Medicine › Surgery

Esophageal Cancer Research and Treatment

Works Count: 67268

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This cluster of papers focuses on the diagnosis, treatment, and management of esophageal cancer, with an emphasis on preoperative chemoradiotherapy, surgery, chemoradiation, and endoscopic resection. It also covers topics such as Barrett's esophagus, neoadjuvant therapy, adenocarcinoma, meta-analyses, and epidemiological trends.

Keywords

Preoperative Chemoradiotherapy; Esophageal Carcinoma; Barrett's Esophagus; Surgery; Chemoradiation; Endoscopic Resection; Neoadjuvant Therapy; Adenocarcinoma; Meta-analysis; Epidemiology

Classification of adenocarcinoma of the oesophagogastric junction

1998-11-01

J. R. Siewert , H. J. Stein

Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial

2015-08-06

Joël Shapiro , J. Jan B. van Lanschot , Maarten C.C.M. Hulshof +7 more

Cancer burden in the year 2000. The global picture

2001-09-01

Donald Maxwell Parkin , Freddie Bray , Susan S. Devesa

Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations

1994-06-01

A.M. Mandard , Frédéric Dalibard , J.-C. Mandard +7 more

Background. The benefits of preoperative chemotherapy and radiation for esophageal carcinoma are under investigation. A pilot study was undertaken to determine if pathologic assessment of tumor regression correlated with disease … Background. The benefits of preoperative chemotherapy and radiation for esophageal carcinoma are under investigation. A pilot study was undertaken to determine if pathologic assessment of tumor regression correlated with disease free survival. Methods. Ninety-three resected specimens from patients treated with cis-dichloro-diamino cisplatin and irradiation before surgery were examined on semiserial sections. Patients selected for surgery were all Status 1 according to the World Health Organization (WHO) classification. Histologic typing was based on the WHO classification. Tumor regression grade (TRG) was quantitated in five grades: TRG 1 (complete regression) showed absence of residual cancer and fibrosis extending through the different layers of the esophageal wall; TRG 2 was characterized by the presence of rare residual cancer cells scattered through the fibrosis; TRG 3 was characterized by an increase in the number of residual cancer cells, but fibrosis still predominated; TRG 4 showed residual cancer outgrowing fibrosis; and TRG 5 was characterized by absence of regressive changes. Survival curves were estimated according to the Kaplan-Meier method. A quantification of the relationship between treatment failure and confounding variables (age, tumor location, tumor size, esophageal wall involvement by residual cancer and/or regressive changes, histology, treatment, adequacy of surgery, pathologic lymph node status, and tumor regression grade) was done using Cox's proportional hazards model. Results. Forty-two percent of specimens were TGR 1–2; 20%, TGR 3; and 33%, TGR 4–5. Univariate analysis found that tumor size, pathologic lymph node status, tumor regression grade, and esophageal wall involvement were highly correlated with disease free survival (P > 0.05). After multivariate analysis, only tumor regression (i.e., TRG 1–3 versus TRG 4–5) remained a significant (P > 0.001) predictor of disease free survival. Conclusions. This study highlights the importance of tumor regression in the survival of patients with esophageal carcinoma treated with preoperative chemoradiotherapy. These findings suggest that tumor regression grade should be considered when evaluating therapeutic results. Cancer 1994; 73:2680–6.

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American Gastroenterological Association Technical Review on the Management of Barrett's Esophagus

2011-03-01

Stuart J. Spechler , Prateek Sharma , Rhonda F. Souza +2 more

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Changing patterns in the incidence of esophageal and gastric carcinoma in the United States

1998-11-15

Susan S. Devesa , William J. Blot , Joseph F. Fraumeni

Incidence rates for esophageal adenocarcinoma previously were reported to be increasing rapidly, especially among white males. Rates for gastric cardia adenocarcinoma also were observed to be rising, although less rapidly. … Incidence rates for esophageal adenocarcinoma previously were reported to be increasing rapidly, especially among white males. Rates for gastric cardia adenocarcinoma also were observed to be rising, although less rapidly. In this article, the authors update the incidence trends through 1994 and further consider the trends by age group.Surveillance, Epidemiology, and End Results (SEER) program data were used to calculate age-adjusted incidence rates for esophageal carcinoma by histologic type and gastric adenocarcinoma by anatomic subsite.Among white males, the incidence of adenocarcinoma of the esophagus rose > 350% since the mid-1970s, surpassing squamous cell carcinoma around 1990. Rates also rose among black males, but remained at much lower levels. To a lesser extent, there were continuing increases in gastric cardia adenocarcinoma among white and black males, which nearly equaled the rates for noncardia tumors of the stomach in white men. The upward trend for both tumors was much greater among older than younger men. Although the incidence also rose among females, rates remained much lower than among males.Previously reported increases of esophageal adenocarcinoma are continuing, most notably among white males. Cigarette smoking may contribute to the trend through an early stage carcinogenic effect, along with obesity, which may increase intraabdominal pressure and predispose to gastroesophageal reflux disease. Further research into esophageal and gastric cardia adenocarcinoma is needed to clarify the risk factors and mechanisms responsible for the upward trends as well as the racial and gender disparities in incidence.

Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial

2012-05-01

Surya S. A. Y. Biere , Mark I. van Berge Henegouwen , K. W. Maas +7 more

Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis

2007-02-16

Val Gebski , Bryan Burmeister , B. Mark Smithers +3 more

A Randomized Trial Comparing Postoperative Adjuvant Chemotherapy with Cisplatin and 5-Fluorouracil Versus Preoperative Chemotherapy for Localized Advanced Squamous Cell Carcinoma of the Thoracic Esophagus (JCOG9907)

2011-08-30

Nobutoshi Ando , Hoichi Kato , Hiroyasu Igaki +7 more

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Rising Incidence of Adenocarcinoma of the Esophagus and nGastric Cardia

1991-03-13

W. J. Blot

Analyses of cancer incidence data from nine areas of the United States revealed steadily rising rates from 1976 to 1987 of adenocarcinomas of the esophagus and gastric cardia. The increases … Analyses of cancer incidence data from nine areas of the United States revealed steadily rising rates from 1976 to 1987 of adenocarcinomas of the esophagus and gastric cardia. The increases among men in this period ranged from 4% to 10% per year, and thus exceeded those of any other type of cancer. In contrast, there were relatively stable trends for squamous cell carcinoma of the esophagus and slight declines for adenocarcinoma of more distal portions of the stomach. Adenocarcinomas of the esophagus and gastric cardia disproportionately affected white men and rarely occurred among women. By the mid-1980s, among white men, adenocarcinomas accounted for about one third of all esophageal cancers, while cardia cancers accounted for about one half of all stomach cancers with specified subsites. The rising incidence rates and similar demographic patterns point to the need for investigation into the causes of these poorly understood cancers.

Epidemiology of esophageal cancer

2013-01-01

Yuwei Zhang

Esophageal cancer (EsC) is one of the least studied and deadliest cancers worldwide because of its extremely aggressive nature and poor survival rate.It ranks sixth among all cancers in mortality.In … Esophageal cancer (EsC) is one of the least studied and deadliest cancers worldwide because of its extremely aggressive nature and poor survival rate.It ranks sixth among all cancers in mortality.In retrospective studies of EsC, smoking, hot tea drinking, red meat consumption, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with a higher risk of esophageal squamous cell carcinoma.Barrett's esophagus is clearly recognized as a risk factor for EsC, and dysplasia remains the only factor useful for identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice.Here, we investigated the epidemiologic patterns and causes of EsC.Using population based cancer data from the Surveillance, Epidemiology and End Results Program of the United States; we generated the most up-to-date stage distribution and 5-year relative survival by stage at diagnosis for 1998-2009.Special note should be given to the fact that esophageal cancer, mainly adenocarcinoma, is one of the very few cancers that is contributing to increasing death rates (20%) among males in the United States.To further explore the mechanism of development of EsC will hopefully decrease the incidence of EsC and improve outcomes.

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Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

2016-09-01

Florian Lordick , C. Mariette , Karin Haustermans +2 more

Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis

2011-06-22

Katrin Marie Sjoquist , Bryan Burmeister , B. Mark Smithers +4 more

Extended Transthoracic Resection Compared with Limited Transhiatal Resection for Adenocarcinoma of the Esophagus

2002-11-20

Jan B.F. Hulscher , Johanna W. van Sandick , Angela G. E. M. de Boer +7 more

Controversy exists about the best surgical treatment for esophageal carcinoma.We randomly assigned 220 patients with adenocarcinoma of the mid-to-distal esophagus or adenocarcinoma of the gastric cardia involving the distal esophagus … Controversy exists about the best surgical treatment for esophageal carcinoma.We randomly assigned 220 patients with adenocarcinoma of the mid-to-distal esophagus or adenocarcinoma of the gastric cardia involving the distal esophagus either to transhiatal esophagectomy or to transthoracic esophagectomy with extended en bloc lymphadenectomy. Principal end points were overall survival and disease-free survival. Early morbidity and mortality, the number of quality-adjusted life-years gained, and cost effectiveness were also determined.A total of 106 patients were assigned to undergo transhiatal esophagectomy, and 114 to undergo transthoracic esophagectomy. Demographic characteristics and characteristics of the tumor were similar in the two groups. Perioperative morbidity was higher after transthoracic esophagectomy, but there was no significant difference in in-hospital mortality (P=0.45). After a median follow-up of 4.7 years, 142 patients had died--74 (70 percent) after transhiatal resection and 68 (60 percent) after transthoracic resection (P=0.12). Although the difference in survival was not statistically significant, there was a trend toward a survival benefit with the extended approach at five years: disease-free survival was 27 percent in the transhiatal-esophagectomy group, as compared with 39 percent in the transthoracic-esophagectomy group (95 percent confidence interval for the difference, -1 to 24 percent [the negative value indicates better survival with transhiatal resection]), whereas overall survival was 29 percent as compared with 39 percent (95 percent confidence interval for the difference, -3 to 23 percent).Transhiatal esophagectomy was associated with lower morbidity than transthoracic esophagectomy with extended en bloc lymphadenectomy. Although median overall, disease-free, and quality-adjusted survival did not differ statistically between the groups, there was a trend toward improved long-term survival at five years with the extended transthoracic approach.

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INT 0123 (Radiation Therapy Oncology Group 94-05) Phase III Trial of Combined-Modality Therapy for Esophageal Cancer: High-Dose Versus Standard-Dose Radiation Therapy

2002-03-01

Bruce D. Minsky , Thomas F. Pajak , Robert J. Ginsberg +6 more

PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. … PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. PATIENTS AND METHODS: A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach, after stratification by weight loss, primary tumor size, and histology, were randomized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil (5-FU) (1,000 mg/m2/24 hours for 4 days) and cisplatin (75 mg/m2 bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy. The trial was stopped after an interim analysis. The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive. RESULTS: For the 218 eligible patients, there was no significant difference in median survival (13.0 v 18.1 months), 2-year survival (31% v 40%), or local/regional failure and local/regional persistence of disease (56% v 52%) between the high-dose and standard-dose arms. Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the standard-dose arm, seven of the 11 deaths occurred in patients who had received 50.4 Gy or less. CONCLUSION: The higher radiation dose did not increase survival or local/regional control. Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm, it did not seem to be related to the higher radiation dose. The standard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy.

Incidence of Adenocarcinoma among Patients with Barrett's Esophagus

2011-10-12

Frederik Hvid‐Jensen , Lars Pedersen , Asbjørn Mohr Drewes +2 more

Accurate population-based data are needed on the incidence of esophageal adenocarcinoma and high-grade dysplasia among patients with Barrett's esophagus.We conducted a nationwide, population-based, cohort study involving all patients with Barrett's … Accurate population-based data are needed on the incidence of esophageal adenocarcinoma and high-grade dysplasia among patients with Barrett's esophagus.We conducted a nationwide, population-based, cohort study involving all patients with Barrett's esophagus in Denmark during the period from 1992 through 2009, using data from the Danish Pathology Registry and the Danish Cancer Registry. We determined the incidence rates (numbers of cases per 1000 person-years) of adenocarcinoma and high-grade dysplasia. As a measure of relative risk, standardized incidence ratios were calculated with the use of national cancer rates in Denmark during the study period.We identified 11,028 patients with Barrett's esophagus and analyzed their data for a median of 5.2 years. Within the first year after the index endoscopy, 131 new cases of adenocarcinoma were diagnosed. During subsequent years, 66 new adenocarcinomas were detected, yielding an incidence rate for adenocarcinoma of 1.2 cases per 1000 person-years (95% confidence interval [CI], 0.9 to 1.5). As compared with the risk in the general population, the relative risk of adenocarcinoma among patients with Barrett's esophagus was 11.3 (95% CI, 8.8 to 14.4). The annual risk of esophageal adenocarcinoma was 0.12% (95% CI, 0.09 to 0.15). Detection of low-grade dysplasia on the index endoscopy was associated with an incidence rate for adenocarcinoma of 5.1 cases per 1000 person-years. In contrast, the incidence rate among patients without dysplasia was 1.0 case per 1000 person-years. Risk estimates for patients with high-grade dysplasia were slightly higher.Barrett's esophagus is a strong risk factor for esophageal adenocarcinoma, but the absolute annual risk, 0.12%, is much lower than the assumed risk of 0.5%, which is the basis for current surveillance guidelines. Data from the current study call into question the rationale for ongoing surveillance in patients who have Barrett's esophagus without dysplasia. (Funded by the Clinical Institute, University of Aarhus, Aarhus, Denmark.).

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Radiofrequency Ablation in Barrett's Esophagus with Dysplasia

2009-05-27

Nicholas J. Shaheen , Prateek Sharma , Bergein F. Overholt +7 more

Barrett's esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barrett's esophagus … Barrett's esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barrett's esophagus and decrease the rate of neoplastic progression.

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Chemoradiation Followed by Surgery Compared With Chemoradiation Alone in Squamous Cancer of the Esophagus: FFCD 9102

2007-03-30

Laurent Bedenne , Pierre Michel , Olivier Bouché +7 more

Uncontrolled studies suggest that chemoradiation has similar efficacy as surgery for esophageal cancer. Therefore, a randomized trial was carried out to compare, in responders only, chemoradiation alone with chemoradiation followed … Uncontrolled studies suggest that chemoradiation has similar efficacy as surgery for esophageal cancer. Therefore, a randomized trial was carried out to compare, in responders only, chemoradiation alone with chemoradiation followed by surgery in patients with locally advanced tumors.Eligible patients had operable T3N0-1M0 thoracic esophageal cancer. Patients received two cycles of fluorouracil (FU) and cisplatin (days 1 to 5 and 22 to 26) and either conventional (46 Gy in 4.5 weeks) or split-course (15 Gy, days 1 to 5 and 22 to 26) concomitant radiotherapy. Patients with response and no contraindication to either treatment were randomly assigned to surgery (arm A) or continuation of chemoradiation (arm B; three cycles of FU/cisplatin and either conventional [20 Gy] or split-course [15 Gy] radiotherapy). Chemoradiation was considered equivalent to surgery if the difference in 2-year survival rate was less than 10%.Of 444 eligible patients, 259 were randomly assigned; 230 patients (88.8%) had epidermoid cancer, and 29 (11.2%) had glandular carcinoma. Two-year survival rate was 34% in arm A versus 40% in arm B (hazard ratio for arm B v arm A = 0.90; adjusted P = .44). Median survival time was 17.7 months in arm A compared with 19.3 months in arm B. Two-year local control rate was 66.4% in arm A compared with 57.0% in arm B, and stents were less required in the surgery arm (5% in arm A v 32% in arm B; P < .001). The 3-month mortality rate was 9.3% in arm A compared with 0.8% in arm B (P = .002). Cumulative hospital stay was 68 days in arm A compared with 52 days in arm B (P = .02).Our data suggest that, in patients with locally advanced thoracic esophageal cancers, especially epidermoid, who respond to chemoradiation, there is no benefit for the addition of surgery after chemoradiation compared with the continuation of additional chemoradiation.

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Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial

2002-05-01

D.J. Girling

The Role of Overdiagnosis and Reclassification in the Marked Increase of Esophageal Adenocarcinoma Incidence

2005-01-18

Heiko Pohl , H. Gilbert Welch

The incidence of esophageal adenocarcinoma is rising dramatically. This increase may reflect increased disease burden, reclassification of related cancers, or overdiagnosis resulting from increased diagnostic intensity, particularly upper endoscopy for … The incidence of esophageal adenocarcinoma is rising dramatically. This increase may reflect increased disease burden, reclassification of related cancers, or overdiagnosis resulting from increased diagnostic intensity, particularly upper endoscopy for patients with gastroesophageal reflux disease or Barrett esophagus.We used the National Cancer Institute's Surveillance, Epidemiology, and End Results database to extract information on incidence, stage distribution, and disease-specific mortality for esophageal adenocarcinoma as well as information on related cancers.From 1975 to 2001, the incidence of esophageal adenocarcinoma rose approximately sixfold in the United States (from 4 to 23 cases per million), a relative increase greater than that for melanoma, breast, or prostate cancer. Reclassification of squamous cell carcinoma is an unlikely explanation for the rise in incidence, because the anatomic distribution of esophageal cancer in general has changed. The only location with increased incidence is the lower third of the esophagus-the site where adenocarcinoma typically arises. Reclassification of adjacent gastric cancer is also unlikely because its incidence has also increased. Because there has been little change in the proportion of patients found with in situ or localized disease at diagnosis since 1975 (from 25% to 31%) and because esophageal adenocarcinoma mortality has increased more than sevenfold (from 2 to 15 deaths per million), overdiagnosis can be excluded as an explanation for the rise in incidence.The rising incidence of esophageal adenocarcinoma represents a real increase in disease burden.

