Esophageal Cancer Past Paper PDF 2024-2025

uplogo UNIVERSITY OF PERUGIA DEPARTMENT OF MEDICINE Master’s Degree in Medical, Veterinary and Forensic Biotechnological Science Academic Year 2024-2025 Digestive System Diseases ESOPHAGEAL...

uplogo UNIVERSITY OF PERUGIA DEPARTMENT OF MEDICINE Master’s Degree in Medical, Veterinary and Forensic Biotechnological Science Academic Year 2024-2025 Digestive System Diseases ESOPHAGEAL CANCER Monia Baldoni  ESOPHAGEAL CANCER The most common histologic types are squamous cell carcinoma (SCC) and adenocarcinoma (AC), which together constitute more than 90% of esophageal malignancies. Rarely, melanoma, sarcoma, small cell carcinoma, or lymphoma may arise in the esophagus. Although SCC is more evenly distributed throughout the length of the esophagus, AC is predominantly a disease of the distal esophagus and gastroesophageal junction. Squamous cell carcinoma and adenocarcinoma are distinct malignancies of the esophagus, with different risk factors and different natural histories. The esophagus can be divided into a cervical and thoracic portion and is lined by a multi-layered, stratified, non-keratinized squamous epithelium.  Worldwide Squamous Cell Carcinoma (SCC) is the most common esophageal cancer; usually, it occurs in the middle 3rd of the esophagus but, because of its characteristic epithelium the SCC can arise from each portion of the esophagus. Site of onset of the esophagus cancer (SCC) the ratio of upper : middle : lower is 15 : 50 : 35. Normal Esophageal Epithelium Barium swallow demonstrating an endoluminal mass in the mid esophagus Squamous Cell Carcinoma Nowadays Adenocarcinoma (AC) is the most common type of esophageal cancer in developed countries; it has increased in incidence more rapidly than any type of cancer in the United States (Adenocarcinoma has increased 350% since 1970). Adenocarcinoma currently accounts for over 70% of esophageal cancer in the USA, in Caucasian males, due to its association with obesity, GERD and Barrett’s esophagus. AC is most common in the lower 3rd of the esophagus, accounting for over 80% of cases. Barrett’s esophagus Adenocarcinoma  ESOPHAGEAL CANCER Can it be a place of secondaries ? Secondary esophageal carcinoma occurs in about 3% of patients dying with carcinoma. Esophageal invasion by secondary carcinoma produces obstruction mimics a benign stricture or primary esophageal carcinoma. The primary tumor site could be lung more frequently, breast, but also kidney, pancreas, cervix (squamous cell), and bladder (transitional cell).  ESOPHAGEAL CANCER Epidemiology Esophageal cancer is the 6th leading cause of cancer deaths. The high-risk areas include South America and the “Asian Esophageal Cancer Belt,” which extends from eastern Turkey, through Iraq, Iran, and the southern part of the former Soviet Union (Kazakhstan, Turkmenistan, Uzbekistan, Tajikistan) to Mongolia and western/northern China. In these regions, the incidence reaches 800 per 100,000 population. ESCC (Esophageal Squamous Cell Carcinoma) is the major type of esophageal cancer in Asia, especially in China. More than half of global ESCC cases occur in China The incidence rises steadily with age, reaching a peak in the 6th to 7th decade of life. Male : Female = 3.5 : 1  Epidemiology High incidence areas: South America, South Africa and East Africa, Turkey, Iran, China Low incidence areas: North America characteristic prevalence of squamous forms in blacks while adenocarcinoma predominates in white JAMA Oncology 2015  3% of gastrointestinal cancers in males 1% of gastrointestinal cancers in females Annual incidence 3-5 / 100000 M: F = 6: 1 High incidence is in : Friuli Venezia Giulia - 5 / 100,000 inhabitants and Sardinia (Sassari): 4.7 / 100,000 inhabitants for the male gender 0.7 / 100,000 inhabitants for the female sex ESOPHAGEAL CANCER ESOPHAGEAL CANCER Risk factors 1. Chronic irritation: Spirits (alcohol drinking) Smoking (cigarette smoking) HPV-infection Caustic injury Drinking very hot liquids (tea, coffee) Previous radiations therapy Gastroesophageal Reflux Disease Obesity  ESOPHAGEAL CANCER Risk factors 2. Dietary: a. Ingestion of exogenous carcinogens and promoting factors as: - Nitrates and nitrosamines - Aflatoxins, a class of mycotoxins produced mainly by the fungal species Aspergillus flavus; Aflatoxins are poisonous carcinogens that are produced by certain molds which grow in soil, decaying vegetation, hay, and grains b. Absence of protective substances in fruits and green vegetables: As vitamin A, B2, C, E, and iron, zinc  ESOPHAGEAL CANCER Risk factors 3- Precancerous conditions: 1. Reflux disease and Barrett’s esophagus -the most important for Adenocarcinoma 2. Achalasia Achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES) in response to swallowing. The LES is hypertensive in about 50% of patients. These abnormalities cause a functional obstruction at the gastroesophageal junction (GEJ) 3. Corrosive strictures 4. Tylosis (hyperkeratosis palmaris et plantaris) is characterized by focal thickening of the skin of the hands and feet and is associated with a very high lifetime risk of developing squamous cell carcinoma of the esophagus.  