Bronchial carcinoma (lung cancer)

​The leading cause of cancer in men is lung cancer, followed by cancer of the prostate. For women it is on rank 2 concerning frequency and mortality, directly after breast cancer. The diagnosis is often made when the disease is already at an advanced stage; thus the 5-year survival rate for all patients with lung cancer is at about only 15 to 20 percent.

Cigarette smoking is clearly regarded as the risk factor number 1. Squamous cell carcinomas and small cell carcinomas are very rare in non-smokers. Additional to cigarette smoking in particular the exposure to certain industrial substances is also considered as being a risk factor; among others these are asbestos, arsenic and chrome components. Patients with a chronic obstructive pulmonary disease (COPD, chronic obstructive bronchitis) have as well an increased risk due to smoking. It is also higher in case of a medical history with tuberculosis with its (secondary) scarred changes.

Lung cancer is broadly divided into two groups:

•    Non-small cell lung carcinoma (NSCLC: large cell carcinoma, adenocarcinoma, squamous cell carcinoma)
•    Neuroendocrine tumors (typical or atypical carcinoid tumor, large cell neuroendocrine carcinoma and small cell carcinoma SCLC)

 

Symptoms

The most frequent carcinomas is the squamous cell carcinoma, that in most cases is located centrally and is growing in the large bronchial tubes and the adenocarcinoma, which in the meantime outstripped the squamous cell carcinoma concerning frequency (most frequent type in females) and lies primarily in the peripheral lung tissue. Accordingly, the former is more likely causing symptoms such as coughing blood, ventilation problems of lungs, respiratory distress and lung inflammation, whereas the later is often randomly detected as a suspicious nodule on X-ray images.

In general, there are no assumable typical symptoms. Anyhow coughing, chest pain, coughing blood, respiratory distress and weight loss appear most frequently. Especially in the case of smokers the possibility of a tumor has to be considered in daily clinical practice, if new or changed symptoms occur. Metastases most likely occur in the central nervous system (brain metastases), in the dorsal vertebrae, the peripheral bones, in the liver, the adrenal glands and the lung itself.

Accordingly, particular attention will be paid during asking for the previous medical history (anamnesis) and at the physical examination.

The group of non-small cell lung carcinomas shows a similar growth and spread behavior and is treated with a similar therapy concept in early stages.

 

Diagnosis

Careful staging is very important for prognosis and therapy.
The process of stage determination is important, as the suggested therapy is heavily depending on the tumor stage. Every suspicious shadow in X-ray images should be checked by means of computer tomography (CT). For logical reasons the liver and the adrenal glands are simultaneously also examined in CT to assure that no metastases remain undetected.

Depending on the tumor position the histology or cytology is performed by means of a bronchoscopy (endoscopy of the bronchia) with brush cytology, aspiration, fine needle biopsy, endobronchial ultrasound (EBUS) with transbronchial needle aspiration (EBUS-TBNA) or with a pleural puncture in case of effusion.

Also a CT-guided puncture might be conducted in case of a nodule suspected to be tumorous in the peripheral lung tissue, whereas the rate of wrong negative results is still high. In this case a minimally invasive keyhole surgery can be used for a wedge resection of tissue with an intra-operative tissue analysis (followed by a correct tumor-oriented surgery in the same session or at a later time).

Medical TV broadcast "praxis gesundheit" from the 1. May 20117 (in german language)

In the CT a possible involvement of lymph nodes is checked additionally to the lung tumor. Usually the tumor spreads through the lymphatic vessels to the lymph nodes at the root of the lung (hilum: hilar lymph nodes) or the room between the lungs (mediastinum: mediastinal lymph nodes).

The differentiation between a negative involvement of the lymph nodes and a hilar, ipsilateral mediastinal and contralateral mediastinal involvement needs to be pursued, as it is important for the further treatment. Therefore a PET/CT is performed. The detection rate in combined clarification with PET and CT examination concerning lymph node metastases is higher compared to computer tomography alone and usually prevents the invasive examination in patients with negative mediastinal results.

For PET-positive lymph nodes (signal concentration), which can also be seen in case of inflammation, or negative PET in central tumors, central hilar lymph nodes involvement (N1), bronchial alveolar carcinoma and at very low signal concentration the invasive examination with EBUS-TBNA (endobronchial ultrasound with transbronchial needle aspiration) or a mediastinoscopy is recommended.

With EBUS-TBNA the tissue can be unambiguously punctuated in most cases and often an evidence for a tumor is rendered. Sometimes no tumor cells can be determined, which is not excluding a tumor, as only one puncture has been performed. With this negative result a mediastinoscopy with biopsy should be subsequently conducted.

Only with precise stage determination a correct therapy can be performed, which needs to be discussed and coordinated in an interdisciplinary tumor board. Basically the later stages should be multidisciplinary treated with recommendations of an experienced tumor center such as ours at the university hospital.