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British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus

2013-10-28

Rebecca C. Fitzgerald , Massimiliano di Pietro , Krish Ragunath +7 more

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett9s oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) … These guidelines provide a practical and evidence-based resource for the management of patients with Barrett9s oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett9s oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett9s oesophagus and related neoplasia.

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Phase III Trial of Trimodality Therapy With Cisplatin, Fluorouracil, Radiotherapy, and Surgery Compared With Surgery Alone for Esophageal Cancer: CALGB 9781

2008-02-28

Joel E. Tepper , Mark J. Krasna , Donna Niedzwiecki +7 more

The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery, although primary radiation therapy with concurrent chemotherapy produces similar results. As both have … The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery, although primary radiation therapy with concurrent chemotherapy produces similar results. As both have curative potential, there has been great interest in the use of trimodality therapy. To this end, we compared survival, response, and patterns of failure of trimodality therapy to esophagectomy alone in patients with nonmetastatic esophageal cancer.Four hundred seventy-five eligible patients were planned for enrollment. Patients were randomly assigned to either esophagectomy with node dissection alone or cisplatin 100 mg/m(2) and fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 concurrent with radiation therapy (50.4 Gy total: 1.8 Gy/fraction over 5.6 weeks) followed by esophagectomy with node dissection.Fifty-six patients were enrolled between October 1997 and March 2000, when the trial was closed due to poor accrual. Thirty patients were randomly assigned to trimodality therapy and 26 were assigned to surgery alone. Patient and tumor characteristics were similar between groups. Treatment was generally well tolerated. Median follow-up was 6 years. An intent-to-treat analysis showed a median survival of 4.48 v 1.79 years in favor of trimodality therapy (exact stratified log-rank, P = .002). Five-year survival was 39% (95% CI, 21% to 57%) v 16% (95% CI, 5% to 33%) in favor of trimodality therapy.The results from this trial reflect a long-term survival advantage with the use of chemoradiotherapy followed by surgery in the treatment of esophageal cancer, and support trimodality therapy as a standard of care for patients with this disease.

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Identification of genomic alterations in oesophageal squamous cell cancer

2014-03-16

Yongmei Song , Lin Li , Yunwei Ou +7 more

Updated Guidelines 2008 for the Diagnosis, Surveillance and Therapy of Barrett's Esophagus

