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MINISTRY OF EDUCATION MINISTRY OF DEFENSE AND TRAINING VIETNAM MILITARY MEDICAL UNIVERSITY TRAN DOAN KET RESEARCH APPLICATION OF ENDOCSOPIC SUBTOTAL THYROIDECTOMY IN TREATMENT OF BASEDOW DISEASE Specialized : Surgery Code : 9720104 DOCTORAL THESIS HANOI - 2019 THE WORK WAS COMPLETED AT VIETNAM MILITARY MEDICAL UNIVERSITY Science instructor: Assoc.Prof Tran Ngoc Luong Assoc.Prof Kieu Trung Thanh Reviewer 1: Assoc.Prof Nguyen Huu Uoc Reviewer 2: Assoc.Prof Mai Van Vien Reviewer 3: Assoc.Prof Le Quang Thuu The thesis will be defended at the Dissertation Panel school level, meeting at the Military Medical University At: The thesis can be found at: National Library Library of Military Medical University BACKGROUND Basedow disease (Grave’s disease) is a hyper function, hypertrophy and hyperplasia thyroid gland, which caused by antibodies stimulates the receptor of TSH lead to a high levels of circulating thyroid hormone The disease is called in many different names: Hyperthyroidism, Graves' disease, Parry's disease, exophthalmos goiter, autoimmune thyroid hyper function or immune hyperthyroidism Grave’s disease is the most common cause of hyperthyroidism The disease can occur in both sexes especially in adolescents and young people.This is an autoimmune disease with a chronic tendency and recurrence In Europe, the incidence rate was 20 / 100,000 people per year, in the US, the rate wasabout 40 / 100,000 people The disease occurred mainly in women, more than mengender from - 10 times and mostly between the ages of 20 - 50 In England in Whickham region, it was found that 2.7% of the population had Grave’sdisease, the rate of female was higher than 10 times In Viet Nam, there have been no a national statistic on Graves’ disease According to LeHuy Lieu, Graves’ diseaseaccounted for 45.8% of patients with endocrine disease and 2.6% ofinternal diseases in Bach Mai Hospital According to Ta Van Binh.at National Hospital of Endocrinology, number of hyperthyroidism patients accounts for 40% of patients examined endocrinology and women accounted for 95% Currently, there were treatment options for Graves’ patient: internal treatment,radioactive iodine therapy and surgery Each method with its own advantage, disadvantage and appropriate indication Open surgery of Grave’s disease had developed strongly from the 90s of the last century and achieved many results: cure rate was 9597%, less complications However, scars in the anterior neck made the patients lose confidence Today besides treatment, aesthetic expectation was also concerned The advent of thyroid endoscopic surgery has satisfied that request Endoscopic thyroid and parathyroid surgery was initiated in 1997 by Gagnet and today,from the basic foundation of open surgery, endoscopic thyroid surgery has been completed and widespread used In Vietnam, Endoscopic Thyroid Surgery was first applied at the National Hospital of Endocrinology in 2003 and later developed in many major hospitals in the country such as Military Hospital 103, Binh Dan Hospital, Nhan Dan Hospital Gia Dinh, Cho Ray Hospital,175 Hospital and Endoscopic Thyroid Surgery have confirmed the advantages such as: scarring is hidden in the shirt, avoiding the risk of scarring and postoperative paresthesia in the neck, significantly improving cosmetic Endoscopic thyroid surgery was more significantly complex than conventional surgery,but so far, there were no studies have adequately evaluated and systematized Clinical, subclinical examinations can support and help surgeon set up the best endoscopic surgery plan for Graves’ patient and help patient to stay stable soon with normal thyroid function We conduct research on this topic with two target: Review some clinical, subclinical feature Grave’s diseases and indication of endoscopic surgery Evaluate results after endoscopic surgery for Grave’s disease at National Hospital of Endocrine during period from 2015 to 2017 The urgency of the topic Basedow disease is also known as Grave ‘sdisease, Parry disease , diffuse thyrotoxicosis, exophthalmos goiter or immune hyperthyroidism This is a common endocrine disease, especially for women in the age of working If patients are not treated well, it will cause many complications and affect to the working ability as well as patient ‘s life Surgical treatment of Grave ‘s disease (subtotal thyroidectomy) has clear and sustainable result, the duration of treatment is short but the disadvantage is always to leave surgical scars They are located on the anterior neck and always affect the aesthetics of patients, while most of them are women of the working age Therefore, the study about endoscopic surgery for treatment of Grave ‘s disease with the advantage of leaving a small surgical scar in armpit has practical and scientific significance, responding to current treatment needs in our country as well as in the world New contributions of the thesis The thesis determined the advantages of thyroid endoscopic surgery compared to open surgeryand its limitations need to be overcome It listed clinical and subclinical characteristics for diagnosis what is bases for indication of laparoscopic surgery It also contributes to the method and techniques of