In order to reduce the trauma and psychological burden of patients and to better cure the primary disease, as well as the progress of science and technology, minimally invasive treatment has gradually become the mainstream of refractory pneumothorax treatment. This article introduces in detail the modern minimally invasive treatment for refractory pneumothorax and its characteristics, and looks into the future development of modern minimally invasive treatment. 1.Concept and clinical characteristics of refractory pneumothorax Pneumothorax refers to the abnormal accumulation of gas in the pleural cavity. It can be divided into three categories: spontaneous pneumothorax (SP), traumatic pneumothorax (TP) and iatrogenic pneumothorax (IP). SSP accounts for most of the self-induced pneumothorax and is often secondary to underlying lung parenchymal lesions or extra-pulmonary diseases that induce the formation of dirty pleura. The pneumothorax is formed by the formation of a pulmonary blister, which then ruptures under the action of some external forces, or by the formation of a bronchopleural fistula caused by some diseases, resulting in continuous air leakage from the pleural cavity. Refractory pneumothorax is defined as a spontaneous pneumothorax that still leaks after more than 2 weeks of closed chest drainage with continuous negative pressure suction [1], and it is also considered as refractory pneumothorax if it recurs after surgery and requires secondary surgery in surgery, and its mechanism is persistent air leakage from the pleural surface caused by various reasons. The common causes [2] are diffuse chronic lung diseases (COPD, pulmonary cystic fibrosis [2,3], interstitial lung lesions [2,4], pulmonary lymphangioleiomyomatosis [2,5,6], asthma [7]), malignancies, congenital pulmonary cysts, etc. Other rare causes are alpha-1 antitrypsin deficiency [2,8], AIDS (acquired immunodeficiency syndrome)-associated pneumothorax, pregnancy-associated pneumothorax, neonatal pneumothorax, menstrual pneumothorax, and refractory pneumothorax due to medically induced injury. Due to continuous air leakage from the pleural cavity, refractory pneumothorax affects the normal respiratory function of patients, and furthermore, refractory pneumothorax can be followed by infection and bleeding in the pleural cavity, which can be life-threatening in some cases. 2, Traditional treatment of refractory pneumothorax Among the general treatment principles of spontaneous pneumothorax [9], in addition to maintaining the stability of respiration and circulation, it is also required to minimize the damage of lung function. If the lung pressure is less than 30% and the symptoms are mild, we should wait for the pneumothorax to absorb on its own under close observation; if the pressure is 30-50% and the symptoms are obvious, we should use puncture and suction treatment, and if the efficacy is not obvious or if there are recurrent episodes, closed drainage of the chest cavity should be placed, which is traditionally done by blunt separation of the intercostal muscle by skin incision of the chest wall (mostly in the second intercostal space lateral to the midclavicular line, or the fourth or fifth intercostal space in the anterior axillary line The lung is still not fully reopened or continues to leak after 2-3 weeks of the above treatment, or in cases of recurrent, bilateral and alternating episodes, surgery should be actively undertaken. Conservative treatment and traditional closed chest drainage are not effective for refractory pneumothorax, so open-chest surgery is mostly used for treatment, and patients who cannot tolerate surgery are temporarily treated with intrapleural injection of pleural adhesives to achieve pleural adhesion sealing gap. Traditional surgical incisions are mostly large incisions (commonly used are posterior lateral incision, anterolateral incision, etc.), and although these incisions are fully exposed, they are more traumatic and have poor cosmetic effects, and the damage to the pectoralis muscle, latissimus dorsi muscle and intercostal nerve will affect the patient’s postoperative activities. The primary lesion is removed after opening the chest, followed by pleural fusion, while patients with refractory pneumothorax who undergo secondary surgery still need to fully separate the adhesions. The traditional ways of pleural fusion include pleural rubbing method (rubbing the wall pleura with dry gauze until it is filled with blood) and talcum powder spraying method, the former operation takes longer and is easy to be missed, the latter may have cancer risk, and its use is still controversial. 