Teorías relacionadas al tema - FACULTAD DE INGENIERÍA

I. INTRODUCCIÓN

1.3. Teorías relacionadas al tema

Treatment

Symptomatic leiomyomas or those that are larger than 5 cm should be excised ( Figure 10.2 ). Smaller tumors require observation with yearly follow-up, as they have a very small risk of malignant conversion. However, the only absolute proof of their benign nature is removal. To remove tumors in the proximal third of the esophagus, a cervical incision is used. For lesions in the middle third, either a right tho-racotomy or video-assisted thoracoscopic surgery (VATS) approach is used, and, finally, tumors in the distal third are approached from the left side. The tumor is located, and the overlying longitudinal esophageal muscle is split in the direction of its fibers, to reveal the mass. The tumor is then gently dissected away from contiguous tissues and the underlying submucosa. Once the tumor has been enucleated, the longitudinal muscle should be reapproxi-mated if possible.

Polyps

Cervical esophageal polyps are intraluminal growths gen-erally covered with normal epithelium, and have a core of fibroelastic material. The polyp may be removed by endoscopic electrocoagulation, or resected under direct vision using a lateral cervical esophagomyotomy.

ESOPHAGEAL CANCER

Esophageal cancer is the sixth most common malignancy worldwide. There are two main types, squamous cell car-cinoma (SCC) and adenocarcar-cinoma. SCC of the esopha-gus is most commonly found in African-Americans, while adenocarcinoma is more common in whites ⁵ . Unfortu-nately, most North American patients present with locally advanced (stage T3 and/or N1) disease, with lymphatic metastasis already present ⁶ . Within North America and Europe, the incidence of adenocarcinoma rose 100% in

Esophagus

Joseph B Zwischenberger , Daina W Parker, Casey M Sm ´ olarz , Kristin Kucera and Brent C Parker

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the 1990s and strongly correlated with gastroesophageal reflux disease (GERD), Barrett's metaplasia and diets high in fat ⁶ .

Risk factors

By far, the biggest risk factors for carcinoma of the esoph-agus are smoking and alcohol abuse. The combination

of both can increase a patient's risk of SCC from 25- to 100-fold. An increased incidence of esophageal carcinoma is found in patients with familial keratosis palmaris et plantaris (tylosis). Other environmental and/or nutri-tional factors that have been incriminated include zinc or nitrosamine exposure, malnutrition, vitamin deficiencies, anemia, poor oral hygiene and dental caries, previous gas-tric surgery, and long-term ingestion of hot foods or bev-erages. Furthermore, the following esophageal insults may also increase a patient's risk for cancer: achalasia, reflux esophagitis, Barrett's esophagus ⁷ , radiation esophagitis ⁸ , caustic burns, Plummer-Vinson syndrome, leukoplakia, esophageal diverticula, and ectopic gastric mucosa.

Characteristics and prognosis

Esophageal cancer, regardless of cell type, is aggressive for local growth and metastatic spread. Lack of an esophageal serosal layer favors local infiltration of surrounding tissue and adjacent lymph nodes, while the tumor tends to metas-tasize via the extensive submucosal lymphatics and blood supply. Cancers of the cervical esophagus drain to the deep cervical, paraesophageal, posterior mediastinal, and tra-cheobronchial lymph nodes and can infiltrate the tracheo-bronchial tree, aorta and left recurrent laryngeal nerve.

Tumors affecting the distal third of the esophagus (includ-ing most esophageal adenocarcinomas) spread to parae-sophageal, celiac and splenic hilar lymph nodes and may invade the diaphragm, pericardium, stomach, lungs, or liver.

The extensive mediastinal lymphatic communication is responsible for the finding of mediastinal, supraclavicular, or celiac lymph node metastasis in at least 75% of patients with esophageal carcinoma.

Histologically, SCC accounts for approximately 95%

of esophageal cancers worldwide. Located mainly in the thoracic esophagus, approximately 60% of these tumors are seen in the middle third and approximately 30% in the distal third. On gross pathology, SCCs can be grouped into four major categories: fungating, ulcerating, infiltrat-ing, and polypoid ⁹ . Polypoid tumors have a 5-year survival rate of 70%, while the other three types have a 5-year survival of less than 15% ¹⁰ .

