Lung biopsy

The first percutaneous transthoracic needle biopsy of the lung was performed in 1883 by Leyden and Günther - even before X-ray examinations were available. Until the 20th century, this method was used several times, but was not generally applied due to the numerous complications. The standard removal of lung parenchyma was only made possible with the development of flexible bronchoscopy in 1964 by the Japanese Shigeto Ikeda.

The removal of a lung biopsy within the framework of a thoracoscopy goes back to the Swede H. C. Jacobaeus, who developed the so-called "internal inspection of the pleural space" in 1910 and modified it in such a way that from 1921 onwards the removal of biopsies within the framework of a thoracoscopy became possible.

Thoracoscopy according to Maaßen represents a modification of the classical thoracoscopy, which W. Maaßen developed in 1972. Now biopsies could be performed under direct visual control.

R.J. Alfidi first described CT-guided puncture in 1975.

The first video-assisted thoracoscopies (VATS) were performed from 1990 onwards. Here, the rapidly growing sector of laparoscopic surgery, which began in 1983, played a decisive role.

Open lung biopsies in the context of a thoracotomy were first described by Klassen et al. in 1949.

Lung biopsy is one of the diagnostic procedures in the field of pulmonary medicine or thoracic surgery, in which lung tissue is removed in order to be subsequently examined histologically, immunohistologically, immunohistochemically, cytologically or genetically to establish a diagnosis.

The lung biopsy can be taken bronchoscopically, thoracoscopically or by an open biopsy. We distinguish the following bioptic methods:

1. transbronchial lung biopsy (TBB) in the context of a bronchoscopy
2. transthoracic under fluoroscopic, sonographic or CT control
3. by internal thoracoscopy as direct biopsy
4. by open thoracoscopy according to dimensions as direct biopsy or atypical resection
5. by video-assisted thoracoscopy (VATS) as atypical resection
6. per limited thoracotomy as atypical resection
7. with conventional thoracotomy as atypical resection

Transbronchial biopsy (TBB): For diffuse lung diseases including sarcoidosis, TBB is the first line of diagnosis. However, only half of the cases can be diagnostically confirmed by transbronchial biopsy. Special attention should be paid to the fact that "heart-shaped fibrosis" is not a definitive diagnosis, as the tissue samples obtained by transbronchial biopsy are too small to be representative of the entire lung tissue. This is true even if several segments have been biopsied.

In principle, at least 4 biopsies should be taken to increase the accuracy of alveolar tissue (Gilman and Wang 1980).

In the case of sarcoidosis in stage I X-rays, Roethe and colleagues (1980) recommend the removal of 10 biopsies each from the upper and lower lobe; in stage II, 4 biopsies are sufficient to obtain a diagnostic yield of more than 90%.

In addition, tumors can be secured and typed after radiological detection by transbronchial biopsy. This is possible in the visible part of the bronchial system in up to over 90 %.

It becomes difficult if the tumour has large necrotic parts, as in this case only necrotic tissue may be histologically and cytologically visible.

Submucosal tumours with (still) intact mucosa, such as metastases, also present a difficulty because they escape cytological examination in the case of superficial biopsy. In this case, the larger forceps of the rigid instrument are recommended, as they allow the removal of deeper biopsies than would be possible with fiber optic instruments.

The more peripherally located tumours can be secured bioptically in up to 75 % by suction of secretion and insertion of a brush under fluoroscopy.

Benign, peripheral tumours cannot usually be secured by a bronchoscopic biopsy, as far peripheral areas are not sufficiently accessible in most cases. In addition, due to the coarse consistency of benign tumours, the biopsy forceps can often only provide an inadequate biopsy.

If a malignant tumour is suspected, the diagnosis must be continued with negativehistological findings up to a thoracotomy (if this is compatible with the patient's condition), since a negative finding does not rule out a malignant tumour.

A transbronchial biopsy in the region of the middle lobe and the lingula should not be performed because of the risk of a pneumothorax if the visceral pleura is punctured or torn. Biopsies from segment 7 should also be avoided because of the proximity to the pericardium and the vena cava. Only one biopsy should be taken from each sub-segment, otherwise there is an increased risk of bleeding (Peter Hien 2011).

In such cases, other types of diagnostics are indicated.