From stage II onwards a head MRI is routinely performed pre-operative to exclude brain metastases.

 

Therapy

In stage I the therapy can be performed by means of surgery. Here once again the importance of a pre-operative PET/CT examination is shown, as a positive lymph nodes involvement has been found in the tissue preparation of up to 20 percent of the CT diagnosed early stages cT1N0 (c = computer tomography) and cT2N0, which wouldn’t have been detected with CT alone.

Up to 50 percent of the enlarged lymph nodes (> 1 cm) then again showed no tumor cells at tissue examination. An exception was the pT2bN0 tumor with a size of more than > 4.5 cm. In this case a complementary (adjuvant) chemotherapy is recommended.

In lymph nodes (N+) a complementary (adjuvant) chemotherapy is always indicated. First line therapy: for adenocarcinoma the combination cisplatin and pemetrexed. For squamous cell carcinoma the combination cisplatin and gemcitabin.

In case of ipsilateral mediastinal involvement (stage IIIA) verified by tumor tissue a pre-operative chemotherapy is performed. The response rate of this therapy is up to 70 percent. In singular mediastinal involvement (contrary to several involved lymph nodes) it also can be operated first, followed by a complementary (adjuvant) chemotherapy.

 

Surgical Techniques

Pulmonary Lobe Resection

The pulmonary lobe resection with radical mediastinal lymph node extraction is regarded as a standard of surgical resection, whereas the later is in particular essential for proper staging.
Controversial data exists concerning the influence of the radical lymph nodes extraction on the overall survival and the rate of local tumor relapse, but altogether it seems to be associated with better results in particular in early stages.

In patients with limited lung function a lung wedge resection can be performed in the case of small tumors (max. 2 cm), whereby the overall survival is only slightly affected.

 

Lung Wedge Resection
 

The pulmonary lope resection with extraction of the mediastinal lymph nodes is increasingly performed in a minimally invasive way by means of keyhole surgeries. In terms of overall survival and the local tumor relapse no differences to open surgeries are shown. Simultaneously a development with fewer complications, quicker recovery and faster integration in work processes is achieved. A stationary rehabilitation is not necessary in most cases and the needed chemotherapy is not only better tolerated but also more likely performed as initially planned.

Minimally Invasive Surgery (Keyhole)


     


 
Operating sequence:

 


Minimally invasive separation of blood vessels and the respiratory tract by means of a stapler (special device for bracket sutures) in the resection of the left lower pulmonary lobe. 

Sleeve Resection

For preserving lung tissue in central tumors a cuff resection can be performed.

 

Carinal Pneumonectomy

Technical steps:

Figure 1a

Fig1A OP Sleeve Pneumonektomie.jpg 

The pulmonary artery and veins are divided with a vascular stapler. The azygos vein is divided with a stapler and the vena cava superior is mobilized in order to obtain a better exposure. The distal trachea and the left main bronchus are exposed, mobilized, and encircled with tapes.

Figure 1 b

Fig 1B.jpg 

First the stay suture at the contralateral edge is tied and the membranous part is sutured in a running fashion beginning from the far edge. After completing the membranous part the stay suture on the near edge is tied.

Figure 1c

Fig 1C.jpg 

For the reconstruction of the cartilaginous part we start from the far edge with already knotted suture of this edge with 2 or 3 continuous stiches and then insert interrupted sutures.

Figure 1d

Fig 1D.jpg 

The sutures are tied after they all have been inserted.

Carina Resection and Neo-Carina Formation

Technical steps:

Figure 1 a-c

 Fig 2A.jpgaFig 2B.jpgbFig 2C.jpgc

For carina resection with "neo-carina" formation first we insert the first stich between the cartilaginous and membranous portion of the two main bronchi. After knotting the cartilaginous parts which are in contact with each other, these are approximated with a running suture (neo-carina). Then the membranous part of the trachea is reconstructed with the membranous part of the both bronchi with a running suture beginning from the far edge and coming to the near edge. The anterior wall (cartilaginous portion) is completed with interrupted sutures placed and tied at the end

 

The 5-year survival rate after adequate therapy is heavily stage-dependent. In stage IA a 5-year survival rate of 70 to 80 percent and in stage IB of already 60 percent is shown. In case of a stage II involvement it varies depending on the number and localization of affected mediastinal lymph nodes and the response to chemotherapy between 20 and 60 percent.

Patients with stage T4 tumors exhibit at the time of diagnosis occasionally extensive (this means also contralateral mediastinal) lymph node involvement or remote metastases, which is in many cases a palliative situation (only a relieving and no curing form of therapy is possible anymore).
Anyhow the possibility of surgical resection can be offered to well-selected patients. The en-bloc resection of the tumor with the neighboring structures is considered as a standard. The best results are shown with patients having an isolated chest-wall infiltration, Pancoast tumor (sulcus superior) and infiltration of the upper vena cava. In these cases 5-year survival rates can be achieved for 40 to 50 percent, if a complete tumor resection (R0) and no lymph node metastases (N0 – patients) are present. These tumors are treated with chemotherapy before or after surgery or sometimes also with radiotherapy.

