of EGJOO.

Heterotopic gastric mucosa of the proximal esophageal (HGMPE) and its potential role in pediatric dysphonia and dysphagia.

OBJECTIVE: Despite a reported incidence of HGMPE of 10%, proof of acid production, and an increased incidence of respiratory symptoms, the pediatric otolaryngology, swallowing and voice care literature is silent on this entity. This case series describes pediatric patients confirmed to have HGMPE with dysphonia and/or dysphagia. METHODS: Retrospective case series of Pediatric Voice, Resonance, and Swallowing Center patients at a tertiary Children's Hospital in 2019. SETTING: Tertiary academic medical center. SUMMARY OF RESULTS: Three patients who underwent triple endoscopy for dysphonia or dysphagia were histologically diagnosed with HGMPE. Esophageal biopsies were otherwise normal. Two of the three patients resolved their primary aerodigestive symptoms following treatment with acid suppression and a protectant (sucralfate). The third patient reported significant improvement in symptoms by phone. The significance of this case series cannot be understated: 1) A need for increased awareness among pediatric otolaryngologists, voice care and swallowing professionals of this entity given its relatively common incidence of 10% offset by a dearth of presentations & scientific publications in our literature clearly exists. 2) Otolaryngologists have abandoned operative upper aerodigestive tract endoscopy in lieu of office-based less comprehensive videolaryngostroboscopy and fiberoptic endoscopic evaluation of swallowing. HGMPE & other esophageal disorders (i.e. eosinophilic esophagitis) support revisiting triple endoscopy in select patients where office endoscopy has failed to diagnose and successfully treat such patients. 3) Both acid suppression therapy and a protectant (sucralfate) may be useful in these patients. 4) Modification of rigid esophagoscopy technique to carefully assess the introitus and superior esophageal segment is paramount 5) Otolaryngologists over-diagnose & over-treat laryngopharyngeal reflux. The pediatric & adult literature is replete with significant safety warnings associated with acid suppression therapy and guidelines admonish their indiscriminate use, raising the liability bar of empiric treatment. Large scale prospective, randomized and controlled studies are needed to confirm the pathophysiologic role of this entity in pediatric aerodigestive disorders. CONCLUSION: HGMPE is a clinical entity that can be easily missed upon swift entry into the esophagus with rigid endoscopy. Careful scrutiny and visualization of the proximal esophagus is critical in order to identify HGMPE, as there is a higher rate of laryngospasm, stricture, and potentially neoplasm in this population.

Characterizing the proximal esophageal segment in patients with symptoms of esophageal dysmotility.

BACKGROUND: Proximal esophageal striated muscle contractility may be abnormal in patients with esophageal symptoms, but is not assessed in the Chicago Classification (CC) v3.0. We aimed to (a) determine the prevalence of abnormal proximal esophageal contractility in patients with esophageal symptoms; (b) compare proximal esophageal contractility in patients with different esophageal motility disorders; (c) assess the association of abnormal proximal esophageal contractility with esophageal symptoms. METHODS: Patients undergoing high-resolution esophageal manometry (HREM) from 7/2019 to 11/2019 and healthy volunteers (HVs) were studied. Measurements of the proximal esophageal segment included the vigor of contractility of the proximal esophagus (proximal contractile integral/PCI). Patients rated gastrointestinal symptoms' severity. KEY RESULTS: HREM was performed on 221 patients (63.8% females, mean age 57.1 ± 1.1 years) and 19 HVs. Mean PCI in HVs was 299.5 ± 30.6 (95% CI 32.3-566.7 mm Hg. s. cm). Of all patients, 61 (27.6%) had abnormal PCI. HVs and patients with different esophageal motility disorders had significantly different PCI (P < .01). Type 1 achalasia patients had weaker PCI than patients with absent contractility (P = .02). Patients with abnormal PCI had more severe dysphagia (P = .02), nausea (P = .03), vomiting (P = .03), and lower bolus clearance (P < .01) than patients with normal PCI. CONCLUSIONS AND INFERENCES: Abnormal PCI was found in a fourth of patients with esophageal symptoms. PCI may be useful to distinguish some esophageal motility disorders. Patients with abnormal PCI had a higher severity of some upper gastrointestinal symptoms than patients with normal PCI. Assessing the proximal esophageal segment on HREM may be useful in characterizing patients with esophageal symptoms.