CHEST WALL, LUNG, MEDIASTINUM, and PLEURA TRACHEA

ANATOMY composed of cartilaginous and membranous portions: cricoid cartilage, the first complete cartilaginous ring of the airway and consists of an anterior arch and a posterior broad-based plate arytenoid cartilages - articulate with the posterior cricoid plate vocal cords - originate from the arytenoid cartilages and then attach to the thyroid cartilage subglottic space - narrowest part of the trachea internal diameter: approximately 2 cm begins at the inferior surface of the vocal cords and extends to the first tracheal ring The remainder of the distal trachea is 10.0 to 13.0 cm long, consists of 1822 rings, and has an internal diameter of 2.3 cm.

TRACHEAL INJURY
postintubation injuries Collectively termed tracheal injuries Injury secondary to endotracheal intubation is most commonly the result of overinflation of the cuff Although high-volume/low-pressure cuffs are now ubiquitous, they can easily be overinflated, and pressures can be generated that are high enough to cause ischemia of the contiguous airway wall. In some patients, periods of ischemia as short as 4 hours may be all that is required to induce an ischemic event significant enough to lead to scarring and stricture. With prolonged overinflation and consequent fullthickness destruction of the airway, fistula development between the innominate artery and esophagus may ensue. Tracheal stenosis is nearly always iatrogenic. secondary to either endotracheal intubation or tracheostomy due to scarring and local injury Factors associated with an increased risk of tracheal stenosis incorrect placement of the tracheostomy through the first tracheal ring or the cricothyroid membrane where the airway is narrowest use of a large tracheostomy tube, transverse incision on the trachea even a properly placed tracheostomy can lead to tracheal stenosis secondary to scarring and local injury mild ulceration and stenosis frequently are seen after tracheostomy removal. can be minimized by using the smallest tracheostomy tube possible and downsizing as soon as the patient will tolerate it, and by using a vertical tracheal incision without removing cartilage. primary symptoms of tracheal stenosis: stridor dyspnea on exertion length of time to onset of symptoms after extubation or after tracheostomy decannulation varies, usually ranging from 2 to 12 weeks; however, symptoms can appear immediately or as long as 1 to 2 years later. Frequently, patients are misdiagnosed as having asthma or bronchitis, and treatment for such illnesses can persist for some time before the correct diagnosis is discovered.

BLOOD SUPPLY enters the airway near the junction of the membranous and cartilaginous portions of the airway It is segmental each entering small branch supplies a segment of 1.0 to 2.0 cm, which limits circumferential mobilization to that same distance. vessels are interconnected along the lateral surface of the trachea by an important longitudinal vascular anastomosis that feeds transverse segmental vessels to the soft tissues between the cartilages. arteries supplying the trachea: inferior thyroid Subclavian supreme intercostals internal thoracic innominate superior and middle bronchial arteries

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ACUTE MANAGEMENT In nearly all postintubation injuries the injury is transmural, and significant portions of the cartilaginous structural support are destroyed treatment of tracheal stenosis: resection and primary anastomosis laser ablation temporizing dilation using a rigid bronchoscope - useful to gain immediate relief of dyspnea and to allow full assessment of the lesion in the early phase of evaluating patients Rarely, if ever, is a tracheostomy necessary. internal stents, typically silicone T tubes - useful for patients who are not operative candidates due to associated comorbidities Wire mesh stents - should not be used, given their known propensity to erode through the wall of the airway use of balloon dilation and tracheoplasty also has been described, although their efficacy is marginal Most intubation injuries are located in the upper third of the trachea, so tracheal resection usually is done through a collar incision. Resection typically involves 2 to 4 cm of trachea for benign stenosis. However, a primary anastomosis can still be performed without undue tension, even if up to one half of the trachea needs to be resected. When resection for a postintubation injury is performed, it is critical to fully resect all inflamed and scarred tissue. Tracheostomies and stents are not required postoperatively, and the patient often is extubated in the operating room or shortly thereafter.

present with bleeding, although it usually is not massive, it must not be ignored or simply attributed to general airway irritation or wound bleeding With significant bleeding, the tracheostomy cuff can be hyperinflated to temporarily occlude the arterial injury. If such an effort is unsuccessful, the tracheostomy incision should immediately be opened widely and a finger inserted to compress the artery against the manubrium.

TRACHEAL FISTULAS
TRACHEOINNOMINATE ARTERY FISTULA
two causes 1. too low a placement of the tracheostomy Tracheostomies should be placed through the second to fourth tracheal rings without reference to the location of the sternal notch. When they are placed below the fourth tracheal ring, the inner curve of the tracheostomy cannula will be positioned to exert pressure on the upper surface of the innominate artery, which will lead to arterial erosion. 2. hyperinflation of the tracheal cuff the tracheal cuff, when hyperinflated, will cause ischemic injury to the airway and subsequent erosion into the artery and fistula development. Most cuff-induced fistulas develop within 2 weeks after placement of the tracheostomy.

The patient can then be orally intubated, and the airway suctioned free of blood. Emergent surgical resection of the involved segment of artery is performed, usually without reconstruction.

TRACHEOESOPHAGEAL FISTULA (TEFs)

occur primarily in patients with an indwelling nasogastric tube who are also receiving prolonged mechanical ventilatory support. Cuff compression of the membranous trachea against the nasogastric tube leads to airway and esophageal injury and fistula development. Clinically, saliva, gastric contents, or tube feeding contents are noted in the material suctioned from the airway. Distention of the stomach secondary to positive pressure ventilation can occur. Diagnosis of a suspected TEF is by bronchoscopy. Withdrawal of the endotracheal tube with the bronchoscope inserted allows the fistula at the cuff site to be seen. Alternatively, esophagoscopy will enable visualization of the cuff of the endotracheal tube in the esophagus.

