The rare anatomical variant of upper lobe: clinical features of 46 cases with surgical procedure

Primary disease in thorax associated with an azygos lobe is extremely rare. It is usually identied 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 October 2018. Methods We the and Results all


Introduction
An azygos lobe is a rare congenital variant. It is recognizedincidentally on chest X-ray or CT for the duration of healthcheckups. Wrisberg rstly described the azygos lobe in 1877 thatis a variant of pulmonary anatomy and presenting in 0.1-1% of thepopulation [1].The different from other accessory lobes of anomalies of the lungis that the abnormal azygos vein crosses the apex of thelung [2]. Theazygos lobe has been recognized in both the right and left lungsfrom the studies [3,4].
According to the review of the literatures from the universalelectronic databases, there are only some cases reports of azygoslobe with primary thorax disease have been reported. This is the rst study containing all the series of patients with azygos lobediagnosed in surgery in English literature. The purpose of thisstudy was to study clinical data, radiological manifestation, andtreatment strategy of patients.

Data sources
Three universal electronic databases, PubMed, EMBASE and Web ofScience, were selected to identify the full-text English literaturepublished from 1 January 1931 to 31 October 2018. Final searchcriteria included the following keywords that were "azygos lobe"and "surgery". Furthermore, we also manually explored the referencelists of relevant papers to detect any one included study with noduplication. The summary of the ndings is listed in Table. Inclusion and exclusion criteria Inclusion criteria (i) azygos lobe were not only found in X-rays or CT, but alsodiagnosed in surgery; (ii) azygos lobe was independentlyinvestigated in original literature; (iii) manuscripts wereaccessible in the full-text literature; and (iv) only Englishlanguage manuscripts were considered for the study.
Exclusion criteria (i) Letters and conference abstracts were excluded; (ii)manuscripts without full-text were excluded; (iii) manuscripts innon-English languages were not accepted; and (iv) patient withoutsurgery in report of the literature.

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

Results
In our Table, there were 26 male patients and 20 female patientsand the male to female ratio nearly to 1.3:1. The mean age was36.5 years old. All the azygos lobes were located in the rightupper lobes. The presenting symptoms were dyspnea, excessivesweating, head injury, murmur in the mesocardiac area, hemoptysis,hoarseness, vomiting according to the Table. There were lots ofdifferent 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 withVATS. One case was operated by Robot-assisted azygos lobectomy foradenocarcinoma (Case 3). The patients with esophageal diseases weretreated with thoracotomy (Case 15, 19 and 20).

Epidemiology
An azygos lobe is a well-known normal variant of the lung thatwas described by Wrisberg [4].The literature has pronounced its incidencefrom 0.4% on chest radiographs to 1.2% on chest CT [5][6][7]. It arises at any age, which varied from0.9 to 76 years( Table 1). As in our analysis, the male to femaleratio was 1.3:1 and the mean age was 36.5 years.

Anatomy
The superior surface of the developing lung will be sliced bythe azygos vein if the normal medial migration of the rightposterior cardinal vein over the apex of the lung fails in theembryo. The lobe medial to the azygos vein is developed as theazygos lobe. The upper lobe is separated into two parts by aslanting ssure. This abnormal ssure closely looks like a normallung ssure, ranging from the lung substance to within. It isclosed by apposition of the surfaces bounding it and is oval onsection. The addition tongue-shaped lobe isolated by the ssureand the material of it is free from macroscopic pathological changewith normal lung.
We can see the interior of the right pleural sac after removalof the right lung from picture 1(quote from Stibbe etal[8]). The upperpart of the pleural cavity is realized to be divided into twosections by a domelike fold seen in picture 1. The fold is areduplication of the parietal pleura. Its bowed margin is attachedalong a line on the thoracic wall; the attachment that commencesposteriorly at the fth thoracic vertebra in right thorax passesimplicitly upwards across the posterior parts of the intercostalspaces to the middle of the second rib [8]. After that it changes downwards andforwards to the rst costal gristle. The azygos vein is containedbetween two layers in the fold and the pleural fold and azygos veinare related to one another [8]. The azygos vein lies behind the esophagusand on the right of the midline till it touches the level of thesixth thoracic vertebra [8]. It dips into the material of the upperlobe and pulls down with the pleural fold.
Summarizing from the literatures, the azygos lobe is dividedinto three types [8]: Type a More or less horizontal and cutting the outer (lateral) surfaceof the lung at some point between the apex and a point two inchesbelow the apex.

Type b
More nearly vertical and dividing the apex of the lung intolaterals halves.

Type c
Vertical and cutting off a small tongue-shaped lobe from theinner surface, the pedicle being attached to the upper margin ofthe root of the lung.

Clinical characteristics
It is very rare to nd an isolated case of azygos lobe withoutany associated anomaly. From our Table, there are many primarythorax 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 radiologicalinvestigation of symptoms related to primary thorax disease. In theeight patients with lung cancer, half of them are asymptomatic,even in our case. In Delalieux et al. [9] report, however, the patient presented withhemoptysis and hoarseness. In the research of patients withspontaneous pneumothorax, most of them presented with dyspnea. 29cases diagnosed as hyperhidrosis presented with excessive sweatingtypically.

