Treatment outcomes and objectification methods of the thoracoscopic sympathectomy in patients with focal hyperhidrosis and blushing syndrome

1 Department of Neurosurgery, Central Hospital of the Ministry of Internal Affairs of Ukraine (Central Police Hospital), Kyiv, Ukraine 2 Medical Center “MedСlinic”, Kyiv, Ukraine 3 Department of Thoracic Surgery and Pulmonology, Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine 4 Department of General Surgery No 2, Bogomolets National Medical University, Kyiv, Ukraine 5 Clinic “EuroDerm Clinic”, Kyiv, Ukraine


S i n g l e -p o r t v i d e o -a s s i s t e d t h o r a c o s c o p i c sympathectomy (VATS)
is an effective minimally invasive surgical method of choice for the treatment of primary focal hyperhidrosis, which is caused by pathological hyperactivity of the sympathetic part of the autonomic nervous system [1][2][3]. Today, this method is also widely used for the treatment of blushing syndrome, a characteristic symptom of which is uncontrolled frequent and intense attacks of redness of the face and neck [4].
Symptoms of decompensated hyperhidrosis of the palms, armpits and feet significantly affect the quality of life, in particular the physiological, mental and social situation of the patient [5,6]. Conservative treatment only temporarily reduces symptoms, while surgical treatment is the most effective and is based on inhibiting Ukrainian Neurosurgical Journal. Vol. 27, N2, 2021 the transmission of impulses from the sympathetic ganglia to the exocrine sweat glands [7].
Thoracoscopic sympathectomy was first proposed in 1942 by J. Hughes. It remained almost unknown until the widespread introduction of video endoscopic techniques in the 1980s [8]. However, when choosing surgical treatment, many questions remain relevant, including the determination of the degree, the number of degrees and the method of interruption of the sympathetic chain [5]. Traditional methods of diagnostic tests to determine the severity of focal hyperhidrosis and blushing syndrome have a number of disadvantages, which require the search for new diagnostic methods to objectify the severity of symptoms in these diseases and the results of surgical treatment.
Objective: To conduct an objective assessment for the improvement of the quality of life of patients with primary focal hyperhidrosis and blushing syndrome after bilateral single-port video-assisted thoracoscopic sympathectomy.

Study participants
The analysis of results of surgical treatment of 62 patients aged 17 to 42 years, including 26 (41.9%) men and 36 (58.0%) women who were inpatient treatment at the Medical Center "MedClinic" in 2015-2021.
All patients gave written informed consent to participate in the study and use its results for the scientific purpose.
The study was approved by Ethics and Bioethics Committee of "MedClinic" Medical Center (Meeting Minutes No. 1 of March 30, 2016).
The study is not associated with an increased risk for study subjects and was carried out in accordance with bioethical norms and scientific standards for conducting clinical trials with the participaton of patients.
Inclusion / exclusion criteria Criteria for recruiting the patients in the study: males and females aged 16 to 60 years; diagnosed with "primary focal hyperhidrosis of the extremities" and / or "blushing syndrome"; ineffectiveness of conservative treatment; performed surgical intervention -bilateral single-port VATS.
Exclusion criteria from the study: persons under the age of 16; patients with secondary hyperhidrosis; patients with mental disorders under the dispensary supervision of a psychiatrist; patients who underwent thoracoscopic sympathectomy for indications other than primary hyperhidrosis and blushing syndrome; inability to continue participating in the study during the follow-up period.
Characteristics of the group Patients were divided into three groups depending on the level of coagulation of the sympathetic trunk: the first group (n = 9) -bilateral single-port sympathectomy at the level of R3 (isolated palmar hyperhidrosis), the second group (n = 31) -at the level of R3-R4 (hyperhidrosis of the palms and armpits), the third group (n = 22) -at the level of R2 (blushing syndrome).

Study design
All patients underwent single-port VATS according to the following method [9]: 1. General anesthesia was given with intubation of the lungs with a double lumen tube.
2. The position of the patient on the operating table is on the back with the upper extremities at 90°.
3. A 15 mm skin incision was performed in the III-IV intercostal space along the anterior-axillary line. A 10 mm trocar was inserted into the III-IV intercostal space and tissue dissection was performed from the skin to the parietal pleura with its perforation (pneumothorax). The lumen of the endotracheal tube, which ventilates the lung was opened on the side of the operation. This caused the collapse of the lung on this side. A 20-millimeter silicone trocar was inserted, through which a 30-degree thoracoscope was inserted into the pleural cavity (Fig. 1A). 4. After revision of the pleural cavity, a curved monopolar hook was inserted, which was used to coagulate the sympathetic trunk.
5. The required level of the sympathetic trunk was determined by anatomic landmarks. (Fig. 1B). 6. The mediastinal pleura of the corresponding rib in the area of 4 cm and the sympathetic trunk were coagulated at this level between the two ribs ( Fig. 2). After coagulation of the sympathetic trunk and its collateral innervation (Kuntz nerves), a drainage tube 18 Fr with water valve through the trocar into the thoracic cavity was inserted to control the lung expansion with increasing airway pressure by artificial ventilation. After the complete expansion of the lung, the drainage was removed and layered closure of the wound was made. 8. A cosmetic suture was applied to the skin and an aseptic dressing.