From stage IIIB, which means with contralateral mediastinal involvement, a palliative therapy is indicated, which in most cases is a combined radiochemotherapy. In these advanced stages the importance of surgical resection is still in evaluation in the course of studies. For instance with solitary remote metastases (for example in the brain or adrenal glands) the 5-year survival rate can be achieved for up to 40 percent by means of radical resection of the metastases and the primary tumor.
For patients with relapsing malignant pleural effusion (stage IV) a talcum bonding of the pulmonary pleurae (thoracoscopic talc pleurodesis) is performed with a keyhole surgery. If there is no adequate unfolding of the lung under visual control, a catheter tunneled in subcutaneous fat tissue can be placed instead (for example a PleurX catheter). It can be handled by the patient at home or with help at a Spitex and increases the life quality. These catheters are covered by health insurance since beginning of 2012.

Patients often show an excellent response with relevant tumor size reduction in palliative therapy with tyrosine kinease inhibitors, such as gefitinib for adenocarcinoma, so that a new staging needs to be performed.

 

Solitary pulmonary nodule

The solitary pulmonary nodule is defined as a round tumor of < 3 to 5 cm completely surrounded by lung tissue, without any additional anomalies such as enlarged lymph nodes. In sizes with > 5 cm it is defined as “mass”. Solitary pulmonary nodules are often randomly detected on lung X-ray images. The compulsory further clarification is performed by means of a computer tomography. If it shows obviously benign characteristics such as serious calcifications or fat content (typical for harmatoma: benign tumor from deformed embryonic tissue) with a size of < 1 cm no additional clarification, but a progress monitoring is necessary. In case of suspicious lesions or growing nodules the further clarification concept results from the patient’s risk profile and the size of the solitary pulmonary nodule. As suspicious characteristics a size of more than 1 cm with irregular border, so-called spiculae, and a long-term smoking anamnesis are defined.

 



Examples for solitary pulmonary nodules: top left and right bronchial carcinoma; bottom left metastasis.

A solitary pulmonary nodule of < 4 mm requires a control CT after 6 months, in case of low patient risk no progress monitoring is necessary (risk for malignant tumors is <1%). 4 to 6 mm requires in smokers and/or elderly patients a control CT after 6 to 12 months with an additional control after 18 to 24 months, whereas with a low risk and unchanged clinical findings a one-time control after 12 months is sufficient. A SPN of 4 to 6 mm should be controlled again after 3 to 6 months with all risk profiles. For all findings of > 8 mm a follow-up CT is recommended as well as PET/CT after three months.

In case of a high-risk profile the extraction and examination of tissue (biopsy) or rather a wedge resection of tissue can also be performed directly. For high-risk patients with findings of > 1 cm with spicular extensions this test should be mandatory and a PET/CT is also indispensable. On the basis of the fact that adenocarcinomas are growing slowly, an observation period of at least two years should be arranged for the “ground-glass” nodules (= milk glass phenomenon), which are typical for these tumors.
 

Rare benign lung tumors

Bronchial adenomas (benign gland tumors), chondromas (cartilage tumors), among them the most frequent subgroup of so-called hamartoma, osteomas (bone tumors), fibromas (connective tissue), lipomas (fat tissue tumors) and tuberculomas (often calcified scar tissue after healed pulmonary tuberculosis) are benign lung tumors. Except from tuberculomas the mentioned benign lung tumors just rarely occur.

 

Symptoms

Benign lung tumors rarely show any symptoms. Most commonly they are randomly detected in the course of a radiological clarification because of another question. Some benign tumors can be identified for certain by using common computer tomographies. It is not unusual that the diagnosis remains initial but indeterminated and that the unclear lung tumor understandably leads to concerns.

Diagnosis

In certain cases it can already be differentiated between benign and malignant tumors by means of computer tomography. For small uncertain tumors a progress imaging makes sense. If the size is not increasing a malignant development can often be excluded. Depending on the appearance and potential growth of findings, an invasive diagnosis might be necessary. CT- or sonography-guided punctures often do not achieve their objective, as a malignity can’t be excluded in many cases. Accordingly, the wedge resection of the tumor is recommended. In case it is a malignant process the oncologically correct surgery can be performed in the same session.

Therapy

A therapy is unnecessary, if the tumor isn’t causing any symptoms and has already been classified as benign with imaging. Otherwise a parenchyma-saving resection is performed, which is in most cases realizable in a minimally invasive way. In case of an intra-operatively diagnosed malignant tumor the oncologically correct surgery is transacted.


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