The rare anatomical variant of upper lobe


 Background

Primary disease in thorax associated with an azygos lobe is extremely rare. It is usually identified incidentally on chest X-ray or CT during health checkups with an incidence of up to 0.2%. This is the first study involving 46 of patients found with azygos lobe in surgery of English literature from January 1931 to July 2020.
Methods

PubMed, EMBASE and the Web of Science databases were searched for full-text literatures met out inclusion criteria. We summarized the clinical data, radiological manifestation, accompanying disease and treatment strategy of all patients.
Results

18 eligible studies involving 46 patients were selected for this research. The mean age was 36.5 years old. There were 26 male patients and 20 female patients and the male to female ratio nearly to 1.3:1. There were many different primary diseases with azygos lobe including lung cancer (n = 8), spontaneous pneumothorax (n = 5), esophageal cancer (n = 1), pulmonary sequestration (n = 1), esophageal atresia (n = 2), hyperhidrosis (n = 29). The azygos lobe (azygos lobe in Figs. 1 and 2) is an uncommon anomaly that is found in 1% of anatomic specimens, on about 0.4% of chest radiographs and 1.2% of high resolution CT. The azygos lobe is a developmental anomaly but not a true accessory lobe. Azygos lobe of all patients was diagnosed during the operation.
Conclusions

Azygos lobe occurs in 0.2% of the population and can make clinical diagnosis difficult. The detection of this anomaly and clarification of its precise anatomical features are important to alert the surgeon to potential problems during surgery.


Abstract
Background Primary disease in thorax associated with an azygos lobe is extremely rare. It is usually identi ed incidentally on chest X-ray or CT during health checkups with an incidence of up to 0.2%. This is the rst study involving 46 of patients found with azygos lobe in surgery of English literature from January 1931 to July 2020.

Methods
PubMed, EMBASE and the Web of Science databases were searched for full-text literatures met out inclusion criteria. We summarized the clinical data, radiological manifestation, accompanying disease and treatment strategy of all patients.

Results
18 eligible studies involving 46 patients were selected for this research. The mean age was 36.5 years old.
There were 26 male patients and 20 female patients and the male to female ratio nearly to 1.3:1. There were many different primary diseases with azygos lobe including lung cancer (n = 8), spontaneous pneumothorax (n = 5), esophageal cancer (n = 1), pulmonary sequestration (n = 1), esophageal atresia (n = 2), hyperhidrosis (n = 29). The azygos lobe (azygos lobe in Figs. 1 and 2) is an uncommon anomaly that is found in 1% of anatomic specimens, on about 0.4% of chest radiographs and 1.2% of high resolution CT. The azygos lobe is a developmental anomaly but not a true accessory lobe. Azygos lobe of all patients was diagnosed during the operation.

Conclusions
Azygos lobe occurs in 0.2% of the population and can make clinical diagnosis di cult. The detection of this anomaly and clari cation of its precise anatomical features are important to alert the surgeon to potential problems during surgery.

Background
An azygos lobe is a rare congenital variant. It is recognized incidentally on chest X-ray or computed tomography (CT) for the duration of health checkups. Wrisberg rstly described the azygos lobe in 1877 that is a variant of pulmonary anatomy and presenting in 0.1-1% of the people [1]. From an anatomical point of view, unlike the accessory lobes of other anatomical abnormalities in the lungs, the sinusoidal vein refers to the abnormal vein that travels through the tip of the lung [2]. According to the literature, azygos lobe may occur in the left or right lobe of the lungs [3,4].
Based on a review of the literature on the general electronic database, there are only a few case reports on the study of the azygos veins, and several cases of primary chest disease with azygous veins are described. This is the rst study that included all patients diagnosed with odd veins through surgical ndings in English literature. This article mainly summarizes the clinical data, radiological manifestations and treatment strategies of azygos lobe to provide new knowledge for doctors as well as empirical diagnosis and treatment thinking.

Data sources
We searched the full-text English paper from PubMed, EMBASE and Web of Science from January 1931 to July 2020. Final search criteria included the following keywords that were "azygos lobe" and "surgery". Furthermore, we also made a second manual exploration of the list of selected references to ensure that the selected articles contained relevant research without duplication. The summary of the ndings is listed in Table. Inclusion and exclusion criteria Inclusion criteria (i) azygos lobe was not only found in X-rays or CT, but also diagnosed in surgery; (ii) azygos lobe was independently investigated in original literature; (iii) manuscripts were accessible in the full-text literature; and (iv) only English language manuscripts were considered for the study.
Exclusion criteria (i) Letters and conference abstracts were excluded; (ii) documents without full text were excluded; (iii) Non-English languages papers were not accepted; and (iv) patient without surgery.