A B
Dermatology Life Quality Index (DLQI) questionnaire [10] and Hyperhidrosis Desease Severity Scale (HDSS) were used to assess the quality of life before and after surgery [11]. A scale from 0 to 30 points was used to assess DLQI: 0-1 points -symptoms did not affect the patient's quality of life, 2-5 points -had little effect, 6-10 points -had a moderate effect, 11-20 points -had a significant effect, 21-30 points -had an extremely large effect. To determine the degree of hyperhidrosis, traditional examination methods were used -Minor test and the gravimetric analysis. The latter was performed with high-precision weighing of filter paper up to 0.01 g. Capillaroscopy was performed in case of blushing syndrome.
To determine the objective assessment of the severity of hyperhidrosis, measurements of transepidermal fluid loss (TEWL-metry) were carried out before and after surgery (in 1 month) using a Tewameter TM 300 apparatus with an open chamber. The unit of measurement is g / h / m 2 [12,13]. According to the degree of transepidermal fluid loss the skin condition was determined: 0-10 -excellent condition, 10-15 -satisfactory condition, 15-25 -normal condition, 25-30 -stressful condition, > 30 -critical condition. Conditions for the testing procedure: in the morning, during the day the exposure to the study site of antiperspirants, moisturizers, alcohol-containing solutions of antiseptics was excluded. Before the study, the patient was indoors for 30 minutes at an air humidity of 20-40% and a temperature of 20-22° C.

Statistical analysis
When processing the statistical data, the arithmetic mean and standard deviation score or median and the interquartile interval (QI -QIII) were determined. To identify differences after surgical treatment Student's test was used for related samples in the case of a normal data distribution law, and Wilcoxon rank sum test was used for linked samples with distribution of data other than normal. To determine the difference between the groups according to the severity of the disease, multiple comparisons were made and Kruskal-Wallis H test was used. Dunnett comparisons post hoc test were made. Statistical data processing was performed using the EZR package EZR v. 1.54 (R statistical software version 4.03, R Foundation for Statistical Computing, Vienna, Austria) [14]. When analyzing the research results the critical significance level was taken as 0.05.
After surgery, all patients were satisfied with the result. There were no postoperative complications in all study groups, including Bernard-Horner syndrome, fatalities, and conversion of VATS to open surgery. No recurrences of the disease were recorded throughout the follow-up period (one year).
The results of surgery at various levels of the sympathetic trunk and its impact on quality of life were assessed using the DLQI questionnaire. One month after surgery, the best quality of life measures were recorded in patients who underwent transection of the sympathetic trunk at the level of R3 (improvement from (20.3 ± 5.9) to (0.8 ± 0.8) points), whereas after surgery at the level of R3-R4 the quality of life improved from ( Compensatory hyperhidrosis of varying severity in patients who underwent VATS regressed in all cases during the first year. Only 10 (16%) people reported symptoms of compensatory hyperhidrosis in the area of trunk, abdomen, back, inner thigh during sports physical training or when the air temperature rises above 30° C. In everyday life, the phenomena of compensatory hyperhidrosis were not observed. This did not affect the quality of life and satisfaction with the outcome of surgical treatment.
Comparison in the study groups revealed a difference in quality of life measures depending on the severity of the disease before surgery. The lowest quality of life measure was observed in patients with the 4th degree of On physical examination: with a slight stress factor, hyperemia of the face and neck, and areas of chest occurs (Fig. 3, 5).
Differential diagnosis was made with hyperthyroidism, pheochromocytoma.
According to the results of capillaroscopy: signs of microcirculatory disorders, local vascular tortuosity of the afferent arteriolar vessels, congestion in the postcapillaryvenular vessels, pronounced perivascular edema (see Fig. 3, 5).
O n S e p t e mb e r 28, 2020, a t h o r a c o s c o p i c sympathectomy was performed. Bilateral VATS at the level of R2. The postoperative period was uneventful.
Result: long -lasting effect from the moment of surgery -no redness attacks (Fig. 4, 6). After the operation according to DLQI -2 points.

Clinical case 2
Patient O., born in 2001, complained of increased sweating of the palms and armpits. The diagnosis of primary palmar and axillary hyperhidrosis of the 3rd degree was made.
On physical examination: palms and armpits are cool and moist to the touch (Fig. 7A, 7B). Differential     Gravimetric analysis: on the right palm the result before surgery -2.17 g, after surgery -1.85 g, on the left palm the result before surgery -2.11 g, the result after surgery -1.78 g.
Result: long -lasting effect from the moment of surgery -dry, warm palms and axillary regions (Fig. 7B,  7D). One month after surgery according to DLQI -2 points.

