Oesophagogastric junctional adenocarcinoma (OGJ adenocarcinoma) is a cancer of the lower part of the oesophagus with a rising incidence in Western countries. [1] This disease is often linked to Barrett's oesophagus.
The incidence of OGJ adenocarcinoma is rising rapidly in Western countries especially in recent decades, in contrast to the declining frequency of distal gastric adenocarcinoma. Treatment options for adenocarcinomas involving the oesophagogastric junction are limited and the overall prognosis is extremely poor, with a five-year survival rate of approximately 30% with surgery alone. [2]
There are several established risk factors for OGJ adenocarcinoma. The biggest risk factors include gastroesophageal reflux disease (GERD) and Barrett's oesophagus. Other risk factors include smoking (with a twofold-increase) and obesity. [3]
The clinical features of OGJ adenocarcinoma are variable depending on the extent of the tumor. Early stages are oftentimes asymptomatic or have difficulty swallowing. More advanced stages can present with signs and symptoms of anemia, especially iron deficiency anemia from chronic gastrointestinal bleeding, weight loss, cervical adenopathy, hoarseness or change in voice, and progressive difficulty with swallowing (initially with solid foods and then with liquids). [4]
Distant metastases typically occur in the liver, lungs, bones, and adrenal glands and can manifest with symptoms typical of involvement with these sites (e.g. abdominal pain, pathological fractures, dyspnea). However, there have been described cases of atypical metastasis sites including the muscle, brain, and skin. [5]
The diagnostic workup for OGJ adenocarcinoma usually involves performing an endoscopy with endoscopic biopsy of suspicious looking tissue. Accurate staging of tumor extent and involvement of surrounding tissue or distant metastases is critical to establishing a prognosis, and is usually guided by endoscopic ultrasound, computed tomography scans, and/or positron emission tomography scans to establish the extent of disease. Additionally, genetic analysis of the tumor may yield mutations that may be clinically significant, as described below.
There is no standardized system for the classification of OGJ adenocarcinoma. The Siewart classification system is a classification scheme used for OGJ adenocarcinomas that has been adopted by many clinicians. [6]
Siewart described three different categories of OGJ adenocarcinoma, all based upon anatomic location:
The classification system establishes guidelines for surgical approaches to tumor resection.
OGJ adenocarcinoma is a highly mutated and heterogeneous disease. Microsatellite instability (MSI) can be observed and coincides with an elevated number of somatic mutations. Potentially actionable coding mutations have been identified in 67 genes, including those in CR2, HGF, FGFR4 and ESRRB.
Numerous genes harboring somatic coding mutations and copy number changes in the microsatellite stable (MSS) OGJ adenocarcinomas are also known to be altered with similar predicted functional consequence in other tumour types. TP53, SYNE1, and ARID1A are among the most frequently mutated genes. [7]
Notably, up to one third of OGJ adenocarcinomas have been found to have human epidermal growth factor receptor 2 (HER2) overexpression or amplification, which may be targetable with trastuzumab, conferring a modest survival benefit based on initial clinical trials. [8] [9]
There is no established consensus on treatment approaches for OGJ adenocarcinoma. The mainstay of treatment is surgical resection, guided by the Siewart classification system, followed by adjuvant chemotherapy for advanced disease. [10]
Gastroenterology is the branch of medicine focused on the digestive system and its disorders. The digestive system consists of the gastrointestinal tract, sometimes referred to as the GI tract, which includes the esophagus, stomach, small intestine and large intestine as well as the accessory organs of digestion which include the pancreas, gallbladder, and liver. The digestive system functions to move material through the GI tract via peristalsis, break down that material via digestion, absorb nutrients for use throughout the body, and remove waste from the body via defecation. Physicians who specialize in the medical specialty of gastroenterology are called gastroenterologists or sometimes GI doctors. Some of the most common conditions managed by gastroenterologists include gastroesophageal reflux disease, gastrointestinal bleeding, irritable bowel syndrome, inflammatory bowel disease (IBD) which includes Crohn's disease and ulcerative colitis, peptic ulcer disease, gallbladder and biliary tract disease, hepatitis, pancreatitis, colitis, colon polyps and cancer, nutritional problems, and many more.
The esophagus or oesophagus, colloquially known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the stomach. The esophagus is a fibromuscular tube, about 25 cm (10 in) long in adults, that travels behind the trachea and heart, passes through the diaphragm, and empties into the uppermost region of the stomach. During swallowing, the epiglottis tilts backwards to prevent food from going down the larynx and lungs. The word oesophagus is from Ancient Greek οἰσοφάγος (oisophágos), from οἴσω (oísō), future form of φέρω + ἔφαγον.
Barrett's esophagus is a condition in which there is an abnormal (metaplastic) change in the mucosal cells lining the lower portion of the esophagus, from stratified squamous epithelium to simple columnar epithelium with interspersed goblet cells that are normally present only in the small intestine and large intestine. This change is considered to be a premalignant condition because it is associated with a high incidence of further transition to esophageal adenocarcinoma, an often-deadly cancer.
Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voice, enlarged lymph nodes ("glands") around the collarbone, a dry cough, and possibly coughing up or vomiting blood.
Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymphomas and mesenchymal tumors may also develop in the stomach. Early symptoms may include heartburn, upper abdominal pain, nausea, and loss of appetite. Later signs and symptoms may include weight loss, yellowing of the skin and whites of the eyes, vomiting, difficulty swallowing, and blood in the stool, among others. The cancer may spread from the stomach to other parts of the body, particularly the liver, lungs, bones, lining of the abdomen, and lymph nodes.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior is driven by mutations in the KIT gene (85%), PDGFRA gene (10%), or BRAF kinase (rare). 95% of GISTs stain positively for KIT (CD117). Most (66%) occur in the stomach and gastric GISTs have a lower malignant potential than tumors found elsewhere in the GI tract.
Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract and accessory organs of digestion, including the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The symptoms relate to the organ affected and can include obstruction, abnormal bleeding or other associated problems. The diagnosis often requires endoscopy, followed by biopsy of suspicious tissue. The treatment depends on the location of the tumor, as well as the type of cancer cell and whether it has invaded other tissues or spread elsewhere. These factors also determine the prognosis.
Adenocarcinoma in situ (AIS) of the lung —previously included in the category of "bronchioloalveolar carcinoma" (BAC)—is a subtype of lung adenocarcinoma. It tends to arise in the distal bronchioles or alveoli and is defined by a non-invasive growth pattern. This small solitary tumor exhibits pure alveolar distribution and lacks any invasion of the surrounding normal lung. If completely removed by surgery, the prognosis is excellent with up to 100% 5-year survival.
Signet ring cell carcinoma (SRCC) is a rare form of highly malignant adenocarcinoma that produces mucin. It is an epithelial malignancy characterized by the histologic appearance of signet ring cells.
Esophageal pH monitoring is the current gold standard for diagnosis of gastroesophageal reflux disease (GERD). It provides direct physiologic measurement of acid in the esophagus and is the most objective method to document reflux disease, assess the severity of the disease and monitor the response of the disease to medical or surgical treatment. It can also be used in diagnosing laryngopharyngeal reflux.
Adenocarcinoma of the lung is the most common type of lung cancer, and like other forms of lung cancer, it is characterized by distinct cellular and molecular features. It is classified as one of several non-small cell lung cancers (NSCLC), to distinguish it from small cell lung cancer which has a different behavior and prognosis. Lung adenocarcinoma is further classified into several subtypes and variants. The signs and symptoms of this specific type of lung cancer are similar to other forms of lung cancer, and patients most commonly complain of persistent cough and shortness of breath.
Endoscopic mucosal resection is a technique used to remove cancerous or other abnormal lesions found in the digestive tract. It is one method of performing a mucosectomy.
Field cancerization or field effect is a biological process in which large areas of cells at a tissue surface or within an organ are affected by carcinogenic alterations. The process arises from exposure to an injurious environment, often over a lengthy period.
Nivolumab, sold under the brand name Opdivo, is a medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction (GEJ) cancer. It is used by slow injection into a vein.
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is given by slow injection into a vein.
Zolbetuximab is an experimental monoclonal antibody against isoform 2 of Claudin-18. It is under investigation for the treatment of gastrointestinal adenocarcinomas and pancreatic tumors. IMAB362 was developed by Ganymed Pharmaceuticals AG. Astellas Pharmaceuticals acquired the rights to Zolbetuximab in December, 2016 when it acquired Ganymed Pharmaceuticals.
Gastrointestinal intraepithelial neoplasia is also known as gastrointestinal dysplasia. Gastrointestinal dysplasia refers to abnormal growth of the epithelial tissue lining the gastrointestinal tract including the esophagus, stomach, and colon. Pancreatic, biliary, and rectal Intraepithelial Neoplasia are discussed separately. The regions of abnormal growth are confined by the basement membrane adjacent to the epithelial tissue and are thought to represent pre-cancerous lesions.
The Siewert-Stein classification is a system of anatomical classification used for adenocarcinomas of the esophagogastric junction.
Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the lining of the respiratory and digestive tracts.
Trastuzumab deruxtecan, sold under the brand name Enhertu, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the topoisomerase I inhibitor deruxtecan. It is licensed for the treatment of breast cancer or gastric or gastroesophageal adenocarcinoma. Trastuzumab binds to and blocks signaling through epidermal growth factor receptor 2 (HER2/neu) on cancers that rely on it for growth. Additionally, once bound to HER2 receptors, the antibody is internalized by the cell, carrying the bound deruxtecan along with it, where it interferes with the cell's ability to make DNA structural changes and replicate its DNA during cell division, leading to DNA damage when the cell attempts to replicate itself, destroying the cell.