Imaging characteristics
Chest radiographs are the most generally performed imaginglearning to evaluate the mass in the thorax, but it may not bepossible to distinguish azygos lobe from others. Typical chestX-ray shows a ne, curved line suggesting the meso-azygos and asmall nodule shaped like a tear drop telling the azygosvein [9,10]. Azygos lobecan be dependably diagnosed by High-resolution chest computedtomography (HRCT). In our case, HRCT scans con rmed presence of anazygos lobe and a GGO measuring 1.2 × 1.0 cm in the anteriorsegment of the right upper lobe adjacent to the arch of the azygosvein (Figs. 2A,B).
On HDCT, the azygos vein is seen as a thicker structurefollowing the same path as the ssure. The position of the azygosarch is higher than normal one [11]. The visceral and parietal layers ofpleura forming the mesoazygos are not fused, as is shown by thecommon occurrence of pleural effusion extending into the azygos ssure [12,13]. This statefavors mobility of the azygos vein and enables it to jump from itsusual position in the ssure and migrate to the mediastinum [14]. Becausethe repositioned azygos vein is joined to a structure whoselocation is higher than the normal anatomic path of theintramediastinal azygos vein [15][16][17][18].

Treatment
In the group of patients with lung cancer, 8 cases were treatedwith surgical procedure. The rst report of a right upperlobectomy by video-assisted thoracic surgery (VATS) in a patientwith an azygos lobe was published by Arai et al [10]. Some tumors may originatedirectly from the azygos lobe reported in several research [9,19,20]. In Fukuharaet al [20]research, they rstly reported the case with operativedemonstration of a primary adenocarcinoma arising from an azygoslobe, which was treated with robot-assisted azygos lobectomy. Asthe azygos lobe is a portion of the right upper lobe isolated bythe azygos vein and not a developmentally separate lobe, lobectomyin the patient with azygos lobe without concurrent resection of theright upper lobe is considered to be a limited resection [20]. However,an azygos lobectomy with mediastinal lymph node dissection may bean acceptable healing alternative for elderly individuals with poorpulmonary function and this method is considered to be a better wayfor preserving of postoperative pulmonary function and reducingmorbidity and mortality [1,21]. Some other cardiopulmonary pathologymight be existing in patients with azygos lobe so that it isimportant to keep this in mind when examining such patients. Asshowed in our case from the Table, we approached the neoplasm withmediastinal lymph node dissection and then it was removed by VATS.The azygos lobe was visible during the operation. The upper part ofthe pleural cavity was seen to be divided into two compartments bya dome-like fold and occupied the ssure. The fold is areduplication of the parietal pleura (Fig. 3).
The presence of an azygos lobe is considered a complicatingissue, especially in cases with hyperhidrosis or spontaneouspneumothorax. An azygos lobe might have a protective effect againstthe improvement of spontaneous pneumothorax reported from somestudies [3,12,14]. Threemechanisms were offered: the re ected pleura might be limiting thesize of a potential pneumothorax; the mechanical stressestransferred to the apex of the lung will be lessening with themeso-azygos; or the changed anatomy may essentially shield againstbullae formation. As it is relatively under-in ated, there isdecreased perfusion and ventilation of the azygos lobephysiologically. The anatomical explanation for the decreasedventilation is distortion of the bronchi caused by the azygos ssure. On the other hand, the similar bronchial anatomy coulddispose the azygos lobe to air trapping and develop into emphysema,bronchiectasis, or atelectasis. VATS is used for the management ofa spontaneous pneumothorax proposing its superiority to openthoracotomy [15,17,18].
Several researches also reported the surgical di culty inpatient with azygos lobe [22][23][24]. As the azygos vein is a thinwall, blood ow and very breakable structure, it has to be pushedaside or ligated with extreme carefulness [5][6][7]25]. The rst case was reported by Sieunarineet al [26] in1997. It was considered that di culty would have been experiencedin achieving haemostasis in the event of injury [26]. Azygos covered thesympathetic chain between the second and fourth thoracic ganglia.The third ganglion was the most di cult one to identify duringthe surgery [22]. When there were no venous tributaries inthe curtain, it was useful to create a window to expose thesympathetic chain [22]. At the end of VATS, it is important tocheck whether the azygos lobe has gone back to its originallocation or there is a possibility of atelectasis [2][3][4]22].
In patients with esophageal diseases, azygos lobe was also foundin surgery [27,28]. Two caseswere babies diagnosed as esophageal atresia. The overarching of theazygos vein in the extrapleural plane compromises the preferredextrapleural approach to the posterior mediastinum. Its apparentpassage through the upper lobe may be disconcerting, and doubtabout the anatomy depresses the surgeon from simply dividing it [27,28]. Theysuggested that once the vessel is recognized, ligation and divisionare safe and permit dissection to continue. Then Koksal et al [29] rstlyreported a child with an extralobar pulmonary sequestrations (ELPS)located in the upper posterior mediastinum associated with theazygos lobe. ELPS is a rare congenital anomaly that commonly occurson the left side [30][31][32]. In their case, ELPS tissue was receivingblood supply from the ascending aorta and right brachiocephalicartery, and draining to the superior vena cava by an accompanyingvein [29].

Conclusions
An azygos lobe is a rare anomaly of the lung. Anatomicvariations may misperceive routine operations while the surgeonperforms a thoracotomy or VATS on the right side. No matter whetherwe preserve the vein or not during the surgery, the surgeon must beinformed about the disparities in vascular drainage to the azygosvein. At the same time, we should pay more attention to where theazygos vein truly drains to so that the operation will beproceeding smoothly. Preoperative contrast CT of the chest isuseful to assess the anatomic variation of the vein.

Declarations
Ethics approval and consent to participate All the data supporting our ndings in this paper were freelydownloaded from the PubMed, EMBASE, the Web of Science and ChinaNational Knowledge Infrastructure websites. No ethical approval orwritten informed consent for participation was required.

Consent for publish
Not applicable.
Availability of data and materials 35. Grismer JT, Read RC. Does the mediastinal anatomycomplementing azygos lobe facilitate endotracheal balloon ruptureof the trachea? Surgery 1998,123(2):243-244. Figure 1 A view of the interior of the right pleural sac after removal of the right lung.