Esophageal Cancer Course 2020-2021 PDF

Titu Maiorescu University of Bucharest Faculty of Medicine Medicine in English Programme COURSE NO. 04 // ESOPHAGEAL CANCER © MCA // 2020-2021 // Rev. 01  DEFINITION CLASIFFICATION ANATOMY  Is a serious condition of the...

Titu Maiorescu University of Bucharest Faculty of Medicine Medicine in English Programme COURSE NO. 04 // ESOPHAGEAL CANCER © MCA // 2020-2021 // Rev. 01  DEFINITION CLASIFFICATION ANATOMY  Is a serious condition of the esophagus, mainly represented by 2 major Definition. histological types: squamous-cell carcinoma (ESCC) and adenocarcinoma Main types (EAC), with a very low survival rates (less than 10% at 5 years).  Esophageal cancer is the eighth most frequently diagnosed cancer worldwide, and because of its poor prognosis it is the sixth most common cause of cancer-related death. It caused about 400,000 deaths in 2012, accounting for about 5% of all cancer deaths (about 456,000 new cases were diagnosed, representing about 3% of all cancers). ESCC (esophageal squamous-cell carcinoma) comprises 60–70% of all cases of esophageal cancer worldwide, while EAC (esophageal adenocarcinoma) accounts for a further 20– Incidence 30% (melanomas, leiomyosarcomas, carcinoids and lymphomas are less common types).The incidence of the two main types of (1) esophageal cancer varies greatly between different geographical areas. In general, ESCC is more common in the developing world, and EAC is more common in the developed world. The worldwide incidence rate of ESCC in 2012 was 5.2 new cases per 100,000 person-years, with a male predominance (7.7 per 100,000 in men vs. 2.8 in women). It was the common type in 90% of the countries studied. ESCC is particularly frequent in the so-called "Asian esophageal cancer belt", an area that passes through northern China, southern Russia, north-eastern Iran, northern Afghanistan and eastern Turkey.  In 2012, about 80% of ESCC cases worldwide occurred in central and south-eastern Asia, and over half (53%) of all cases were in China. The countries with the highest estimated national incidence rates were (in Asia) Mongolia and Turkmenistan and (in Africa) Malawi, Kenya and Uganda. The problem of esophageal cancer has long been recognized in the eastern and southern parts of Sub-Saharan Africa, where ESCC appears to predominate. Incidence In Western countries, EAC has become the dominant form of the disease, following an (2) increase in incidence over recent decades (in contrast to the incidence of ESCC, which has remained largely stable). In 2012, the global incidence rate for EAC was 0.7 per 100,000 with a strong male predominance (1.1 per 100,000 in men vs. 0.3 in women). Areas with particularly high incidence rates include northern and western Europe, North America and Oceania. The countries with highest recorded rates were the UK, Netherlands, Ireland, Iceland and New Zealand. EPIDEMIOLOGY and ETIOLOGY  Squamous-cell Carcinoma (ESCC): Is more common in the developing world Arises from the epithelial cells Agravating causes include: tobacco, alcohol, very hot drinks, poor diet, Etiology. and chewing betel nut. Achalasia Epidemiology Postcaustic esophagitis Human papilloma virus (1) Tylosis: is a rare familial disease with autosomal dominant inheritance that has been linked to a mutation in the RHBDF2 gene, present on chromosome 17: it involves thickening of the skin of the palms and soles and has a high lifetime risk of squamous cell carcinoma rates. Low rates of incidence under 40 years Prototype of less affected pacients: male, white, Caucasian, non-smoking and non-drinking.  Esophageal Adenocarcinoma (EAC), More common in the developed world. Arises from glandular cells present in the lower third of the esophagus, often where they have already transformed to intestinal cell type (a condition known as Barrett's esophagus) The most common causes of the Etiology. adenocarcinoma type are smoking tobacco, obesity, and acid reflux. Epidemiology 3 main origins: (2) Malignant transformation of the columnar epithelium of the esophagus (a preexisting Barrett disease); Heterotopic islands of columnar epithelium; Submucosal glands of the lower-third part of the esophagus. 1-2% of all Barrett cases will develop into a EAC. GERD is common in patients with sclerodermia. 