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TREATMENT: weaning the patient from the ventilator and then extubating as soon as possible. During the weaning period, the nasogastric tube should be removed, with attention given to ensuring that the cuff of the endotracheal tube is placed below the fistula and that it is not overinflated. Then a gastrostomy tube should be placed for aspiration (to prevent reflux) and a jejunostomy tube for feeding. If aspiration is relentless and is not managed by the aforementioned steps, esophageal diversion with esophagostomy can be performed. Once the patient is weaned from the ventilator, a single-stage operation should be done, consisting of: tracheal resection and primary anastomosis repair of the esophageal defect, and interposition of a muscle flap between the trachea and esophagus

TRACHEAL NEOPLASM
The most common primary tracheal neoplasms (approximately 65%): squamous cell carcinomas (related to smoking) and, adenoid cystic carcinomas The remaining 35% small cell carcinomas, mucoepidermoid carcinomas, adenocarcinomas, lymphomas, and others Primary tracheal neoplasms are exceedingly rare diagnosis frequently is delayed present with cough, dyspnea, hemoptysis, stridor, or symptoms of invasion of contiguous structures (such as the recurrent laryngeal nerve or the esophagus) tracheal stenosis: most common radiologic finding of tracheal malignancy is, but it is seen in only 50% of cases

Squamous cell carcinomas

often present with regional lymph node metastases frequently not resectable at the time of presentation biologic behavior is similar to that of squamous cell carcinomas of the lung

**Single-stage operation for closure of a tracheoesophageal fistula and tracheal resection. A. The fistula is divided and the trachea is transected below the level of damage. B. The fistula is closed on the tracheal side in a single layer and on the esophageal side in a double layer. C. The damaged trachea segment is resected. D. View of completed tracheal anastomosis

Adenoid cystic carcinomas

a type of salivary gland tumor generally slow growing, spread submucosally, and tend to infiltrate along nerve sheaths and within the tracheal wall Spread to regional lymph nodes can occur Although indolent in nature, they are malignant and can spread to the lungs and bones

THERAPY
Evaluation and treatment of patients with tracheal tumors should include neck and chest computed tomography (CT) and Bronchoscopy Rigid bronchoscopy permits general assessment of the airway and tumor allows dbridement or laser ablation of the tumor to provide relief of dyspnea If the tumor is judged to be completely resectable, primary resection and anastomosis is the treatment of choice. The length limit of tracheal resection is roughly 50% of the trachea. To prevent tension on the anastomosis postoperatively, specialized maneuvers are necessary anterolateral tracheal mobilization, suturing of the chin to the sternum with the head flexed forward for 7 days, laryngeal release, and right hilar release

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For most tracheal resections (which involve much less than 50% of the airway), anterolateral tracheal mobilization and suturing of the chin to the sternum for 7 days are done routinely. Radiotherapy is frequently given postoperatively after resection of both adenoid cystic carcinomas and squamous cell carcinomas, due to their radiosensitivity. For recurrent airway compromise, stenting or laser therapies should be considered part of the treatment algorithm.

LYMPHATIC DRAINAGE Lymph nodes that drain the lungs are divided into two groups according to the tumor, node, and metastasis (TNM) staging system for lung cancer a. pulmonary lymph nodes, N1 b. mediastinal nodes, N2

N1 lymph nodes:
1. intrapulmonary or segmental nodes - lie at points of division of segmental bronchi or in the bifurcations of the pulmonary artery lobar nodes - lie along the upper, middle, and lower lobe bronchi interlobar nodes - located in the angles formed by the bifurcation of the main bronchi into the lobar bronchi hilar nodes - located along the main bronchi

LUNG
Anatomy

2. 3. 4.

*lymphatic sump of Borrie where all of the pulmonary lobes of the corresponding lung drain

N2 lymph nodes:
1. 2. 3. 4. anterior mediastinal posterior mediastinal Tracheobronchial paratracheal

COMPUTED TOMOGRAPHY
Spiral (helical) CT
allows continuous scanning as the patient is moved through a scanning gantry entire thorax can be imaged during a solitary breath hold In general, slice thickness is proportional to image resolution Slice thickness is determined by the structure being imaged as well as by the indication for the study a. Thin sections (1- to 2-mm collimation) used to evaluate pulmonary parenchyma and peripheral bronchi and pulmonary metastases b. For assessing the trachea and central bronchi, collimation of 3 to 5 mm is recommended

Thoracic Surgical Approaches

SEGMENTAL ANATOMY Note the continuity of the pulmonary parenchyma between adjacent segments of each lobe. In contrast, separation of the bronchial and vascular stalks allows subsegmental and segmental resections, if the clinical situation requires it or if lung tissue can be preserved.

*Video-assisted thoracic surgery (VATS) *Thoracotomy

Comparing this two, there has not been a documented change in mortality using these approaches. But in terms of pain level, functional status, and recovery, all favors VATS over thoracotomy.

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*Special Circumstances under Which Lobectomy by VideoAssisted Thoracic Surgery May Be Preferable Pulmonary compromise Cardiac dysfunction Extrathoracic malignancy Poor physical performance Rheumatologic/orthopedic condition Advanced age Vascular problems Recent or impending major operation Psychologic/neurologic conditions

*Anterolateral thoracotomy
traditionall used in trauma victims This approach allows quick entry into the chest with the patient supine When hemodynamic instability is present, the lateral decubitus position significantly compromises control over the patient's cardiopulmonary system and resuscitation efforts, whereas the supine position allows the anesthesiologist full access to the patient The incision is submammary, beginning at the sternal border overlying the fourth intercostal space and extending to the midaxillary line Should more exposure be necessary, the sternum can be transected and the incision carried to the contralateral thoracic cavity ("clamshell" thoracotomy)

*Mediastinoscopy
generally used for diagnostic assessment of mediastinal lymphadenopathy and staging of lung cancer performed via a transverse 2- to 3-cm incision approximately 1 cm above the suprasternal notch Care is taken to avoid any venous structures that may overlie the muscles

*Bilateral anterior thoracotomy with transverse

sternotomy clamshell thoracotomy standard operative approach to the heart and mediastinum in certain elective circumstances

*Posterolateral thoracotomy
most frequently used incision for an open procedure in thoracic surgery patient is placed in the lateral decubitus position A pitfall of thoracic incisions in a lateral decubitus position is the potential for injury to the brachial plexus and axillary vascular structures secondary to displacement of the shoulder skin incision typically starts at the anterior axillary line just below the nipple level and extends posteriorly below the tip of the scapula The pleural space is entered at the fifth interspace
A. Skin incision from the anterior axillary line to the lower extent of the scapula tip. B&C. Division of the latissimus dorsi and shoulder girdle musculature. D. The pleural cavity is entered after dividing the intercostal muscles along the lower margin of the interspace, with care taken not to injure the neurovascular bundle lying below each rib.

