Esophageal cancer is an aggressive malignancy that carries a high mortality rate. The treatment of locally advanced resectable esophageal cancer requires a multimodal approach involving chemotherapy, radiation therapy, and surgical resection. Optimal treatment combinations and sequences for squamous cell carcinoma (SCC) versus adenocarcinoma (AC) histological subtypes are still being determined. For very early stage esophageal cancers, endoscopic therapies or surgical resection without chemotherapy and radiation are preferred. Neoadjuvant chemoradiation followed by surgical resection has been the standard in locally advanced resectable esophageal cancer based on the landmark CROSS trial. Definitive chemoradiation is recommended for patients who are not surgical candidates or decline surgery. Perioperative chemotherapy without radiation can be considered for lower esophageal AC and gastroesophageal (GE)-junction AC based on landmark MAGIC and FLOT4 trials. Additional trials are underway to compare preoperative chemoradiation to perioperative chemotherapy in esophageal and GE-junction ACs. Thus far, targeted therapies against vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor 2 (HER2) have not been successful in the neoadjuvant/adjuvant setting. The roll of immunotherapy in perioperative/adjuvant setting is promising. Based on the CheckMate 577 trial, adjuvant nivolumab should be considered for all patients following neoadjuvant chemoradiation and R0 resection with residual pathologic disease. Additional trials involving various immunotherapy agents are underway.

Barrett's esophagus (BE) is recognized as a risk factor for esophageal adenocarcinoma. An expert panel was organized in Italy with the aim of drafting a series of statements on BE to guide diagnosis and management of patients with BE.

The working Group Coordinators worked on a literature search to identify key topics regarding critical steps of the endoscopic approach to BE. Based on the search and their expert opinion, a list of most meaningful questions was prepared and emailed to all members who were asked to vote the questions. When the survey was completed a consensus meeting was organized. According to the survey results, Group Coordinators proposed a draft statement that was voted. By definition, the statement was formulated when there was an agreement of ≥50% among participants.

Twenty nine participants deliberated 18 questions. The agreement was reached for 16 questions for which a recommendation was formulated.

The generated statements highlight the Italian contribution to the European Position Statement of the European Society of Gastrointestinal Endoscopy. The Italian statements preserve peculiarities when dealing with the endoscopic management of BE and wishes to be considered as a contribution for the care of BE patients even with a low risk of progression to esophageal neoplasia.

Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study is to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal adenocarcinoma. This study includes patients with esophageal adenocarcinoma who had failed or were not candidates for conventional therapy enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from 11 academic and community practices. Endoscopic spray cryotherapy was performed until biopsy proven local tumor eradication or until treatment was halted due to progression of disease, patient withdrawal or comorbidities. Eighty-eight patients with esophageal adenocarcinoma (median age 76, 80.7% male, mean length 5.1 cm) underwent 359 treatments (mean 4.4 per patient). Tumor stages included 39 with T1a, 25 with T1b, 9 with unspecified T1, and 15 with T2. Eighty-six patients completed treatment with complete response of intraluminal disease in 55.8%, including complete response in 76.3% for T1a, 45.8% for T1b, 66.2% for all T1, and 6.7% for T2. Mean follow-up was 18.4 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 12 of 88 patients (13.6%) but were present before spray cryotherapy in 3 of 12. This study suggests that endoscopic spray cryotherapy is a safe, well-tolerated, and effective treatment option for early esophageal adenocarcinoma.

The thermal destruction of non-dysplastic Barrett's esophagus (BE) and its replacement by squamous epithelium is an attractive, but unproven strategy to avoid further development of dysplasia or cancer. The goal of this study was to estimate the persistence of restoration of squamous epithelium and the risk of cancer in BE that was eradicated using argon plasma coagulation (APC) in the absence of high-grade dysplasia, 16 years after its application.

We followed 32 patients with BE who underwent eradication of metaplastic epithelium using APC, up to 16 years later.

At the end of the initial treatment, 25 of 32 patients (78%) had complete endoscopic eradication, there was partial squamous re-epithelialization in four patients (13%) and it was absent in three patients (9%). We observed buried metaplastic glands under new squamous epithelium in 6 of the 25 patients who had complete endoscopic eradication. At follow-up, sustained complete endoscopic eradication was observed in 16 of 32 patients (50%), partial eradication in 11 of 32 patients (35%); there were two patients (6%) lost to follow-up and three patients (9%) developed esophageal adenocarcinoma. Two of the latest cases arose from the buried glands under neosquamous epithelium after complete eradication and one arose from a small remaining Barrett's segment.