33-50% of these patients develop a Barrett syndrome PATHOLOGY  Anatomical distribution: 20% develops in the upper esophagus to the aortic arch, in 50% of cases it affects the middle third of the esophagus, and 30% is placed at the level of the distal esophagus, without ever invading cardia (according to some authors). Macroscopically we have 3 forms: Proliferative (vegetative): it presents as a papillomatous tumor with a broad implantation base, which develops in the esophageal lumen; easily bleeds to the touch, causes occult bleeding Pathology // and by ulceration takes an ulcerative appearance; Ulcerative form: looks loke as a crateriform ESCC ulceration on a hard infiltrating background, having thick and prominent edges; the bottom of the ulceration is irregular, of a skinny appearance. This form bleeds more often, becomes infected early, and can lead to penetration or even perforation; Infiltrative forms: evolves slowly, silently, as it belatedly obstructs the esophageal lumen. A special form is represented by "early cancer" carcinoma, described by the Japanese gastroenterologists, particularly by screening methods in the infraclinical stage, being characterized by tumor infiltration strictly limited to mucosa and submucosa, which can nevertheless give ganglion metastases.  EAC develops more than 90% in the distal esophagus, with three possible different origins: Proximal progression of gastric cancer located in the fornix; Cardia as a primary location; From the mucosa of the distal esophagus, wallpapered with a cylindrical single-layer gastric epithelium, (BARRETT esophagus). Adenocarcinomas developed against the background of a BARRETT esophagus represent about 20 – 50% of all adenocarcinomas developed at the Pathology // gastroesophageal junction. In these cases it is difficult to determine whether the primary EAC tumor is gastric or esophageal (metaplastic columnar cells). The Japanese Society for Esophagus Diseases categorizes this tumor type into three categories: esocardial, when the most important tumor mass is above the cardia; cardially, when the tumour masses are evenly distributed below and above the cardia, synonymous with the term cardied carcinoma, which applies to adenocarcinomas of the esogastric junction, defined with a limit of 5 cm proximal and distal to the true junction or line Z; cardioesophageal), when the most significant tumor mass is on the gastric fornix. EXTENSION ROUTES  3 main extension routes: The local extension by invasion of the mucosa, mucosal corion, submucosa, muscle tunic, propagating in a longitudinal direction on the submucosa path and towards neighboring tissues by contiguity (the absence of serous tunic makes dysphagia occur only when the tumor affects 60% of the circumference, respectively of the esophageal lumen. In general, it is considered that if the axial invasion on the esophagus is greater than 6 to 8 cm, the tumor is non- resectable. Between 5 and 10% of patients with squamocellular carcinoma, develop tracheo-esophageal or broncho- Extension esophageal fistulas. Aortic invasion is a rare cause of aorto- esophageal fistula, as the last complication of this tumor. Routes Lymphatic extension by the lymphatic collectors, which leave the epiesophageal lymph nodes, accompanying the vague vessels and nerves reaching the paraesophageal ganglia and then the main mediastinal ganglia. Lymphatic propagation usually takes place along the main vessels, draining the lymph into the lymphatic canals of the internal, cervical, supraclavicular, paratracheal, subcardial, para-esophageal, para-aortic, pericardial, gastric coronary, gastro-hepatic or hepatoduodenal and celiac ligament. Remote lymphatic metastasis, the so-called "jump metastasis", occur in the lymph nodes of the neck or mediastinal, without the gradual and progressive invasion of adjacent lymph nodes.  SIGNS and SYMPTOMS  Dysphagia is the most pronounced, late and perhaps the most common symptom of esophageal syndrome that usually sets in insidiously in esophageal carcinoma. It can be accompanied or preceded by asthenia, dyspeptic disorders, diarrhea, subfebrile state, anemia, regurgitation and sialorea, followed by the appearance of pain which is also a rather late sign. occurs when the esophageal lumen has been reduced by 50- 75% of its normal size or when 2/3 of the circumference of the esophageal wall has been invaded. Signs and Unfortunately, the appearance of dysphagia is also associated with an advanced phase of the disease. Many patients are symptomatic of two to four months before. Symptoms In some patients, dysphagia may be absent. Dysphagia, at first, can be intermittent, then it is progressive, selective first for solid or semi-solid foods, and then for // liquids, in order to finally become quasi-total, representing one of the determining causes of inanimation and neoplastic cheese. Even if at first it can have some small oscillations in intensity due to the over-added functional element, it has no ESCC (1) paradoxical shades and no oscillations too large, as in achalasia. Regurgitation is a late symptom in esophageal cancer and occurs when dysphagia is well shaped. Weight loss is a constant sign of esophageal carcinoma, with an average decrease of about 10 to 20 kg. Persistent retrosternal pain unrelated to swallowing and sudden onset of hiccups, are obvious signs of invasion of the mediastinum or diaphragm The hoarseness or bitonal voice is due to direct invasion of the larynx or paralysis of the recurrent nerve, invaded by the tumor process.  