2008-03-01

Kenneth K. Wang , Richard E. Sampliner

PREAMBLE The guidelines for the diagnosis, surveillance and therapy of Barrett's esophagus were originally published by the American College of Gastroenterology in 1998 and updated in 2002. These and other … PREAMBLE The guidelines for the diagnosis, surveillance and therapy of Barrett's esophagus were originally published by the American College of Gastroenterology in 1998 and updated in 2002. These and other guidelines undergo periodic review. Significant advances have occurred in the area of Barrett's esophagus over the past four years leading to another revision of the prior guidelines. These advances include the potential use of esophageal capsule endoscopy for the diagnosis and screening of Barrett's esophagus, data regarding the outcome of low-grade dysplasia, the treatment of high-grade dysplasia using photodynamic therapy, and the development of new ablation techniques such as radiofrequency ablation. These guidelines are intended to be applied by physicians who see Barrett's esophagus patients and are intended to indicate a preferred, but certainly not the only, acceptable approach. Physicians need to choose the course best suited to the individual patient and to the variables that exist at the time of decision making. The guidelines are for adult patients with the diagnosis of Barrett's esophagus, as defined herein. Both these and the original guidelines were developed under auspices of the American College of Gastroenterology and the Practice Parameters Committee and approved by the Board of Trustees. The world literature was reviewed extensively for the original guidelines and once again reviewed using the National Library of Medicine database. Search terms used included Barrett's esophagus, esophageal neoplasm, esophagus, intestinal metaplasia, esophageal diseases, and adenocarcinoma, all appropriate studies and any additional ones found in reference to these papers were obtained and reviewed. Evidence was available from a hierarchy of trials and randomized controlled trials were given the greatest weight. Abstracts presented at national and international meetings were only used when unique data from ongoing trials were presented. When scientific data were lacking, recommendations are based on expert opinion. The recommendations made are based on the level of evidence found. Grade A recommendations imply that there is consistent level 1 evidence (randomized controlled trials), Grade B indicates that the evidence would be level 2 or 3 which are cohort studies or case control studies. Grade C recommendations are based on level 4 studies meaning case series or poor quality cohort studies, and Grade D recommendations are based on level 5 evidence meaning expert opinion. SIGNIFICANCE OF BARRETT'S ESOPHAGUS Barrett's esophagus continues to be increasingly recognized in the United States and is believed to be the major risk factor for the development of esophageal adenocarcinoma. The incidence of adenocarcinoma of the esophagus continues to rise rapidly. The rate of rise is alarming and is widespread in Western countries. In a review by the epidemiologists of the National Cancer Institute of cancer incidences normalized to the year 1975, esophageal adenocarcinoma incidence rates were found to outpace even those of melanoma, breast cancer and prostate cancer in terms of the rapidity of rise (1). These epidemiologists also found there was no concomitant decrease in diagnoses of gastric cancers or more proximal cancers, making a classification change unlikely to be responsible for this increase in adenocarcinoma. In the Danish Cancer Registry, adenocarcinoma incidence rates actually decrease in patients older than 85 (14.14/100,00 (80–84 yr) decreasing to 7.2/100,000 (85+ yr) unlike squamous cancer rates suggesting that this rise in adenocarcinoma incidence may be truly a recent phenomenon as evidenced by this age cohort effect (2). DEFINITION OF BARRETT'S ESOPHAGUS Barrett's esophagus is a change in the distal esophageal epithelium of any length that can be recognized as columnar type mucosa at endoscopy and is confirmed to have intestinal metaplasia by biopsy of the tubular esophagus. (Grade B recommendation). This working definition of Barrett's esophagus has changed little over the last 10 years. A recent "critical review of the diagnosis" of Barrett's esophagus concluded that "the working definition of BE is displacement of the squamocolumnar junction proximal to the gastroesophageal junction" and "endoscopy with multiple systematic biopsies is needed to establish the diagnosis of Barrett's esophagus" (3). This definition does not distinguish between short and long segment Barrett's esophagus and implies that only columnar lined esophagus should be biopsied. Although intestinal metaplasia is not specifically mentioned in this definition, clearly the reason to do multiple biopsies in the columnar appearing esophagus is to identify the presence of intestinal metaplasia, the premalignant lesion for esophageal adenocarcinoma (EAC). The vast majority of adenocarcinomas of the esophagus are accompanied by intestinal metaplasia in multiple cohort studies (4–8) and many adenocarcinomas of the esophagogastric junction are also associated with esophageal intestinal metaplasia (9–11). The incidence of adenocarcinoma of the esophagus has continued to rise in the United States, at least until the year 2002 (12). Supporting the primary role of BE as the premalignant lesion for EAC is the unmasking of underlying BE by chemotherapy of adenocarcinoma of the distal esophagus. A retrospective study reviewed 79 patients with locally advanced EAC who had preoperative chemotherapy and had restaging endoscopy and biopsy prior to resection. Pre-therapy endoscopy showed BE in 75%, whereas 97% had documented BE on post-chemotherapy biopsy or in the resected specimen (13). This suggests that the cancer overgrows the fertile field of BE so that at presentation of the patient with EAC, BE may no longer be detectable. Esophagitis might also mask Barrett's esophagus. In a recent study of 172 patients with erosive esophagitis, a full 12% were found to have Barrett's metaplasia after healing of the esophagitis (14). There is not universal agreement on the inclusion of intestinal metaplasia as a criterion for BE. The British Society of Gastroenterology has excluded the need for IM from the diagnosis of BE (15). It is well recognized that the yield of IM decreases as the segment of columnar lining shortens and fewer biopsies are taken. Repeat endoscopy and biopsy are often necessary to establish the presence of IM (16, 17). In patients with >1cm of columnar lined esophagus at endoscopy, multiple biopsies may be necessary to confidently detect intestinal metaplasia. Based on a recent retrospective study, eight biopsies may provide an adequate assessment of the presence of intestinal metaplasia (18). The issue becomes when to label a patient as having BE and having an increased risk for EAC compared to someone lacking BE. Because of the implication of the label of BE in the United States for obtaining health insurance and the increased cost of life insurance in the United States (19), it seems appropriate to establish the presence of IM before committing the patient to the diagnosis of BE and to surveillance endoscopy. There are no data on the risk of EAC in columnar lined esophagus lacking IM. Another new development in the endoscopic standardization of Barrett's esophagus is the Prague classification system of circumferential (CM) and maximal length (M). This system identifies the landmarks of the squamocolumnar junction, the gastroesophageal junction, the extent of circumferential columnar lining and the most proximal extension of the columnar mucosa excluding islands to determine the length of Barrett's esophagus. Twenty-nine endoscopists scored 29 videos with centimeter intervals marked on the image (20). The reliability coefficients (RC) for C 0.95, M 0.94, the gastroesophageal junction 0.88 and the location of the hiatus 0.85 were excellent. The overall RC for the endoscopic recognition of BE ≥1cm was 0.72. However, for less than 1cm of columnar lining the coefficient was only 0.22. In an era of growing endoscopic therapy for neoplastic BE, this standardization is important. Unfortunately, proximal islands of columnar lining and ultra-short BE <1cm are not included in this schema. In summary, a strategy to decrease the recent rise in esophageal cancer would be earlier diagnosis of Barrett's esophagus. The diagnosis should be made with endoscopy and biopsy of columnar lined esophagus only (Grade B Recommendation). Histological changes of intestinal metaplasia (goblet cells) are needed for the diagnosis prior to recommendations of surveillance. Ideally, erosive esophagitis should be healed prior to biopsy to increase the yield and avoid missing short segments of columnar lining (Grade B Recommendation). Endoscopic descriptions of a Barrett's esophagus should be precise and ideally follow established classification systems (Grade D Recommendation). SCREENING Screening for Barrett's esophagus remains controversial because of the lack of documented impact on mortality from EAC. The large number of patients that lack reflux symptoms but have Barrett's esophagus provides a diagnosis challenge. The highest yield for Barrett's is in older (age 50 or more) Caucasian males with longstanding heartburn. Patients with the highest likelihood of BE are older Caucasian males with chronic reflux symptoms. The challenges to screening for BE include the inability to predict who has BE prior to endoscopy, the lack of evidence based criteria, the invasiveness and expense of endoscopy, and the increasing documentation of a subgroup of patients with BE who lack reflux symptoms. Investigators have attempted to predict BE with clinical and demographic features comparing documented BE patients to patients with GERD lacking BE. Predictors included age >40 (21), heartburn (21–23), long duration GERD symptoms (more than 13 years) (23), and male gender (22). Yet the only consistent correlation in most studies was heartburn and the sensitivity was poor. With the nation's increasing obesity problems, it is not surprising that increased body mass index is correlated with Barrett's esophagus, particularly visceral adiposity characterized by CT scan of the abdomen (24). The emerging data on the potential mechanistic role of cytokines from increasing visceral fat will bear watching. The epidemiology of EAC in the United States identifies risk factors of male gender and Caucasian ethnicity: the annual incidence of EAC in Caucasian men is 3.6/100,000 compared to 0.8 in African American men and 0.3 in Caucasian women (12). The precise magnitude of risk for gender, ethnicity and age are not defined. Esophageal capsule endoscopy is a new technique that has the potential to provide a noninvasive diagnosis of suspected BE, i.e. a columnar lined esophagus. Early studies of small numbers of patients showing high sensitivity have been followed by data sets in abstract form documenting substantially lower sensitivity (25, 26). Although intriguing, this technique cannot be recommended in the screening setting at this time (Grade B Recommendation). It is anticipated that the cost of the capsule and its accuracy will be barriers to lowering the threshold for screening for BE. A more definitive estimate of the population prevalence of BE −1.6% - provides evidence of asymptomatic BE. Forty-four percent of the BE patients from a random sample of adults in 2 communities in Sweden lacked "troublesome heartburn and/or regurgitation over the past 3 months" (27). The inability to distinguish these patients' poses a major problem in developing an effective screening strategy for BE based upon symptoms. There are no current risk factors recognized to identify asymptomatic patients with BE. Such identification will be necessary before screening can be expected to effectively detect the majority of patients with BE. The natural history of asymptomatic BE is undefined. In summary, screening for Barrett's esophagus in the general population cannot be recommended at this time. (Grade B recommendation) The use of screening in selective populations at higher risk remains to be established (Grade D recommendation) and therefore should be individualized. SURVEILLANCE OF BARRETT'S ESOPHAGUS The grade of dysplasia determines the appropriate surveillance interval. Any grade of dysplasia by histology should be confirmed by an expert pathologist. Surveillance endoscopy remains controversial because of the lack of randomized trials supporting its value. Critical analysis of the literature does suggest a survival advantage of endoscopic surveillance. Multiple retrospective studies have been published, all of which indicate that survival is statistically enhanced if the cancers are detected by endoscopic surveillance rather than presenting with symptoms (Table 1). In a California community-based population, surveillance detected cancer had lower staging with better survival (28). A larger SEER/Medicare database documented that an EGD 1 year prior to the diagnosis of EAC was associated with earlier stage and improved survival (29).Table 1: Retrospective Surgical Series of Survival for EAC Based on Surveillance StatusSurveillance is practiced by the vast majority of endoscopists in the US (30, 31). The strongest rationale for early case detection of EAC is the poor 5 year survival of EAC of 13% even with contemporary therapy (32). A patient with documented BE needs to be assessed as a candidate for surveillance. It is recommended that patients be advised of the benefits and risks of surveillance endoscopy. Consideration for beginning a surveillance program should include age, likelihood of survival over the next five years, patient's understanding of the process and its limitations for detection of cancer, and the willingness of the patient to adhere to the recommendations (Grade B Recommendation). Surveillance endoscopy should be performed in patients whose reflux symptoms are controlled with proton pump inhibitor therapy. The goal is healing the esophagitis to reduce the likelihood of the inflammatory process interfering with the visual recognition of BE (14) and contributing to cellular changes confusing the reading of dysplasia. Four quadrant biopsies every 2cm of the Barrett's mucosa sample only a small fraction of the lining but offer the possibility of recognizing dysplasia. Ideally the biopsies from a given segment of Barrett's esophagus should be submitted to pathology in a separate container to enable the focusing of subsequent biopsies on the area if dysplasia is identified. Cost effectiveness studies are needed to evaluate this approach. Even if the initial two endoscopies within one year lack dysplasia, there is no guarantee of the subsequent lack of neoplasia, but may allow an interval of three years for surveillance (Table 2). A combined cohort of BE patients documented that half of patients who developed HGD/EAC had no dysplasia on their first two endoscopies (33).Table 2: Dysplasia Grade and Surveillance IntervalThe finding of low grade dysplasia (LGD) warrants a follow-up endoscopy within six months to ensure that no higher grade of dysplasia is present in the esophagus. If none is found, then yearly endoscopy is warranted until no dysplasia is present on two consecutive annual endoscopies. LGD should be confirmed by an expert GI pathologist because of the problem of reading variability (34). When two pathologists agree on the diagnosis of LGD, the patient has a greater likelihood of neoplastic progression (35). Forty percent of biopsies following the recognition of LGD will be negative (20). Two thirds of 156 patients with LGD had no dysplasia after a mean follow-up of 4 years. The finding of high grade dysplasia (HGD) in flat mucosa should lead to confirmation by an expert GI pathologist and a subsequent endoscopy within three months. HGD with mucosal irregularity should undergo endoscopic mucosal resection. Although the natural history of HGD is variable, there is a five year risk of EAC exceeding 30% (not excluding prevalent cases in the first year). It is because of the high risk of prevalent cancers that these patients are often evaluated as if cancer is present. Staging procedures with endoscopic ultrasonography, CT scans, and even PET scans have been performed although there is not sufficient evidence to warrant their routine application. Patients with confirmed high grade dysplasia, even if unifocal should be counseled regarding their therapeutic options including intensive surveillance, esophagectomy, or ablative therapies. Most experts would use HGD as a threshold for therapeutic intervention or intensive surveillance. Patient's who appear to have lost their dysplasia on surveillance should be treated according to the highest degree of dysplasia previously found. This recommendation is based upon the problem of sampling error on subsequent biopsies. Complete absence of intestinal metaplasia mucosa can also occur especially with short segments of columnar lining, so the patient should still undergo periodic surveillance. If ablative therapy has been applied, patients should be followed and biopsied in the entire area of prior Barrett's mucosa at intervals appropriate for their prior grade of dysplasia until there is reasonable certainty of complete ablation is documented on at least three consecutive endoscopies. (Grade D recommendation) Periodic surveillance is still recommended since Barrett's mucosa has been known to occur again. Precise recommendations regarding these intervals are not made given the paucity of data about recurrence of intestinal metaplasia but case series have established that the phenomenon does occur. In summary, the surveillance of Barrett's esophagus does have indirect evidence suggesting benefit. The more advanced the disease in terms of dysplasia, the more frequently surveillance is needed. However, using histological evidence of dysplasia as the primary biomarker to establish surveillance programs is problematic. There are issues with interpretation, sampling, and need for frequent endoscopies which make this an imperfect approach that will need future refinement. Surveillance is recommended but is a Grade C recommendation as long term prospective controlled studies are not available. THE MANAGEMENT OF DYSPLASIA Low grade dysplasia requires expert pathologist confirmation and more frequent endoscopy and biopsy. High grade dysplasia (HGD) also requires confirmation by an expert pathologist and represents a threshold for intervention. A more intensive biopsy protocol is necessary to exclude the presence of concomitant adenocarcinoma. Any mucosal irregularity, such as nodularity or ulcer, is best assessed with endoscopic resection for a more extensive histologic evaluation and exclusion of cancer. Management of patients with high grade dysplasia is dependent on local expertise, both endoscopic and surgical and the patient's age, comorbidity and preferences. Esophagectomy is no longer the necessary treatment response to HGD. Studies have suggested that for high-grade dysplasia the spacing of four quadrant biopsies should be every 1 cm because larger intervals (2 centimeter) lead to a 50% greater miss rates of cancer (36). In addition, any nodular areas within the Barrett's segment, especially if high-grade dysplasia has previously been found, should undergo endoscopic resection to obtain adequate tissue for more accurate diagnosis. Nodularity has been demonstrated to be associated with a much higher frequency of malignancy (37) and with spread to regional lymph nodes. Despite careful endoscopic surveillance, occult malignancy may still be present. Lacking mucosal abnormalities, these occult lesions are likely intramucosal carcinoma without lymph node involvement (38). The use of large capacity forceps has been advocated, especially in the setting of high-grade dysplasia, although direct comparisons to standard biopsy forceps have not been conducted in terms of measuring changes in patient outcome. The endoscopic technique to be used to maximize tissue yield is a turn-and-suck technique, which should bring the mucosa in direct apposition to the biopsy forceps (39). Endoscopic brush cytology has also been used during surveillance of Barrett's esophagus in the hope that increased ability to sample the cells might lead to better diagnoses (40). Studies are conflicting as to how much additional information can be obtained from cytological examination. However, the use of new genetic markers, such as fluorescent in situ hybridization may be promising in increasing the clinical utility of brush cytology (41). Mucosal ablation therapy has also been advocated to decrease the risk of development of cancer within Barrett's esophagus. This is always done in conjunction with acid suppression, which appears to be a key element. The degree of acid suppression has not been established (42). However, all studies on mucosal ablation therapy have been in conjunction with at least daily and most often twice daily proton pump inhibitor therapy. Photodynamic therapy has been the only therapy shown in a randomized prospective control trial to significantly decrease cancer risk in Barrett's esophagus (43). In this study, 208 patients were randomized 2:1 to photodynamic therapy plus PPI or PPI alone with the primary endpoint of eliminating HGD. Photodynamic therapy using sodium porfimer, 630 nanometer red light, and photoradiating balloons, was demonstrated to decrease the risk of carcinoma by 50% but not eliminating the development of cancer after at least 48 months of follow up. The therapy was also able to eliminate high-grade dysplasia in 78% of patients treated, although 39% of patients in the control arm also lost high-grade dysplasia during follow-up. These endpoints were reached if high-grade dysplasia regressed at any subsequent endoscopy. Thermal ablation techniques were originally utilized for the treatment of Barrett's esophagus lacking dysplasia. The initial thermal coagulation devices were lasers that produced deep tissue injury. The feasibility of mucosal ablation was first demonstrated with these laser devices (42, 44). Thermal ablation has subsequently been primarily done with either argon plasma coagulation or multipolar coagulation, which appear to have relatively similar effects based upon recent small randomized prospective trials (45, 46). Argon plasma coagulation at high power outputs (80 watts) has been shown in case series to be able to treat high-grade dysplasia and even small cancers, although long-term follow-up is not available (47). Multipolar coagulation has been used to treat primarily low-grade dysplasia and nondysplastic Barrett's. Success rates of ablating the entire Barrett's mucosa usually are in the 80–90% range with multiple applications of the devices. Most of the thermal devices have been utilized in relatively small cohorts of patients followed over short periods of time. Photodynamic therapy with 5-aminolevulinic acid, an oral agent with superficial effects, has been utilized in Europe. It is very successful in eliminating high-grade dysplasia and early EAC in case series (48). It does have drawbacks of hypotension and even reported patient death (49). Radiofrequency ablation using a balloon based catheter system has been reported to be of value in elimination of Barrett's esophagus in 70% 12 months after initiation of treatment (50). Recently, a targeted radiofrequency application device mounted on the endoscope has enabled treatment of focal areas with this technique. This device was created to target the superficial mucosal of the esophagus with high power radiofrequency energy. Though infrequent, stricture formation and esophageal perforation have been reported (FDA Maude database). Endoscopic application of cryotherapy has also been reported to eliminate Barrett's esophagus, although there is very limited data about its efficacy (51). Surgical resection (esophagectomy) has been a standard of therapy for Barrett's esophagus with high grade dysplasia based upon concerns that endoscopic surveillance protocols may not detect early cancers in up to 43% of patients and the opportunity for intervention prior to development of incurable metastatic cancer may be missed (38). More recently, the frequency of EAC at resection in patients with HGD at biopsy has been as low as 17% (52). Also, recent studies have indicated that the risk of metastatic cancer in the setting of intramucosal carcinoma is low at 4% (3/78) especially if there is no evidence of mucosal lesions (53). Most cancers detected in the presence of prior high grade dysplasia are early stage (54). This has led to changes in the way esophagectomy is performed in these patients. Esophagectomy can be performed with minimally invasive techniques that involve the use of laparoscopy and thoracoscopy (55). However, despite the decreased invasiveness of the procedures, one large series of 206 patients reported the over-all major complication rates (32%), mean time in hospital (7 days), and time of procedures (4 hours) to be similar to that reported from trans-hiatal esophagectomy (56). Vagal-sparing esophagectomy which involves leaving the adventia of the esophagus intact while replacing the mucosa and muscle layers with colonic tissue has also been advocated in order to decrease the dumping syndrome after esophagectomy. This procedure has been shown to maintain vagal integrity but has not generally been accepted by the surgical community because of the need for the colonic interposition (57). Patients requiring esophagectomy need to be referred to a higher volume institution for the best results. A recent analysis of the literature has suggested there needs to be at least 20 esophagectomies done a year at an institution to decrease operative mortality to 5% or less (58). A recent retrospective comparison study comparing the long-term mortality of 199 patients with high-grade dysplasia treated with photodynamic therapy and endoscopic mucosal resection compared with surgical resection found similar morality (9% versus 8.5%) between the two groups at about 60 months of follow-up. No patients in either group had an esophageal cancer related death (59). In summary, high-grade dysplasia is associated with a 30% risk of cancer development. Treatment needs to be individualized with options of careful intensive surveillance, endoscopic ablation therapy, and surgical resection being presented to the patient based on their appropriateness for these options and the expertise available to provide them. At the current time, it appears as if surveillance with intensive biopsies, endoscopic ablative techniques (most likely a combination of techniques), or esophagectomy may produce similar outcomes in retrospective cohort studies from expert centers. The selection of which of these therapies must be individualized and will depend on the expertise available in the patient's community, the patient's preferences, and the gastroenterologists own experience (Grade B recommendation). IMAGING IN BARRETT'S ESOPHAGUS Barrett's esophagus has been the focus of several new imaging modalities. It is not surprising since the esophagus is easily accessible using existing fiberoptic technology and the degree of mucosa to be examined is limited. There have been several different technologies proposed to help image Barrett's esophagus. The most commercially available technique is narrow band imaging, a method of filtering the illuminating light to two major colors, blue and green which are actually absorbed more by blood vessels in the mucosa and subepithelium. These differences help the endoscopist to visually the mucosa better in combination with a high resolution endoscope. This technology has been termed narrow band imaging since the white light illumination source has been filtered or narrowed. A similar enhancement can be performed after image acquisition and has been termed FICE by another endoscope manufacturer. The imaging is based on spectral emission technology with specific wavelengths of enhancement determined by the user. Both of these technologies can be applied to Barrett's esophagus (60–62). In one study of 51 patients with Barrett's esophagus studied with NBI, 7 of whom had high grade dysplasia, the sensitivity of NBI detection for a irregular mucosal pattern was 100% with a specificity of 98.7% (63). However, studies regarding the interobserver variation in interpretation of these patterns has not been studied. Autofluorescence imaging has also been used in investigations to help discern areas of dysplasia in Barrett's esophagus. This technology uses blue light illumination to detect fluorescence from cellular components in the esophagus. Areas of dysplasia do not have as intense autofluorescence as normal tissues and appear dark red. This technology may be more suitable for screening larger areas of mucosa. In Barrett's esophagus, one study has found that autofluorescence was 100% sensitive for areas of high grade dysplasia in 20 patients but had a 40% false positive rate (64). Older technologies have been used to image the esophagus with chromoendoscopy. Methylene blue stain binds to the mucosa of areas of intestinal metaplasia but will not bind if there is high grade dysplasia or cancer present. The method by which methylene blue is applied and the degree of mucus clearing performed prior to application of the methylene blue affects this technique (65). Studies have had mixed results and prospective crossover studies have not found a clear advantage to methylene blue chromoscopy in comparison to random four quadrant biopsies in detection of dysplasia (66–68). Other contrast agents such as crystal violet, indigo carmine, and acetic acid have also been proposed to enhance the detection of mucosal patterns in Barrett's esophagus in combination with high resolution endoscopy (69). There is promise in these technologies although it is unclear how easily reproducible the identification of patterns will be in clinical practice. The above imaging methods can examine the entire mucosa; however, other techniques have been developed that examine very small areas mucosa that might be suspicious on these broader imaging techniques. These technologies include optical coherence tomography and laser confocal microscopy which can magnify the mucosa and actually image cellular structures. Initial studies are promising in detecting neoplasia in Barrett's esophagus. Laser confocal micocroscopy in 63 patients had an accuracy of 94% for detection of neoplasia (70). Optical coherence tomography which functions in a manner more similar to ultrasonography but using light to create interference patterns also has promising results for the detection of intestinal metaplasia at the gastric junction although prior studies have not been very rewarding in detecting dysplasia (71). Spectroscopic devices can analyze the light coming from the mucosa and assess its components to determine the degree of dysplasia that is present. Newer instruments that can assess optical properties such as reflectance, fluorescence, and light scattering have been combined to allow improved characterization of the mucosa (72). At the present time, commercial availability of these instruments is limited to laser confocal microscopy in an endoscope and probe systems. Although very promising, there is not sufficient evidence at this time to recommend the use of these imaging systems on a routine clinical basis. BIOMARKERS IN BARRETT'S ESOPHAGUS Multiple biomarkers have been proposed but very few have actually been adequately studied prospectively. There is promise in the use of nuclear DNA content abnormalities such as aneuploidy and tetraploidy in biopsy specimens in predicting cancer risk, as well as loss of heterozygosity of specific genes such as P16 and P53. In addition, recent studies demonstrate that methylation of P16, RUNX3 and HPP1, as well as demographic characteristics of the patients and BE length are indicators of cancer risk. No biomarkers or panel is currently ready for routine clinical use. There is a large cohort of patients that has been followed systematically with biomarkers measuring the DNA content in the mucosa. This has been done using flow cytometry of fresh frozen specimens that have been flow cytometry sorted by ki67 to acquire a very pure concentration of epithelial cells. Based on these studies, there is virtually no risk of cancer development for five years if there is no evidence of increased tetraploidy (greater than 6%) or aneuploidy present. However, if tretraploidy was present, there was an increased risk of cancer (relative risk= 11.7, 95% CI = 6.2–22) whereas evidence of aneuploidy increased relative risk 9.5 fold (CI = 4.9–18) (73). However, these methods have been difficult to translate into clinical practice because of the number of biopsies required in the processing needed to maintain laboratory consistency. In addition, the same group in Seattle, Washington, has looked at loss of heterozygosity as a marker using single nucleotide polymorphisms to detect loss of heterozygosity of p16 and p53. Once again, these markers are quite indicative of cancer with a 16 fold increased relative risk of cancer if loss of heterozygosity is detected (74). However, these techniques have really only been applied to tissues that have been specially processed. Clinical validation of these markers in a multi-center study is needed before it can be recommended for standard practice. In a recent publication, an evaluation of tissue from patients who had developed cancer compared to case controls who had not found that methylation of three genes, RUNX3 HPP1 and P16 in their promoter regions once again helped to predict cancer risk. These tests could be done on paraffin-fixed tissues, which is an advantage over the previously mentioned techniques. However, these studies have only been done retrospectively on patient samples and have not been applied in a large prospective fashion (75). Additional biomarkers that have been proposed over time include markers of cell immortalization, loss of apoptotic control, angiogenesis, cell proliferation, and cell cycle abnormalities. Although multiple markers have been shown to be important in small sub-sets of patients, none of these has been validated in prospective multicenter studies. The ideal biomarker panel for the detection of GERD patients who will progress to BE would be noninvasive – i.e. non-endoscopic – and sensitive −85% or better. The ideal biomarker panel to risk stratify patients with BE would be noninvasive and relatively specific, thus enabling the focusing of surveillance endoscopy on this high risk group for EAC. This panel would identify patients with BE who will progress to EAC early enough for curative interventions, perhaps even identifying the appropriate therapy. A low risk group could also be identified, which might not require follow-up. More cost effective surveillance would thus be possible. At this time, validated biomarkers that can be performed on a clinical basis for widespread laboratory use are not available. CHEMOPREVENTION IN BARRETT'S ESOPHAGUS Chemoprevention represents a promising future strategy. Chemoprevention in the pre-malignant stage of esophageal adenocarcinoma represented by Barrett's esophagus seems reasonable. Unfortunately, sufficient prospective evidence that any treatment prevents cancer and more importantly, cancer related deaths in this setting is lacking. The best evidence for any chemoprevention agent lies with non-steroidal anti-inflammatory agents that have been shown in multiple epidemiological studies to be associated with a significantly reduced risk of cancer with an odds ratio of 0.57 (95% confidence interval 0.47–0.71) (76). This decreased risk has also been substantiated with the observation that known biomarkers such as aneuploidy and tetraploidy were also reduced with NSAIDs (77). Unfortunately, in a randomized trial not meeting its patient recruitment goals, celecoxib 200mg bid was not more effective than placebo in patients with BE and dysplasia in the intermediate endpoint of the change of the proportion of biopsies with dysplasia (78). Animal model studies have shown risk reduction of cancer in rats given cyclo-oxygenase inhibitors (79). Large scale trials are being conducted investigating the use of aspirin and low and high dose proton pump inhibitor therapy in Barrett's esophagus but these will take several years to complete (80). Data from two retrospective cohort studies suggest that PPI therapy significantly reduces the likelihood of developing dysplasia (81–82). This provides a rationale to treat even asymptomatic BE patients with PPI. The benefit of acid suppressive therapy as a means of preventing cancer has not been documented prospectively. No recommendation can be made to use these drugs as chemoprevention agents. REFLUX CONTROL IN PATIENTS WITH BARRETT'S ESOPHAGUS For patients with Barrett's esophagus, the goal of pharmacologic acid suppression with agents such as the proton pump inhibitors is to control reflux symptoms. Reflux symptoms can be controlled in most patients with proton pump inhibitor (PPI) therapy. Twice a day dosing may be necessary in a subgroup of patients. Retrospective studies have shown a decrease in development of dysplasia in patients treated with or prescribed proton pump inhibitors (81). Studies have suggested that normalization of esophageal acid exposure may decrease markers of proliferation (83). However there are currently no data that directly support the use of high dose antisecretory therapy to delay or prevent the development of EAC. Patients who are optimal candidates for surgery may elect fundoplication. These include patients lacking major comorbidity and whose reflux symptoms are controlled with PPI therapy. Long term results are disappointing with a 20% failure rate at 5 years (84). The vast majority of data do not provide support that fundoplication prevents EAC (85). ANTICIPATED DEVELOPMENTS Non-endoscopic detection of B: It is anticipated that in the short term non-endoscopic methods may become available that identify Barrett's mucosa based on high resolution, spectroscopic or colorimetric means. A randomized trial assessing impact of surveillance endoscopy. A multicenter randomized controlled trial of surveillance is needed to determine the validity of this practice. Optical recognition of dysplasia: Various techniques are available that can distinguish degrees of dysplasia. These range from fluorescence, light scattering, reflectance, and Raman spectroscopy to imaging devices such as laser confocal microscopy, endomicroscopy, and optical coherence tomography. One or more of these technologies will become clinically available. Prospective definition of risk of diffuse versus focal dysplasia. Advances in the technology of endoscopic ablation therapy: Further evaluation of the most recent technology; radiofrequency ablation is awaited. Cryotherapy is beginning clinical trials and older technologies are becoming more refined e.g.: photodynamic therapy with the development of new agents. Documentation of the frequency and duration of the surveillance protocol after endoscopic ablation therapy requires careful study. Validation of a biomarker panel to risk stratifies BE patients: There are many potential biomarkers but few clinical trials that validate their use. This undoubtedly will change given the many markers currently being investigated. ACKNOWLEDGMENT Linda LaFleur, for her dedicated manuscript preparation.

Chemoradiation With and Without Surgery in Patients With Locally Advanced Squamous Cell Carcinoma of the Esophagus

2005-03-30

M. Stahl , Martin Stuschke , Nils Lehmann +7 more

Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer. The value of adding surgery to chemotherapy and radiotherapy … Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer. The value of adding surgery to chemotherapy and radiotherapy is unknown.Patients with locally advanced squamous cell carcinoma (SCC) of the esophagus were randomly allocated to either induction chemotherapy followed by chemoradiotherapy (40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiotherapy (at least 65 Gy) without surgery (arm B). Primary outcome was overall survival time.The median observation time was 6 years. The analysis of 172 eligible, randomized patients (86 patients per arm) showed overall survival to be equivalent between the two treatment groups (log-rank test for equivalence, P < .05). Local progression-free survival was better in the surgery group (2-year progression-free survival, 64.3%; 95% CI, 52.1% to 76.5%) than in the chemoradiotherapy group (2-year progression-free survival, 40.7%; 95% CI, 28.9% to 52.5%; hazard ratio [HR] for arm B v arm A, 2.1; 95% CI, 1.3 to 3.5; P = .003). Treatment-related mortality was significantly increased in the surgery group than in the chemoradiotherapy group (12.8% v 3.5%, respectively; P = .03). Cox regression analysis revealed clinical tumor response to induction chemotherapy to be the single independent prognostic factor for overall survival (HR, 0.30; 95% CI, 0.19 to 0.47; P < .0001).Adding surgery to chemoradiotherapy improves local tumor control but does not increase survival of patients with locally advanced esophageal SCC. Tumor response to induction chemotherapy identifies a favorable prognostic group within these high-risk patients, regardless of the treatment group.