We observed long-term re-epithelialization in the majority of patients who had previously had complete eradication of Barrett's esophagus. This did not provide protection against cancer development, as the incidence of cancers arising from buried glands or from residual Barrett's esophagus was similar to that observed in patients undergoing no specific treatment.

Management of esophageal cancer has evolved since the two last decades. Esophagectomy remains the primary treatment for early stage esophageal cancer although its specific role in superficial cancers is still under debate since the development of endoscopic mucosal treatment. To date, there is strong evidence to consider that locally advanced cancers should be recommended for a multimodal treatment with a neoadjuvant chemotherapy or a combined chemoradiotherapy (CRT) followed by surgery. For locally advanced squamous cell carcinoma or for a part of adenocarcinoma, some centers have proposed treating with definitive CRT to avoid related-mortality of surgery. In case of persistent or recurrent disease, a salvage esophagectomy remains a possible option but this procedure is associated with higher levels of perioperative morbidity and mortality. Despite the debate over what constitutes the best surgical approach (transthoracic versus transhiatal), the current question is if a minimally procedure could reduce the periopertive morbidity and mortality without jeopardizing the oncological results of surgery. Since the last decade, minimally invasive esophagectomy (MIE) or hybrid operations are being done in up to 30% of procedures internationally. There are some consistent data that MIE could decrease the incidence of the respiratory complications and decrease the length of hospital-stay. Nowadays, oncologic outcomes appear equivalent between open and minimally invasive procedures but numerous phase III trials are ongoing.

The management of Barrett's oesophagus and associated neoplasia has evolved considerably in recent years. Modern endoscopic strategies including endoscopic resection and mucosal ablation can eradicate dysplastic Barrett's and prevent progression to invasive oesophageal cancer. However, several aspects of Barrett's management remain controversial including the stage in the disease process at which to intervene, and the choice of endoscopic or surgical therapy. A review of articles pertaining to the management of Barrett's oesophagus with or without associated neoplasia, was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, Embase and Cochrane databases were searched to identify literature relevant to eight pre-defined areas of clinical controversy. The following search terms were used: Barrett's oesophagus; dysplasia; intramucosal carcinoma; endotherapy; endoscopic resection; ablation; oesophagectomy. A significant body of evidence exists to support early endoscopic therapy for high-grade dysplasia (HGD). Although not supported by randomised controlled trial evidence, endoscopic therapy is now favoured ahead of oesophagectomy for most patients with HGD. Focal intramucosal (T1a) carcinomas can be managed effectively using endoscopic and surgical therapy, however surgery should be considered the first line therapy where there is submucosal invasion (T1b). Treatment of low grade dysplasia is not supported at present due to widespread over-reporting of the disease. The role of surveillance endoscopy in non-dysplastic Barrett's remains controversial.

While the destructive actions of a cryoablative freeze cycle are long recognized, more recent evidence has revealed a complex set of molecular responses that provides a path for optimization. The importance of optimization relates to the observation that the cryosurgical treatment of tumors yields success only equivalent to alternative therapies. This is also true of all existing therapies of cancer, which while applied with curative intent; provide only disease suppression for periods ranging from months to years. Recent research has led to an important new understanding of the nature of cancer, which has implications for primary therapies, including cryosurgical treatment. We now recognize that a cancer is a highly organized tissue dependent on other supporting cells for its establishment, growth and invasion. Further, cancer stem cells are now recognized as an origin of disease and prove resistant to many treatment modalities. Growth is dependent on endothelial cells essential to blood vessel formation, fibroblasts production of growth factors, and protective functions of cells of the immune system. This review discusses the biology of cancer, which has profound implications for the diverse therapies of the disease, including cryosurgery. We also describe the cryosurgical treatment of diverse cancers, citing results, types of adjunctive therapy intended to improve clinical outcomes, and comment briefly on other energy-based ablative therapies. With an expanded view of tumor complexity we identify those elements key to effective cryoablation and strategies designed to optimize cancer cell mortality with a consideration of the now recognized hallmarks of cancer.

Recently developed endoscopic resection (endoscopic submucosal dissection [ESD]/ endoscopic mucosal resection) has dramatically changed the therapeutic approach for Barrett's esophageal cancer. The rationale for endoscopic resection is that lesions confined to the mucosal layer have negligible risk for developing lymph node metastasis and can be successfully eradicated by endoscopic treatment as a curative treatment with minimal invasiveness. According to some reports that analyzed the rate of lymph-node involvement relative to the depth of mucosal or submucosal tumor infiltration, endoscopic resection is clearly indicated for intramucosal carcinoma and might be extended to lesions with invasion into the submucosa (<200 μm, sm1) because of the low risk for lymph node metastasis. Most Japanese experts recommend ESD for Barrett's esophageal cancer after accurate diagnosis of the margin of cancer using narrow band imaging with magnifying endoscopy because of its high curative rate. However, few studies have evaluated the long-term outcomes of endoscopic resection for Barrett's esophageal cancer in Japan. Further investigations should be conducted to establish endoscopic resection for Barrett's esophageal cancer.