*Partial median sternotomy

can be added to an anterior thoracotomy ("trap door" or "hemiclam" thoracotomy) for access to mediastinal structures. A hypesthetic nipple is a frequent complication of this approach.

*Median sternotomy incision

allows exposure of anterior mediastinal structures principally used for cardiac operations. The surgeon has access to both pleural cavities and can avoid incision into the pleural cavity if it is unnecessary. The skin incision extends from the suprasternal notch to the xiphoid process decreased postoperative pain and less compromise of pulmonary function than with a lateral thoracotomy increased risk of infection if a tracheostomy is needed concomitantly or before the sternotomy is completely healed.

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Video-Assisted Thoracoscopic Surgery (VATS)

Diagnosis and treatment of pleural effusions and recurrent pneumothorax, and for lung biopsy, lobectomy or segmental resection, resection of bronchogenic and mediastinal cysts, esophageal myotomy, and intrathoracic esophageal mobilization for esophagectomy. Performed via two to four incisions measuring 0.5 to 1.2 cm in length to allow insertion of the thoracoscope and instruments. Endoscopic staplers are used to divide the major vascular structures and bronchus. At the conclusion of a thoracic operation: Chest tube placementnot needed if pleural viscera is not violated Positive pressure ventilationto re-expand the lungs

Epidural anesthesia inserted at about the T6 level, roughly at the level of the scapular tip. Fentanyl with bupivacaine or robivacaine urinary retention Paravertebral anesthesia 2.5 cm lateral to the spinous process at T4 to T6 narcotics with topical analgesics Local anesthesia may cause hypotension or vasodilation IV narcotics often in conjunction with ketorolac Oversedation and narcotization of patients risk of secretion retention and development of atelectasis or pneumonia The patient typically is transitioned to oral pain medication on the third or fourth postoperative day. During both the parenteral and oral phase of pain management, use of a standardized regimen of stool softeners and laxatives is advisable to prevent severe constipation.

Post Operative Care

Chest Tube
2 purposes: a. For air evacuation b. For blood and pleural fluid drainage The ability of the pleural lymphatics to absorb fluid is substantial. It can be as high as 0.40 mL/kg per hour in a healthy individual, possibly resulting in the absorption of up to 500 mL of fluid over a 24-hour period. pleural tubes can be removed after VATS lobectomy or thoracotomy with 24-hour drainage volumes as high as 400 mL without subsequent development of pleural effusions. If the pleural space is altered, strict adherence to a volume requirement before tube removal is appropriate. The use of suction and the management of air leaks vary. To eradicate residual air spaces and to control postoperative parenchymal air leaks, suction level of -20 H2O have been commonly used. Evaluation of an air leak and/or incompletely drained pneumothorax with associated pulmonary collapse Check for tube patency Ask patient to cough or perform valsalva maneuver During the cough, the water seal chamber is observed. ( bubbles = air leaks ) , (stationary fluid level = mech. blockade )

Respiratory Care
Patient should be able to deliver an effective cough, if it is impossible to cough, use of suction is required to remove secretions. Preoperatively, give instructions of applying pressure over the wound Postoperatively, proper pain control without over sedation is essential.

Postpneumonectomy
pulmonary edema occurs in 1 to 5% of patients undergoing pneumonectomy, with a higher incidence after right pneumonectomy. symptoms of respiratory distress manifest hours to days after surgery. Radiographically, diffuse interstitial infiltration or frank alveolar edema is seen. The pathophysiologic causes remain poorly understood but are related to factors that increase permeability and filtration pressure and decrease lymphatic drainage from the affected lung. The syndrome reportedly is associated with a nearly 100% mortality rate even with aggressive therapy Treatment consists of 1.ventilatory support 2.fluid restriction 3.diuretics

Pain Control
The most common routes for pain medication are: Epidural Paravertebral IV

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Postoperative Complications
1. 2. air leak bronchopleural fistula Postoperative air leaks are common after pulmonary resection, particularly in patients with emphysematous changes, because the fibrotic changes and destroyed blood supply impair healing of surface injuries. Prolonged air leakslasting over 5 daysmay be treated by diminishing or discontinuing suction (if used), by continuing chest drainage, or by instilling a pleurodesic agent, usually talcum powder. If the leak is moderate to large, a high index of suspicion should be maintained for bronchopleural fistula from the resected bronchial stump, particularly if the patient is immunocompromised or received induction chemotherapy and/or radiation therapy.