3.Modern minimally invasive treatment methods for refractory pneumothorax and their characteristics The concept of minimally invasive treatment for refractory pneumothorax is reflected in clarifying the cause and severity of pneumothorax, choosing appropriate minimally invasive means, and minimizing trauma without affecting the treatment effect. At present, minimally invasive treatment methods for refractory pneumothorax mainly include small axillary incision surgery, television thoracoscopic surgery (VATS), VATM (video – assisted thoracoscopy plus minithoracotomy), minimally invasive fibrinoscopic treatment techniques, interventional treatment techniques, etc. 3.1 History of the development of minimally invasive treatment for refractory pneumothorax The treatment of refractory pneumothorax has undergone a long development from the initial large incision open-chest surgery to the later small axillary incision surgery, thoracoscopic surgery, and other types of minimally invasive treatment forms (such as interventional treatment, fibrinoscopy, etc.). Before the introduction of television thoracoscopic surgery (VATS), many scholars carried out innovations and reforms of small dissection incisions [11], for example, Noirclerc (1973), Becker (1976), Kittle (1988), Bethencourt (1988) and others proposed muscle-preserving dissection incisions (including the auditory triangle incision Ginsberg (1993) proposed an axillary incision without dissecting the skin flap to prevent the possibility of postoperative seroma. These surgical incisions have reduced surgical trauma to the chest wall to varying degrees and have laid the foundation for the development of VATS. The history of the development of minimally invasive treatment of complex pneumothorax is most importantly the history of thoracoscopy [13]. In 1937 Sattler first reported the application of thoracoscopy for the treatment of spontaneous pneumothorax, and in 1980 Weissberg et al. used thoracoscopy to explore and resect pulmonary blisters, as well as to release pleural adhesions that prevented pulmonary reopening.In the early 1990s, VATS began to be used in clinical practice in China, where the most treated were spontaneous pneumothorax, and refractory pneumothorax was also included. In early clinical practice, when thoracoscopic exploration revealed pulmonary herpes, the root of the pulmonary herpes was clamped with titanium clips, and then the pulmonary herpes was cut with scissors or its root was cauterized with electric cautery to cause local degeneration and necrosis, thus achieving the purpose of preventing and controlling air leakage. With the development of endoscopic instruments, the lumpectomy linear cutting suture (Endo GIA) has brought great clinical convenience, which can close the lung residual surface at the base while removing the pulmonary blister, greatly reducing the postoperative air leak at the cut edge. The development of technology has also greatly reduced the recurrence of postoperative pneumothorax, but adhesives have certain side effects on human body, people are still controversial about its use, and there are also many scholars are studying new pleural adhesives with less side effects and good efficacy, nowadays VATS has become one of the standard procedures for the treatment of spontaneous pneumothorax and some refractory pneumothorax. 3.2 Modern minimally invasive treatment for refractory pneumothorax 3.21 Small axillary incision treatment for refractory pneumothorax Small axillary incision surgical treatment is suitable for: the first attack of spontaneous pneumothorax with air leakage after closed chest drainage for more than 5 d; two or more attacks of ipsilateral spontaneous pneumothorax; spontaneous hemopneumothorax, bilateral spontaneous pneumothorax; the first attack of special occupations, such as field workers, pilots, divers, etc. Divers, etc. The main contraindications are: extensive adhesions in the chest cavity; previous history of open-heart surgery on the affected side or history of chest diseases that may cause adhesions in the chest cavity. With the exception of a small number of patients with severe intrathoracic adhesions requiring conventional open-heart surgery, most patients can be treated with this method. Many patients with refractory pneumothorax, especially those requiring secondary surgery, have severe pleural adhesions and should be adequately evaluated with preoperative imaging such as chest CT for the degree of adhesions. The intercostal incision should be selected according to the lesion or pleural adhesions, and a small spreader should be used to open the intercostal space so that the incision is in a rectangular shape, which provides the maximum operative range without enlarging the skin incision. After entering the chest and exploring in sequence, the surgical operation includes loosening the pulmonary adhesions, ligating the lung to remove