Currently, adenocarcinoma is the most common type of esophageal cancer in the US. It originates from the super-ficial and deep glands of the esophagus most frequently near the gastroesophageal junction ( Figure 10.3 ). The ratio of whites to African-Americans with adenocarcinoma is 4 : 1, while the ratio of male : female is 8 : 1. The prognosis for patients with adenocarcinoma is largely dependent on tumor size ¹² . Tumors less than 5 cm in diameter are local-ized 40% of the time, while 25% have spread beyond the esophagus, and 35% have metastasized or are unresectable.

Conversely, when the tumor is larger than 5 cm, 10% are Figure 10.1 Esophagogram shows a typical leiomyoma.

Figure 10.2 Operation for leiomyoma of the esophagus. (a) Incision of the muscle wall. (b) Dissection of the muscle wall. (c) A traction stitch placed through the tumor. (d) Separation of the tumor from the mucosa. (e) Closure of the myotomy. Adapted from reference 4 , with permission.

localized, 15% have invaded mediastinal structures, and 75% have metastasized ¹² .

Diagnosis

Esophageal carcinoma may present with non-specific retrosternal discomfort, followed by dysphagia and weight loss ( Table 10.1 ). Patients tend to present in later stages of the disease because usually two-thirds of the lumen must be obstructed to cause dysphagia. Patients frequently complain of food ‘getting stuck’ at the location of the lesion. Pain can be caused by spasms or contractions proxi-mal to an obstruction, tumor invasion, interference with swallowing, or related to metastases in the surrounding esophageal lymph nodes. Because dysphagia is the chief complaint in 80–90% of patients with esophageal carci-noma ¹⁵ , any adult with symptoms should undergo esoph-agoscopy to rule out carcinoma. Likewise, esophesoph-agoscopy and biopsy are mandatory in every patient found to have esophageal stricture. Coughing and hoarseness are two other less common complaints and are usually associated with tumors of the cervical esophagus. As the tumor enlarges, esophageal obstruction results in progressive weight loss, regurgitation and aspiration. These factors contribute to the morbidity and mortality, regardless of the selected therapeutic regimen.

Various imaging techniques (chest X-ray, barium swal-low, computed tomography (CT), and positron emission tomography (PET)) can determine the presence and extent of disease; however, the diagnosis of esophageal cancer is based upon esophageal biopsy. Plain chest X-ray is abnor-mal in only 50% of patients with esophageal cancer.

The abnormalities most commonly seen are an air-fluid level in the obstructed esophagus, a dilated esophagus, abnormal mediastinal soft tissue representing adenopathy, or tracheal deviation. Unfortunately, the chest X-ray may be nor-mal even when the patient has advanced disease. Double-contrast barium swallow is used to determine tumor length and location. Advanced cancers present with luminal nar-rowing, ulceration and strictures, with an abrupt shelf-like proximal border ( Figure 10.4 ). CT or endoscopic ultra-sound may be used to identify the anatomic location and enlargement of the mediastinal, perigastric, or celiac lymph nodes. When used, contrast-enhanced CT scans should extend from the thoracic inlet to the liver, during full inspiration. Although magnetic resonance imaging (MRI) has not shown significant advantages over CT scan, recent studies show that T2-weighted MRI images are capable of showing seven layers of the esophagus. Further studies may reveal advantages of MRI compared with CT ¹⁶ .

Esophagoscopy, with subsequent brush cytology and tissue biopsy, is used to diagnose and determine the extent of longitudinal intramural tumor spread. The accuracy of brush cytology alone ranges from 85 to 97%, and biopsy alone ranges from 83 to 90%. When combined, they are more than 97% accurate ¹⁶ . If the depth of the tumor pre-vents diagnosis by biopsy or brush cytology, endoscopic ultrasound-guided fine-needle aspiration (FNA) should be used. Since the incidence of esophageal cancer is still relatively low in Western countries, early detection pro-grams (i.e. mass screening with barium swallow, flexible fiber optic esophagoscopy, or exfoliative cytology) are not cost effective.

Staging

Survival is closely correlated with the T and N stage, and celiac node involvement ¹⁷ . Stages of esophageal cancer are associated with 5-year survival rates of stage I 50–94%, stage II 15–65%, stage III 6–23%, and stage IV less than 5%, although reported stage IV survival varies ( Table 10.2 ) ¹⁸ ^, ¹⁹ . Figure 10.3 Adenocarcinoma of the esophagogastic junction.