Other postoperative complications 1. If a bronchopleural fistula is suspected, flexible bronchoscopy is performed. Management options include continued prolonged chest tube drainage, reoperation and reclosure (with stump reinforcement with intercostals or a serratus muscle pedicle flap), or, for fistulas <4 mm bronchoscopic fibrin glue application. Patients often have concomitant empyemas, and open drainage may be necessary. 2. Solitary pulmonary nodule is typically described as a single, well-circumscribed, spherical lesion. 3 cm in diameter and is completely surrounded by normal aerated lung parenchyma. The American College of Chest Physicians discourages use of the term coin lesion because these lesions are spherical. majority detected incidentally on chest radiographs or CT scans obtained for some other purpose. Originally defined by findings on chest radiographs, solitary pulmonary nodules were identified on 0.09 to 0.2% of all chest radiographs in large screening studies as early as 1950. Approximately 150,000 solitary nodules are found incidentally each year. The clinical significance of such a lesion depends on whether or not it represents a malignancy

In unselected patient populations, a new solitary pulmonary nodule observed on a chest radiograph has a 20 to 40% likelihood of being malignant, with the risk approximately 50% or higher in smokers. Factors influencing the probability of cancer in a solitary pulmonary nodule include > evidence for growth over time > density of the lesion on CT scan - 40 to 50% of partial solid nodules cancerous compared with only 15% of solid nodules <1 cm and nonsolid nodules > patient age, sex, cigarette smoking history, occupational history, and the prevalence of endemic granulomatous disease. Infectious granulomas arising in response to a variety of organisms comprise 70 to 80% of this type of benign solitary nodule hamartomas are the next most common single cause, accounting for approximately 10%. The differential diagnosis of a solitary pulmonary nodule should include a broad variety of congenital, neoplastic, inflammatory, vascular, and traumatic disorders.

Imaging 1. Chest thin section CT scanning is critical in characterizing nodule location, size, margin morphology, calcification pattern, and growth rate. often reveals more than a single pulmonary nodule; up to 50% of patients thought to have a single lesion based on chest radiograph are proven to harbor multiple nodules when examined by CT. Lesions >3 cm are regarded as masses and are more likely malignant. Irregular, lobulated, or spiculated edges strongly suggest malignancy. Calcification within a nodule suggests a benign lesion. Four patterns of benign calcification are common: a. Diffuse b. Solid c. Central d. laminated or "popcorn." Granulomatous infections such as tuberculosis can demonstrate the first three patterns, whereas the popcorn pattern is most common in hamartomas. PET scanning takes advantage of another biologic property of neoplasms: increased glucose uptake commensurate with increased metabolic activity. F-fluorodeoxyglucose (FDG) - is used to measure glucose metabolism in cells imaged by PET. Most lung tumors have increased signatures of glucose uptake, compared with healthy tissues. PET is becoming widely used to help differentiate benign from malignant nodules.

2.

Differential Diagnosis: can be distilled down to a differentiation between malignancy and other numerous benign conditions. diagnostic approaches would provide a clear distinction, so that definitive surgical resection could be reserved for the malignant nodule and resection avoided when the nodule is benign.

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Biopsy vs. Resection Only through biopsy can a pulmonary nodule be definitively diagnosed. Bronchoscopy has a 20 to 80% sensitivity for detecting a neoplastic process within a solitary pulmonary nodule, depending on the nodule size, its proximity to the bronchial tree, and the prevalence of cancer in the population being sampled. Transthoracic fine-needle aspiration (FNA) biopsy can accurately identify the status of peripheral pulmonary lesions in up to 95% of patients; the false-negative rate ranges from 3 to 29%. VATS often is used for excising and diagnosing indeterminate pulmonary nodules. Lesions most suitable for VATS are those that are located in the outer one third of the lung and those that are <3 cm in diameter. The nodule must not be directly manipulated with instruments, the visceral pleura overlying the nodule must not be violated, and the excised nodule must be extracted from the chest within a bag to prevent seeding of the chest wall. Some groups advocate proceeding directly to VATS in the work-up of a solitary pulmonary nodule in appropriate clinical circumstances, citing superior diagnostic accuracy and low surgical risks.

are extraordinarily rare in the absence of cigarette smoking. The risk of developing lung cancer escalates with the number of cigarettes smoked and the number of years of smoking, and is higher when unfiltered cigarettes are used. Even after smoking cessation, however, the risk never drops to that of people who never smoked, regardless of the length of abstinence. Approximately 25% of all lung cancers worldwide and 53% of cancers in women are not related to smoking, and the majority of these (62%) are adenocarcinomas.

Secondhand (or passive) smoke exposure has been shown to confer an excess risk of developing lung cancer of 24% when a nonsmoker lives with a smoker.Pre-existing lung disease confers an increased risk of lung cancerup to 13%for individuals who have never smoked. This increase is thought to be related to poor clearance of inhaled carcinogens and/or to the effects of chronic inflammation. Other causes of lung cancer include : exposure to a number of industrial compounds, including asbestos, arsenic, and chromium compounds. Of particular note is the ominous combination of asbestos exposure and cigarette smoking, which together have a multiplicative effect on risk, as opposed to an additive effect. Patients with COPD are at higher risk for lung cancer than would be predicted based on smoking risk alone. A previous history of tuberculosis with secondary scar formation also leads to a higher risk of primary lung carcinoma. Over 3000 chemicals have been identified in tobacco smoke, but the main chemical carcinogens are polycyclic aromatic hydrocarbons. Once inhaled and absorbed, these compounds become mutagenic through their activation by specific enzymes, binding to macromolecules such as DNA and then inducing mutations. The lung can be conveniently viewed as two linked components: a. the tracheobronchial tree (or conducting airways component) b. the alveolar spaces (or gas exchange component). The tracheobronchial tree consists of approximately 23 airway divisions to the level of the alveoli. It includes the: main bronchi lobar bronchi segmental bronchi (to designated bronchopulmonary segments)

Lung Neoplasms
Lung cancer is the leading cancer killer in the United States. Every year, it accounts for 30% of all cancer deathsmore than cancers of the breast, prostate, and ovary combined. It is the second most frequently diagnosed cancer in the United States, behind prostate cancer in men and breast cancer in women. In the annual report to the nation on the status of cancer in 2007, it was noted that the incidence of lung cancer in men has begun to decrease, while incidence has remained stable in women. most patients are diagnosed at an advanced stage of disease, so therapy is rarely curative. The overall 5-year survival for all patients with lung cancer is 15%, which makes lung cancer the most lethal of the leading four cancers.