Statistical analysis
The statistical analysis was performed using IBM SPSS Statistics, version 16.0 (IBM Corporation, Armonk, NY, USA).

Results
In our Table, there were 26 male patients and 20 female patients and the ratio nearly to 1.3:1. The mean age was 36.5 years old. All the azygos lobes were located in the right upper lobes. The presenting symptoms were dyspnea, excessive sweating, head injury, murmur in the mesocardiac area, hemoptysis, hoarseness and vomiting. There were lots of different primary diseases with azygos lobe including lung cancer (n = 8), spontaneous pneumothorax (n = 5), esophageal cancer (n = 1), pulmonary sequestration (n = 1), esophageal atresia (n = 2) and hyperhidrosis (n = 29). Most of them were treated with video-assisted thoracic surgery (VATS). One case was operated by Robot-assisted azygos lobectomy for adenocarcinoma (Case 3). The patients with esophageal diseases were treated with thoracotomy (Case 15, 19 and 20).

Epidemiology
Azygos lobe is a rare abnormality anatomy of the lung, described by Wrisberg [4]. The literature has pronounced its incidence from 0.4% on chest radiographs to 1.2% on chest CT [5][6][7]. It arises at any age, which varied from 0.9 to 76 years( Table 1). As in our analysis, most of the patients are young and middleaged male and the mean age was 36.5 years.

Anatomy
During the embryonic development period, if the main vein in the posterior part of the right or left thoracic cavity is displaced in the embryo at the normal medial side of the apex of the lung, the upper surface of the upper lobe in the developmental stage will be cut by the atypical vein. The lobe medial to azygos vein is developed as the azygos lobe. The upper lobe is separated into two parts by a slanting ssure. This abnormal ssure closely looks like a normal lung ssure, ranging from the lung substance to within. It is closed by apposition of the surfaces bounding it and is oval on section. The addition tongue-shaped lobe isolated by the ssure and the material of it is free from macroscopic pathological change with normal lung.
We can see the interior of the right pleural sac after removal of the right lung from picture 1(quote from Stibbe Clinical characteristics From our Table, there are many primary thorax diseases with azygos lobe, such as lung cancer (n = 8), spontaneous pneumothorax (n = 5), esophageal cancer (n = 1), pulmonary sequestration (n = 1), esophageal atresia (n = 2), hyperhidrosis (n = 29). The azygos lobe is typically asymptomatic. It tends to be incidentally discovered during radiological investigation of symptoms related to primary thorax disease. In the eight patients with lung cancer, half of them are asymptomatic, even in our case. In Delalieux et al. [9] report, however, the patient presented with hemoptysis and hoarseness. In the research of patients with spontaneous pneumothorax, most of them presented with dyspnea. 29 cases diagnosed as hyperhidrosis presented with excessive sweating typically.

Imaging characteristics
Using the most common chest X-ray examination, we can see that the typical azygous veins appear as small nodular changes in the upper lobe of the lungs. But such changes may be overlooked by most clinicians [9,10]. Azygos lobe can be diagnosed by High-resolution chest computed tomography (HRCT). In our case, chest The CT scan con rmed that there were azygos lobe in the right upper lobe near the tip of the lung, while a ground glass opacity (GGO) was observed on the outer side of the azygos lobe near the azygous vein whose size was 1.2 × 1.0 cm (Fig. 1A, B). On HRCT, the position of the azygos arch of the azygos lobe is relatively high compared to the normal azygos vein [11]. From an anatomical point of view, it is understood that the inner pleura is not fused with the top layer of azygos, which ultimately makes the azygos arch appear more plentiful [12,13]. The elevation of the azygos arch will facilitate the migration of the azygous vein [14]. The azygous vein, based on the azygos arch, is more higher connected to the mediastinum than the normal anatomical path [15][16][17][18].