Contraindication

• Pleural Empyema
• bacterial pneumonia
• Oxygen insufflation with PaO2_< 60 mmHg
• severe restriction (in case of pneumothorax, the lung can no longer expand)
• severe emphysema (there is a high risk of pneumothorax)
• Presence of only one functional lung
• Blood coagulation disorders
• severe heart failure
• pulmonary hypertension (high risk of bleeding)
• PEEP ventilation (danger of barotrauma)

The principle of transbronchial biopsy is based on placing a flexible forceps through the bronchoscope into the non-visible periphery and gently advancing the open forceps again. As soon as you feel any resistance, the forceps is closed and removed with a jerk.

Konietzko (1995) generally performs TBB under X-ray control, which other authors do not consider necessary in the case of disseminated findings. In the case of circumscribed findings, however, X-ray control is indispensable.

If the biopsy is used for localized shadows, imprint cytology should be made of the removed lung tissue in order to assess whether the biopsy needs to be extended.

After the puncture, an expiratory X-ray must be taken 2 - 4 hours later to exclude a pneumothorax.

Konietzko (1995) recommends inpatient monitoring of the patient for 24 h, whereas other authors recommend outpatient monitoring.

Transbronchial lung cryobiopsy (TBLC): In transbronchial lung cryobiopsy, lung tissue is removed by refrigeration using so-called cryoprobes. For this purpose, the tissue is frozen in the area of the probe tip during a bronchoscopy and then extracted through the bronchoscope.

This makes it possible to remove even larger biopsies, which in turn significantly improves the diagnosis of interstitial diseases (Kreuter 2016). Thanks to the rapid freezing (5 seconds until the minimum temperature is reached) morphological structures are better preserved than with other bioptic procedures:

• no crushing artifacts
• no bleeding into the bioptate

Disadvantages of the method are

• an increased pneumothorax rate with 5 % - 30
• a slightly increased bleeding rate
• the necessity of intubation

Several international multicentre studies are currently underway to better assess the role of cryobiopsy in rare lung diseases (Kreuter 2016).

A study published in 2016 by Ravaglia et al in Karger Kompass Pneumology comparing transbronchial cryobiopsy (TBLC) with (surgical) transcutaneous / transthoracic lung biopsy (SLB) showed that the length of hospital stay was lower, as was the death rate (deaths: SLB: 2.7%; TBLC: 0.3%). Only in the area of diagnostic confirmation was SLB ahead of TBLC (SLB: 98.7 %; TBLC: 82.8 %).

Cryobiopsy is therefore safe and, compared to SLB, has significantly lower complication and mortality rates. TBLC is therefore recommended as the diagnostic approach of choice for the diagnosis of interstitial lung diseases. If it is not possible to make a reliable diagnosis, SLB must still be used.

Transcutaneous / transthoracic lung biopsy (SLB): The indication for transcutaneous biopsy must be strictly defined. The morbidity rate is very high at 42% - 44%, the mortality rate is 0.5% - 1.1% (Hecker 2003). Risk and benefit should therefore be carefully weighed.

For example, a round focus suspected of being tumorous is usually always approached surgically, regardless of any previous histological or cytological confirmation. In this case, a puncture should only be performed if the patient is inoperable and a puncture would have therapeutic consequences.

The diagnostic certainty of a transthoracic biopsy is given by Hecker (2003) with 63 % - 75 %.

However, the success rate is very low for benign tumours. The benign tumours are mostly of very solid consistency. For this reason, the biopsy needle does not provide enough material for histological examination.

Indications for SLB exist:

• - if the diagnosis could not be confirmed by the transbronchial biopsy
• - in the case of focal lesions that are predominantly peripheral to the lungs
• - in the case of infiltrative processes in the lungs that are not yet clear

Contraindications for an SLB:

• - any form of haemorrhagic diathesis (e.g. thrombocytopenia, coagulopathies such as von Willebrand-Jürgens syndrome, vascular haemorrhagic diathesis such as Purpura-Schoenlein-Henoch and M. Osler, etc.)
• - Therapy with anticoagulants
• - pulmonary hypertension
• - Suspicion of a vascular process (e.g. arteriovenous aneurysm; in case of doubt, angiography is required before biopsy)
• - cardiac or respiratory insufficiency
• - high grade or bullous emphysema
• - upper influence jam

Transthoracic biopsy requires at least 24-hour monitoring.

The biopsy is performed under fluoroscopy while lying down. If the puncture under fluoroscopy is difficult in the case of a focal point localisation, it is recommended that it be carried out under computer tomographic control and, in the case of processes involving walls, under sonographic control.