From reference 11 , with permission.

Table 10.1 Clinical features of esophageal cancer

Sign or symptom Patients with symptom (%)

Dysphagia 87–95

Weight loss 42–71

Vomiting or regurgitation 29–45

Pain 20–46

Cough or hoarseness 7–26

Dyspnea 5

From reference 13 , with permission.

T1 lesions are limited to the mucosa or submucosa. T2 lesions penetrate into the muscularis propria, but not beyond ( Figure 10.5 ). T3 lesions penetrate the muscularis propria. T4 lesions invade locally into an adjacent struc-ture, such as the aorta ²¹ . T4 cancers can be reliably identi-fied by endoscopic ultrasound to prevent unnecessary surgical procedures while reducing associated morbidity and costs.

Lymph nodes (N stage)

Esophageal lymphatics are extensive and form a continu-ous network from the neck to the abdomen. Lymph node

involvement may be assessed using endoscopic ultrasound, CT, PET, MRI, or VATS combined with laparoscopy ( Table 10.3 ). Lymph nodes are considered malignant by endoscopic ultrasound when they are larger than 1 cm, hypoechoic with distinct margins, and are round in shape ²² . CT and endoscopic ultrasound imaging both rely on the anatomic size of the node to predict malignancy, but nei-ther can differentiate between hyperplastic nodes and nodes enlarged due to metastasis. Cytological sampling of lymph nodes and PET are currently used to evaluate N status. Endoscopic ultrasound and CT are used for image-directed FNA of mediastinal or celiac nodes. A more inva-sive staging technique, when indicated, combines VATS with laparoscopy, and has a 90–94% accuracy.

Unfortunately, even patients with negative nodal involvement often have recurrent disease. A study by Aloia et al . utilized immunohistochemical analysis using multiple tumor markers in node-negative esophageal cancer patients and showed significant prognostic value of certain tumor markers (low-level P-gp expression, high-level expression Figure 10.4 Double-contrast barium swallow shows abrupt

shouldered narrowing (arrow) at the transition between normal-appearing esophagus and the esophageal cancer.

Table 10.2 American Joint Committee on Cancer (AJCC) stage groupings for esophageal cancer

AJCC stage TNM grouping

Stage 0 Tis, N0, M0

Stage I T1, N0, M0

Stage IIA T2, N0, M0; T3, N0, M0 Stage IIB T1, N1, M0; T2, N1, M0 Stage III T3, N1, M0; T4, any N, M0 Stage IV Any T, any N, M1

Stage IVA Any T, any N, M1a Stage IVB Any T, any N, M2a

Figure 10.5 A T2 esophageal carcinoma. (a) A T2 tumor as seen by endoscopic ultrasound. The hypoechoic (black) tumor invades the hypoechoic (black) fourth ultrasound layer (muscularis propria) but does not breach the boundary between the fourth and fifth ultrasound layers (arrows). (b) A T2 tumor invades but does not breach the muscularis propria. From reference 20 , with permission.

of p53, and low-level expression of transforming growth factor- α (TGF- α )) in predicting outcomes following esophagectomy. Genetic mapping does continue to show promise regarding risk stratification ²³ .

Distant metastasis (M stage)

Endoscopic ultrasound is ideal for visualizing lymph nodes around the celiac axis and the left liver lobe; how-ever, it cannot fully assess the extent of metastatic disease.

It is the most accurate method for assessing locoregional disease, including depth of tumor invasion, length of tumor, degree of luminal stenosis, regional nodal disease, and involvement of adjacent structures. Endoscopic ultra-sound has a reported accuracy of 80–92% for T stage and 45–100% for N stage ²⁴ . CT is the most efficient screen for locoregional and distant metastatic disease. Although CT and MRI can detect mediastinal lymphadenopathy, mediastinal invasion and distant metastases ²⁵ , FNA or transbronchial biopsy is necessary to document malig-nancy. Patients with tumors of the upper and middle third of the esophagus also require bronchoscopy to view the pharynx, larynx and tracheobronchial tree for syn-chronous and metasyn-chronous malignancies. Furthermore, if a patient complains of bone pain, a bone scan should be ordered to evaluate for bone metastases ²⁶ .