Treatment
In the group of patients with lung cancer, all of them were treated with surgical procedure. Arai et al reported the rst case of azygos lobe in a patient with lung cancer and underwent by VATS of right upper lobectomy [10]. According to some researches, tumors may exist directly in the azygos lobe [9,19,20]. In Fukuhara et al [20] research, they reported that lesions present in the azygos lobe can be removed by robot-assisted minimally invasive surgery and ultimately con rmed by pathological ndings as primary lung adenocarcinoma. Since the azygos lobe are not isolated, but part of the lung tissue separated from the right upper lobe, if the patient only simply removes the azygos lobe and leave the remaining part of the right upper lobe, it will be considered as a limited operation [20]. Some other cardiopulmonary pathology might be existing in patients with azygos lobe so that it is important to keep this in mind when examining such patients [1,21]. As we showed from the table and the surgical picture, we performed a mediastinal lymph node dissection and a complete resection of the right upper lobe by VATS. During the operation, we can clearly see the azygos lobes located in the upper lobe of the right lung through the display. The area of the pleural cavity near the top of the right chest appears to be divided into two spaces. The parietal pleura and the azygous vein are connected by a dome-like fold (Fig. 2).
According to a small number of studies, in some benign lung diseases, especially in the case of hyperhidrosis or spontaneous pneumothorax, the presence of azygos lobes may be related to these diseases [3,12,14].
Azygos lobe has an inhibitory effect in spontaneous pneumothorax possibly. This theoretical basis is mainly derived from three possible mechanisms. Firstly, the re exed pleura may limit the size of the potential pneumothorax; Secondly, the mechanical stress generated by the azygos lobe at the top of the lung can reduce the pleural effusion of the spontaneous pneumothorax tension in order to avoid the occurrence of pneumothorax; Thirdly, it may directly change the anatomy of the lung lobe to substantially prevent the formation of bullae. VATS is used for the management of a spontaneous pneumothorax proposing its superiority to open thoracotomy [15,17,18].
Several researches also reported the surgical di culty in patient with azygos lobe [22][23][24]. Since the azygous vein is a thin wall, blood ow and a very fragile structure, it must be carefully pushed aside by the surgeon or ligated if necessary during surgery [5][6][7]25]. Some scholars believe that it is di cult to achieve hemostasis in the case of damaged of azygous veins [26]. The Azygos vein covers the sympathetic chain between the second and fourth of thoracic ganglia. The third ganglion is the most di cult to identify ganglion in surgery and should be highly valued during surgery [22]. When venous tributaries are not seen in the surgical eld, it is useful to create a operating eld of exposure to the sympathetic chain for safety reasons [22]. Reminding all thoracic surgeons that at the end of the VATS, it is important to check if the azygos lobe has returned to their original position. If it does not return to its original position, there will be a problem of atelectasis. [2][3][4]22].
In the group of patients with esophageal diseases, azygos lobe was also found in surgery [27,28]. Two cases were babies diagnosed as esophageal atresia. Due to the abnormal anatomical structure of the azygous vein, the azygous lobes are produced, which makes the surgeon di cult to separate the azygous veins during the operation. In some operations, the azygous veins may not be separated successfully [27,28]. Therefore, literature studies suggest that once the vein is found, the dissection of the azygos vein is safe. Then Koksal et al [29] rstly reported a child with an extralobar pulmonary sequestrations (ELPS). ELPS is a rare congenital lobular abnormality commonly found in the left lobes [30][31][32]. Under normal circumstances, ELPS receives blood supply from the ascending aorta and right brachiocephalic artery, and through the accompanying venous drainage to the superior vena cava [29].

Conclusions
An azygos lobe is a rare anomaly of the lung. Anatomic variations may misperceive routine operations while the surgeon performs a thoracotomy or VATS on the right side. No matter whether we preserve the vein or not during the surgery, the surgeon should attach great importance to the azygous lobes caused by the abnormal anatomy of the azygous vein to avoid unnecessary bleeding or other complications during surgery. At the same time, we should pay more attention to where the azygos vein truly drains to so that the operation will be proceeding smoothly. Preoperative contrast CT of the chest is useful to assess the anatomic variation of the vein.

Abbreviations
CT computed tomography ELPS extra lobar pulmonary sequestrations GGO ground-glass opacity HRCT High-resolution chest computed tomography VATS video-assisted thoracic surgery.

Declarations
Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for publish
All the authors consent to publish the paper.

Availability of data and materials
The datasets supporting the conclusion of this article are included within the article.

Competing interests
The authors declare that they have no competing interests.