ESOPHAGEAL CANCER Risk factors Adenocarcinoma Squamous Cell Carcinoma GERD Alcohol use (3- to 5-fold with >3 drinks per day) (five- to sevenfold risk) Smoking (ninefold risk) Barrett’s Esophagus Achalasia (10-fold risk) Age 50-60 years Age 60 to 70 years Male sex (eightfold risk) Black race (3-fold risk) White race (fivefold) Obesity (2.4-fold risk) High-starch diet without fruits and vegetable Smoking (twofold risk)  Association between tobacco smoke and oesophageal cancer Tobacco smoke contains: Substances with promoting and carcinogenic effects Aromatic hydrocarbons (3,4 benzopyrene) exerts an irritating effect on the mucous membranes, due to the high temperatures developed during combustion Basal tone of LES Oesophageal clearance Chronic Esophagitis  Association between tobacco smoke and alcohol intake Spirits contain: Nitrosamine and N-nitroso-derived compounds, with high carcinogenic action. Preservatives with promoting action. Chronic Esophagitis The risk in heavy smokers and chronic alcoholics of occurrence of esophageal carcinoma increased by 54.2% compared to non- exposed subjects. Association between caustic injury strictures and Esophageal Cancer The risk of developing carcinomas of the esophagus is increased by 1000-fold compared to the general population. Latency: 5-20 years. Onset on scarring stenosis Association between Human Papilloma Virus (HPV) and Esophageal Cancer HPV tied to 3-fold greater risk for esophageal cancer HPV is a very common sexually transmitted virus that is known to cause cervical cancer, anal cancer, and some cancers of the reproductive organs and the upper throat.  Endemic in South Africa and China. Serotype 16 and 18 PCR on cytological samples of 2.020 esophageal carcinomas: 15.2% of positivity for viral DNA Immunohistochemistry showed that the positive rates of hpv16 + 18 E6 and E7 in HPV- positive EC samples were 56.4% and 37.0%, respectively. HPV-DNA integration rate in HPV-positive EC tissues (88.79%) was higher than that in adjacent tissues (54.17%). HPV antibody was found in the serum of EC patients by a serological test.  Association between Barrett’s Esophagus and Esophageal Adenocarcinoma  Acquired condition in response to Gastro-esophageal reflux leading to columnar lined epithelium in the distal esophagus  Intestinal metaplasia, characterized by goblet cells, is biologically unstable with greatest risk of neoplastic progression  Making it a major risk factor in development of esophageal adenocarcinom DEFINITION OF BARRETT’S ESOPHAGUS  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 esophagus  Clearlyvisible endoscopically above the GEJ (>1cm) and confirmed pathologically with distal esophageal biopsies of columnar lined epithelium  Barrett’s esophagus: endoscopic view Barrett’s Esophagus Gastro-esophageal Junction GEJ Barrett’s esophagus Barrett’s esophagus Barrett’s esophagus From Barrett’s esophagus to Adenocarcinoma Negative for Indefinite for dysplasia dysplasia Low grade High grade dysplasia dysplasia Role of chronic inflammation Role of chronic inflammation  From Barrett’s esophagus to Adenocarcinoma Neoplastic transformation of BE is a stepwise process that includes non- dysplastic disease, low-grade dysplasia, high-grade dysplasia and AC, although patients with BE under endoscopic surveillance often develop cancer without prior biopsy detection of each of these stages. In 2000, the World Health Organization International Agency, according to Vienna classification system, changed the term ‘dysplasia’ into ‘intraepithelial’ or ‘noninvasive’ neoplasia, a definition that more appropriately identifies a neoplastic lesion in its early pre-invasive stage. Risk factors and pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma.  