the potential for recurrence and fixing the pleura to prevent pneumothorax recurrence. Many years of clinical practice have shown that axillary mini-incision surgery and TV thoracoscopy have comparable efficacy [14, 15] and lower cost [16] in the treatment of spontaneous pneumothorax, and can be used universally in some areas where VATS is not popular, but there are also some shortcomings when comparing axillary mini-incision surgery with VATS [17], such as significantly longer ventilation time and operation time for one lung, less satisfactory postoperative patient scores than VATS, etc. Other shortcomings are that the surgical field of view is not as good as that of VATS. Other shortcomings include small surgical field of view, inadequate visualization, operational limitations, and difficulties in two-person cooperation. 3.22 VATS treatment of refractory pneumothorax As recommended in the SP treatment guidelines published by the British Thoracic Society [18], the indications for VATS of spontaneous pneumothorax are: recurrent spontaneous pneumothorax; long-term air leakage after placement of a chest drain after the occurrence of pneumothorax and failure to reopen the lung; bilateral pneumothorax or hemothorax; pneumothorax combined with large pulmonary blisters on the lung surface; pneumothorax in special occupations (pilots, divers Thus, it can be seen that most of the refractory pneumothoraxes requiring surgery are good indications for VATS. With the development of anesthesia and endoscopic techniques, the indications for refractory pneumothorax are no longer limited to the above-mentioned cases, and thoracoscopy can perform more difficult pneumothoracic surgeries. In general, three incisions are chosen for VATS pneumothorax surgery, namely the sixth intercostal space in the anterior or mid-axillary line, the fourth or fifth intercostal space in the anterior axillary line, and the fifth intercostal space in the posterior axillary line, with a three-point course inverted triangle. The size and location of the three incisions are not absolutely fixed, but vary according to individual habits and the location of the lesion, and this is especially true for refractory pneumothorax, where different types of Trocar are placed in each of the three incisions, with the larger caliber being the main The larger one is the main operating tract, and there are also thoracoscopic and secondary operating tracts. The existing scholars should successfully apply the treatment of pneumothorax with two-hole and single-hole VATS, Tsuboshima K [19] et al. compared 31 patients with different VATS for spontaneous pneumothorax, including 11 patients with Endo-Close (a two-hole VATS) and 20 patients with three-hole VATS, and the results were: operative time (58,6± 18,3 min vs 63,0±15,1 min), postoperative drainage time (1,0±0 days vs 1,3±0,5 days), postoperative hospital days (3,0±1,5 days vs 3,7±1,4 days), and surgical bleeding was essentially the same in both, Foroulis CN [20] et al. compared modified two-port VATS for recurrent pneumothorax surgery and small axillary incision surgery, the postoperative results were essentially the same except for the longer operative time in the former, but the dual-port VATS surgery was more acceptable to patients. Some scholars, such as Chen PR [21], have even applied single-port VATS to successfully complete the routine operation of pneumothorax surgery, achieving the same efficacy as traditional three-port VATS surgery and having the advantages of less postoperative pain and high patient satisfaction. In addition to reducing the incision, the diameter of the thoracoscope is also becoming smaller, and Hazama K et al [ 22] had laser resection of pulmonary bullae ( n = 60, pulmonary bullae diameter < 2 cm ) with a pinhole thoracoscope (2 mm diameter), and compared with conventional thoracoscopic Stapler resection ( n= 54, pulmonary bullae diameter > 2 cm ), the complications such as operative time, postoperative analgesic drug use, and postoperative air leak were There was no significant difference in recurrence rate and no postoperative scarring. Double-hole, single-hole VATS and pinhole thoracoscopy further embody the concept of minimally invasive surgery, but their clinical promotion needs to be further followed up. The surgical steps of VATS are generally intra-thoracic exploration to identify the primary lesion, treatment of the primary lesion (e.g. pulmonary herpes cutting and suturing, electrocautery, pulmonary decompensation for COPD), pleural fusion to reduce recurrence, and postoperative drainage. The operative focus varies for different types of refractory pneumothorax. As in the case of postoperative recurrent pneumothorax treated with rethoracoscopic surgery [23], it is necessary to