Are similar to squamocellular carcinoma, dysphagia, odinophagia and weight loss being the most common symptoms. Small differences might suggest Signs and EAC, such as: anorexia, early satiety, nausea, vomiting or Symptoms hemorrhage. Anorexia and weight loss precede the // appearance of dysphagia. The history of the disease may EAC (1) be suggestive for clinical diagnosis, with a history of long- term gastroesophageal reflux disease, BARRETT's esophagus or long-term consumption of alcohol and tobacco in a man over 60 years of age. DIAGNOSIS  Imaging Techniques: Radiological: Simple RX; Barium intake (static); Barium intake (dynamic, Paraclinical fluoroscopy); CT Scan; Diagnosis PET-CT MRI Upper digestive endoscopy Tumor markers  Recommended procedure: thin layer of Gastrographin or the double-contrast technique, with the patient laying on the back, with a concurrent Valsalva`s maneuver. Paraclinical Main radiological markers: narrowing of the esophagus, with Diagnosis irregular contour and and segmental stiffness; filling defect (lacunary image) with or // without interruption of transit; incontinent cardia, when the tumor process keeps the cardia permanently Ba. Intake open as a result of parietal neoplastic infiltration; discharge through a filiform channel, anfractuous and rigid and eccentric, with slight retro-dilation; multiple, irregular lacunary images with an anarchic disposition, able to radically alter the normal appearance of esophageal transit. ESCC ESCC EAC EAC EAC  The endoscopic aspect of esophageal cancer: a segmental ulceration or infiltration, either in the form of a vegetative, proliferative formation, which bleeds easily to the touch. Endoscopy allows the assessment of circumferential extension and Paraclinical degree of obstruction, as well as the presence or absence of BARRETT-type metaplasia. Diagnosis // The method can be combined with Upper the harvesting of esophageal cytological material, but cytology sometimes has contradictory Endsocopy results. Esophageal cytology harvested by brushing the mucosa with an esophageal probe or by abrasive endoscopic brushing, will be followed by a histological examination on the blade, with positive results in 85% of cases.  Better viewing of the layers involved in the tumoral extension Paraclinical Diagnosis // Endoscopic Ultrasound  Has an accuracy of 82 – 98% Indispensable to TNM classification Paraclinical Diagnosis // CT Scan  Has an accuracy of 82 – 98% Indispensable to TNM classification Paraclinical Diagnosis // CT Scan Paraclinical Diagnosis // MRI  The most widely used tracer is 18-FDG (Fluoro-2-Dezoxy-D- Glucose) Paraclinical Diagnosis // PET-CT Paraclinical Main markes: Diagnosis // CEA: carcino-embriogenic Cancer antigen; SCA: squamo-cellular antigen Markers STADIALIZATION  TNM is the most widely used staging system Latest 8th Edition of AJCC (American Joint Committee on Cancer): T status Tis High-grade dysplasia T1 Invasion into the lamina propria, muscularis mucosae, or submucosa T2 Invasion into muscularis propria Staging // T3 T4a Invasion into adventitia Invades resectable adjacent structures (pleura, pericardium, diaphragm) TNM T4b Invades unresectable adjacent structures (aorta, vertebral body, trachea) System N status N0 N1 No regional lymph node metastases 1 to 2 positive regional lymph nodes N2 3 to 6 positive regional lymph nodes N3 7 or more positive regional lymph nodes M status M0 No distant metastases M1 Distant metastases Histologic grade G1 Well differentiated G2 Moderately differentiated G3 Poorly differentiated G4 Undifferentiated  AJCC 8th Ed. Stage Groupings: Adenocarcinoma Squamous cell carcinoma Stage T N M Grade T N M G Location 0 is 0 0 1 is 0 0 1 Any IA 1 0 0 1-2 1 0 0 1 Any IB 1 0 0 3 1 0 0 2-3 Any 2 0 0 1-2 2-3 0 0 1 Lower Staging // IIA 2 0 0 3 2-3 0 0 1 Upper, middle TNM 2-3 0 0 2-3 Lower System IIB 3 0 0 Any 2-3 0 0 2-3 Upper, middle 1-2 1 0 Any 1-2 1 0 Any Any IIIA 1-2 2 0 Any 1-2 2 0 Any Any 3 1 0 Any 3 1 0 Any Any 4a 0 0 Any 4a 0 0 Any Any IIIB 3 2 0 Any 3 2 0 Any Any IIIC 4a 1-2 0 Any 4a 1-2 0 Any Any 4b Any 0 Any 4b Any 0 Any Any Any 3 0 Any Any 3 0 Any Any IV Any Any 1 Any Any Any 1 Any Any TREATMENT  Treatment with the intention of radicalization or curative: block esophagemectomy, total esophagectomy with radical