Clinical case 3
Patient K., born in 1992, complained of increased sweating of the palms.
On physical examination: wet palms, significant sweating from the palmar surface of both hands (Fig. 8A).
Differential diagnosis was made with hyperthyroidism, pheochromocytoma.
TEWL test results, g / h / m 2 : Gravimetric analysis: on the right palm the result before surgery -2.17 g, after surgery -1.82 g, on the left palm the result before surgery -2.11 g, after surgery -1.79 g On May 14, 2020, a thoracoscopic sympathectomy was performed. Bilateral VATS at R3 level. In the postoperative period, the patient did not notice the phenomenon of compensatory hyperhidrosis.
Result: long -lasting effect from the moment of surgery -dry, warm palms (Fig. 8B). One month after surgery according to DLQI -0 points.

Discussion
Currently, various approaches and methods of surgical treatment of upper limb hyperhidrosis and blushing syndrome are used, which involve the interruption of the upper thoracic sympathetic trunk, usually from the second to the fourth thoracic ganglion [15 ]17]. The most common are two-and three-portal VATS modifications. However, these approaches have a number of disadvantages compared to the singleportal approach due to the high trauma rate and the number of postoperative complications. In this study, coagulation and separation of the sympathetic trunk through a single port using a 20 mm diameter silicone port was performed by the authors. This operation was less traumatic for soft tissues, and an excellent clinical result was obtained -all patients were satisfied with the achievement of a quick effect. Discussions continue on the optimal level of sympathectomy for a specific nosology with the most stable effect with the lowest risk of complications, side effects or disease recurrence. Thus, for the treatment of blushing syndrome or facial hyperhidrosis, it is recommended to perform a sympathectomy at the R3 or R2 and R3 levels, for the treatment of palmar hyperhidrosis -at the R3 or R4 levels, for the treatment of axillary hyperhidrosis -at the R4 and R5 levels or R5, for the treatment of combined palmar and axillary hyperhidrosis -at the R4 or R5 level [16]. Higher level of R2 sympathectomy is associated with the risk of Bernard-Horner syndrome due to possible damage to the cervicothoracal (stellate) ganglion or its branches. And too low levels (R5 and lower) threaten to damage the thoracic cardiac branches of the sympathetic trunk, which are involved in the formation of the cardiac plexus, and can cause cardiac arrhythmias [12,15,16].
A series of long-term studies by R. Jeganathan et al. found that sympathectomy provides a long-term positive effect without relapse, but compensatory hyperhidrosis is the most common side effect [18]. This is consistent with the data of most studies, according to which its frequency varies from 17 to 100% [16,19,20]. In our study, it was identified only 10 (16%) patients with compensatory hyperhidrosis of varying severity, which regressed in all cases within one year. This indicator is explained by the careful selection of patients for the surgery, which provided for highly specific preoperative diagnostic testing, much less traumatic techniques, as well as the correct determination of the level of sympathectomy. Some authors suggest that a larger volume of sympathectomy (up to R4 or R5 level) is associated with an increased risk of compensatory hyperhidrosis [15,20], which was also observed to a certain extent in our study. The highest rate was noted in the second group -6 patients after VATS at two levels (R3-R4).
In the given clinical cases, TEWL-metry, traditional Minor test and gravimetric analysis were performed to determine the intensity of sweating.
Despite the simplicity of the Minor test and the high sensitivity of the test (up to 83%), this method has certain disadvantages and low specificity (up to 57%) [21,22]. Gravimetric analysis is performed to quantify hyperhidrosis. The filter paper is weighed 60 s after contact with the area of increased sweating. The disadvantages of this method are the inability to determine the severity of hyperhidrosis (which is important when choosing a method of treatment), when the amount of sweat is not excessive.
Unlike the Minor test, which is used only to determine the limits of increased sweating, the main advantages of the TEWL test are the accuracy of transepidermal sweat loss and ease of implementation, which allows you to objectively assess the severity of hyperhidrosis and determine the indications for outpatient surgery. It was found that the condition of the skin with fluid loss 25-30 g / h / m 2 transepidermally corresponds to the intense, with fluid loss> 30 g / h / m 2 -critical. This may be a criterion for choosing the surgical treatment.
Patient K. with hyperhidrosis, who underwent a single-port VATS at the R3 level, in the postoperative period had a long-lasting effect from the moment of surgery, sweating from the palmar areas was reduced by half (from 44.9 to 22.0 g / h / m 2 ) and axillary regions (from 48.5 to 21.0 g / h / m 2 ), less noticeable changes were in the feet area (from 20.2 to 19.5 g / h / m 2 ). On examination one month after surgery, the patient assessed the effect of sweating on quality of life as 0 points according to DLQI.
In patient M. with blushing syndrome capillaroscopy was performed to objectively assess changes in the skin of the face, neck and chest. In the postoperative period, regression of redness and the absence of prolonged erythema was observed, the capillaroscopic picture corresponed to norm for this anatomical region.
These results indicate that in order to objectively assess the severity of hyperhidrosis during the diagnostic examination of patients, it is necessary to perform TEWL-metry, and when examining persons with blushing syndrome -capillaroscopy.
The study carried out a comparative analysis of the results of a single-port bilateral VATS at different levels of the sympathetic trunk. The findings may be useful for neurosurgeons, thoracic surgeons, general surgeons, and family physicians.