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Phase III Comparison of Preoperative Chemotherapy Compared With Chemoradiotherapy in Patients With Locally Advanced Adenocarcinoma of the Esophagogastric Junction

2009-01-13

M. Stahl , Martin K. Walz , Martin Stuschke +7 more

Preoperative chemotherapy is an accepted standard in the treatment of localized esophagogastric adenocarcinoma. Adding radiation therapy to preoperative chemotherapy appears promising, but its definitive value remains unknown.Patients with locally advanced … Preoperative chemotherapy is an accepted standard in the treatment of localized esophagogastric adenocarcinoma. Adding radiation therapy to preoperative chemotherapy appears promising, but its definitive value remains unknown.Patients with locally advanced (uT3-4NXM0) adenocarcinoma of the lower esophagus or gastric cardia were randomly allocated to one of two treatment groups: induction chemotherapy (15 weeks) followed by surgery (arm A); or chemotherapy (12 weeks) followed by chemoradiotherapy (3 weeks) followed by surgery (arm B). Primary outcome was overall survival time. A total of 354 patients were needed to detect a 10% increase in 3-year survival from 25% to 35% by addition of radiation therapy. The study was prematurely closed due to low accrual.The median observation time was 46 months. A total of 126 patients were randomly assigned and 119 eligible patients were evaluated. The number of patients undergoing complete tumor resection was not different between treatment groups (69.5% v 71.5%). Patients in arm B had a significant higher probability of showing pathologic complete response (15.6% v 2.0%) or tumor-free lymph nodes (64.4% v 37.7%) at resection. Preoperative radiation therapy improved 3-year survival rate from 27.7% to 47.4% (log-rank P = .07, hazard ratio adjusted for randomization strata variables 0.67, 95% CI, 0.41 to 1.07). Postoperative mortality was nonsignificantly increased in the chemoradiotherapy group (10.2% v 3.8%; P = .26).Although the study was closed early and statistical significance was not achieved, results point to a survival advantage for preoperative chemoradiotherapy compared with preoperative chemotherapy in adenocarcinomas of the esophagogastric junction.

Chemoradiotherapy of Locally Advanced Esophageal Cancer

1999-05-05

Jay S. Cooper , Matthew Guo , Arnold Herskovic +7 more

ContextCarcinoma of the esophagus traditionally has been treated by surgery or radiation therapy (RT), but 5-year overall survival rates have been only 5% to 10%. We previously reported results of … ContextCarcinoma of the esophagus traditionally has been treated by surgery or radiation therapy (RT), but 5-year overall survival rates have been only 5% to 10%. We previously reported results of a study conducted from January 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy.ObjectiveTo report the long-term outcomes of a previously reported trial designed to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma.DesignRandomized controlled trial conducted 1985 to 1990 with follow-up of at least 5 years, followed by a prospective cohort study conducted between May 1990 and April 1991.SettingMulti-institution participation, ranging from tertiary academic referral centers to general community practices.PatientsPatients had squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, adequate renal and bone marrow reserve, and a Karnofsky score of at least 50.InterventionsCombined modality therapy (n=134): 50 Gy in 25 fractions over 5 weeks, plus cisplatin intravenously on the first day of weeks 1, 5, 8, and 11, and fluorouracil, 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1, 5, 8, and 11. In the randomized study, combined therapy was compared with RT only (n=62): 64 Gy in 32 fractions over 6.4 weeks.Main Outcome MeasuresOverall survival, patterns of failure, and toxic effects.ResultsCombined therapy significantly increased overall survival compared with RT alone. In the randomized part of the trial, at 5 years of follow-up the overall survival for combined therapy was 26% (95% confidence interval [CI], 15%-37%) compared with 0% following RT. In the succeeding nonrandomized part, combined therapy produced a 5-year overall survival of 14% (95% CI, 6%-23%). Persistence of disease (despite therapy) was the most common mode of treatment failure; however, it was less common in the groups receiving combined therapy (34/130 [26%]) than in the group treated with RT only (23/62 [37%]). Severe acute toxic effects also were greater in the combined therapy groups. There were no significant differences in severe late toxic effects between the groups. However, chemotherapy could be administered as planned in only 89 (68%) of 130 patients (10% had life-threatening toxic effects with combined therapy vs 2% in the RT only group).ConclusionCombined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone.

The Vienna classification of gastrointestinal epithelial neoplasia

2000-08-01

Ronald J. Schlemper

<h3>BACKGROUND</h3> Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. … <h3>BACKGROUND</h3> Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. <h3>AIM</h3> To develop common worldwide terminology for gastrointestinal epithelial neoplasia. <h3>METHODS</h3> Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. <h3>RESULTS</h3> The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). <h3>CONCLUSION</h3> The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

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Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer

2012-05-31

Pieter van Hagen , Maarten C.C.M. Hulshof , J. Jan B. van Lanschot +7 more

The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this … The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population.

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Long-Term Results of a Randomized Trial of Surgery With or Without Preoperative Chemotherapy in Esophageal Cancer

2009-09-22

William Allum , Sally Stenning , J Bancewicz +2 more

OEO2 is a randomized, controlled trial of preoperative chemotherapy in patients undergoing radical surgery for esophageal cancer. Random assignment was to surgery alone (S) or to two cycles of combination … OEO2 is a randomized, controlled trial of preoperative chemotherapy in patients undergoing radical surgery for esophageal cancer. Random assignment was to surgery alone (S) or to two cycles of combination cisplatin and fluorouracil before surgery (CS). Initial results reported in 2002 demonstrated an advantage for both disease-free and overall survival in the CS group. The analysis has now been updated after a median follow-up of 6 years.OEO2 recruited 802 patients, 400 on CS and 402 on S. The nature of the first recurrence event and cause of death are detailed. Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test. Survival by extent of resection is presented.There were 655 deaths, 335 for S and 320 for CS. The survival benefit has been maintained with a hazard ratio (HR) of 0.84 (95% CI, 0.72 to 0.98; P = .03) which in absolute terms is a 5-year survival of 23.0% for CS compared with 17.1% for S. The treatment effect is consistent in both adenocarcinoma and squamous cell carcinoma. The first disease-free survival event was macroscopic residual disease from incomplete resection (R2) or no resection in 26.4% of the S group versus 14.3% of the CS P < .001. Three-year survival by type of resection was R0 42.4%, R1 was 18.0%, and R2 was 8.6%.Long-term follow-up confirms that preoperative chemotherapy improves survival in operable esophageal cancer and should be considered as a standard of care.

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Global incidence of oesophageal cancer by histological subtype in 2012

2014-10-15

Melina Arnold , Isabelle Soerjomataram , Jacques Ferlay +1 more

<h3>Objective</h3> The two major histological types of oesophageal cancer—adenocarcinoma (AC) and squamous cell carcinoma (SCC)—are known to differ greatly in terms of risk factors and epidemiology. To date, global incidence … <h3>Objective</h3> The two major histological types of oesophageal cancer—adenocarcinoma (AC) and squamous cell carcinoma (SCC)—are known to differ greatly in terms of risk factors and epidemiology. To date, global incidence estimates for individual subtypes are still lacking. This study for the first time quantified the global burden of oesophageal cancer by histological subtype. <h3>Design</h3> Where available, data from Cancer Incidence in Five Continents Vol. X (CI5X) were used to compute, age-specific, sex-specific and country-specific proportions of AC and SCC. Nine regional averages were computed for countries without CI5X data. The proportions were then applied to all oesophageal cancer cases from GLOBOCAN 2012 and age-standardised incidence rates calculated for both histological types. <h3>Results</h3> Worldwide, an estimated 398 000 SCCs and 52 000 ACs of the oesophagus occurred in 2012, translating to incidence rates of 5.2 and 0.7 per 100 000, respectively. Although SCCs were most common in South-Eastern and Central Asia (79% of the total global SCC cases), the highest burden of AC was found in Northern and Western Europe, Northern America and Oceania (46% of the total global AC cases). Men had substantially higher incidence than women, especially in the case of AC (male to female ratio AC: 4.4; SCC: 2.7). <h3>Conclusions</h3> These first global estimates of oesophageal cancer incidence by histology suggested a high concentration of AC in high-income countries with men being at much greater risk. This quantification of incidence will aid health policy makers to plan appropriate cancer control measures in the future.

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The Development and Validation of an Endoscopic Grading System for Barrett’s Esophagus: The Prague C & M Criteria

2006-08-17

Prateek Sharma , John Dent , David Armstrong +7 more

Randomized Trial of Preoperative Chemoradiation Versus Surgery Alone in Patients With Locoregional Esophageal Carcinoma

2001-01-15

Susan G. Urba , Mark B. Orringer , Andrew T. Turrisi +3 more

PURPOSE: A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin, fluorouracil, and vinblastine before surgery showed a median … PURPOSE: A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin, fluorouracil, and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution. We designed a randomized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone. MATERIALS AND METHODS: One hundred patients with esophageal carcinoma were randomized to receive either surgery alone (arm I) or preoperative chemoradiation (arm II) with cisplatin 20 mg/m 2 /d on days 1 through 5 and 17 through 21, fluorouracil 300 mg/m 2 /d on days 1 through 21, and vinblastine 1 mg/m 2 /d on days 1 through 4 and 17 through 20. Radiotherapy consisted of 1.5-Gy fractions twice daily, Monday through Friday over 21 days, to a total dose of 45 Gy. Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42. RESULTS: At median follow-up of 8.2 years, there is no significant difference in survival between the treatment arms. Median survival is 17.6 months in arm I and 16.9 months in arm II. Survival at 3 years was 16% in arm I and 30% in arm II (P = .15). This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years, with at least 80% power. CONCLUSION: This randomized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference.

American Gastroenterological Association Medical Position Statement on the Management of Barrett's Esophagus

2011-03-01

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ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

2015-11-03

Nicholas J. Shaheen , Gary W. Falk , Prasad G. Iyer +1 more

Barrett's esophagus (BE) is among the most common conditions encountered by the gastroenterologist. In this document, the American College of Gastroenterology updates its guidance for the best practices in caring … Barrett's esophagus (BE) is among the most common conditions encountered by the gastroenterologist. In this document, the American College of Gastroenterology updates its guidance for the best practices in caring for these patients. These guidelines continue to endorse screening of high-risk patients for BE; however, routine screening is limited to men with reflux symptoms and multiple other risk factors. Acknowledging recent data on the low risk of malignant progression in patients with nondysplastic BE, endoscopic surveillance intervals are attenuated in this population; patients with nondysplastic BE should undergo endoscopic surveillance no more frequently than every 3-5 years. Neither routine use of biomarker panels nor advanced endoscopic imaging techniques (beyond high-definition endoscopy) is recommended at this time. Endoscopic ablative therapy is recommended for patients with BE and high-grade dysplasia, as well as T1a esophageal adenocarcinoma. Based on recent level 1 evidence, endoscopic ablative therapy is also recommended for patients with BE and low-grade dysplasia, although endoscopic surveillance continues to be an acceptable alternative. Given the relatively common recurrence of BE after ablation, we suggest postablation endoscopic surveillance intervals. Although many of the recommendations provided are based on weak evidence or expert opinion, this document provides a pragmatic framework for the care of the patient with BE.

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Chemoradiotherapy Followed by Surgery Compared with Surgery Alone in Squamous-Cell Cancer of the Esophagus

1997-07-17

Jean-François Bosset , M Gignoux , Jean–Pierre Triboulet +7 more

We conducted a multicenter, randomized trial to compare preoperative chemoradiotherapy followed by surgery with surgery alone in patients with stage I and II squamous-cell cancer of the esophagus. We conducted a multicenter, randomized trial to compare preoperative chemoradiotherapy followed by surgery with surgery alone in patients with stage I and II squamous-cell cancer of the esophagus.

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Symptomatic Gastroesophageal Reflux as a Risk Factor for Esophageal Adenocarcinoma

1999-03-18

Jesper Lagergren , Reinhold Bergström , Anders Lindgren +1 more

The causes of adenocarcinomas of the esophagus and gastric cardia are poorly understood. We conducted an epidemiologic investigation of the possible association between gastroesophageal reflux and these tumors. The causes of adenocarcinomas of the esophagus and gastric cardia are poorly understood. We conducted an epidemiologic investigation of the possible association between gastroesophageal reflux and these tumors.

A Comparison of Multimodal Therapy and Surgery for Esophageal Adenocarcinoma

1996-08-15

T. N. Walsh , N. Noonan , Donal Hollywood +3 more

Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, … Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery.

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Chemotherapy Followed by Surgery Compared with Surgery Alone for Localized Esophageal Cancer

1998-12-31

David P. Kelsen , Robert J. Ginsberg , Thomas F. Pajak +7 more

We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer.Preoperative chemotherapy for patients randomly assigned to the … We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer.Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival.Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites.Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.

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Integrated genomic characterization of oesophageal carcinoma

2017-01-01

Epidemiology of Esophageal Squamous Cell Carcinoma

2017-08-18

Christian C. Abnet , Melina Arnold , Wenqiang Wei

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Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

2019-07-01

Jaffer A. Ajani , Thomas A. D’Amico , David J. Bentrem +7 more

Abstract Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common … Abstract Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.

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Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial

2019-09-30

Ken Kato , Byoung Chul Cho , Masanobu Takahashi +7 more

Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer

2021-03-31

Ronan J. Kelly , Jaffer A. Ajani , Jarosław Kużdżał +7 more

No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer.

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Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study

2021-08-01

Jong‐Mu Sun , Lin Shen , Manish A. Shah +7 more

Oesophageal carcinoma

2013-02-01

Arjun Pennathur , Michael K. Gibson , Blair A. Jobe +1 more

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Oesophageal cancer

2017-06-23

Jesper Lagergren , Elizabeth Smyth , David Cunningham +1 more

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INT 0123 (Radiation Therapy Oncology Group 94-05) Phase III Trial of Combined-Modality Therapy for Esophageal Cancer: High-Dose Versus Standard-Dose Radiation Therapy

2002-03-01

Bruce D. Minsky , Thomas F. Pajak , Robert J. Ginsberg +6 more

PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. … PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. PATIENTS AND METHODS: A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach, after stratification by weight loss, primary tumor size, and histology, were randomized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil (5-FU) (1,000 mg/m 2 /24 hours for 4 days) and cisplatin (75 mg/m 2 bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy. The trial was stopped after an interim analysis. The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive. RESULTS: For the 218 eligible patients, there was no significant difference in median survival (13.0 v 18.1 months), 2-year survival (31% v 40%), or local/regional failure and local/regional persistence of disease (56% v 52%) between the high-dose and standard-dose arms. Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the standard-dose arm, seven of the 11 deaths occurred in patients who had received 50.4 Gy or less. CONCLUSION: The higher radiation dose did not increase survival or local/regional control. Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm, it did not seem to be related to the higher radiation dose. The standard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy.

Esophageal Carcinoma

2014-12-24

Anil K. Rustgi , Hashem B. El–Serag

The 5-year survival rate in esophageal cancer, although poor, has improved over the past decade. This review discusses the epidemiologic aspects, pathogenesis, prevention, and therapy of esophageal adenocarcinoma and squamous-cell … The 5-year survival rate in esophageal cancer, although poor, has improved over the past decade. This review discusses the epidemiologic aspects, pathogenesis, prevention, and therapy of esophageal adenocarcinoma and squamous-cell carcinoma, focusing on recent advances.

Esophageal Cancer

2003-12-03

Peter C. Enzinger , Robert J. Mayer

Cancers arising from the esophagus, including the gastroesophageal junction, are relatively uncommon in the United States — the lifetime risk of this cancer is 0.8 percent for men and 0.3 … Cancers arising from the esophagus, including the gastroesophageal junction, are relatively uncommon in the United States — the lifetime risk of this cancer is 0.8 percent for men and 0.3 percent for women, and it increases with age. The presentation is insidious; at diagnosis, more than 50 percent of patients have either unresectable cancer or radiographically visible metastases, rendering management problematic. This review discusses the pathogenesis of esophageal cancer, as well as the clinical presentation, treatment, and prognosis.

