- el 100% de los operados tubo anhidrosis palmar despues de simpatectomia del T2-T3
- que despues de 6 meses de operados observaron sc pero los medicos lo hachacan a que coincidio con el verano


http://www.springerlink.com/content/ug735w173765wh83/fulltext.html
http://www.ncbi.nlm.nih.gov/pubmed/18461392?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Surgical Endoscopy
And Other Interventional TechniquesOfficial Journal of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and European Association for Endoscopic Surgery (EAES)  
 Springer Science+Business Media, LLC 2008 
10.1007/s00464-008-9922-z 

Quantification of eccrine sweat glands with acetylcholine sweat-spot test and anatomical redistribution of sweating after T2T3 thoracoscopic sympathicolysis 
Ricard Ramos1 , Cristina Masuet2, Maria Badia3, Valerio Perna4, Ivan Macia4, Ignacio Escobar4, Rosa Villalonga4 and Juan Moya1

(1)  Department of Thoracic Surgery and Unit of Human Anatomy and Embryology, Servei de Cirurgia Torcica, Hospital Universitari de Bellvitge, School of Medicine, University of Barcelona, LHospitalet de Llobregat, Feixa Llarga s/n 08907, Barcelona, Spain 
(2)  Department of Preventive Medicine and Biostatistics, Hospital Universitari de Bellvitge, LHospitalet de Llobregat, Barcelona, Spain 
(3)  Department of Pharmacology, Hospital Universitari de Bellvitge, LHospitalet de Llobregat, Barcelona, Spain 
(4)  Department of Thoracic Surgery, Hospital Universitari de Bellvitge, LHospitalet de Llobregat, Barcelona, Spain 


 Ricard Ramos
Email: ricardramos@ub.edu 

Received: 25 November 2007  Accepted: 12 February 2008  Published online: 7 May 2008 

Abstract
Background  In this study, patients treated by thoracoscopic sympathicolysis for palmar hyperhidrosis were evaluated to determine the number and response of sweat glands to intradermal acetylcholine stimulus. 
Methods  A total of 30 patients were included in the study. Group A consisted of 10 patients with palmar hyperhidrosis who underwent thoracoscopic sympathicolysis in October 2005, and group B consisted of 20 patients who underwent surgery during the years 1999, 2000, and 2001. The study procedure involved applying iodine alcohol to the palm and then intradermally injecting 0.1 ml 1% acetylcholine. This activated the sweat glands, which were then photographed and counted. The study procedure was performed prospectively over different periods in group A and retrospectively in group B. 
Results  In group A, the mean number of glands activated 1, 3, 6, and 12 months after surgery were 41, 174.20, 522.8, and 747.2, respectively; this gradual increase was statistically significant over the first 6 months (p = 0.004) but not between months 6 and 12 (p = 0.255). The trend towards an increasing number of active glands occurred in both groups, with a mean of 1369.8 active glands in group B compared to 747.2 (p = 0.095) in group A after 12 months. 
Conclusion  It is well-known that Cannons law of denervation (1939) is not applicable to the sweat glands, that is, there is no hyperactivation following intradermal acetylcholine stimulation. However, some response, which increased over the first 6 months following surgery, was observed in our study. Nevertheless, this activation is subsequently self-limiting, resulting in no gland atrophy, and reinnervation occurs without patient awareness. 
Keywords  Thoracoscopy - Sympathicolysis - Hyperhidrosis 


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Primary hyperhidrosis is characterized by excessive secretion of all the eccrine sweat glands in the body, particularly in those zones where gland density is highest: the palms, soles, and axillae. 

In addition to sweating, affected patients present typical clinical manifestations of sympathetic hyperfunction such as facial reddening, palpitations, tremor, and nonspecific epigastric pain [4]. 

Recent studies describe the existence of eccrine sweat glands with morphological indications of hyperstimulation, though without evidence of intrinsic gland alterations. The etiology of this disorder is therefore believed to involve either generalized or local sympathetic hyperfunction at the level of the thoracic sympathetic ganglia [5]. 