The role of PET in esophageal cancer staging is evolving;

uniquely, PET does not rely on anatomic or structural distortion for detecting malignancy. ¹⁸ F-fluorodeoxyglu-cose (FDG)-PET increases recognition of distant metas-tasis, with increased emission in areas of increased glucose metabolism, but provides poor overall anatomic detail ²⁷ . The sensitivity of PET in evaluating distant metastases ranges from 67 to 88%, compared with 61–83% for CT.

The specificity of PET ranges from 92 to 93%, compared with 71–75% for CT ²⁷ ^– ²⁹ . Postchemoradiotherapy FDG-PET was found to be predictive of pathological response and survival in patients who underwent preoperative

chemoradiotherapy ³⁰ ^– ³² . Additional studies such as MRI, bone scan and staging mediastinoscopy are not performed routinely, and should be performed only if indicated based on the patient's complaints. MRI accurately detects T4 and metastatic disease, especially disease involving the liver; however, it tends to overstage lymph node involve-ment and is only 56–74% accurate in detecting lymph node involvement ³³ ^– ³⁵ . Comparing CT with MRI, the sen-sitivity and specificity for metastatic detection are almost equal, although CT scan is more cost-effective. Recent studies have found incremental increase in staging value of FDG-PET over CT scan, and some authors recom-mend PET-CT as the most effective preoperative staging technique ²³ .

Thoracoscopy and minimally invasive staging

VATS enables the surgeon to evaluate the extent of dis-ease because the entire thoracic cavity and esophagus can be visualized. In addition, lymph node biopsies may be taken as well ³⁴ . Thoracoscopy can also visualize metastatic disease involving nearby or adjacent structures, such as the trachea, azygos vein, aorta, pericardium, and diaphragm.

Krasna et al . ³⁶ reported the sensitivity, specificity, and positive and negative predictive values to be 80%, 100%, 100%, and 88%, respectively, with an accuracy of 93%

for the detection of thoracic lymph node involvement in patients with a primary esophageal tumor.

Abdominal laparoscopy is useful to determine whether the cancer has metastasized to the abdominal cavity. Dur-ing this procedure, biopsies are taken from the celiac axis, the surface of the peritoneal cavity, the esophagogastric junction, and the liver ³⁷ . Finally, laparoscopic ultrasound can visualize lymph nodes as small as 3 mm in diameter and helps to improve overall TNM staging accuracy.

Treatment

Tumor stage determines whether therapy should be curative or palliative. Patients who have lower-stage tumors (stage T1 or T2N0M0) have acceptable surgical cure rates.

Patients with more advanced tumors (T3 or N1) may require multimodality treatment as survival is less with surgery alone. Patients with T4 lesions with local invasion into surrounding vital structures and those with evidence of metastases should be treated palliatively.

Curative approaches

Early esophageal cancers are rare; however, when detected before invading beyond the mucosa and submucosa, less invasive methods of therapy may be used. Superficial esophageal cancers have been treated endoscopically by Table 10.3 Accuracy of staging techniques

Accuracy (%)

Modality T N M

Computed tomography 49–60 39–74 85–90 Endoscopic ultrasound 76–92 50–88 66–86 Magnetic resonance imaging 96 56–74

Positron emission tomography 48–76 71–91 Thoracoscopy or laparoscopy 90–94

From reference 13 , with permission.

mucosal resection, laser therapy, argon plasma coagulation, or photodynamic therapy.

Typically curative treatment for tumors staged higher than ‘ in situ ’ consists of a multimodality approach tailored to specific patient presentations. The multimodality approach is used because numerous reviews and clinical trials have failed to show that using any of the treatment options as a monotherapy decreases morbidity or mortality in patients with esophageal cancer. In patients with oper-able gastric or lower esophageal adenocarcinomas, a peri-operative regimen of cisplatin, epirubicin, and fluoroura-cil has been reported to decrease tumor size and stage and significantly improve overall survival ³⁸ .

However, there are many co-morbid factors that may decrease the likelihood of a patient tolerating a curative surgical procedure. These include heart disease, liver fail-ure, metastatic disease, malnutrition, infection, multisystem dysfunction, or invasion of a vital structure.