Risk factors for the development of Barrett’s esophagus and esophageal adenocarcinoma. Gastro-esophageal reflux plays a central role in the pathogenesis of BE and several factors are thought to contribute to its occurrence. Patients with central obesity are more predisposed to hiatal hernia and present an increased intra-gastric pressure that enhances reflux. In addition, they usually have higher basal insulin and insulin-like-growth factor-1 (IGF-1) levels, which promote cell proliferation and determine cell differentiation. Three IGF-1 gene polymorphisms have been shown to be associated with esophageal AC or its precursors and can be considered as risk markers. Moreover, these patients exhibit higher serum levels of leptin, a hormone secreted by visceral fat that possibly promotes carcinogenesis by mitogenic and angiogenic means. Risk factors and pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma.  Risk factors for the development of Barrett’s esophagus and esophageal adenocarcinoma. Esophageal mucosal injury from acid reflux is considered a prerequisite for the development of BE although, as already stated, additional factors besides acid reflux are likely responsible for the development of intestinal metaplasia. Probably, intestinal metaplasia develops as a protective mechanism against chronic acid reflux at the molecular level. Several mucosal defenses have been identified, including the secretion of bicarbonate and mucus, expression of claudin- 18 tight junctions, over-expression of defense and repair genes, and resistance to prolonged and repeated acid exposure. Additional risk factors are diet low in fruit and vegetables, cigarette smoking, elevated levels of nitrites and bile acids. Risk factors and pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma.  Risk factors for the development of Barrett’s esophagus and esophageal adenocarcinoma. Elevated concentrations of nitric oxide, that are potentially mutagenic, are detected at the gastro-esophageal junction in this acidic microenvironment. Nitrites are present in the saliva and derive from reduction of dietary nitrates effected by oral bacteria. Nitrites are reduced into nitric oxide by gastric juice with higher concentrations in correspondence of the gastro-esophageal junction and gastric cardias, thus inducing a potentially increased risk of metaplasia and carcinogenesis. Nitric oxide has also been shown to induce DNA double- strand breaks in primary BE cells. Risk factors and pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma.  Risk factors for the development of Barrett’s esophagus and esophageal adenocarcinoma. Additional risk factors are bile acids. Different bile acids have been identified in the GER, including glycocholic acid, taurocholic acid, glycodeoxycholic acid and glycochenodeoxycholic acid. Bile acids can cause injury to the esophageal epithelium and lead to the development of metaplasia by inducing mitochondrial alterations, oxidative stress or DNA damage. In contrast to the mentioned enhancing factors, H. pylori infection and gastro-esophageal mucosal defenses exert a protective role against the formation of BE. Risk factors and pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma.  Risk factors for the development of Barrett’s esophagus and esophageal adenocarcinoma. Familiarity may be an important predisposing factor to the development of BE and eventually esophageal adenocarcinoma. No single causative gene has been identified, although the condition is more prevalent in first-degree relatives of patients with BE. Familiarity can be detected in about 7% of patients in whom BE and AC have been diagnosed, a percentage which is higher than that reported in general population surveys.  Molecular pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma. Reprogramming and/or trans-differentation of stem cells situated in the basal layer of the normal squamous epithelium, as well as modifications of stromal cells characterized by mesenchimal-to-epithelial transition, are presently the object of intense investigation for their presumed role in the pathogenesis of BE. Risk factors and pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma.  