In 1946, Randal [15] described the distribution of eccrine glands following iontophoretic stimulation with acetyl-beta-methacholine (510 min at 4.55 mA). Maximum gland density (600700 glands/cm2) was observed in the palms and soles while the lowest density was found in the trunk; no eccrine glands were identified in the area of the lips, external auditory canal, the clitoris, or minor labia (i.e., regions typically presenting apocrine glands). 

Cannons law of 1939 [6] states that a denervated organ shows hypersensitivity to extrinsic agonists. The present study was thus designed to explore the quantity and response of sweat glands to intradermal acetylcholine stimulus in patients who underwent thoracoscopic sympathicolysis for palmar hyperhidrosis. 


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Patients and methods
The study included 30 patients (18 females and 12 males), with a mean age 27.35 years (range, 1743 years), diagnosed with primary hyperhidrosis of the palms and subjected to bilateral thoracoscopic sympathicolysis. The study, considered a clinical case series with pre- and postoperative comparisons, was approved by the Ethics Committee at our hospital. At their initial visit, all patients received an information sheet that explained the technique, results and risks of the intervention, and the study procedure. Informed consent was obtained in all cases prior to the intervention. 

All subjects underwent standard preoperative evaluation, which included clinical history, plain chest X-rays, an electrocardiogram, complete blood count, and study of coagulation and biochemical parameters. 

Patients
Group A
Ten patients referred to the Department of Thoracic Surgery by the Departments of Dermatology and/or General Medicine (Bellvitge University Hospital, Barcelona, Spain) for primary palmar hyperhidrosis were randomly selected and operated upon. Local sweat gland response to intradermal acetylcholine stimulus was evaluated 1, 3, 6, and 12 months after the operation. 

Preoperative administration of acetylcholine was ruled out because abundant sweating at baseline made gland quantification impossible. 

Group B
A total of 20 randomly selected patients who had undergone bilateral thoracoscopic sympathicolysis by the same surgical team (two senior thoracic surgeons) during the years 1999, 2000, and 2001 underwent the same study procedure as in group A. 

Methodology
Inclusion and exclusion criteria
Group A was comprised of patients with primary hyperhidrosis mainly affecting the palms. None of these patients had any endocrinemetabolic, dermatological or neurological antecedents that contraindicated the study technique. 

Group B consisted of randomly selected patients who had undergone surgery during the aforementioned 3-year period and who had achieved palmar anhidrosis after the intervention. 

Data collection and evaluation of body sweat redistribution
A database and form were created to record the study variables. All patients were evaluated prior to the intervention to rule out associated pathology and family antecedents of primary hyperhidrosis. 

The degree of sweating in different regions of the body (palms, soles, axillae, abdomen, back, and thighs) was scored using a visual analog scale (VAS) ranging from 0 (no perspiration) to 3 (excessive perspiration). 

Quantification of eccrine sweat glands
Quantification of sweat and eccrine sweat glands was based on the Minor iodinestarch test, first described by Minor in 1927 [9] and later modified by Ryder [16] and Altomare [1, 2] to differentiate patients with peripheral neuropathy and presenting chronic ischemia amenable to lumbar sympathectomy. This technique is now commonly used by dermatology departments to treat palmar hyperhidrosis via botulinum toxin injection [4, 18]. 

The amount of palmar sweating was quantified by injecting 0.1 ml 1% acetylcholine intradermally over a 3 cm2 area that had been previously coated with 2% iodine solution (2 g iodine in 10 ml oilalcohol) and corn starch (50%) and peanut oil (50%). The reaction between the sweat and the iodine solution revealed small black dots corresponding to the sweat glands. The coated area was photographed with a digital camera and the number of black dots counted. 

In order to obtain an identical image of all patients and thus avoid sample error, we designed an instrument to position the right hand of all the patients. A Nikon 4500 digital camera with a resolution of 5.1 megapixels and fitted with a Nikkor Zoom 4 lens with an autofocusing capacity of 1 cm (GA) to 8 was positioned at a distance of 2 cm from the point of acetylcholine administration (Fig. 1). 