lymphadenectomy, standard resections, stations I and II; radical radiotherapy, for early cancer; laser photocoagulation and photodynamic therapy of "in situ" tumors; "stripping“- esophagemectomy in the esophageal cancer in situ and stages I and II; association of surgery with non-surgical methods for Strategies preoperative "sterilization" of esophageal cancer, stage I: immunotherapy, radiotherapy, chemotherapy. Palliative treatment: surgical: surgical bypass, abdomino-cervical esophagectomy, "standard" esophagemomies; palliative radiotherapy; just chemotherapy; transtumor intubation or stenting; external bypass; non-specific immunotherapy. Adjuvant and neoadjuvant therapy  Thoracic esophageal tumors: Given that the resection safety margin is 10 cm, we have only 1 option: subtotal esophagectomy. Combined 2-stage approach (the Ivor-Lewis / Lewis – Tanner): initial laparotomy (to construct the gastric tube) + right thoracotomy (to excise the tumor and perform the anastomosis) Types of Combined 3-stage approach (the MCKewon procedure): Ivor-Lewis + a cervical incision procedures for upper anastomosis; Esophagectomy by transhiatal abdominal (1) and cervical approach (w/o thoracotomy): the Orringer procedure. Consists of an abdominal incision + cervical incision. Drawbacks: blind dissection of the esophagus through cervical and abdominal approach; Esophageal stripping: the stomach is prepared through an abdominal incision and the esophagus is sectioned through a cervical incision.  Eso-gastric junction tumors: Based on a 3-type discition (by Siewert): Type 1: EAC of the lower esophagus with a top-to-down invasion of the gastric junction; Type 2: EAC developed directly in the cardia (the “true cardia EAC); Types of Type 3: Subcardia EAC with a down-to-top invasion of the gastric junction. procedures Options: (2) For type 1: esophagectomy + upper polar gastrectomy (mediastinal or thoracic approach); For type 2: total esophagectomy + resection of the gastric fundus + station 2 lymph ganglia resection w eso-gastric anastomosis; For type 3: distal esophagectomy + total gastric resection with an transhiatal approach.  Gastric tube preparation: The stomach is preferred due to its plastic Types of characteristics, proximity to the esophagus, good blood supply from many sources, length and the procedures possibility of using just 1 anastomosis. As the vagus nerves are severed during (2) esophagectomy, we must associate a pyloroplasty procedure to ensure proper gastric clearance. Buchner technique: constructing a large gastric tube out of the great curvature. Postoperative X-Ray Control (normal) Specimens: esophagus and fornix  Complications: Fistula is the most feared complication; Pneumothorax; Pleural retentions; Pneumonia; Acute respiratory deficiency. Types of procedures (3)  Forms of endoscopic therapy have been used for stage 0 and I disease: endoscopic mucosal resection (EMR) and mucosal ablation using radiofrequency ablation, photodynamic therapy, Nd-YAG laser, or argon plasma coagulation. Laser therapy is the use of high-intensity light to destroy tumor cells while affecting only the treated area. This is typically done if the cancer cannot be removed by surgery. Photodynamic therapy, a type of laser therapy, involves the use of drugs that are absorbed by cancer cells; when exposed to a special light, the drugs become active and destroy the cancer cells. Stenting is reserved for patients that cannot undergo Other surgery. Metalic self-expandable mesh stents are generally used. options  Chemotherapy depends on the tumor type but tends to be cisplatin-based (or carboplatin or oxaliplatin) every three weeks with fluorouracil (5-FU) either continuously or every three weeks. In more recent studies, addition of epirubicin was better than other comparable regimens in advanced nonresectable cancer. Adjuvant Chemotherapy may be given after surgery (to reduce risk of recurrence), before Treatment surgery (neoadjuvant) or if surgery is not possible; in this case, cisplatin and 5-FU are used. Radiotherapy is given before, during, or after chemotherapy or surgery, and sometimes on its own to control symptoms. In patients with localized disease but contraindications to surgery, "radical radiotherapy" may be used with curative intent.  Preoperative radiotherapy (ext): For 4 weeks, up to a total of 40 Gy (received), with surgery after 4 – 6 weeks (to allow the inflammatory response to calm down); Postoperative radiotherapy (ext): Adjuvant Most used dosage: 45 Gy, in 20 sessions, 5 session per week. Treatment By some authors reduces the local occurrence by 30 – 50%; Internal (brachytherapy) may be used, and it is based on Cobalt-60, Iridium-192 or Cesium-137 Thank you!