Epidemiology Cigarette smoking is the primary cause of lung cancer, with smoking-related cancers accounting for approximately 75% of all lung cancers worldwide in 2007. Two lung cancer types 1. squamous cell carcinoma 2. small cell carcinoma

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terminal bronchioles (i.e., the smallest airway vessels, which lack alveoli and are lined by bronchial epithelium).

*Lined by pseudostratified ciliated columnar cells and mucous (or goblet) cells, both of which derive from basal cells. Ciliated cells predominate. Goblet cells which release mucus, can significantly increase in number in acute bronchial injury, such as exposure to cigarette smoke. also contains bronchial submucosal glands, which are mixed salivary-type glands containing mucous cells, serous cells, and Kulchitsky cells. Kulchitsky cells are neuroendocrine cells found within the surface epithelium. *The bronchial submucosal glands can give rise to salivary glandtype tumors (previously referred to as bronchial gland tumors), including mucoepidermoid carcinomas and adenoid cystic carcinomas. *The alveolar spaces or alveoli have two primary cell types, 1. type I pneumocytes cover 95% of the surface area of the alveolar wall but constitute only 40% of the total number of alveolar epithelial cells. These cells are not capable of regeneration because they have no mitotic potential. 2. type II pneumocytes cover only 3% of the alveolar surface but constitute 60% of the alveolar epithelial cells. In addition, clusters of neuroendocrine cells are seen in the alveolar spaces.

increased cell size, an increased number of cell layers, an increased nucleus:cytoplasm ratio, increased mitoses, and changes in cellular polarity. Gradations are considered mild, moderate, or severe.

Carcinoma in situ
represents carcinoma still confined by the basement membrane.

Invasive squamous cell carcinoma

Once the in situ tumor invades beyond the basement membrane,

Atypical Adenomatous Hyperplasia

lesion <5.0 mm consisting of epithelial cells lining the alveoli that are similar to type II pneumocytes.

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

are lesion representing a diffuse proliferation of neuroendocrine cells but without invasion of the basement membrane. It can exist as a diffuse increase in the number of single neuroendocrine cells or as small lesions <5.0 mm in diameter. Lesions that are >5.0 mm in size or that breach the basement membrane are carcinoid tumors.

MALIGNANT LESIONS
Bronchial Carcinoma- any epithelial carcinoma occuring
in the bronchopulmonary tree Non- Small Cell Lung Carcinomas Squamous Cell Carcinoma Large Cell Carcinoma Adenocarcinoma Bronchoalveolar carcinoma Neuroendocrine Tumors - Typical Carcinoid - Atypical Carcinoid - Large cell neuroendocrine carcinoma. - Small Cell Carcinoma Currently, the pathologic diagnosis of lung cancer is based on light microscopic criteria. Immuno-histochemical staining & electron microscopy are used as adjuncts in diagnosis, particularly in the assessment of neuroendocrine tumors.

Preinvasive Lesions
Three precancerous lesions: 1. squamous dysplasia and carcinoma in situ 2. atypical adenomatous hyperplasia 3. diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Note: The term precancerous does not mean that an inevitable progression to invasive carcinoma will occur, but such lesions, particularly those with high-grade dysplasia,do constitute a clear marker of the potential for later development of invasive cancer.

Squamous Dysplasia and Carcinoma In Situ

Cigarette smoke can induce a metaplastic change of the tracheobronchial pseudostratified epithelium to squamous mucosa, which is a normal response to injury. With the development of cellular abnormalities in the metaplastic squamous mucosa, squamous dysplasia evolves.

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Non- Small Cell Lung Carcinoma

Encompasses many tumor cell types, including adenocarcinoma, squamous cell carcinoma & large cell carcinoma. Although they differ in appearance histologically, their clinical behavior & treatment options are similar.

GRADE I NEC (Classical/Typical)

Low grade epithelial tumor. Arises primarily in central airways but can occur peripherally. Tumor cells are arranged in the cords and clusters with a rich vascular stroma. Regional lymph node metastases are seen in 15% of patients but rarely spread systematically of cause death. Classicaly presents with: Hemoptysis Airway obstruction Pneumonia

Squamous Cell Carcinoma

30-40% of lung cancers. Males> Females; highly associated with cigarrete smoking. Histologically: cells develop a pattern of clusters with intracellular bridges & keratin pearls. Primarily located centrally & arises in the major bronchi. - Hemoptysis - bronchial obstruction - Atelectasis Central Necrosis is frequent with resultant abscess formation.

GRADE II NEC
Histologic findings may include necrosis, nuclear polymorphism & higher mitotic rates. Lymph node metastases are found 30-50% of the patients Aggressive clinical behavior. - Etiologically linked to cigarrete smoking - Peripherally located

Adenocarcinoma
25-40% of all lung cancers. Females> Males. Peripherally based tumor. Histologically: composed of glands with or without mucin production, combined with destruction of contiguous lung architecture.

GRADE III NEC

Tumor consists of smaller cells (10-20um) that have very little cytoplasm & very dark nuclei. Tumors have mitotic rate & areas of extensive necrosis. Multiple mitoses are easily seen. Most malignant. Small Cell Lung Carcinoma. 25% of all lung cancers. Leading producers of paraneoplastic syndromes. Tumors are centrally located.

Bronchoalveolar Carcinoma
5% of all lung cancers. Its a subtype of adenocarcinoma. Differs from adenocarcinoma in that, rather than invading & destroying lung parenchyma, its tumor cells multiply and fill the alveolar spaces. It grows within alveoli/alveolar spaces: tumor cells can seed aerogenously to other parts of the same lobe, lung or contralateral lung. Columnar Cells proliferate along the framework of alveolar septae.

Salivary gland-type neoplasm

Histologically identical to those seen in the salivary glands. The 2 most common are adenoid cystic carcinoma & mucoepidermoid carcinoma. Both occurs centrally. Its a slow-growing tumor that is locally and sytemically invasive.. It tends to grow submucosally and infiltrate along perineural sheaths.