Molecular pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma. The cellular origin of the columnar cells of BE is not yet clear. Formerly Barrett’s metaplasia was considered the result of migration of gastric columnar cells to the gastro-esophageal junction. It is now widely accepted that columnar cells arise within the esophagus, possibly as the result of a modification in the stem cells responsible for the constant replenishing of the esophageal lining epithelium, such that they are reprogrammed to produce columnar, rather than squamous cells. It seems reasonable to hypothesize that pluripotent stem cells located distally within the duct lining become exposed following erosive esophagitis consequent to chronic reflux and promote the differentiation into intestinal-type columnar cells that migrate out to repopulate the injured epithelium. Bone marrow-derived stem cells have also been reported to contribute to metaplasia in a rat model of BE. Molecular pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma. Alternatively, the acidic environment determined by chronic GER may induce cellular trans-differentiation through an epigenetic effect on post-mitotic cells. During development, the esophagus is initially lined by a columnar-type epithelium, that is replaced by the mature squamous epithelium during late embryogenesis through trans- differentiation. This suggests that columnar cells which characterize Barrett’s metaplasia may result from a change in the developmental program. Another possibility is that Barrett’s metaplasia arises indirectly as a consequence of mutational and/or environmental modifications in the stromal cells (eg. myofibroblasts, inflammatory cells, etc.) of the submucosa. Cytokines and other regulatory signals from the stromal cells could potentially influence the differentiation and development of cells within the epithelial layer. It has also been suggested that the columnar epithelium of BE arises directly from stromal cells via a mesenchymal-to-epithelial transition. Risk factors and pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma.  Molecular pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma Genetic and epigenetic studies have shown modifications of intestinal-specific transcription factors (CDX1 and CDX2), which are homeobox genes, a family of DNA-binding proteins, and protein BMP4 (bone morphogenetic protein 4), that regulate the development and differentiation of the intestinal columnar epithelium. Overexpression of COX2 and HER2/neu have also been claimed to lead to the development of BE. Risk factors and pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma.  Molecular pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma Genomic instability seems to be a fundamental property of neoplastic progression. Acid and bile in the GER, either directly or indirectly, induce genetic and/or epigenetic changes that lead to the onset of BE and its progression to esophageal AC. Multiple genetic changes are indeed present in BE. Whole genome studies have demonstrated that the majority of BE samples show some level of chromosomal instability, including copy number gains, copy number losses and loss of heterozygosity (LOH). Genetic abnormalities increase during different stages of carcinogenesis: from less than 2% of the genome in early stages Barrett’s metaplasia to over 30% in late stages. The most frequent genetic alteration is loss of the short arm of chromosome 9p, (CDKN2A/p16). In early stage BE, additional abnormalities have been detected, such as copy loss on 3p and 16q. Among genetic alterations usually associated with cancer, loss of p53 (chromosome 17p), APC (chromosome 5q), and RB (chromosome 13q), and overexpression of cyclin D1, Bcl2 and SRC should be mentioned. Molecular pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma  Molecular pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma Flow cytometric, cytogenetic, comparative genomic hybridization (CGH) and other studies have shown that aneuploidy, LOH, and cell cycle alterations are more frequent when grades of dysplasia are higher. Aneuploid cell populations are found in approximately two-thirds of patients with high-grade dysplasia and in about 90% of those with esophageal AC. Tumor suppressor genes, like other genes, may be inactivated by mutation, LOH, or by epigenetic suppression of gene expression by DNA hypermethylation, which involves the abnormal addition of methyl (CH3) groups to cytosine bases at particular sites (CpG dinucleotides) in gene promoter regions. The relative risk of developing esophageal AC at 5 years in those with baseline 9pLOH and 17pLOH and a DNA content abnormality was 79%, compared to no case of AC in patients with none of these abnormalities at baseline Molecular pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma Molecular pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma In a longitudinal study, baseline analysis of blood samples has revealed that a shorter telomere length was associated with increased risk of progression to esophageal AC. Therefore, telomere length may be a useful biomarker to stratify risk in people with BE  Molecular pathways for the development