Nuclear Medicine Lymphoscintigraphy: Applications and Technical Overview

2025-06-26

| Radiographics

Podcast: Innovations in GU Cancer Treatment at ASCO25

2025-06-26

| Default Digital Object Group

Letter to editor about “Group-based trajectory analysis of postoperative quality of recovery and outcomes after esophagectomy”

2025-06-25

Zhijia Shen , Limei Yin , Z. Qian | International Journal of Surgery

Radiotherapy as an organ‐preserving alternative to surgery in patients with locally advanced esophageal squamous cell carcinoma achieving major pathologic response after induction immunochemotherapy

2025-06-25

X. Song , Lin Lin , Yang Yang +7 more | International Journal of Cancer

Abstract With the advancement of immunotherapy, neoadjuvant immunochemotherapy has emerged as an effective approach for treating locally advanced esophageal squamous cell carcinoma (LA‐ESCC). However, whether radiotherapy can serve as a … Abstract With the advancement of immunotherapy, neoadjuvant immunochemotherapy has emerged as an effective approach for treating locally advanced esophageal squamous cell carcinoma (LA‐ESCC). However, whether radiotherapy can serve as a reliable organ‐preserving alternative following induction immunochemotherapy (IICT), and which patient subgroups benefit most, remains uncertain. In this retrospective study, 388 patients with LA‐ESCC were analyzed, including 299 who underwent surgery and 89 who received radiotherapy after IICT. Responses to immunochemotherapy were classified as major pathologic response (MPR) or non‐MPR based on pathologic examination for surgical patients and a previously developed MPR predictive model for radiotherapy patients. Survival outcomes were assessed using the Kaplan–Meier method, while prognostic factors were evaluated through Cox regression analyses. Propensity score matching (PSM) was used to minimize confounding factors. Surgery was associated with better progression‐free survival (PFS) compared to radiotherapy ( p = 0.002 before PSM; p = 0.017 after PSM), but no significant difference in overall survival (OS) was observed ( p = 0.144 before PSM; p = 0.241 after PSM). Among MPR patients, radiotherapy achieved PFS and OS outcomes similar to surgery (PFS: p = 0.136; OS: p = 0.255) after PSM. Failure patterns differed, with local or regional recurrence being more common in the radiotherapy group, while distant metastasis was prevalent in surgery patients. Major postoperative complications occurred in 9.36% of surgery patients, and 11.2% of radiotherapy patients had grade 3–4 adverse events. These findings indicate that radiotherapy could be a safe and effective organ‐preserving alternative for LA‐ESCC patients, especially those achieving MPR, offering more personalized and less invasive treatment options while maintaining quality of life.

Correction: Evaluating the quality of online resources for patient education on robotic esophagectomy

2025-06-25

Susheian Kelly , Rajika Jindani , Sophia Yanis +7 more | Journal of Robotic Surgery

Carcinoma of Esophagus

2025-06-24

Joseph J.�Y. Sung , Dongxin Lin , Rebecca C. Fitzgerald +3 more | Journal of Gastroenterology and Hepatology

ABSTRACT Carcinoma of esophagus is one of the most common cancer worldwide, but its epidemiology is changing. Squamous cell carcinoma is declining in the East, but adenocarcinoma is rising in … ABSTRACT Carcinoma of esophagus is one of the most common cancer worldwide, but its epidemiology is changing. Squamous cell carcinoma is declining in the East, but adenocarcinoma is rising in the West, probably related to the pandemic of obesity and changing lifestyle. Screening of esophageal cancer (both endoscopic and nonendoscopic methods) is recommended in patients suffering from long‐term acid reflux symptoms associated with high‐risk factors and surveillance in patients with Barrett's esophagus. Endoscopy with virtual chromoendoscopy, endoscopic ultrasound, and CT scan is essential for diagnosis and staging of the disease. Endoscopic therapy can be used to treat early diseases. Surgery remains a mainstay treatment. Multimodality treatment strategies involving combinations of chemotherapy, radiotherapy, and more recently immunotherapy and target therapies are gaining momentum.

Austrian Society of Surgical Oncology consensus paper on the classification and treatment of anastomotic leaks after esophageal resections

2025-06-24

Oliver O. Koch , Franz Singhartinger , Eva Wallner +7 more | European surgery. Supplement/European surgery

Summary Background Anastomotic leakage is still the most frequent cause of postoperative mortality following gastroesophageal surgery. This consensus paper contains the first classification and treatment recommendations from the Austrian Society … Summary Background Anastomotic leakage is still the most frequent cause of postoperative mortality following gastroesophageal surgery. This consensus paper contains the first classification and treatment recommendations from the Austrian Society of Surgical Oncology (ACO ASSO) for specialists treating patients with anastomotic leakage after esophageal resections. Methods The Board of Directors of the ACO ASSO identified classification and treatment recommendations for anastomotic leakage after esophageal resections as an important topic for study and invited experts to participate in the drafting of a consensus paper. This panel of experts was tasked with determining an outline, reviewing the relevant literature, and preparing a written document with a recommendation on the classification and treatment of anastomotic leaks after esophageal resections. In order to reach a consensus on the classification of anastomotic leakage, the expert panel invited all members of the ACO ASSO upper gastrointestinal tract working group to take part in a survey to determine which classification they would prefer. The paper was written based on the results of the survey and the research of the expert panel. Results The majority of the ACO ASSO upper gastrointestinal tract working group members surveyed chose the German CAES ( Chirurgische Arbeitsgemeinschaft für Endoskopie und Sonographie ) classification as the one they would prefer in their daily practice. Based on this, the respective treatment recommendations were created in alignment with clinical decision-making by linking each grade of insufficiency to recommended interventions. Conclusion With this consensus paper, the ACO ASSO has created a clear guideline for current treatment and a recommendation for the classification of anastomotic leaks after esophageal resections. This will help to streamline treatment protocols and improve clarity in clinical documentation and research.

Robotic-assisted minimally invasive esophagectomy: experience at the University of Pittsburgh Medical Center

2025-06-24

Marissa A. Matto , Evan T. Alicuben , Samuel K. Luketich +4 more | Mini-invasive Surgery

Robotic-assisted minimally invasive esophagectomy (RAMIE) is increasingly used in the treatment of resectable esophageal cancer. This is a report on the current technique of RAMIE at University of Pittsburgh Medical … Robotic-assisted minimally invasive esophagectomy (RAMIE) is increasingly used in the treatment of resectable esophageal cancer. This is a report on the current technique of RAMIE at University of Pittsburgh Medical Center (UPMC), including a summary of early data on 65 patient outcomes reported in an ongoing esophageal cancer database. To date, we have performed over 200 cases of RAMIE at UPMC from September 2013 to July 2024, and the analysis of the data will be presented soon. The practice has evolved into a near-total RAMIE experience for several surgeons, while others remain in a learning curve. It is our experience that the initial performance of RAMIE requires strong mentoring by an experienced robotic surgeon. However, at this time, we are unable to provide guidelines for specific case numbers to achieve proficiency. As more patients with esophageal cancer are treated with robotic-assisted minimally invasive esophagectomy (MIE) at UPMC, data have shown that patient outcomes are not compromised compared with that of traditional MIE. In fact, RAMIE may demonstrate superiority in the median number of lymph nodes harvested, which could contribute to increased accuracy in pathologic staging. This approach has developed a strong surgeon preference for both new graduates and experienced MIE surgeons alike.

Analysis of Recurrence Sites in Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiation with Elective Nodal Irradiation: Insights for Radiation Field Optimization

2025-06-24

Ye Jin Yoo , Jeong Yun Jang , Sung-Bae Kim +4 more | Annals of Surgical Oncology

The Importance of the Circumferential Radial Margin After Resection of Esophageal Cancer

2025-06-24

Raul Caso , Daniela Molena | Foregut The Journal of the American Foregut Society

Survival among patients with esophageal cancer is poor, and surgery remains an integral part of the multimodal management of these patients. The circumferential radial margin is not routinely evaluated intraoperatively … Survival among patients with esophageal cancer is poor, and surgery remains an integral part of the multimodal management of these patients. The circumferential radial margin is not routinely evaluated intraoperatively and is currently not part of the staging system. Although definitions of radial margin differ, accumulating evidence suggests that radial margin positivity is associated with aggressive tumor types. Additionally, despite the heterogeneity of the available evidence, abundant data indicate that radial margin positivity is associated with poor oncologic outcomes after resection of esophageal cancer. Here, we review the current evidence on the circumferential radial margin after resection of esophageal cancer.

Endoscopic biopsy techniques in Barrett esophagus patients: a multidesign study

2025-06-24

Ilse N. Beaufort , Sjoerd G. Elias , Elisabeth Akkerman +5 more | Endoscopy

Abstract The impact of different random biopsy techniques for Barrett esophagus (BE) surveillance on histopathological quality is unclear. We compared the double- vs. single-biopsy method and advance-and-close vs. turn-and-suction technique. … Abstract The impact of different random biopsy techniques for Barrett esophagus (BE) surveillance on histopathological quality is unclear. We compared the double- vs. single-biopsy method and advance-and-close vs. turn-and-suction technique. In a multicenter, factorial design trial (Part I), BE patients were randomly assigned to the double- or single-biopsy method and advance-and-close or turn-and-suction technique (1:1:1:1). In a before–after study (Part II), the optimal biopsy method and technique were implemented in clinical practice. The primary end point in both parts was biopsy size. In Part I (107 patients, 1024 biopsies), single-method biopsies were 25% larger than double-method biopsies (3.34 mm2 [95%CI 3.10–3.57] vs. 2.68 mm2 [95%CI 2.45–2.92]; P < 0.001). Mean (95%CI) biopsy size was 2.95 mm2 (2.72–3.19) and 3.08 mm2 (2.85–3.31) with advance-and-close and turn-and-suction techniques, respectively (P = 0.44). The interaction term between the co-primary comparisons was P = 0.08. Mean (95%CI) biopsy size for double-biopsy + advance-and-close, double-biopsy + turn-and-suction, single-biopsy + advance-and-close, and single-biopsy + turn-and-suction was 2.77 mm2 (2.44–3.09), 2.61 mm2 (2.29–2.93), 3.14 mm2 (2.81–3.46), and 3.54 mm2 (3.22–3.86), respectively. In Part II, 46 and 44 patients were included before and after implementation of the single-biopsy method and turn-and-suction technique, in whom this combination was used in 16/46 (35%) and 44/44 (100%) patients, respectively. Mean (95%CI) biopsy size increased by 18%, from 3.31 mm2 (2.95–3.68) to 3.90 mm2 (3.50–4.29; P = 0.03). BE surveillance biopsies should be taken with the single-biopsy method and turn-and-suction technique to increase biopsy size. BE surveillance biopsies should be taken with the single-biopsy method and turn-and-suction technique to increase biopsy size.

Global trends in esophageal cancer: sex and age disparities in health inequalities from 1990 to 2021, with projections to 2050

2025-06-24

Ying Liu , Erman Wu , Cheng Fang +7 more | Frontiers in Oncology

Background Esophageal cancer remains one of the deadliest cancers globally, highlighting significant health challenges and socioeconomic disparities. This study aims to measure its global burden, assess disparities by sex, age, … Background Esophageal cancer remains one of the deadliest cancers globally, highlighting significant health challenges and socioeconomic disparities. This study aims to measure its global burden, assess disparities by sex, age, and region, and evaluate health inequalities, with projections to 2050. The goal is to provide evidence to guide resource allocation and reduce the disease burden. Methods Using data from the Global Burden of Disease (GBD) 2021 study, we analyzed trends in prevalence, incidence, mortality, and Disability-Adjusted Life Years (DALYs) across sexes, age groups, and 204 countries and territories. Age-standardized rates (ASR) were calculated to account for population age structures. Trends over time were assessed using the estimated annual percentage change (EAPC). Health inequalities were evaluated using the Slope Index of Inequality (SII) and Concentration Index (CI). Future burdens were projected using Bayesian Age-Period-Cohort (BAPC) models. Results From 1990 to 2021, esophageal cancer cases increased: prevalence from 551.62 to 1004.2 thousand, incidence from 354.73 to 576.53 thousand, mortality from 356.26 to 538.6 thousand, and DALYs from 9753.57 to 12999.26 thousand. However, age-standardized rates declined: prevalence from 13.34 to 11.47, incidence from 8.86 to 6.65, mortality from 9.02 to 6.25, and DALYs from 235.32 to 148.56 per 100,000 people. The burden rises sharply after age 40, with males and low-SDI regions experiencing higher burdens. Health inequalities widened, with the SII for prevalence increasing from 2.52 to 5.67, and for deaths from 1.45 to 2.94. West Africa, North Europe, and North America saw rising prevalence rates, while East Asia showed a declining trend. A decreasing trend is observed in most countries and regions worldwide, particularly in East Asia, with projections suggesting a continued decline in the future. Conclusion Although projections indicate a decreasing trend, health inequalities have intensified. Regions such as West Africa, North Europe, and North America are experiencing rising prevalence. To address these disparities, targeted interventions, enhanced healthcare access, and preventive measures in high-burden areas are essential to reduce the global burden and advance health equity.

Impact of seasons on elderly patients with esophageal squamous cell carcinoma following esophagectomy: a propensity score matching analysis

2025-06-23

Kai Li , Simiao Lu , Changding Li +7 more | Discover Oncology

ASO Author Reflections: Open Versus Thoracoscopic Esophagectomy Across Pathological Stages in Esophageal Squamous Cell Carcinoma: Consistent Survival Benefit with a Minimally Invasive Approach

2025-06-23

Xiaocan Jia , Yun Gao , Tongtong Ren +4 more | Annals of Surgical Oncology

Current trends and future projection for addressing the burden of esophageal carcinoma in Asia: a comprehensive analysis (1990–2040)

2025-06-23

Peng Ma , Xiaohong Tan , Tingting Hao +3 more | Frontiers in Oncology

Background Esophageal carcinoma (EC) significantly impacts global health, particularly in Asia, where many low- and middle-income countries face substantial burdens despite advancements in some regions. Objective This study analyzed EC’s … Background Esophageal carcinoma (EC) significantly impacts global health, particularly in Asia, where many low- and middle-income countries face substantial burdens despite advancements in some regions. Objective This study analyzed EC’s spatial and temporal distribution in Asia using the Global Burden of Disease (GBD) database, aiming to forecast future burdens and support effective prevention strategies. Methods Data from 48 Asian countries (1990-2021) were extracted from the GBD database, covering incidence, prevalence, deaths, disability-adjusted life years (DALYs), risk factors, and socio-demographic index (SDI). R and GraphPad Prism were used to assess changes and predict future trends. Results From 1990 to 2021, EC’s disease burden in Asia generally declined, with significant regional and sex disparities. East Asia showed the most improvement despite having the highest burden. Conversely, South and Southeast Asia experienced limited progress, with some areas seeing increased burdens. Males consistently had higher burdens than females, especially in East Asia. Future projections (from 2022 to 2040) suggested a slight rise in incidence in East Asia, while improvements in South and Southeast Asia may remain limited, though an overall burden decline was expected. Conclusion The reduction in Asia’s EC burden underscored the impact of medical advances and public health efforts, but regional and sex disparities persist. Future strategies should enhance health resources in under-resourced and high-risk areas and implement targeted policies to address health inequalities and promote balanced public health development across Asia.

Esophagectomy for very low body weight: a case report and literature review

2025-06-23

Tianyu Zhang , Ruyuan He , Yongguang Xiao | Frontiers in Oncology

Esophageal cancer (EC) has been widely concerned because of its high incidence, high mortality and high recurrence rate. However, the traditional surgical treatment of EC has poor prognosis and high … Esophageal cancer (EC) has been widely concerned because of its high incidence, high mortality and high recurrence rate. However, the traditional surgical treatment of EC has poor prognosis and high recurrence rate. Malnutrition is the most common problem in patients with EC before and after surgery, and it has gradually attracted people’s attention because of its important impact on the efficacy, prognosis and treatment of patients with EC. However, EC patients are often accompanied by malnutrition, and their low BMI is often one of the difficulties in the treatment. Here, we report a very low body weight patient with advanced EC treated with neoadjuvant chemoradiotherapy combined with surgery. Our case shows that very low body weight caused by malnutrition should not be a contraindication for surgical treatment, and combined treatment for EC remains to be popularized.

Comparative outcomes of patients with esophageal cancer undergoing single-port and four-port thoracoscopic esophagectomy: a single-center experience

2025-06-23

Xiaobo Chen , Yanan Bao , Yue Cui +5 more | Updates in Surgery

We aimed to compare the outcomes and postoperative complications of patients with esophageal cancer after single-port thoracoscopic esophagectomy (SPTE) and four-port thoracoscopic esophagectomy (FPTE). We retrospectively collected data from patients … We aimed to compare the outcomes and postoperative complications of patients with esophageal cancer after single-port thoracoscopic esophagectomy (SPTE) and four-port thoracoscopic esophagectomy (FPTE). We retrospectively collected data from patients who underwent surgery at the First Affiliated Hospital of Kunming Medical University from February 2019 to November 2022. In total, 86 patients were included in the SPTE group and 114 patients were included in the FPTE group. Compared to patients undergoing FPTE, significantly shorter postoperative hospital stay (13.54 ± 3.88 vs. 19.08 ± 5.09 days), shorter chest drainage time (6.06 ± 2.16 vs. 7.45 ± 1.68 days), lower estimated intraoperative blood loss (226.05 ± 94.87 vs. 363.16 ± 78.92 mL), and longer overall length of surgery (346.34 ± 53.86 vs. 332.89 ± 28.86 min) and longer length of abdominal surgery (183.46 ± 33.33 vs. 166.05 ± 22.07 min) were observed among patients undergoing SPTE; however, no significant difference was observed regarding 3-month, 6-month, and 12-month overall survival, time to start oral feeding, and length of thoracic surgery. Furthermore, postoperative intractable pain lasting for 3 months (39.5% vs. 21.0%), pneumonia (34.2% vs. 11.6%), empyema (14.9% vs. 3.5%), and chylothorax (10.5% vs. 2.3%) were significantly more frequent in the FPTE group, whereas postoperative gastrointestinal symptoms (41.9% vs. 23.7%) were significantly more frequent in the SPTE group. There was no significant difference between the groups regarding postoperative arrhythmia, recurrent laryngeal nerve injury, esophagotracheal fistula, second surgery, and intractable pain lasting for 6 and 12 months. Compared to FPTE, SPTE may improve patients' outcomes and prevent some of the major complications.