Once the patient is accepted for surgery, there are four described techniques for esophagectomies. These include transhiatal, transthoracic, en bloc, and video-assisted approaches. It is noteworthy that no one technique has been shown to significantly decrease morbidity and mortality or increase survival rates. However, the majority of surgeons do agree that the tumor location, surgeon experience and co-morbities should influence the surgical approach ³⁹ . Trans-thoracic exposure is recommended for mid- and upper-esophageal tumors that are adherent to adjacent structures.

Preoperative management

If the patient is malnourished and the esophageal obstruc-tion is tight, endoscopic dilataobstruc-tion of the malignant

stricture and insertion of a nasogastric feeding tube or an intraluminal stent for enteral nutrition are performed to achieve an intake of approximately 2000 calories per day.

Additionally total parenteral nutrition can be started for severe malnutrition. Some recommend a gastric feeding tube. Although expedient, a transabdominal gastric feed-ing tube can compromise the stomach for reconstruction.

Abscessed or severely carious teeth should be removed or repaired preoperatively to minimize the infection risk. If the patient has a history of prior gastric operations that may preclude the use of the entire stomach as an esopha-geal substitute, a barium enema or colonoscopy should be performed to assess the suitability of the colon as an esophageal replacement. Furthermore, the patient should undergo appropriate bowel prep in the event that a colonic interposition is required.

Transhiatal esophagectomy

Orringer et al. ⁴⁰ ^, ⁴¹ developed the transhiatal esophagec-tomy without thoracoesophagec-tomy to avoid pulmonary and intrathoracic leak complications. During a transhiatal esophagectomy, the entire thoracic esophagus is resected via an enlarged hiatus and reconstructed by connecting the stomach to the residual cervical esophagus above the level of the clavicles ( Figure 10.6 ). A recent review of the literature and subsequent meta-analysis has shown that no esophagectomy technique has proven superior. Transhiatal esophagectomies, however, result in significantly less blood loss when compared with the transthoracic approach ⁴³ . Contraindications specific to the transhiatal approach include evidence of tumor invasion of the aorta, pericar-dium, and/or tracheobronchial tree ⁴⁴ .

Figure 10.6 Overview of transhiatal esophagectomy with gastric mobilization and gastric pull-up for cervical-esophagogastric anastomosis.

Adapted from reference 42 .

While the transhiatal approach results in fewer pul-monary complications versus transthoracic resections, it results in a higher rate of leaks at the cervical anastomosis.

The majority of these leaks, however, are found with rou-tine postoperative barium swallows and will resolve spon-taneously or with drainage ⁴³ . Because there are fewer risks associated with the transhiatal approach, some surgeons advocate its use regardless of tumor location if no local tumor invasion is anticipated.

Transthoracic esophagectomy

Transthoracic esophagectomy allows complete lymph node dissection under direct vision, complete resection of tumor mass and adjacent tissue, but is associated with higher perioperative morbidity. The stomach is mobilized using a midline celiotomy and either a right thoracotomy (to approach proximal esophageal lesions) or a left thora-cotomy (to approach distal lesions). Unfortunately, a com-bined thoracic and abdominal operation in a debilitated patient may lead to respiratory insufficiency that requires prolonged mechanical ventilatory assistance and increased mortality ⁴⁵ ^, ⁴⁶ . Although disruption of an intrathoracic esophageal anastomosis is reported less frequently than a cervical anastomotic leak from a transhiatal esophagec-tomy, the consequences, including mediastinitis and sepsis, are fatal in 50% of patients. An additional disadvantage of the intrathoracic esophageal anastomosis is inadequate long-term relief of dysphagia due to anastomotic suture-line tumor recurrence or the development of reflux esophagitis above the anastomosis. Finally, intrathoracic esophago-gastric anastomoses are almost invariably associated with the development of reflux esophagitis, due to disruption of the lower esophageal sphincter mechanism.

En bloc esophagectomy

Because many patients present with metastases to regional lymph nodes and surrounding tissue and organs, a more radical resection, the en bloc esophagectomy, may be nec-essary. An envelope of normal tissue is removed, along with the spleen, celiac nodes, posterior pericardium, azygos vein, thoracic duct, and adjacent diaphragm. With this aggressive surgery, operative mortality ranges from 5.1 to

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