of Barrett’s esophagus and esophageal adenocarcinoma Overexpression of COX2 and HER2/neu have also been claimed to lead to the development of BE. There is a tissue overexpression of cyclo-oxygenase-2 (COX- 2) in BE and esophageal AC, but it is not known at what stage they may act in the esophageal inflammation-metaplasia-AC sequence. Therefore, the use of aspirin and NSAIDs is probably associated to a reduced risk of BE development. HER-2/neu oncogene is also overexpressed/amplified in about 15–30% of patients with BE or esophageal AC. HER2/neu has a possible role in the early transition from dysplasia to AC and correlates with a poor prognosis. Thus, it could help to identify patients at high risk of malignant transformation and could be a target for treatment of esophageal premalignant and malignant lesions. 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. ESOPHAGEAL CANCER A- Annular type: more common in lower 1/3. B- Ulcerative type: raised irregular edge - necrotic floor - indurated base C- Cauliflower-shaped type (60%): polypoid lesion. A B C  ESOPHAGEAL CANCER Spread (1) Direct: (main method): to the surrounding (2) Lymphatic: mainly in a downward direction. ** Cervical esophagus → lower deep cervical L.N. ** Thoracic esophagus → para-esophageal & tracheo-bronchial lymph nodes ** Abdominal esophagus → lymph nodes along the lesser curvature of the stomach → coeliac axis L.N. (3) Blood (rare): Liver, lung, bone, brain ESOPHAGEAL CANCER Spread  ESOPHAGEAL CANCER Clinical Presentation 1 Dysphagia (the cardinal symptom): difficult in swallowing characterized by a- Onset: Late onset b- Course: Continuous and progressive course c- Duration: Short duration (few months). d- First to: solid but not to fluids, later to both fluids & solids e- Associated with: very bad general condition  ESOPHAGEAL CANCER More common in Old male than female (> 50 years)  ESOPHAGEAL CANCER Dysphagia in male > 50 years > 2 weeks considered esophageal cancer until proved otherwise.  ESOPHAGEAL CANCER Clinical Presentation (2) Regurgitation (3) Pain: usually a late manifestation. It can be related to swallowing itself (odynophagia) or to the local extension of the tumor into adjacent structures, such as the pleura, mediastinum, or vertebral bodies (4) Complications ❑ Weight loss, Malnutrition, dehydration, anemia. ❑ Aspiration pneumonia. ❑ Distant metastasis. ❑ Invasion of nearby structures: e.g. 1. Recurrent laryngeal nerve → Hoarseness 2. Trachea → Stridor → cough, choking & cyanosis 3. Perforation into the pleural cavity → Empyema 4. Phrenic nerve→ Hiccups  ESOPHAGEAL CANCER A- For diagnosis: Cancer lower 1/3 Filling defect (1) Barium (ulcerative type)swallow: a. Fungating and ulcerative mass: narrowed irregular filling defect. b. Annular mass: - If middle stricture: Apple core appearance Rate tail appearance with evident shouldering Apple core - If lower stricture: Rat tail appearance. appearance  ESOPHAGEAL CANCER A- For diagnosis: (2) Upper Endoscopy + Biopsy and cytology (the most important) ESOPHAGEAL CANCER Upper Endoscopy ESOPHAGEAL CANCER staging Modality Clinical Utility Overall Accuracy (%) Invasion of local Computed tomography (chest, structures (airways, ≥90% abdomen) aorta) Metastatic disease ≥90% Local tumor (T) staging Endoscopy 80%–90% (operator dependent) Ultrasonography (with or without Local nodal (N) staging fine-needle aspiration of lymph 70%–90% (operator dependent) nodes) Positron emission tomography Metastatic disease ≥90%  ESOPHAGEAL CANCER staging B- For evaluation of resectability: (1) Endoscopic US: to detect wall penetration and regional LN status. T4 esophageal T3 N1 esophageal cancer cancer ESOPHAGEAL CANCER staging  ESOPHAGEAL CANCER B- For evaluation of resectability: (2) CT and MRI. ESOPHAGEAL CANCER ESOPHAGEAL CANCER  ESOPHAGEAL CANCER C- For staging: Lung: chest x-ray & CT Liver: US & CT Bone: Bone scan Brain: CT  ESOPHAGEAL CANCER D- Laboratory: 1- Complete blood picture: iron deficiency, anemia. 2- Occult blood in stool 3- Tumor markers: CEA  ESOPHAGEAL CANCER E- Positron emission tomography (PET): - Noninvasive method of detecting primary, nodal, distant metastases & locally recurrent tumor - The technique estimates area of high glucose metabolism (the tumor) by measurement of the uptake of radiotracer (Flurodeoxyglucose FDG).  