Fig. 1 Instrument used for positioning the right hand of the patient in order to obtain the image with the digital camera mounted on the horizontal metal bar 

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The digital photograph was obtained after 120 s and stored for subsequent study.

All the images were recorded and transformed using the IMAT program developed by the Scientific-Technical Service of the University of Barcelona (Spain), with the images cropped to limit the area of each image to 730.4601 mm2. 

The black dots were manually counted by the Image Processing Unit of the Scientific-Technical Service of the University of Barcelona (Spain) using the aforementioned IMAT program. Quantification was made by a single person (thoracic surgeon), and was checked by the computer science technician of the unit, with a kappa index of >0.7. 

Surgical technique
Although already described in other publications [10, 11], we provide here a brief description of the normal surgical procedure. General anesthesia is administered with selective bronchial intubation, with the patient placed in dorsal decubitus with 25 trunk anteversion, abduction of the upper limbs, and partial extension of the forearms; the table is turned 10 laterally away from the surgical side, and a single access port for the Wolf 5/10-mm thoracoscope is prepared at the level of the third intercostal space (midaxillary line). The upper thoracic chain is then located and sympathicolysis of the T2T3 ganglia via coagulation is performed using 25 W monopolar forceps with 510 discharges. Hemostasis is achieved and the pneumothorax is aspirated through the thoracoscopic port without pleural drainage. The patient is discharged 17 h after the operation provided that the postoperative X-ray is normal. 

Statistical analysis
The data were analyzed using the SPSS 12.0 Statistical Software Package. A descriptive analysis was made of the study parameters based on central tendency and dispersion measures. The normality distribution of the variables was evaluated using the KolmogorovSmirnov test. Sweat distribution scored by the VAS was based on the McNemar nonparametric test (preoperativepostoperative paired data), while the black dots were analyzed with the Friedman test (repetitive beforeafter data at 1, 3, 6, and 12 months), as required. The Friedman test or Wilcoxon test for paired data, as appropriate, was used to evaluate the gland quantification data. The MannWhitney U-test was used for independent data (prospective versus retrospective), as required. A p-value < 0.05 was considered statistically significant. 


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Results
Group A
In all cases, the intervention was performed without incident, achieving complete anhidrosis after surgery with patient discharge after 24 h. The sole exception was a woman who underwent right-side surgery and presented abundant pleuropulmonary adherences requiring insertion of a chest tube for 24 h. Two patients (20%) had a first-degree relative with hyperhidrosis. 

Study follow-up, with all quantification at the established time points, was carried out in five patients (three men and two women); the mean age (SD) of these subjects was 27.2 (5.85) years. 

Distribution of primary hyperhidrosis
In terms of anatomical redistribution, the aforementioned scale showed that T2T3 sympathicolysis led to sweat redistribution, with a reduction or increase in sweating occurring in some areas of the body. An immediate, transient, and statistically significant postoperative reduction in perspiration was observed in the soles of the feet (p = 0.034). A significant reduction was also observed over the longer term (after 1, 3, 6, and 12 months) in the palms (p = 0.025); in contrast, however, sweating in the region of the trunk-abdomen and back increased significantly 12 months after surgery (p = 0.046, p = 0.034 respectively), statistical significance not being reached (p > 0.05) at either the thigh or axillary level. 

Gland quantification after acetylcholine stimulation
After intradermal acetylcholine administration, the mean number of active sweat glands was 41 (35.5) at 1 month after surgery, 174.20 (84.1) at 3 months, 522.8 (340.5) at 6 months, and 747.2 (99.7) at 12 months. The gradual increase over months 1, 3, and 6 proved significant (p = 0.004), although the increase between months 6 and 12 was not significant (p = 0.255) (Figs. 2 and 3). 