Prophylactic endoscopic pylorus dilatation prior to esophagectomy for esophageal cancer to prevent delayed gastric emptying, study protocol for a placebo-controlled randomized trial (PROPPER trial)

2025-06-23

Carolina Mann , Felix Berlth , Vladimir J. Lozanovski +7 more | Trials

Delayed gastric emptying (DGE) due to pyloric dysfunction remains a common postoperative complication after esophagectomy for cancer and can lead to severe secondary complications. As shown in a retrospective study, … Delayed gastric emptying (DGE) due to pyloric dysfunction remains a common postoperative complication after esophagectomy for cancer and can lead to severe secondary complications. As shown in a retrospective study, prophylactic EPBD performed 1 day before surgery can reduce the rate of postoperative DGE by reducing pyloric resistance. The objective of this study is to analyze the effect of prophylactic EPBD on postoperative DGE rates in patients receiving minimally invasive esophagectomy for cancer by gastric pull-up. This study is designed as a multicenter randomized controlled trial (RCT) including patients with esophageal cancer or cancer of the gastroesophageal junction (adenocarcinoma and squamous cell carcinoma, with or without neoadjuvant treatment) scheduled for minimally invasive esophagectomy with gastric pull-up. After randomization, patients will either receive preoperative EPBD or a sham intervention in the routine preoperative endoscopy performed 1 day before surgery. The primary endpoint of this study will be rates of DGE, particularly those resulting from pyloric dysfunction, requiring intervention. Secondary outcomes will be major and minor postoperative complication rates, in-hospital mortality, adverse events during gastroscopy, length of ICU and hospital stay as well as postoperative pain and quality of life. In order to detect a difference between both groups at a two-sided 5% significance level, to achieve a power of 0.8 with a calculated dropout rate of approximately 20%, a sample size of 118 patients with 59 patients in every study arm will be needed. The presented PROPPER trial is the first multicenter RCT that will provide evidence regarding the efficacy of preoperative EPBD in reducing DGE after minimally invasive esophagectomy for cancer. This trial was registered in the German Clinical Trials Register (DRKS), under the identifier DRKS00034360. Registered on May 29, 2024. The WHO trial registration data set can be found here: http://drks.de/search/en/trial/DRKS00034360 .

Identification and characterization of survival-dependent genes in esophageal cancer via the DepMap database: unraveling their association with immune infiltration

2025-06-22

Xiuzhong Yao , Jian He , Wentao Xiao +2 more | Discover Oncology

Abstract Background Esophageal cancer ranks as the 11th most diagnosed cancer worldwide and the 7th leading cause of cancer-related deaths, mainly due to late-stage diagnosis. Identifying novel biomarkers is essential … Abstract Background Esophageal cancer ranks as the 11th most diagnosed cancer worldwide and the 7th leading cause of cancer-related deaths, mainly due to late-stage diagnosis. Identifying novel biomarkers is essential for enhancing prognostic evaluations and targeting patients for immunotherapy. Methods We used the DepMap database to identify survival-dependent genes in esophageal carcinoma cells. A prognostic model was developed using univariate and multivariate Cox regression and LASSO, validated with the GEO dataset. WGCNA and GSEA analyses were conducted to explore mechanisms, alongside ESTIMATE and ssGSEA for prognosis. Results We constructed a novel four-gene prognostic signature (CPSF6, IGBP1, MTG2, TCP1) based on SDG expression and survival data. This signature stratified esophageal cancer patients into high- and low-risk groups with significantly different survival, with the high-risk group showing shorter survival. WGCNA and GSEA analyses linked prognosis to immune pathways, including interferon-γ response and IL6-JAK-STAT3 signaling. ssGSEA revealed reduced infiltration of 19 immune cell types in high-risk patients, and ESTIMATE analysis confirmed the association between immune infiltration and poor prognosis. Conclusion This study establishes a four-gene survival signature for esophageal cancer that distinguishes high-risk from low-risk populations, providing novel prognostic indicators. Immune response pathways were downregulated in high-risk patients, offering potential targets for understanding esophageal cancer mechanisms and developing immunotherapeutic strategies.

Long-Term Results of Single- and Multi-Incision Minimally Invasive Esophagectomy for Esophageal Cancer: Experience of 348 Cases

2025-06-21

Yung-Hsin Chen , Pei‐Ming Huang , Ke-Cheng Chen +1 more | Biomedicines

Importance: While minimally invasive esophagectomy is currently accepted as an effective treatment for patients with esophageal cancer, the long-term survival outcomes of single-incision minimally invasive esophagectomy in these patients are … Importance: While minimally invasive esophagectomy is currently accepted as an effective treatment for patients with esophageal cancer, the long-term survival outcomes of single-incision minimally invasive esophagectomy in these patients are still unknown, particularly when compared to those of the more invasive multi-incision minimally invasive esophagectomy. Objective: To determine the long-term oncological outcomes of single-incision minimally invasive esophagectomy in patients with esophageal cancer and to compare these outcomes with those of multi-incision minimally invasive esophagectomy. Design: This was a prospective, randomized, and propensity score-matched study wherein we analyzed patients who underwent treatment from February 2005 to May 2022. Setting: Our study was carried out by a single surgical team in a tertiary medical center. Participants: We analyzed 348 patients with esophageal cancer who underwent single-incision minimally invasive esophagectomy and 469 who underwent multi-incision minimally invasive esophagectomy. Main Outcomes and Measures: We aimed to determine the long-term survival outcomes of single-incision minimally invasive esophagectomy and compare these to those of multi-incision minimally invasive esophagectomy in our study population, and further conducted a propensity score-matching (n = 251 in each arm) study. Results: The disease progression-free (DFS) and overall survival (OS) rates of patients who underwent single-incision minimally invasive esophagectomy (SIMIE) was significantly better than that of those who underwent by multi-incision minimally invasive esophagectomy (MIMIE) (p = 0.024 for OS and p = 0.027 for PFS). This trend of difference was observed in the subsequent propensity-score matching analysis (p = 0.009 and 0.016 for OS and PFS, respectively). Conclusions and Relevance: The single-incision technique applied in minimally invasive esophagectomy to treat esophageal cancer is feasible without compromising the patient’s long-term oncological outcome, as opposed to that applied using multi-incision minimally invasive esophagectomy.

Artificial intelligence-based marks detection and incision guide line prediction model in esophageal endoscopic submucosal dissection: a multicenter study (with video)

2025-06-20

Ruide Liu , Xianglei Yuan , Kaide Huang +7 more | Surgical Endoscopy

Clinical efficacy of different neoadjuvant therapies for resectable esophageal squamous cell carcinoma

2025-06-20

Xiaoyang Wang , Danxia Wen , Huiting Feng +1 more | World Journal of Surgical Oncology

This study aims to evaluate the clinical efficacy of neoadjuvant chemoradiotherapy (NCRT), neoadjuvant chemotherapy (NCT), and neoadjuvant CT plus immunotherapy (NICT) in locally advanced esophageal squamous cell carcinoma (ESCC). 175 … This study aims to evaluate the clinical efficacy of neoadjuvant chemoradiotherapy (NCRT), neoadjuvant chemotherapy (NCT), and neoadjuvant CT plus immunotherapy (NICT) in locally advanced esophageal squamous cell carcinoma (ESCC). 175 treatment-naïve patients with ESCC (clinical stage II-IV) undergoing neoadjuvant therapy were included. Clinical data were systematically extracted from institutional electronic health records, including pre/post-treatment TNM staging, treatment-related adverse events, and oncologic outcomes. The categories were compared for quantitative variables using a one-way ANOVA and the chi-square test of variance. A t-test was used for comparison of continuous variables, and categorical variables were compared by a χ2 test or Fisher's exact test. Kaplan-Meier survival analysis was performed to generate curves, with intergroup comparisons conducted by the log-rank test. All enrolled 175 patients underwent esophagectomy at Meizhou People's Hospital between March 2020 and March 2024. Significant downstaging was observed in both postoperative T stages (t=-11.451, P < 0.001) and N stages (t=-10.272, P < 0.001) compared to baseline. Intergroup analysis revealed distinct therapeutic profiles. The NICT group demonstrated reduced postoperative nerve injury incidence compared to other modalities (χ²=7.811, P = 0.020), while no significant differences were observed in lymphovascular invasion rates or circumferential resection margins. Lymph node dissection analysis showed superior nodal yield in the NICT group versus NCRT (F = 4.88, P = 0.009), with correspondingly fewer metastatic lymph nodes in the NICT cohort compared to NCT alone (F = 4.256, P = 0.016). Notably, NCRT was associated with significantly longer neoadjuvant-to-surgery intervals compared to both NCT and NICT groups (F = 12.39, P < 0.001). No significant differences in recurrence rates were observed across treatment modalities during follow-up (χ²=0.530, P = 0.768). With a 28.5-month median follow-up, survival significantly differed between groups (log-rank p = 0.048). NICT had superior overall survival (median not reached vs. 31.2 months in NCRT and 34.5 months in NCT), with 2-year rates of 76.2%, 68.9%, and 63.3%, respectively. NCRT, NCT, and NICT demonstrated effective tumor downstaging and surgical outcomes in locally advanced ESCC patients. Differences in surgical outcomes and adverse events highlight the potential benefits and considerations of combining immunotherapy with conventional treatments in this cohort.

Current advances and challenges in minimally invasive esophagectomy

2025-06-19

E. Booka , Hiroya Takeuchi | International Journal of Clinical Oncology

ModFusion: Modality feature representation and hierarchical fusion for esophageal lesions segmentation

2025-06-19

Keyu Chen , Zhiyou Yang , Ma Luo +5 more | Knowledge-Based Systems

Evaluation of Spectral Imaging for Early Esophageal Cancer Detection

2025-06-19

Li‐Jen Chang , Chu‐Kuang Chou , Arvind Mukundan +5 more | Cancers

Objective: Esophageal carcinoma (EC) is the eighth most prevalent cancer and the sixth leading cause of cancer-related mortality worldwide. Early detection is vital for improving prognosis, particularly for dysplasia and … Objective: Esophageal carcinoma (EC) is the eighth most prevalent cancer and the sixth leading cause of cancer-related mortality worldwide. Early detection is vital for improving prognosis, particularly for dysplasia and squamous cell carcinoma (SCC). Methods: This study evaluates a hyperspectral imaging conversion method, the Spectrum-Aided Vision Enhancer (SAVE), for its efficacy in enhancing esophageal cancer detection compared to conventional white-light imaging (WLI). Five deep learning models (YOLOv9, YOLOv10, YOLO-NAS, RT-DETR, and Roboflow 3.0) were trained and evaluated on a dataset comprising labeled endoscopic images, including normal, dysplasia, and SCC classes. Results: Across all five evaluated deep learning models, the SAVE consistently outperformed conventional WLI in detecting esophageal cancer lesions. For SCC, the F1 score improved from 84.3% to 90.4% in regard to the YOLOv9 model and from 87.3% to 90.3% in regard to the Roboflow 3.0 model when using the SAVE. Dysplasia detection also improved, with the precision increasing from 72.4% (WLI) to 76.5% (SAVE) in regard to the YOLOv9 model. Roboflow 3.0 achieved the highest F1 score for dysplasia of 64.7%. YOLO-NAS exhibited balanced performance across all lesion types, with the dysplasia precision rising from 75.1% to 79.8%. Roboflow 3.0 also recorded the highest SCC sensitivity of 85.7%. In regard to SCC detection with YOLOv9, the WLI F1 score was 84.3% (95% CI: 71.7-96.9%) compared to 90.4% (95% CI: 80.2-100%) with the SAVE (p = 0.03). For dysplasia detection, the F1 score increased from 60.3% (95% CI: 51.5-69.1%) using WLI to 65.5% (95% CI: 57.0-73.8%) with SAVE (p = 0.04). These findings demonstrate that the SAVE enhances lesion detectability and diagnostic performance across different deep learning models. Conclusions: The amalgamation of the SAVE with deep learning algorithms markedly enhances the detection of esophageal cancer lesions, especially squamous cell carcinoma and dysplasia, in contrast to traditional white-light imaging. This underscores the SAVE's potential as an essential clinical instrument for the early detection and diagnosis of cancer.

Decreasing Complications After Ivor‐Lewis Esophagectomy: Is a Totally Minimally Invasive Approach the Solution?

2025-06-18

Parit T. Mavani , Caitlin Sok , Pranay S. Ajay +7 more | Journal of Surgical Oncology

ABSTRACT Background Despite improvements over time, Ivor Lewis Esophagectomy (ILE), a potentially curative surgical option for patients with invasive esophageal cancer, carries high morbidity and mortality. We analyzed postoperative outcomes … ABSTRACT Background Despite improvements over time, Ivor Lewis Esophagectomy (ILE), a potentially curative surgical option for patients with invasive esophageal cancer, carries high morbidity and mortality. We analyzed postoperative outcomes in patients undergoing ILE at our institution, comparing open (OE), hybrid (HE), and totally minimally invasive (TMIE) approaches. Methods We reviewed the records of patients who underwent elective ILE for benign or malignant pathology at our institution (2018–2022). Patients who underwent transhiatal or McKeown esophagectomy, as well as those undergoing emergent procedures, were excluded. Factors associated with major postoperative complications (Clavien‐Dindo Grade ≥ 3) were assessed using multivariable analysis (MVA). Results Of 260 patients, 135 met the inclusion criteria: 40 (29.6%) underwent OE, 50 (37.0%) underwent HE, and 45 (33.3%) underwent TMIE. Median length of stay was shorter for patients undergoing TMIE compared to OE and HE (9 vs. 12 and 13 days, p < 0.001). A higher major postoperative complication rate was noted in patients undergoing OE and HE compared to TMIE (32.5% and 36% vs. 13.3%) ( p = 0.03). This result persisted on MVA (OE: aOR 3.4, p = 0.04; HE: aOR 5.5, p = 0.002; reference:TMIE). Conclusion A totally minimally invasive approach to Ivor‐Lewis Esophagectomy is associated with lower major postoperative complications and shortened length of stay at our institution. Prospective evaluations in the United States population are warranted to optimize and standardize surgical approaches.

Clinical efficacy and biomarkers of neoadjuvant chemoimmunotherapy in locally advanced esophageal squamous cell carcinoma

2025-06-18

Siyou Deng , Qi Wang , Yueping Li +7 more | Cancer Immunology Immunotherapy

Neoadjuvant immunotherapy has emerged as a promising strategy for treating esophageal squamous cell carcinoma (ESCC). This study evaluates the therapeutic efficacy and safety of neoadjuvant immunochemotherapy (nICT) in ESCC and … Neoadjuvant immunotherapy has emerged as a promising strategy for treating esophageal squamous cell carcinoma (ESCC). This study evaluates the therapeutic efficacy and safety of neoadjuvant immunochemotherapy (nICT) in ESCC and explores potential biomarkers associated with treatment outcomes. Patients with locally advanced ESCC were enrolled and received two cycles of nICT followed by surgical resection. The primary endpoint was the pathological complete response rate, while secondary endpoints included overall survival (OS), event-free survival (EFS), safety, and the identification of predictive biomarkers. A total of 47 patients were enrolled in the study, with 42 undergoing surgical resection, all of whom achieved R0 resection. The rates of complete and partial pathological responses were 28.5% and 16.7%, respectively. The 1-year and 2-year EFS rates were 82% and 37.3%, while OS rates were 100% and 71.4%, respectively. The majority of treatment-related adverse events were Grade 1-2, and no surgical delays were observed. RNA sequencing analysis identified epithelial-mesenchymal transition as the most significantly enriched pathway in non-responders. Notably, higher infiltration of normal fibroblasts was associated with improved pathological response and enhanced long-term survival, while myofibroblastic cancer-associated fibroblasts (myCAF) negatively impacted treatment efficacy and clinical outcomes. Neoadjuvant PD-1 inhibitors combined with chemotherapy show promising potential for patients with locally advanced ESCC, inducing a robust immune response that correlates with clinical outcomes. The infiltration of myCAF emerges as a potential predictive biomarker for treatment response and disease progression, underscoring the need for further mechanistic exploration and validation in larger cohorts.

Endoscopic mucosal resection for Barrett’s neoplasia: Long-term outcomes from the largest Canadian single-center experience

2025-06-17

Yusuke Fujiyoshi , Kareem Khalaf , Daniel Kai Long Tham +7 more | Endoscopy International Open

Abstract Endoscopic mucosal resection (EMR) remains an important treatment for high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) in Barrett’s esophagus (BE). However, there are limited data regarding long-term recurrence … Abstract Endoscopic mucosal resection (EMR) remains an important treatment for high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) in Barrett’s esophagus (BE). However, there are limited data regarding long-term recurrence rates. This study aimed to investigate the neoplasia recurrence rate following EMR with long-term follow-up. This was a retrospective cohort study at a tertiary-referral center in Canada. Patients with Barrett’s neoplasia (HGD/EAC) treated with EMR between January 2001 and December 2023 were included. The primary outcome was long-term neoplasia recurrence rate after complete remission of neoplasia (CRN). Secondary outcomes were residual/metachronous neoplasia rate at first follow-up, CRN rate, and long-term rate of patients successfully managed by endoscopy. A total of 552 patients (83.7% male, mean age 66.3 years) were included (HGD: 22.5%, EAC: 77.5%). After EMR, 475 patients were deemed to have had successful endoscopic resection (low lymph-node metastasis risk with tumor-free deep margin), 455 of whom underwent surveillance follow-up. At first follow-up, residual/metachronous neoplasia was observed in 20.9% (95/455), but 95.6% (435/455) eventually achieved CRN after undergoing a median of two EMR sessions (interquartile range: 1–4). As a primary outcome, the 5-year neoplasia recurrence rate was 10.5%, the 10-year rate was 21.6%, and the 15-year rate was 34.9%. During surveillance, neoplasia recurrence was observed in 38 patients, but 68.4% of them (26/38) were managed with endoscopic therapy. The overall rate of patients successfully managed by endoscopy was 93.0% (423/455). While the success rate of EMR for BE is excellent, this study highlights substantial long-term risk of neoplastic recurrence, underscoring the need for indefinite surveillance for patients who had HGD or EAC.