ESOPHAGEAL CANCER Treatment of esophageal cancer Tr e at m en t Operable Inoperable Radical surgery Palliative procedure followed by chemoradiotherapy  ESOPHAGEAL CANCER Unfit patient Tr e at m en t Presence of distant metastases Criteria of inoperability Unresectable tumor Infiltration of important structure as trachea, aorta  ESOPHAGEAL CANCER Operable esophageal cancer Tr e at m en t Upper 1/3 Middle 1/3 Lower 1/3 Total Partial Subtotal esophago- esophagectomy esophagectomy gastrectomy  ESOPHAGEAL CANCER After esophagectomy The esophagus is replaced by Treatment Colon interposition Gastric pull up Tr e at m en t ESOPHAGEAL CANCER Tr e at m en t ESOPHAGEAL CANCER  ESOPHAGEAL CANCER Inoperable esophageal cancer Tr e at m en t Non Obstructed Obstructed Palliative 1. LASER tunneling with chemoradiotherapy endoluminal stenting 2. Photodynamic therapy 3. Jejunostomy or Gastrostomy for feeding  ESOPHAGEAL CANCER Very bad prognosis (5-year survival rate 5%) due to: 1- Old age 2- Bad general condition before operation 3- Early local spread 4- High morbidity after operation e.g. empyema, leakage from anastomosis ESOPHAGEAL CANCER  ESOPHAGEAL CANCER Is Radiation Plus Chemotherapy as Good as Surgery? Radiation alone has such a poor cure rate for esophagus cancer that many studies have evaluated combining radiation with chemotherapy which improves the cure rates. Some studies have compared chemo/radiation with surgery and found the results similar, suggesting that surgery may not be necessary. A recent study compared chemotherapy (Mitomycin/ 5FU/ leukovorin) plus Radiation (50-60Gy) and had survival rates by stage: stage I 55%/5y, stage II 16%/5y and stage III 8%/5y. The overall results with chemoradiation (25%/5y survival) were the same as those patients treated with surgery (23%/5y survival.)  ESOPHAGEAL CANCER Numerous novel chemotherapeutic and targeted agents have been explored in the locally advanced unresectable and metastatic disease settings for esophageal cancer. Inhibition of the HER-2 receptor by trastuzumab. Approximately 4,000 patients with either gastric or gastroesophageal junction carcinoma were screened, and 22% were found to be positive for HER-2. These patients were then randomly assigned to either chemotherapy with or without trastuzumab. Response, progression-free, and overall survival rates were all improved for those patients who received trastuzumab in combination with chemotherapy.  ESOPHAGEAL CANCER PD-1 Checkpoint Inhibition - prime line treatment Until recently, treatment options for patients with unresectable/locally advanced or metastatic esophageal cancer have been limited. Five-year survival rates are less than 5%. However, adding a checkpoint inhibitor to chemotherapy may bolster the effectiveness of frontline treatment for these malignancies and dramatically improve survival rates, according to results of 2 global, phase 3 clinical trials, KEYNOTE-590 (NCT03189719)2 and CheckMate649 (NCT02872116),3 presented at the European Society for Medical Oncology Virtual Congress 2020. ESOPHAGEAL CANCER Early esophageal cancer: Transhiatal esophagectomy Endoscopic Eradication Therapy  ESOPHAGEAL CANCER Early esophageal cancer: Transhiatal esophagectomy Endoscopic Eradication Therapy Endoscopic therapy has marked the end of esophagectomy as a treatment of choice in patients with HGD and intramucosal cancer EARLY ESOPHAGEAL CANCER Transhiatal esophagectomy Endoscopic Eradication Therapy Guidelines published in 2016 from the American College of Gastroenterology recommend endoscopic screening for BE in men with chronic (>5 years) and/or frequent (weekly or more) GERD symptoms and two or more risk factors for BE or EAC, including age >50, Caucasian race, central obesity, history of tobacco smoking, and a family history (first-degree relative) of BE or EAC EARLY ESOPHAGEAL CANCER Transhiatal esophagectomy Endoscopic Eradication Therapy While upper endoscopy (with high-definition white light endoscopy, and systematic random biopsies) remains the gold standard for BE screening, it is associated with considerable costs related to endoscopy, histopathology examination, and sedation, and the possibility of missed lesions, and complications from curative treatment. Consequently, there has been interest in studying the use of endoscopic advanced imaging techniques and less invasive screening tools, which can be performed without the need for sedation (including transnasal endoscopy (TNE) and esophageal capsule cytology). All that in order to improve the efficiency and diagnostic yield, and reduce the cost of BE surveillance  EARLY ESOPHAGEAL CANCER The device is a sponge Esophageal capsule cytology within a capsule covered in a gelatin layer which dissolves after swallowing, after which the sponge is released. A string attached to the device is used to pull it from