Barrett's oesophagus is the major risk factor for the development of oesophageal adenocarcinoma. The management of Barrett's oesophagus entails treating reflux symptoms with acid-suppressing medication or surgery (fundoplication). However, neither form of anti-reflux therapy produces predictable regression, or prevents cancer development. Patients with Barrett's oesophagus usually undergo endoscopic surveillance, which aims to identify dysplastic changes or cancer at its earliest stage, when treatment outcomes should be better. Alternative endoscopic interventions are now available and are suggested for the treatment of early cancer and prevention of progression of Barrett's oesophagus to cancer. Such treatments could minimize the risks associated with oesophagectomy. The current status of these interventions is reviewed. Various endoscopic interventions have been described, but with long-term outcomes uncertain, they remain somewhat controversial. Radiofrequency ablation of dysplastic Barrett's oesophagus might reduce the risk of cancer progression, although cancer development has been reported after this treatment. Endoscopic mucosal resection (EMR) allows a 1.5-2 cm diameter piece of oesophageal mucosa to be removed. This provides better pathology for diagnosis and staging, and if the lesion is confined to the mucosa and fully excised, EMR can be curative. The combination of EMR and radiofrequency ablation has been used for multifocal lesions, but long-term outcomes are unknown. The new endoscopic interventions for Barrett's oesophagus and early oesophageal cancer have the potential to improve clinical outcomes, although evidence that confirms superiority over oesphagectomy is limited. Longer-term outcome data and data from larger cohorts are required to confirm the appropriateness of these procedures.

The emergence of endoscopic therapies for Barrett's esophagus (BE)-associated dysplasia has significantly altered the management of this complex disease. Over the past decade, there has been a paradigm shift from that of pure surveillance to a more therapeutic approach in eradicating dysplastic BE. This strategy includes less invasive options than esophagectomy for high-grade dysplasia and early eradication of confirmed low-grade dysplasia. Although multiple modalities exist for endoscopic therapy, endoscopic mucosal resection coupled with radiofrequency ablation appears to be the most effective therapy, with minimal complications. Recent advances in endoscopic eradication therapies for dysplastic BE have fueled excitement for a significant weapon against the rising incidence of esophageal cancer.

High-grade dysplasia (HGD) in Barrett's esophagus (BE) is the critical step before invasive esophageal adenocarcinoma. Although its natural history remains unclear, an aggressive therapeutic approach is usually indicated. Esophagectomy represents the only treatment able to reliably eradicate the neoplastic epithelium. In healthy patients with reasonable life expectancy, vagal-sparing esophagectomy, with associated low mortality and low early and late postoperative morbidity, is considered the treatment of choice for BE with HGD. Patients unfit for surgery should be managed in a less aggressive manner, using endoscopic ablation or endoscopic mucosal resection of the entire BE segment, followed by lifelong surveillance. Patients eligible for surgery who present with a long BE segment, multifocal dysplastic lesions, severe reflux symptoms, a large fixed hiatal hernia or dysphagia comprise a challenging group with regard to the appropriate treatment, either surgical or endoscopic.

Esophageal adenocarcinoma is the most rapidly increasing cancer in western countries. High-grade dysplasia (HGD) arising from Barrett's esophagus (BE) is the most important risk factor for its development, and when it is present the reported incidence is up to 10% per patient-year. Adenocarcinoma in the setting of BE develops through a well known histological sequence, from non-dysplastic Barrett's to low grade dysplasia and then HGD and cancer. Endoscopic surveillance programs have been established to detect the presence of neoplasia at a potentially curative stage. Newly developed endoscopic treatments have dramatically changed the therapeutic approach of BE. When neoplasia is confined to the mucosal layer the risk for developing lymph node metastasis is negligible and can be successfully eradicated by an endoscopic approach, offering a curative intention treatment with minimal invasiveness. Endoscopic therapies include resection techniques, also known as tissue-acquiring modalities, and ablation therapies or non-tissue acquiring modalities. The aim of endoscopic treatment is to eradicate the whole Barrett's segment, since the risk of developing synchronous and metachronous lesions due to the persistence of molecular aberrations in the residual epithelium is well established.