Fig. 2 Distribution of the number of activated eccrine sweat glands according to time elapsed from surgery. Friedman test: A gradual and significant increase is seen in the first 6 months (p = 0.004), after which the increase becomes nonsignificant (p = 0.255) 

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Fig. 3 (A) Acetylcholine stimulation in the first month after surgery; (B) stimulation 3 months after the operation; (C) result of stimulation after 6 months; (D) image 12 months after the intervention 

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Group B
A total of 20 patients were randomly selected, although only 13 subjects (65%) underwent testing because the other seven patients refused to participate. The mean age of the subjects who underwent evaluation was 27.5 years (range, 1943 years), with five males (38.5%) and eight females (61.5%). 

In terms of pre- and postoperative distribution of sweating, a statistically significant reduction was observed in the palms (p = 0.007), although no significant differences were recorded in the thighs (p = 0.620), abdomen (p = 0.202), back (p = 0.107), axillae (p = 0.072), or soles (p = 0.283). 

The mean number of sweat glands was 1369.8 (780.32), a figure similar to that observed in group A [747.2 (99.66)] at 12 months post intervention (p = 0.095) (Fig. 4). 

Fig. 4 Comparison of activated sweat glands between the prospective and retrospective study groups MannWhitney U-test for paired data: both groups show parallel trends, without reaching statistical significance 

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Discussion
In our study, T2T3 thoracic sympathicolysis induced palmar anhidrosis in 100% of patients and also caused a significant decrease in sweating at the axillary and plantar levels. However, sweating increased in areas where perspiration had been absent, minimal, or inconsequential before surgerya finding that corresponds with those described in the literature [1214]. 

The increase in perspiration in the trunk area (anterior chest and dorsal regions) was statistically significant at 6 months after surgery. While we are unable to account for this observation, it could be due to the period in which testing was performed compared to the time of the surgical procedure; in other words, testing took place during the summer when increased environmental temperatures cause increased compensatory sweating in these areas of the body. 

The sweat glands are innervated by sympathetic postganglionic fibers belonging to the class C amyelinic fiber network. Unlike sympathetic innervation in the rest of the body, the neurotransmitter associated with these fibers is acetylcholine, although some fibers release adrenergic compounds [17]. 

According to Cannons law, any denervated organ shows hypersensitivity to stimulation by the corresponding specific agonist. The sweat glands are an exception, however. As a result, stimulation of these glands is used to study the degree of functional innervation in processes involving peripheral neuropathy, such as diabetic neuropathy [3]. 

Desensitization to stimulating agents is the main functional evidence of postganglionic denervation of the sweat glands, since it was shown, in 1952, that preganglionic denervation does not reduce the degree of sweating [7]. 

Although a certain response to stimulation exists, it is incomplete. This suggests the existence of a mediator between the postganglionic fiber and the sweat gland, conditioning gland capacity to respond to pharmacological stimulation. In situations of nerve degeneration, a co-neurotransmitter such as vasoactive intestinal peptide (VIP) is known to be necessary to induce the local vasodilatation required for correct gland response [1]. 

Gland response to intradermal acetylcholine administration was observed to increase over time following surgery, in contrast with the findings of Kahn et al. [8] who described a progressive reduction in response to acetylcholine after denervation. In our study, the observed response was zero or almost zero at 1 month after surgery because at this point in time the glands were completely denervated. However, over the subsequent months the number of active glands increased in a nonuniform manner. This may indirectly suggest that the glands undergo reinnervation of which the patient is unaware, since, as we discussed above, the subjects reported no sweating of the palms. No significant differences were noted on comparing gland response after 12 months with previously treated patients. This suggests that structural reorganization occurs after the operation, and subsequently becomes self-limiting and stable. This would explain the anhidrosis of all the patients. 

Although few patients were included in our study, in view of the invasive nature of the test, the results suggest reorganization in the first 6 months after surgery, followed by gradual stabilization. Cannons law is thus confirmed, and we can conclude that there is no gland atrophy 2 years after denervation. Indeed, reinnervation phenomena take place, though without reaching the level of patient awareness. 



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