Surgical Timing and Outcomes in Esophageal Cancer: Insights from One- and Two-Stage Esophagectomies in a Polish Cohort

2025-06-17

Bartłomiej Strzelec , Piotr Paweł Chmielewski , Wojciech Kielan +1 more | Journal of Clinical Medicine

Objectives: Esophagectomy is a central component of surgical treatment for esophageal cancer, with both one- and two-stage procedures frequently employed. However, these procedures are associated with a high rate of … Objectives: Esophagectomy is a central component of surgical treatment for esophageal cancer, with both one- and two-stage procedures frequently employed. However, these procedures are associated with a high rate of postoperative complications. This study aimed to assess the rates and types of complications following one- and two-stage esophagectomies, and to identify predictors of adverse outcomes in patients with esophageal cancer. Methods: We analyzed clinical data from patients undergoing one-stage (Ivor Lewis) or two-stage esophagectomies. Postoperative complications were defined as events occurring within 30 days after surgery. Variables such as patient demographics, clinical staging, histological tumor grade, and neoadjuvant chemoradiotherapy were assessed for their association with complications. Statistical analyses included logistic regression and chi-squared tests. Results: Among 61 patients, postoperative complications occurred in 24.6% of cases. The most frequent were pneumonia (22.2%), anastomotic leakage (22.2%), and hemothorax (27.8%). Significant predictors of complications included intraoperative disease staging, histological tumor grade, and the use of neoadjuvant chemoradiotherapy. The odds ratio for complications following neoadjuvant chemoradiotherapy was 8.75. The frequency of anastomotic leakage was similar in one- and two-stage procedures (30.8% vs. 26.3%, respectively). Conclusions: Postoperative complications remain a significant challenge in esophageal cancer surgery, particularly in the context of advanced disease or neoadjuvant chemoradiotherapy. These findings underscore the necessity for precise surgical planning and comprehensive postoperative care to mitigate risks and optimize patient outcomes. While postoperative risk is high, it is primarily driven by tumor characteristics and preoperative therapy.

Effective surgical conversion after neoadjuvant immunochemotherapy improves clinical outcomes in borderline resectable esophageal cancer

2025-06-17

Benhua Xu , Chengcheng Zhang , Tao Luo +5 more | Research Square (Research Square)

<title>Abstract</title> <bold>Background</bold>: Immune checkpoint inhibitors have demonstrated preliminary safety and efficacy in treating borderline resectable esophageal squamous cell carcinoma (BR-ESCC). We aimed to compare treatment and survival outcomes between patients … <title>Abstract</title> <bold>Background</bold>: Immune checkpoint inhibitors have demonstrated preliminary safety and efficacy in treating borderline resectable esophageal squamous cell carcinoma (BR-ESCC). We aimed to compare treatment and survival outcomes between patients with locally advanced resectable ESCC (cT3r) and those with borderline resectable ESCC (cT3br) who underwent surgery following neoadjuvant immunochemotherapy (NICT). <bold>Methods</bold>: After NICT, 12 patients in the cT3br group were deemed unresectable, while 102 patients with clinically staged T3 ESCC underwent surgery and were included in the study. Patients were categorized into cT3r and cT3br groups based on the likelihood of adjacent vital organ invasion as observed on pre-treatment CT scans. <bold>Results</bold>: Among the participants, 52 patients were included in the cT3br group and 62 in the cT3r group. The surgical conversion rate for cT3br tumors was 76.9% (40/52). Both groups exhibited comparable outcomes in terms of surgical treatment and postoperative complications (<italic>P </italic>> 0.05). Although the non-R0 resection rate was significantly higher in the cT3br group than in the cT3r group (20.0% vs 3.2%, <italic>P </italic>= 0.005), no significant differences were observed in postoperative overall survival (OS) or disease-free survival (DFS) between the two groups (3-year OS: 76% vs 67%, <italic>P </italic>= 0.453; 3-year DFS: 69% vs 47%, <italic>P </italic>= 0.155). Non-R0 resection was significantly associated with worse OS (<italic>P </italic>= 0.001) and showed a trend toward association with DFS (<italic>P </italic>= 0.069). <bold>Conclusion</bold>: Surgery following NICT is an effective treatment strategy for BR-ESCC, achieving treatment outcomes and survival prognoses comparable to those in patients with cT3r.

Additional chemoradiotherapy following endoscopic submucosal dissection in patients with esophageal squamous cell carcinoma: a narrative review

2025-06-16

Yan Lin , Shoufeng Wang , Huan-Wei Liang +3 more | Frontiers in Oncology

This review offers a critical synthesis of additional therapeutic strategies following endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma, providing evidence-based recommendations to optimize clinical decision-making. For pT1a-EP/LPM lesions, … This review offers a critical synthesis of additional therapeutic strategies following endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma, providing evidence-based recommendations to optimize clinical decision-making. For pT1a-EP/LPM lesions, ESD alone demonstrates curative potential with lymph node metastasis rates ranging from 0.0% to 3.3%. In contrast, pT1b-MM tumors exhibiting lymphovascular invasion warrant adjuvant chemoradiation therapy, associated with 21.4% nodal metastasis rates. For pT1b-SM1 lesions, chemoradiation is indicated-particularly demonstrating 13.2% nodal involvement without lymphovascular invasion versus 60.0% metastasis risk in cases with vascular invasion during observation. Timing of additional chemoradiotherapy should be expedited, with immediate initiation (1–2 months post-ESD) showing superior outcomes. Radiation dosing optimization reveals equivalent efficacy between lower radiation doses (40-41.4 Gy) and higher doses (50-50.4 Gy), with reduced treatment-related toxicity. Target volume delineation should prioritize the ESD bed with appropriate margins over elective nodal coverage, maintaining therapeutic efficacy while minimizing radiation exposure. The role of concurrent chemotherapy remains controversial, with retrospective evidence suggesting definitive radiotherapy may provide comparable local control.

Comparison of recurrence patterns between patients with thoracic esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and postoperative adjuvant chemoradiotherapy

2025-06-16

Kunhan Ni , Yixuan Huang , Simiao Lu +7 more | Frontiers in Oncology

Purpose To compare the recurrence patterns and survival outcomes between patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (NCRT) and adjuvant chemoradiotherapy (ACRT). Methods We retrospectively analyzed … Purpose To compare the recurrence patterns and survival outcomes between patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (NCRT) and adjuvant chemoradiotherapy (ACRT). Methods We retrospectively analyzed 267 patients with locally advanced ESCC who received treatment at Sichuan Cancer Hospital and Institute (Chengdu, China) between January 2018 and December 2020. Based on different treatment protocols, the patients were divided into two groups: NCRT (n=181) and ACRT (n=86). After propensity score matching, each group included 74 patients. This study compared the recurrence types, sites, frequencies, and timing, as well as overall survival (OS), disease-free survival (DFS), and prognostic risk factors between the two groups. Results The recurrence rates in the NCRT and ACRT groups were 59.5% (44/74) and 33.8% (25/74), respectively; the difference was statistically significant (P=0.002). Recurrences primarily occurred within 2 years following esophagectomy. The ACRT group had a higher 3-year OS rate than the NCRT group (67.8% versus [vs.] 50.6%, respectively; P=0.019). In the subgroup of patients with local recurrence, the 3-year OS rate was higher in the NCRT group compared to the ACRT group (53.8% vs. 0%, respectively; P=0.029). In terms of DFS, the ACRT group exhibited better results than the NCRT group (P&lt;0.001). Multivariate analysis revealed that pathological N staging was an independent risk factor affecting the OS prognosis of patients in the NCRT group. Margin status and pathological T staging were identified as independent risk factors influencing OS in the ACRT group, while sex and treatment regimen were independent risk factors affecting DFS in patients with postoperative pathological lymph node positivity. Conclusion There was significant difference in the OS and DFS prognosis of patients with ESCC treated with NCRT and ACRT. Recurrence primarily occurs within 2 years following esophagectomy. The recurrence rate was higher in the NCRT group compared to the ACRT group. Patients with early recurrence had a poorer survival prognosis compared to those with late recurrence. Pathological N staging was identified as an independent risk factor affecting OS in the NCRT group. Furthermore, margin status and pathological T staging were independent risk factors influencing OS in the ACRT group.

Texture and Colour Enhancement Imaging (TXI) versus White Light Endoscopy for Detection of Dysplasia Within Barrett’s Esophagus: a Pilot Study

2025-06-16

Edward J. Young , Hamish Philpott , Rajvinder Singh | Digestion

Introduction: Esophageal cancer is a leading global health issue, with increasing prevalence of esophageal adenocarcinoma and its precursor lesion, Barrett’s esophagus (BE). Despite the opportunity to treat dysplasia prior to … Introduction: Esophageal cancer is a leading global health issue, with increasing prevalence of esophageal adenocarcinoma and its precursor lesion, Barrett’s esophagus (BE). Despite the opportunity to treat dysplasia prior to adenocarcinoma development, rates of missed advanced dysplasia at BE surveillance remain high. This pilot study aimed to assess whether Texture and Colour Enhancement Imaging (TXI), a new advanced mucosal imaging modality, improves dysplasia detection during BE surveillance compared to white light endoscopy (WLE). Methods: Patients undergoing endoscopy for BE assessment or surveillance at a single centre were included for analysis. Patients were randomized in a 1:1 ratio to examination with WLE then TXI or vice versa, followed by Narrow-Band Imaging (NBI). Targeted biopsies were taken from any suspicious areas and 4-quadrant surveillance biopsies were taken at 1cm intervals in the entire BE segment. Results: A total of 50 patients were included in the study, with 27 suspicious lesions seen in 22 patients. 93.3% (n=14/15) of high-grade dysplasia or early adenocarcinoma was detected as endoscopically visible lesions on TXI and NBI. However, 4 such lesions were not detected on WLE. On per-patient analysis, the sensitivity and NPV of TXI in combination with magnified NBI were both 100% with specificity of 84.6%, surpassing all PIVI thresholds for dysplasia diagnosis in BE. Conclusion: This pilot study demonstrates the feasibility of TXI as a potential addition to the armamentarium of advanced mucosal imaging available to proceduralists surveilling Barrett’s Esophagus. Further large multi-centre studies would be required to make statistical comparisons with existing imaging modalities.

Twenty-four-hour pH monitoring of gastric conduit in post-esophagectomy patients: correlation with clinical and endoscopic parameters in a prospective cohort study from India

2025-06-15

Vishu Jain , Vaibhav Kumar Varshney , Subhash Soni +5 more | Daehan nae'si'gyeong bog'gang'gyeong oe'gwa haghoeji/Journal of minimally invasive surgery

Esophagectomy for malignancy leads to decreased gastric conduit acidity due to bilateral vagotomy and fundic gland area reduction. However, reflux symptoms occur. The changes in pH of gastric conduit and … Esophagectomy for malignancy leads to decreased gastric conduit acidity due to bilateral vagotomy and fundic gland area reduction. However, reflux symptoms occur. The changes in pH of gastric conduit and esophageal remnant post-esophagectomy were studied and correlated clinically, endoscopically and with Helicobacter pylori positivity. We studied 20 patients prospectively undergoing esophagectomy for malignancy from January 2022 to December 2023. The patients underwent pre- and postoperative clinical assessment, 24-hour pH monitoring, and esophagoduodenoscopy with H. pylori testing and analysis. Postoperatively, the total percent (%) time pH <4 was nonsignificantly increased to 17.95% (p = 0.754) in the esophageal remnant and significantly decreased to 53.5% (p = 0.012) in the stomach. Postoperatively, the H. pylori-positive patients had a non-significantly higher total % time pH <4 in the esophageal remnant than H. pylori-negative patients (29.47 ± 33.54 vs. 6.44 ± 11.58, p = 0.064) and slightly lower total % time pH <4 in the stomach (53.30 ± 46.08 vs. 53.71 ± 31.20, p = 0.982). The total % time pH <4 in the gastric conduit was significantly correlated with the esophageal remnant (p = 0.002), showing a correlation coefficient of 0.629. There is a significant increase in gastric conduit pH post-esophagectomy with increased exposure to the esophageal remnant mucosa proportional to gastric acidity. H. pylori infection does not affect gastric aciditiy and acid reflux after esophagectomy.

Robot-assisted minimally invasive esophagectomy in patients with esophageal cancer: an update on experiences from a tertiary cancer care center in India

2025-06-15

Rajnish Nagarkar , Vikas Jain , Nayana Kulkarni +2 more | Daehan nae'si'gyeong bog'gang'gyeong oe'gwa haghoeji/Journal of minimally invasive surgery

Robot-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancers, has gained traction in the last decade due to its positive surgical outcomes. The present study is an update to our earlier … Robot-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancers, has gained traction in the last decade due to its positive surgical outcomes. The present study is an update to our earlier published data, in which we discuss the new developments in terms of perioperative and postoperative outcomes of our patients. This is a single-center, retrospective data of patients who underwent RAMIE for esophageal cancers between January 2020 to October 2024 at a tertiary cancer center in India. A total of 52 patients have undergone RAMIE at our center to date. The median age of the cohort was 56.02 ± 11.69 years, with a slight male predominance (n = 29, 55.77%). Majority of the patients were of American Society of Anesthesiologists physical status classification II (n = 40, 76.92%), Eastern Cooperative Oncology Group status 1 (n = 35, 67.30%), with no comorbidities (n = 36, 69.23%), and presented with stage 2 disease (n = 21, 40.37%). Squamous cell carcinoma was the predominant histological subtype (n = 31, 59.62%). The median operative time was 111.6 (range, 60-180) minutes with a median lymph node harvest of 12 (range, 7-24). The median intensive care unit stay was 2 (range, 2-5) days, and the median total hospital stay was 6 (range, 3-9) days. No major postoperative complications were observed. The 30-day mortality rate was reported in two patients (3.85%). The results of our research indicate that RAMIE may serve as a safe and effective surgical option for esophageal cancers, leading to improved perioperative and postoperative outcomes.

Evaluation of the efficacy and safety of salvage photodynamic therapy with talaporfin sodium for lesions beyond those indicated for investigator-initiated clinical trials

2025-06-15

Nobuhito Ito , Kohei Funasaka , Kazuhiro Furukawa +7 more | Esophagus

Lymph node metastasis and treatment outcomes of endoscopic submucosal dissection for superficial spreading esophageal squamous cell carcinoma ≥ 50 mm in size

2025-06-15

Satoshi Masuda , Yuji Urabe , Yoshiki Hatsushika +7 more | Esophagus

ASO Author Reflections: Postoperative Recurrence of Clinical Stage I Esophageal Cancer: a Call for Optimal Postoperative Follow-Up

2025-06-14

Takeo Bamba , Ken Kato , Hiroyuki Daiko +7 more | Annals of Surgical Oncology

Prognostic Impact of Thoracic Extra-regional Lymph Node Metastasis Defined By the 12th Japanese Classification Following Definitive Radiotherapy for Esophageal Squamous Cell Carcinoma

2025-06-14

Masahiro Inada , Kiyoshi Nakamatsu , Junki Fukuda +6 more | Journal of Gastrointestinal Cancer

Abstract P3-03-16: Molecular stromal signature to predict Ductal Carcinoma in Situ (DCIS) progression

2025-06-13

Niki Prekete , Michael D. Allen , Eleni Maniati +1 more | Clinical Cancer Research

Abstract Ductal Carcinoma in Situ (DCIS) is a pre-invasive breast carcinoma, where the cancer cells proliferate within the breast duct. Because the ducts are not connected to the circulatory or … Abstract Ductal Carcinoma in Situ (DCIS) is a pre-invasive breast carcinoma, where the cancer cells proliferate within the breast duct. Because the ducts are not connected to the circulatory or the lymphatic system, DCIS does not constitute a lethal disease. Due to the implantation of the mammographic screening programme, the percentage of women diagnosed with DCIS is increasing. These women who are diagnosed with DCIS are currently treated as if they were going to progress to invasive cancer, as there is no way to predict the progression of the disease and stratify patient treatment. Analysis of the neoplastic cells of DCIS has not revealed genetic changes linked to the risk of progression, the scientific interest has been turned to the tumour microenvironment. This study hypothesised that changes that take place in the stromal compartment surrounding DCIS ducts can promote the invasive capacity of the carcinoma and as a result promote the progression from DCIS to invasive disease. The study aimed to discover alterations in the stromal area of normal, pure DCIS and invasive carcinomas that may indicate risk of future progression and create a signature to distinguish the progressive and the non-progressive DCIS. A cohort of four patients with matched clinicopathological characteristics who were previously diagnosed with invasive breast cancer and did not have neoadjuvant treatment was selected. RNA sequencing was performed on samples from the invasive, DCIS and normal breast areas of these patients (n=12). Although the samples contained the whole tissue, they were selected to represent more the microenvironmental compartment of each disease stage. The analysis of the RNA sequencing samples led to the identification of 50 genes, that showed a stepwise increase (n=18) or decrease (n=32) in expression from normal, pure DCIS or invasive cases. The majority of the pathways and processes the genes of the signature involved were connected to elements of the microenvironment, such as collagen degradation and crosslinking, avβ3 integrin, and biological processes including T-cell activation. Interestingly, the RNA sequencing results in these whole tissue samples showed a much higher number of differentially expressed genes between the Invasive Tumour vs DCIS comparison than in the DCIS vs Normal comparison suggesting that the whole tissue DCIS is more similar to the Surround than in the invasive tumour disease stage. Gene targets; FN1, VCAN and MMP11 were validated through Immunohistochemistry or RNAScope in an external sample cohort comprised of normal, pure DCIS and DCIS with invasion cases. Finally, the genes were combined in a signature and an in silico analysis of public datasets that included independent normal, DCIS and invasive cases from patients also validated our polygenic risk score. This study has managed to identify a panel of genes showing altered expression between normal, pure DCIS and invasive cancer tissues. The results emphasised the importance of the tumour microenvironment in disease progression. The findings were then combined in a multigene signature associated with prognosis and risk of progression on public datasets. Citation Format: Niki Prekete, Michael Allen, Eleni Maniati, Louise Janet Jones. Molecular stromal signature to predict Ductal Carcinoma in Situ (DCIS) progression [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-03-16.