Large Cell Carcinoma

10-20% of lung cancers. Maybe located centrally or peripherally. 30-50 m. They are often admixed with other cell types such as squamous cells or adenocarcinoma.

CLINICAL PRESENTATION
Wide range of symptoms and signs is related to: 1. Histologic features which often help determine the anatomic site of origin in the lung 2. The specific tumor location in the lung and its relationship to surrounding structures 3. Biologic features and the production of a variety of paraneoplastic syndromes 4. The presence or absence of metastatic disease

Neuroendocrine Neoplasms
Essential Neuroendocrine Markers for Dx: Chromogranins Synapthophysin CD57 Neuron-specific Enolase

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Clinical Presentation of Lung Cancer

Pulmonary symptoms Cough Bronchus irritation or compression Dyspnea Airway obstruction or compression Wheezing >50% airway obstruction Nonpulmonary thoracic symptoms Hemoptysis Tumor erosion or irritation Pneumonia Airway obstruction Pleuritic pain Parietal pleural irritation or invasion Local chest Rib and/or muscle involvement wall pain Radicular chest painIntercostal nerve involvement Pancoast's syndrome Stellate ganglion, chest wall, brachial plexus involvement HoarsenessRecurrent laryngeal nerve involvement Swelling of head and arms : 1.Bulky involved mediastinal lymph nodes 2.Medially based right upper lobe

SYMPTOMS depending on the extent of chest wall involvement 1.pleuritic pain 2.localized chest wall pain 3.radicular pain

Superior sulcus tumors (usually adenocarcinomas)

may produce the Pancoast syndrome Tumor at the apex of the lung or superior sulcus that may involve the brachial plexus, sympathetic ganglia, and vertebral bodies, leading to pain, upper extremity weakness, and

Horners syndromeInjury to the cervical sympathetic

chain(MAP) 1. Miosis (small pupil) 2. Anhydrosis of ipsilateral face 3. Ptosis *Depending on the exact tumor location, symptoms can include Apical chest wall ,shoulder pain, radicular arm pain * Invasion of the primary tumor into the mediastinum may lead to involvement of the phrenic or recurrent laryngeal nerves. Direct invasion of the phrenic nerve occurs with tumors of the medial surface of the lung, or with anterior hilar tumors. Symptoms may include 1.shoulder pain (referred), 2.hiccups, and dyspnea with exertion Because of diaphragm paralysis Diagnosis;chest radiograph,fluoroscopic examination of the diaphragm and with breathing and sniffing (the sniff test) Recurrent laryngeal nerve (RLN) most commonly occurs on the left side. Paralysis may occur 1. invasion of the vagus nerve above the aortic arch by a medially based left upper lobe (LUL) tumor, 2.invasion of the RLN directly by a hilar tumor, 3.invasion by hilar or aortopulmonary lymph nodes involved with metastatic tumor.

TUMOR HISTOLOGY

Squamous cell and small cell carcinomas:

Arise in main lobar, or first segmental bronchi{central airways} Adenocarcinomas: located peripherally, Asymptomatic peripheral lesion on chest radiograph BAC : solitary nodule, as multifocal nodules, or as a diffuse infiltrate mimicking(PNEUMONIC FORM) air bronchograms may be seen radiographically within the tumor SITE OF TUMORS Squamous cell 66% occur centrally in lung hilus(sq=central) AdenocarcinomaPeripheral Small (oat) cellCentral, highly malignant, not operable Large cellUsually peripheral, very malignant TUMOR LOCATION Pulmonary Symptoms direct effect of the tumor on the bronchus or lung tissue Symptoms : cough,dyspnea, wheezing , hemoptysis pneumonia and lung abscess

Symptoms: Voice change,often referred to as hoarseness, Loss of tone associated with a breathy quality, Coughing( when drinking liquids)

Nonpulmonary Thoracic Symptoms

OCCURS DUE TO invasion of the primary tumor directly into a contiguous structure or from mechanical compression of a structure by enlarged tumor-bearing lymph nodes Peripherally located tumors ( adenocarcinomas) extending through the visceral pleura lead to irritation or growth into the parietal pleura and to continued growth into the chest wall structures

Tumor Biology
Lung cancers both nonsmall-cell and small-cell carcinoma
Capable of producing a variety of paraneoplastic syndrome Most often from tumor production and release of biologically active materials systemically.

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Majority of such syndromes are caused by small-cell carcinomas, including many endocrinopathies.

Diagnosis, Evaluation & Staging

Assessment encompasses 3 areas:
1. 2. 3. Primary tumor Presence of metastatic disease Functional status patients ability to tolerate a pulmonary resection

Paraneoplastic syndromes - Early diagnosis. Presence does not influence resectability or the potential to successfully treat the tumor. Symptoms of the syndrome often will abate with successful treatment, and recurrence may be heralded by recurrent paraneoplastic symptoms. 5 general types of paraneoplastic syndromes. 1. Metabolic: Cushings, SIADH, hypercalcemia 2. Neuromuscular: Eaton-Lambert,cerebellar ataxia 3. Skeletal: hypertrophic osteoarthropathy 4. Dermatologic: acanthosis nigricans 5. Vascular: thrombophlebitis

1. Assessment of Primary Tumor

Historysymptoms, PE Location of tumorCXR, CT Scan Determination of Invasion Presence of pain Chest CT with contrast delineation of mediastinal lymph nodes Invasion of contiguous structures MRINo improvement over CT scan Reserved for those with allergies to contrast agents or with suspected vascular or vertebral body invasion Proof of invasion may require thorcoscopy or even thoracotomy Tissue Diagnosis BronchoscopyCentrally located tumors Visualization of tracheobronchial tree Transthoracic needle aspiration Peripheral lesions not accessible by bronchoscopy Under imaging guidance Primary complication is pneumothorax Thoracotomy Occasionally necessary (<5% of patients) Deep-seated lesions: a. With indeterminated needle biopsy result Lobectomy may be necessary b. could not be biopsied for technical reasons excisional biopsy is preferred

SCLC : hypertrophic pulmonary osteoarthropathy (HPO)

Most common paraneoplastic syndromes characterized by tenderness and swelling of the ankles, feet, forearms, and hands. Because of periostitis of the fibula, tibia, radius, metacarpals, and metatarsals.