The complications of a transthoracic lung biopsy are:

• Pneumothorax (most frequent complication; the figures vary between 10 - 30 %, depending on the time of X-ray control)
• Air embolism (to avoid this, the patient should lie strictly 24 hours after the procedure, especially not raise his head or lie high)
• bronchopleural fistula
• Empyema
• Bleeding
• Stub channel metastasis

Thoracoscopic lung biopsy: Thoracoscopiclung bi opsy has the advantage that material can be removed under visual control. This can be done with puncture needles, forceps or by punching. Through thoracoscopic puncture, biopsies up to a size of 3 cm can be removed - usually without technical problems - with the help of a recovery bag.

A prerequisite for the removal of biopsies in this way is the possibility of rapid coagulation. Viskum (1989) recommends the routine insertion of a pleural drainage after sampling.

This form of examination allows the diagnosis to be confirmed in about 80 % of patients.

A distinction must be made between:

• internal thoracoscopy
• surgical thoracoscopy
• video-assisted thoracoscopy

Internal Thoracoscopy: The so-called internal thoracoscopy is performed by pulmonologists and is primarily used to inspect the pleural space. It is used both for diagnostic and therapeutic purposes (pleurodesis, evacuation, adhesiolysis and placement of a drainage).

Bioptates of the lung can only be taken from the so-called lung mantle.

The advantage of internal thoracoscopy is that the examination can take place under local anaesthesia and intubation is not necessary. Therefore, the examination is also suitable for a clientele that would not be suitable for a more extensive procedure.

Contraindications:

• manifest pulmonary insufficiency
• manifest heart failure
• Coagulation disorders (Quick < 60 %, thrombocytes < 80,000)
• drug-based anticoagulation
• Anemia with a Hb < 6 mm/l
• Less than 6 weeks ago after myocardial infarction
• severe kyphoscoliosis (both positioning problems and pulmonary complications possible)

Patients should be monitored in the recovery room for 1-2 h after the procedure (Heine 2007). During transport to the normal ward, x-rays should be taken to check lung expansion and the correct position of the drainage.

The complication rate is low at 2.34 % (Heine 2007). However, the risk of infection increases with increasing length of time the drainage is in place. The specificity of internal thoracoscopy is very high and lies between 90 % - 95 % (Hecker 2003). The sensitivity is low because the biopsy is only obtained from the periphery and is only 60 % - 75 % (Hecker 2003)

Surgical Thoracoscopy: Surgical thoracoscopy, also called thoracoscopy to measure, is performed by the thoracic surgeon and is a modification or extension of internal thoracoscopy. It can be performed under local anesthesia, but is usually performed under general anesthesia.

Contraindications:

• global respiratory insufficiency
• severe untreated arrhythmias
• Currently fresh myocardial infarction
• Blood clotting disorders (Quick < 40 %, platelet count < 40,000 cmm)
• it must be capable of anaesthesia

The first video-assisted thoracoscopies (VATS) were performed in 1990. In the beginning the laparoscopic instruments were used. In the following years, however, special thoracoscopic instruments were quickly developed. This led to a better handling.

After the introduction of the endoscopic stapling devices, the possibility of taking lung biopsies improved once again decisively with regard to blood and also air tightness.

VATS is performed in double lumen intubation. The standard access in 3-point technique can be located in the axillary line as well as in the posterior or anterior axillary line and thus the changed areas can be reliably identified.

Both sensitivity and specificity are well over 90%. The morbidity is < 2 %, the lethality is zero.

VATS is considered the "golden standard" (in relation to elective lung biopsy).

If necessary, VATS can also be extended to include classic thoracotomy.

Lung biopsy as part of a thoracotomy: More than 2/3 of patients with interstitial lung disease require an open lung biopsy for a clear diagnosis.

However, the thoracotomy for biopsy collection should only be performed when less aggressive procedures have not led to a clear diagnosis. In the case of diseases for which a thoracotomy is required anyway for therapeutic reasons, preoperative histology is not necessary. The open lung biopsy in the context of a thoracotomy has been technically possible since the beginning of the 20th century (Hecker 2003). A thoracotomy for taking biopsies is a so-called "small diagnostic thoracotomy", also called minithoracotomy.

However, this method cannot be used if larger pleural adhesions exist.

Both the sensitivity and the specificity of these bioptates are well over 90%. The mortality rate is below 2 %. The open lung biopsy is therefore equal in both the diagnostic results and the complication rate of VATS. The biopsy site should always be above the lung area with the most obvious pathological changes. In the anterior axillary line an infusion of approx. 4 - 6 cm is made.

The lesion resulting from the biopsies must be treated with puncture ligature, a stapler or similar. An intrathoracic drainage is then inserted.

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