Abstract P2-05-27: Revealing prognostic subtypes and related model of early-stage TNBC

2025-06-13

Haixing Shen , Qing Chen , Jing Zhang +7 more | Clinical Cancer Research

Abstract Background: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Effective approach stratifying the risk of recurrence for early-stage TNBC patients is still lacking. This study … Abstract Background: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Effective approach stratifying the risk of recurrence for early-stage TNBC patients is still lacking. This study aims to explore the molecular heterogeneity of early-stage TNBC yielding a practical tool evaluating the risk of disease recurrence. Methods: This retrospective study included stage I-III TNBC patients treated at our institution between December 2013 and December 2019. RNA sequencing was performed on surgical samples, and correlations were analyzed with clinical data and prognosis. Results: A total of 240 patients were included, with a median follow-up of over 5 years. Patients were categorized into two cohorts: recurrence-free within 3 years post-surgery (good prognosis, n=203) and recurrence within 3 years (bad prognosis, n=34). Differential gene analysis revealed 423 up-regulated and 1,818 down-regulated genes in patients with good prognosis. Consensus cluster analysis identified three clusters (C1, C2, C3). C1 had the worst prognosis for DFS (p=0.020) and OS (p=0.055). Further analysis of the three groups' characteristics showed that C1 patients exhibited significant upregulation of angiogenesis, hypoxia, and glycolysis signals. Differential gene analysis indicated that NOX1, HNF1A, CXCL8, TGFBI, and NT5E (CD73) were significantly upregulated in C1 patients. This suggests that tumors in these patients might create a hypoxic microenvironment through NOX1 upregulation, promoting glycolysis and adenosine metabolism, which in turn stimulates ATP and lactate release, angiogenesis, and immune evasion, creating a tumor growth-promoting microenvironment. Given the notably shorter DFS in this group, therapies targeting angiogenesis or CD73 may improve clinical outcome of C1 patients. C2 patients showed enrichment of canonical oncogenic pathways like WNT, NOTCH signaling. C3 patients displayed pro-inflammatory tumor microenvironment with elevated IFN-γ signatures. Additionally, potential infiltration of activated dendritic cells, activated CD8+ T cells, CD4+ T cells, and plasma cell signature (IGHV1OR15-2, IGKV1D-43, IGHV2-26) were observed in the C3 group. This deconvoluted estimation of TME indicated the presence of matured tertiary lymphoid structures (TLS) in the C3 group. Eight subtype and prognosis related genes (ABCD2, ACSM3, ADCYAP1, ADM, CXCL13, GLO1, PIGR, RRP8) were selected. A prognostic prediction model was constructed, categorizing patients into high-risk and low-risk groups. In the training set (n=166), high-risk patients had significantly lower OS than low-risk patients (P&lt;0.0001), with an AUC of 0.874 for predicting 3-year recurrence. The validation set (n=71) showed an AUC of 0.844, with high-risk patients having significantly lower OS (P&lt;0.0001). External validation with the GSE103191 dataset showed an AUC of 0.761 for predicting 3-year survival. Conclusions: This study disclosed novel molecular subtypes with prognostic and therapeutic significance. A subtype-derived prognostic model was also constructed and validated to stratify recurrence risk for early-stage TNBC patients. Further validation via multi-center study was warranted. Citation Format: Haixing Shen, Qing Chen, Jing Zhang, Shuqian Wang, Jing Zhao, Changbin Zhu, Xiaotian Zhang, Xing Li, Tianze Yu, Jinfei Ma, Yanyuan Li, Peifen Fu. Revealing prognostic subtypes and related model of early-stage TNBC [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-05-27.

Integration of machine learning in biomarker discovery for esophageal squamous cell carcinoma: Applications and future directions

2025-06-13

Wanli Yang , Lili Duan , Xinhui Zhao +4 more | Pathology - Research and Practice

Abstract P4-11-10: Long-term Outcome of Slowly Proliferating Luminal Type ILC versus IDC

2025-06-13

Ji Won Yoo , Jai Min Ryu , Se Kyung Lee +5 more | Clinical Cancer Research

Abstract Introduction: Invasive lobular carcinoma (ILC) ranks as the second most common histopathological subtype of breast cancer, following invasive ductal carcinoma (IDC). Prior studies have demonstrated that while ILC patients … Abstract Introduction: Invasive lobular carcinoma (ILC) ranks as the second most common histopathological subtype of breast cancer, following invasive ductal carcinoma (IDC). Prior studies have demonstrated that while ILC patients initially exhibit better survival rates within the first 5 years, their long-term outcomes are comparable to, or worse than, those of IDC patients. However, the lower prevalence of ILC relative to IDC and their distinct clinicopathological characteristics complicate direct comparisons between the two groups. This study aims to evaluate the long-term outcomes of luminal type A IDC versus ILC. Methods: This retrospective cohort study analyzed data from January 2008 to December 2015 at Samsung Medical Center. The study included patients with patients with primary breast cancer who underwent surgery and were histologically diagnosed with either IDC or ILC, were hormone receptor-positive, HER2-negative, and had a Ki-67 index ≤20. Patients with mixed histopathology, those undergoing palliative surgery, and those treated with neoadjuvant chemotherapy were excluded. Cohort analyses were performed in various subsets: real-world setting, patients receiving more than 2 years of endocrine therapy, and propensity score-matched cohorts. Results: In the real-world setting, of the 3439 patients, 3156 had IDC and 283 had ILC. With a median follow-up of 110 months (range 0-195 and 1-190 months, respectively), ILC patients exhibited worse long-term outcomes. Although breast cancer-specific survival (BCSS) did not show a significant difference (p=0.081), analysis by 5-year periods indicated significantly poorer survival for ILC patients beyond 5 years (5 to 10 years, p=0.004; 10 to 15 years, p=0.014). Disease-free survival (DFS) and distant metastasis-free survival (DMFS) were significantly worse in the ILC group (p&lt;0.001 and p=0.005, respectively). In the second analysis, excluding patients with less than 2 years of endocrine therapy, 2919 IDC and 269 ILC patients remained. With median follow-ups of 112 months (range 17-195 months) and 110 months (range 19-190 months) respectively, the ILC group showed poorer long-term DFS and DMFS (p&lt;0.001 and p=0.007, respectively). However, the ILC group exhibited a significantly higher incidence of synchronous contralateral breast cancer, pathologic T and N stages, and a lower nuclear grade compared to the IDC group (p&lt;0.001, p&lt;0.001, p=0.040, p&lt;0.001, respectively). The third analysis used propensity score matching to control for confounding variables, including age, BMI, menopausal status, BRCA status, synchronous contralateral breast cancer, pathologic T and N stages, TNM stage, nuclear grade, histologic grade, adjuvant chemotherapy, and duration of endocrine therapy. In this analysis, long-term survival outcomes did not significantly differ between groups (BCSS p=0.248, DFS p=0.265, DMFS p=0.429). Conclusion: The study reveals that in the real-world setting, the long-term outcomes of ILC are worse compared to IDC. However, when adjusted for clinicopathological parameters, the long-term outcomes of ILC do not significantly differ from those of IDC. Citation Format: Ji Won Yoo, Jai Min Ryu, Se Kyung Lee, Byung Joo Chae, Jonghan Yu, Seok Won Kim, Seok Jin Nam, Jeong Eon Lee. Long-term Outcome of Slowly Proliferating Luminal Type ILC versus IDC [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-11-10.

Immune checkpoint inhibitors in the first-line treatment of esophageal squamous cell carcinoma: Minireview for a big shift

2025-06-13

Giulia Massaro , A. Crastes de Paulet , Daniele Lavacchi +7 more | World Journal of Gastrointestinal Oncology

Esophageal cancer is an aggressive malignancy often diagnosed at advanced stages, with esophageal squamous cell carcinoma being the predominant subtype worldwide. Standard first-line chemotherapy provides limited survival benefits, with a … Esophageal cancer is an aggressive malignancy often diagnosed at advanced stages, with esophageal squamous cell carcinoma being the predominant subtype worldwide. Standard first-line chemotherapy provides limited survival benefits, with a median overall survival of less than 1 year. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have transformed the treatment landscape, improving overall survival and progression-free survival. However, response rates remain variable, with programmed death ligand 1 (PD-L1) expression being the primary predictive biomarker. The variability in PD-L1 testing methods and immune microenvironment alterations after prior treatments complicate patient selection for ICIs. Several phase 3 trials, including KEYNOTE-590 and CheckMate 648, have demonstrated the efficacy of ICIs combined with chemotherapy, particularly in patients positive for PD-L1. Despite these advances, long-term survival remains low, emphasizing the need for better biomarkers and novel therapeutic strategies. This review explored current first-line treatment options for esophageal squamous cell carcinoma, challenges in biomarker-based patient selection, and emerging therapeutic approaches.

Abstract P4-10-24: Extracellular matrix remodelling is a targetable feature of invasive lobular carcinoma (ILC)

2025-06-13

Renée L. Flaherty , Francis M. Hughes , George Sflomos +7 more | Clinical Cancer Research

Abstract Background: Invasive lobular carcinoma (ILC) has previously been identified as overexpressing collagens and elastin as well as LOXL1, a collagen cross-linking enzyme belonging to the lysly oxidase (LOX) family. … Abstract Background: Invasive lobular carcinoma (ILC) has previously been identified as overexpressing collagens and elastin as well as LOXL1, a collagen cross-linking enzyme belonging to the lysly oxidase (LOX) family. Abberant LOX activity can promote breast cancer invasion and metastasis through remodelling of the extracellular matrix (ECM). The clinical stage pan-LOX inhibitor PXS-5505 has demonstrated anti-tumour potential through the disruption of the collagen matrix in models of pancreatic and myeloid cancer, and exhibits an excellent safety profile. Given that ILCs are enriched for ECM remodelling, we propose that inhibition of LOX be investigated as a therapeutic strategy in the treatment of ILC. Methods: We xenograft ILC cells into the milk ducts of mice (MIND) to faithfully recapitulate ILC disease progression including ECM remodelling processes. We used cell line and PDX MIND models of ILC to examine their response to LOX inhibition (LOXi) alone and combination with ovariectomy (OVX) to mimic aromatase inhibition (AI). Results: Treatment with LOXi alone significantly decreased primary tumour growth compared to vehicle in cell line and patient derived xenograft models of ILC. This was accompanied by changes in the “matrix structure” and downmodulation of proliferative markers, and a transcriptional level MYC and ER signalling pathways. The magnitude of response to LOXi differed across ER+ ILC models, either being sufficient to reduce primary tumour growth alone (SUM44, p=0.000410), or in combination with OVX (MM134, p=0.032). In the metastatic ER- IPH-926 model LOXi significantly reduced metastatic dissemination to the lungs (p=0.013). Histologically, combination treatment decreased collagen matrix density and alignment as well as the Ki67 index. Proteomic profiling revealed LOXi alone and in combination with OVX downmodulated matrix-associated proteins, as well as MYC transcription factor targets. Functional pathway and keyword enrichment analysis identified down modulation of cell adhesion, cell cycle and apoptosis-related pathways. Conclusion: These data demonstrate that ECM remodelling is a targetable feature of ILC and suggest that the LOXi PXS-5505, a well tolerated drug provides additional benefit to standard of care endocrine therapy. Changes in fibrillar collagen and matrix-associated proteins result in decreased MYC activity, which may serve as an endpoint in a prospective window trial. Citation Format: Renee Flaherty, Flavia Hughes, George Sflomos, Carlos Ronchi, Hazel Quinn, Solene Pezot, Samuel Jouny, Harveena Padda, Theo Roumeliotis, Giovanna Ambrosini, Beatrice Howard, Cathrin Brisken. Extracellular matrix remodelling is a targetable feature of invasive lobular carcinoma (ILC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-10-24.

Unravelling the potential of plasma DNA methylation in the detection and surveillance of esophageal cancer

2025-06-13

Jatinder Singh Arora , Mahmoud Nassar , Bahaaeldin Baraka | World Journal of Gastrointestinal Oncology

Esophageal cancer (EC) continues to pose a significant clinical challenge due to the absence of a reliable early detection method, leading to late-stage diagnoses and poor patient outcomes. The recent … Esophageal cancer (EC) continues to pose a significant clinical challenge due to the absence of a reliable early detection method, leading to late-stage diagnoses and poor patient outcomes. The recent study by Liu et al presents a promising breakthrough, demonstrating that plasma DNA methylation markers-SHOX2, SEPTIN9, EPO, and RNF180-offer a non-invasive approach for early EC detection with 76.19% sensitivity and 86.27% specificity. Given the urgent need for effective screening strategies, the potential integration of this assay into clinical practice could significantly enhance early diagnosis, patient monitoring, and overall survival rates. While further validation is necessary, this advancement marks an important step toward improving EC detection and management.

Spatial heterogeneity of PD-L1 expression influence its assessment in esophageal squamous cell carcinoma

2025-06-12

Boyao Yu , Cong Qi , Zhichao Liu +5 more | Translational Oncology

Alterations of the composition and spatial organization of the microenvironment following non-dysplastic Barrett's esophagus through progression to cancer

2025-06-12

Meng‐Lay Lin , John W. Hickey , Adam M. Passman +7 more | bioRxiv (Cold Spring Harbor Laboratory)

Abstract Barrett’s esophagus (BE), a metaplastic condition that is the only known precursor for esophageal adenocarcinoma (EAC), is relatively common, but progression to cancer is infrequent. BE is inflamed but … Abstract Barrett’s esophagus (BE), a metaplastic condition that is the only known precursor for esophageal adenocarcinoma (EAC), is relatively common, but progression to cancer is infrequent. BE is inflamed but the contribution of the immune system to the carcinogenic process is unknown. To this end, we contrasted non-dysplastic metaplasia of BE patients, captured when they did not progress (non-progressors), did subsequently, but had not yet progressed (pre-progressors) or had already progressed to EAC (progressors). Using spatial multiplexed 56-protein analysis, serial laser capture microdissection (LCM) RNAseq and shallow whole genome sequencing, we identified prooncogenic immune neighbourhoods and dysregulated immune cell populations predictive of subsequent progression to EAC. Indeed, spatial analysis revealed that M1 macrophages, regulatory natural killer (NK) cells, neutrophils and altered ratios of intraepithelial CD4 + and CD8 + lymphocytes typify tumor microenvironmental (TME) changes associated with cancer initiation. Spatially derived cell-to-cell interactions revealed progression-specific immune cell interaction signatures predominantly involving M1 macrophages NK cells and plasma cells. Furthermore, LCM RNAseq analysis identified gene expression ‘hot’ signatures enriched in pre-progression and progression samples. Notably, we also observed a correlation between immune cells and copy number alterations in progressor metaplasia. By exposing coordinated changes in the immune cell landscape in patients at high risk of developing EAC, this multi-omic dataset provides novel diagnostic and therapeutic opportunities

Surveillance and treatment of Barrett’s Esophagus: results from a Portuguese tertiary center

2025-06-12

AC. Cardoso Guimaraes Vasconcelos , Marco Pereira , Diogo Libânio +2 more | GE Portuguese Journal of Gastroenterology

Introduction: Barrett’s esophagus (BE) is a premalignant condition that requires surveillance, in order to diagnose and treat dysplasia, improving survival. Results from surveillance and endoscopic treatment are well-described in different … Introduction: Barrett’s esophagus (BE) is a premalignant condition that requires surveillance, in order to diagnose and treat dysplasia, improving survival. Results from surveillance and endoscopic treatment are well-described in different populations. This is the first evaluation of the outcomes of endoscopic resection and ablation of BE patients in a Portuguese center. Methods: This is a single-center retrospective cohort study analyzing the results of endoscopic surveillance and treatment of patients with BE between January 2004 and September 2024. The following outcomes were evaluated: detection of dysplasia and/or visible lesions; rate of curative endoscopic resection; rate of BE refractory to ablation; adverse event (AE) rates of endoscopic resection and ablation; BE-related mortality and survival. Results: Eighty-nine patients were followed for a median of 3 years (IQR 1-6). A total of 37 lesions were identified, and treated with endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD) and other modalities in 76%, 16% and 8% of patients respectively, with curative resection and AE rates of 86% (95% CI 67%-96%) and 11% (95% CI 2%-28%) for EMR, and 67% (95% CI 22%-96%) and 17% (95% CI 0%-64%) for ESD, respectively. A response rate of 97% was observed in 33 patients submitted to mucosal ablation, with one patient presenting refractory disease and one patient showing recurrence of intestinal metaplasia. One patient died of BE-related neoplasia. Conclusion: Our study shows results of BE treatment generally comparable to published literature, in a low-prevalence country. A high curative resection and a high success rate of mucosal ablation was achieved, with low refractory and recurrent disease.