Hypercalcemia
10% of patients with lung cancer and is most often because of metastatic disease 15 % of cases are because of secretion of ectopic parathyroid hormonerelated peptide, most often with squamous cell carcinoma Diagnosis of ectopic parathyroid hormone secretion can be made by measuring elevated serum levels of parathyroid hormone; the clinician must also rule out concurrent metastatic bone disease by a bone scan.

Metastatic Symptoms
METASTASES occur most commonly Central nervous system (CNS), Vertebral bodies, Bones,Liver, Adrenal glands, Lungs,Skin and Soft tissues. 10 % of patients with lung cancer have CNS metastases 1015 %will develop CNS metastases SYMPTOMS: headache, nausea and vomiting, seizures, hemiplegia, and speech difficulty.

2. Assessment of Metastatic Dse

Presence imply inoperability Begins with hx , with focus on: NEW bone pain, neurologic symptoms, skin lesions Evidence of weight loss PE: Evaluation of cervical and supraclavicular LN and oropharynx Strong association of oropharyngeal primary tumors and lung cancer in tobacco users Routine Laboratory studiesHepatic enzymes, calcium levels

Nonspecific Symptoms
Anorexia Weight loss Fatigue Malaise *The cause of these symptoms is often unclear, should raise concern about possible metastatic disease

Mediastinal Lymph Nodes Metastasis

CT Scanmost effective non-invasive method Positive CT: nodal diameter > 1cm 30% due to noncancerous reactive causes Requires histologic confirmation

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PET Scan Detection of positrons emitted by fluorodeoxyglucoseglucose analogue labelled with positron-emitting fluorine Accumulate in cancers because of higher glucose metabolism A single FDG injection allows evaluation of whole body, especially the primary lung lesion, mediastinal LN and distant organs CT Scan vs. PET Scan PET has higher sensitivity & accuracy Recent development of combined PET-CT Scanners may improve accuracy Endoesophageal ultrasound (EUS) Recently emerged as method of staging in NSCLC Visualize mediastinal paratracheal LN, and lesions contiguous or near esophagus Obtain tissue samples Unable to visualize anterior (pretracheal) mediastinum Cervical mediastinoscopy Mediastinoscopy is standard method of tissue staging of the mediastinum Mediastinoscope is introduced through suprasternal skin incision Allows sampling of paratracheal and subcarinal LN visual determination of presence of extracapsular extension of nodal metastases biopsy

**With any radiologic assessment, accuracy must be ensured. The patient must be given the benefit of any doubt about the accuracy of the scan; the result must be proven, most often by biopsy, to be true-positive.

3. Assessment of Functional Status

Historymost important tool for gauging risk Clinical assessment entails observation of the patients vigor and attitude Patients attitude toward the disease was the best indicator for long term survival Except in life-threatening situations, patients should never be cajoled or forced into accepting surgery Determining patient tolerance for resection Walk on flat surface indefinitely without dyspnea > thoractomy and lobectomy Can walk up to 2 flight of stairs without dyspnea pneumonectoomy Nearly all patient can tolerate periods of single-lung ventilation and wedge resection Smoking Increased risk of postop complications Significant risk reduction requires cessation of smoking at least 8 weeks preoperatively In cancer patients, ideally for 2 weeks before surgery Physical Examshould focus on signs of COPD or airflow limitation: Cyanosis Peripheral edema Mild post-cough SOB Wheezes, crackles Wet cough Pulmonary function studiesperformed when resection greater than wedge resection will be performed FEV1 and DLCO are most valuable FEV1 guidelines: >2 L can tolerate pneumonectomy < 1.5 L can tolerate lobectomy Reported as percent predicted based on corrections made for age, height and gender Predicted postop value for FEV1 and DLCO percent predicted value is multiplied by fraction of remaining lung after surgery Ex: A man with 30% FEV1 removing 3 segments from total of 20 will leave patient with 85% of original lung capacity post percent predicted FEV1 of 25% Quantitative perfusion scanningestimate functional contribution of a lobe or whole lung Exercise testingyield maximum oxygen consumption (VO2max) <10 ml/kg/ minuteprohibits any major pulmonary resection due to mortality rate of 26% >15ml/kg/minutetolerate pneumonectomy

It is particularly important to prove pathologically that mediastinal lymph nodes are involved before deciding that the patient is not a candidate for resection

Malignant Pleural Effusion

Often secondary to atelectasis or consolidation seen with central tumors Can be diagnosed only by finding malignant cells in a sample of pleural fluid examined microscopically

Distant Metastases
Combination of chest CT scan and multiorgan scanning Chest CT Scan Always include upper abdomen and allow visualization of liver and adrenal glands Further evaluation by MRI scanning Bone Scans High sensitivity but low specificity False-positive rate of 40% PET Scan Metastases to liver, adrenal glands and bones Combined with CT Scan for routine evaluation of patients with lung cancer Integrated PET-CT Scanners demonstrate better accuracy Brain MRI if with risk of brain metastases

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**Risk assessment is based on a combination of clinical judgement and data. This risk assessment must be integrated with the experienced clinicians sense of the patient and with the patients attitude toward the disease and toward life

Treatment of Lung Neoplasms

Early-Stage Disease - is defined as stages I and II. - In this group are T1 and T2 tumors (with or without local N1 nodal involvement) and T3 tumors (without N1 nodal involvement). Current Standard Of Treatment surgical resection accomplished by lobectomy or pneumonectomy, depending on the tumor location. Appropriate surgical procedures for patients with early-stage disease lobectomy sleeve lobectomy occasionally pneumonectomy with mediastinal lymph node dissection or sampling.