the stomach, across the gastroesophageal junction and out through the mouth, brushing along the esophageal mucosa and capturing cells for analysis. Immunohistochemistry is then performed to analyze for markers such as trefoil factor 3, which can differentiate the cells of BE from other columnar cells found in the normal gastric cardia and upper airway EARLY ESOPHAGEAL CANCER Transhiatal esophagectomy Endoscopic Eradication Therapy The endoscopic eradication therapy (EET) of dysplastic Barrett's esophagus is associated with a reduced risk of developing esophageal adenocarcinoma. EET has transformed the way we manage dysplastic BE and early (T1a) EAC, and has virtually eliminated the need for surgery in the majority of these patients. EARLY ESOPHAGEAL CANCER Transhiatal esophagectomy Endoscopic Eradication Therapy Endoscopic eradication therapy with radiofrequency ablation, photodynamic therapy or EMR (Endoscopic Mucosal Resection) is recommended, rather than surveillance, in patients with T1a EAC, BE with confirmed HGD, and BE with confirmed LGD. Endoscopic therapy is not recommended in patients with NDBE. EARLY ESOPHAGEAL CANCER Transhiatal esophagectomy Endoscopic Eradication Therapy Endoscopic ablation in BE can be performed using thermal energy, photochemical injury, or freezing with the goal of inducing superficial tissue necrosis, followed by healing with neo- squamous epithelium. While endoscopic therapy is currently only recommended in BE with dysplasia, once initiated, the goal of endoscopic ablation is the complete eradication of intestinal metaplasia EARLY ESOPHAGEAL CANCER Radiofrequency Ablation (RFA) RFA is the most commonly used method of endoscopic ablation in BE. RFA uses a bipolar electrode array and a generator to generate a thermal injury of limited depth (500–1,000 µm). Different sized ablation devices are designed for circumferential (360 degrees) or focal (90 or 60 degrees) RFA. EARLY ESOPHAGEAL CANCER Radiofrequency Ablation (RFA) Focal RFA Circumferential RFA  EARLY ESOPHAGEAL CANCER EMR (Endoscopic Mucosal Resection) Mucosectomy Advantages: allows an earlier histological diagnosis for initial tumors. Disadvantages: removes only small, initial tumors, and in these cases must be associated with other treatments  ENDOSCOPIC MUCOSECTOMY: TECHNIQUES One method utilizes submucosal fluid injection followed by the use of a cap to facilitate snare resection, and the other uses a banding device to create a “pseudopolyp” which can then be removed with a snare. EARLY ESOPHAGEAL CANCER: MUCOSECTOMY Inoperable esophageal cancer Palliative Therapy for Esophageal Cancer Palliative therapy is treatment aimed at preventing or relieving symptoms instead of trying to cure the cancer. The main purpose of this type of treatment is to improve the patient’s comfort and quality of life. Inoperable esophageal cancer Palliative Therapy for Esophageal Cancer Esophageal dilation This procedure is used to stretch out an area of the esophagus that is narrowed or blocked to allow better swallowing. A small balloon-like device or a device shaped like a cylinder is passed down the throat and pushed through the narrowed area to stretch it out. Inoperable esophageal cancer Palliative Therapy for Esophageal Cancer Other endoscopic procedures Several types of endoscopic procedures can be used to help keep the esophagus open in people who are having trouble swallowing. Procedures that may be used include: Esophageal stent placement Photodynamic therapy Electrocoagulation Laser ablation Argon plasma coagulation Inoperable esophageal cancer Esophageal stent placement A stent is a device that, once in place, self-expands (opens up) to become a tube that helps hold the esophagus open. Inoperable esophageal cancer Esophageal stent placement Stents are made of mesh material. Most often stents are made of metal, but they can also be made of plastic. Inoperable esophageal cancer Esophageal stent placement Using endoscopy, a stent can be placed into the esophagus across the length of the tumor. Inoperable esophageal cancer Percutaneous endoscopic gastrostomy or Jejunostomy for nutritional palliation in patients with inoperable esophageal cancer Esophageal cancer, is well known to have a poor prognosis. It is often diagnosed in the late stages, with dysphagia being the major symptom. Insufficient nutrition and lack of stimulation of the intestinal mucosa may worsen immune compromise due to toxic side effects. A poor nutritional status is a significant prognostic factor for increased mortality. Inoperable esophageal cancer P.E.G P.E.J.