fully explore, identify the air leak, completely remove the primary focus, selectively release ectopic adhesions and other thoracic adhesions affecting pulmonary resuscitation, and appropriately peel the fibrous membrane formed on the lung surface. Total pleural friction fixation can be performed, and two postoperative chest drains can be placed in the upper and lower chest. For refractory pneumothorax with COPD, the diffuse pulmonary blister should be excised together with the non-functional lung tissue at its base, and treated by interrupted mattress suture with atraumatic thread with bovine pericardial spacer, or by bovine pericardial piece with linear cutting sutures. A tubular naive repair material with a linear cutting suture can also be used. Combined application of biologic glue to prevent air leak, additional pleural friction or pleural fixation with partial pleurectomy after surgery to prevent recurrence. In addition, for some patients with poor cardiopulmonary function and high risk of general anesthesia [24,25,26], thoracoscopic exploration under local anesthesia , and injection of autologous blood, OK-432 [6,23], and diluted fibrinogen gel [27] can be performed to seal the fissure. Among the current surgical treatment measures for pneumothorax, VATS is considered the most effective and standard procedure of choice [28], and Joshi V et al [29] retrospectively analyzed the results of 163 patients with pneumothorax (86 with VATS and 77 with open thoracotomy) and found that there was no significant difference between the two procedures in terms of postoperative recurrence rate, and patients in the VATS group had, compared with those with open thoracotomy Fatimi SH et al[30] compared 39 patients with spontaneous pneumothorax treated with conventional open chest and VATS and found that the postoperative tube time was shorter in the VATS group than in the conventional open chest group, and patient satisfaction was higher. However, years of clinical practice have also shown that VATS has its limitations, as the operator cannot use his hands to perceive the size, shape, texture and its relationship with the surrounding tissues especially in deep intrathoracic lesions during the operation. 3.23 VATS-assisted minithoracotomy for refractory pneumothorax Video-assisted thoracoscopy plus minithoracotomy (VATM) is a procedure based on VATS, supplemented by a small intercostal incision (the location of the small incision in the chest is not yet standardized, the location of the surgical incision must first The indications for VATM are essentially the same as those for VATS [31] and will not be discussed further. pulmonary blister (DBSP) more completely, easy and reliable operation, safe and economic, small incision, and mild pain, which is the ideal surgical method for DBSP [32], and in terms of operation time, the VAMT group is significantly shorter than the VATS group, which can significantly reduce the trauma caused by anesthesia [33]. 3.24 Minimally invasive fibrinoscopic treatment of refractory pneumothorax As a minimally invasive endoscope operating through the natural lumen, fibrinoscopy is increasingly used in the treatment of refractory pneumothorax.Lee DY et al [34] used fibrinoscopy to seal the air-leaking bronchi in patients with emphysema by placing watanabe spigots in the focal bronchi, Zeng Y et al [35] used fibrinoscopy to selectively seal the air-leaking bronchi. Zeng Y et al [35] used ciliofibroscopy to selectively seal air-leaking bronchi to treat patients with refractory pneumothorax caused by bronchopleural fistula. In addition, the application of fibrinoscopy instead of thoracoscopic injection of albumin has been reported for the treatment of refractory pneumothorax complicated by chronic obstructive pulmonary emphysema in the elderly [36]. 4. Prospects of modern minimally invasive treatment for refractory pneumothorax Minimally invasive concept is the mainstream concept of contemporary thoracic surgery and even the whole surgical science, and it is also the trend of refractory pneumothorax treatment. Some more minimally invasive methods such as double-hole, single-hole VATS and pinhole thoracoscopy will be further developed and gradually applied to clinical practice. With the advancement of technology, the introduction of material technology and the development of pharmacology, new lung tissue cutting anastomoses, repair materials and pleural adhesives will be applied to clinical practice more often to effectively treat refractory pneumothorax and reduce its recurrence. In addition, some future surgical techniques, such as computer-assisted surgery and robotic minimally invasive techniques, may also intersect with the treatment of refractory pneumothorax to further improve the surgical results.