LUNG CANCER STAGING SYSTEMS

Based on tumor, node and metastasis (TNM) system T: size and relationship of primary tumor to surrounding structures N: regional lymph nodes M: presence or absence of metastatic disease

Sleeve resection
- is performed for tumors located at airway bifurcations when an adequate bronchial margin cannot be obtained by standard lobectomy.

Pneumonectomy
- is rarely performed - primary indications for pneumonectomy in early-stage disease include the presence of large central tumors involving the distal main stem bronchus and inability to completely resect involved N1 lymph nodes.

Carcinoma arising in the extreme apex of the chest

- with associated arm and shoulder pain - atrophy of the muscles of the hand - and Horner syndrome was first described by Henry Pancoast in 1932.

Pancoast's tumor
Any tumor of the superior sulcus, including tumors without evidence of involvement of the neurovascular bundle. Pancoast's tumors have been difficult to treat, with high rates of local recurrence and poor 5year survival with radiation and/or surgical resection.

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Surgical excision is performed via thoracotomy with en bloc resection of the chest wall, vascular structures, and anatomic lobectomy.

2. 3.

En bloc resection
- is used for other locally advanced tumors (T3) with direct invasion of the adjacent chest wall, diaphragm, or pericardium. - If a large portion of the pericardium is removed, reconstruction with thin Gore-Tex membrane will be required to prevent cardiac herniation and venous obstruction

4.

5. 6. 7.

Locoregional Advanced Disease

Surgical resection as sole therapy has a limited role in treatment of stage III disease. T3 N1 tumors can be treated with surgery alone, and a 5-year survival rate of approximately 25% is seen with such therapy. Patients with clinically evident N2 disease (i.e., bulky adenopathy on CT scan or mediastinoscopy, with lymph nodes often replaced by tumor) have a 5-year survival rate of 5 to 10% with surgery alone. Two strategies for delivery are available: Sequential chemoradiation - involves full-dose systemic chemotherapy (i.e., cisplatin combined with a second agent) followed by standard radiotherapy (approximately 60 Gy). Concurrent chemoradiation - An alternative approach, is to administer chemotherapy and radiotherapy at the same time. - The advantages of this approach are: a) improved local control of the primary tumor and associated nodal disease b) a lack of delay in administering radiotherapy. - Disadvantage of this approach: is the necessary reduction in chemotherapy dosage to diminish overlapping toxicities, which can potentially lead to undertreatment of systemic micrometastases.

tumor remaining postoperatively), which would increase radioresistance. The primary tumor may be downstaged with enhanced resectability. Patients are better able to tolerate chemotherapy before surgery and are more likely to complete the prescribed regimen than when chemotherapy is given after surgery. Preoperative chemotherapy functions as an in vivo test of the primary tumor's sensitivity to chemotherapy. Response to chemotherapy can be monitored and used to guide decisions about additional therapy. Systemic micrometastases are treated. Patients who have progressive disease (nonresponders) are identified and spared a pulmonary resection.

Potential disadvantages include the following: 1. In theory the perioperative complication rate may increase (predominantly in patients requiring right pneumonectomy after induction chemotherapy). 2. While the patient is receiving chemotherapy, potentially curative resection is delayed; if the patient does not respond, this delay could result in tumor spread.

Surgery in Stage IV Disease

Chemotherapy - treatment of patients with stage IV disease. - However, on occasion, patients with a single site of metastasis are encountered, particularly patients with adenocarcinomas who have a solitary brain metastasis. Small Cell Lung Carcinoma - accounts for approximately 20% of primary lung cancers and generally is not treated surgically. - These aggressive neoplasms have early, widespread metastases. - they can be difficult to distinguish from lymphoproliferative lesions and atypical carcinoid tumors. Three groups of SCLC are recognized 1. pure small cell carcinoma (oat cell carcinoma) 2. small cell carcinoma with a large cell component 3. combined (mixed) tumors.

Preoperative (Induction) Chemotherapy for Non Small Cell Lung Cancer

The use of chemotherapy before possible surgical resection has a number of potential advantages: 1. The tumor's blood supply is still intact, which allows better chemotherapy delivery and avoids tumor cell hypoxia (in any residual microscopic #vhaine

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*The clinical stage of SCLC is defined broadly by the presence of either local "limited" or distant "disseminated" disease. 1. limited SCLC - presenting with bulky locoregional disease but no evidence for distant metastatic disease - the primary tumor is large and associated with bulky mediastinal adenopathy, which may lead to obstruction of the superior vena cava. 2. disseminated - presents with metastatic disease throughout the patient's body. - Regardless of the stage of presentation, treatment is primarily chemotherapy and radiation. - Surgery is appropriate for the rare patient with an incidentally discovered peripheral nodule that is found to be SCLC. - If a stage I SCLC is identified after resection, postoperative chemotherapy usually is given.

General Principles Governing Appropriate Selection of Patients for Pulmonary Metastasectomy a. Primary tumor must already be controlled. b. Patient must be able to tolerate general anesthesia, potential single-lung ventilation, and the planned pulmonary resection. c. Metastases must be completely resectable based on computed tomographic imaging. d. There is no evidence of extrapulmonary tumor burden. e. Alternative superior therapy must not be available.

Metastatic Lesions to the Lung

Features suggestive of metastatic disease are: - multiplicity - smooth, round borders on CT scan - temporal proximity to the original primary lesion *One must always entertain the possibility that a single new lesion is a primary lung cancer. The likelihood of a new primary lung cancer is highest in patients with a history of: - uterine carcinoma (74%) - bladder carcinoma (89%) - lung carcinoma (92%) - head and neck carcinoma (94%) Resection of pulmonary metastases - is associated with modest survival benefits in a very select group of patients.

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