laparoscopic surgery for Grave ‘s disease which achieved good results, especially overcome the limitations of open surgery such as less invasion, aesthetic It performed a pre-operative procedure and surgery in a unified way It evaluated results in and after surgery with strict, scientific research criteria, and the following up duration was up to 36 months Thesis layout The thesis consists of 127 pages (except appendix) Background: pages;Chapter 1: Overview: 37 pages; Chapter 2: Objects and methods research: 18 pages; Chapter 3: Results: 29 pages; Chapter 4: Discussion: 39 pages Conclusion: pages In this thesis, there are 36 tables and charts, 12 illustrations, diagram Reference: 116 (45 Vietnamese references; 71 English references) Chapter 1: OVERVIEW 1.1 Definition Basedow disease (Grave’s disease) is a hyper function, hypertrophy and hyperplasia thyroid gland, which caused by antibodies stimulates the receptor of TSH lead to a high levels of circulating thyroid hormone 1.2 Pathogenesis Grave’s disease is the most common cause of hyperthyroidism The disease can occur in both sexes especially in adolescents and young people This is an autoimmune disease with a chronic tendency and recurrence It is involved a combination of environmental factor such as: stress, injury, infection, … In white people, Grave’s disease is related to HLA-B8 and HLADR3 antigen, however in each race are associated with different HLA for examples DR5 in Japanese, DR9 in Chinese and DR5 / DR8 in Korean White people carry HLA-DR3 at risk times higher than people not have this antigen The cause is due to the appearance of autoantibodies that stimulate the Receptorof TSH (TRAb), resulting in continuous stimulation of thyroid cells synthesis and excretion of T4 and T3 - The structure of TRAb has been clearly studied, it is a antibody has a high specificity, the nature is IgG1 only in humans There are types of structures of TRAb and also have three different ways of attaching to receptors that cause different clinical manifestations: stimulation, intermediation and inhibition 1.3 Clinical The most common symptoms are nervous excitement, nervousness, palpitations, weight loss, fatigue, reduced ability to work, hot feeling, bright eyes, frequent defecation, hair loss, insomnia, memory loss or watery eyes, unfocused thoughts, menstrual cycle disorders in women During the examination, the patient was sitting restless, irritabilities, or bulging eyes 1.3.1 Functional symptoms Symptoms of heat sensitivity and an increase in perspiration or warm, moist skin and weight loss 1.3.2 Goiter A diffusely enlarged thyroid gland has always happened However, the size of the goiter is not related to the severity of the disease About the size of the tumor there are many different ways of classification, but more commonly, according to the World Health Organization(WHO) in 1995 Goiter classification of the World Health Organization in 1995 - Grade O: no goiter presence is found -GradeIa: The thyroid gland, however palpable, remains invisible, even in full extension of the neck - Grade Ib: Goiter is palpable in normal position and visible in upright position ( full extension) of the neck - Grade II: Large thyroid gland is visible in normal position of the neck - Grade III: Very large goiter is clearly visible from distance 1.3.3 Heart beat Tachycardia appears relatively early, sometimes is the first manifestation of the diseaseand patients always have palpitations Frequent tachycardia with heart beat always more than100 times per minute, even ifrest If patients work or are emotional, heart beat can be faster Hear the heart can feel systolic murmur Blood pressure: Systolic blood pressure increases, diastolic blood pressure does not increase A strong pulse, especially large blood vessels, can be felt clearly, called a signpulse signal agitation 1.3.4 Eye Ophthalmopathy is a hallmark of Grave’s disease In Grave’s disease expressionshow with lid lag, lid retraction or proptosis Proptosis is seen in 20-30% of patients with Grave’s disease, often occurs bilaterally, sometimes only one side However, there are many cases without proptosis In addition, there are a number of other symptoms such as: pretibial myxedema,digestive disorders 1.4 Subclinical 1.4.1 Thyroid hormone The trio of TSH, FT4 (T4), T3 (FT3) is usually quantified for full evaluation thyroid function In this trio, the test is the most valuable test is: - TSH reduced - FT4 (T4) increased - FT3 (T3) increased 1.4.2 TSH receptor antibody (TRAb) TRAb is an autoantibody that affects the receptor of TSH receptors on the surfacethyroid cells Normal value of TRAb 100 times per minute even whenrest - Eye disease; lid retraction, lid lag, protosis, ….according to NOSPECS classification Of American Thyroid Association (1969) - Hand tremor with small amplitude and fast frequency - Subclinical feature: Thyroid hormone quantification (T3, FT4 increased), pituitary hormone (TSH decrease), TRAb increased, thyroid color Doppler ultrasound, thyroid ultrasound, ECG According to the American Medical Association, Australia and the European Thyroid Association, the diagnosis of Grave’ s diesae is mainly based on the concentration of hormones in the blood when TSH is present below or equal to 0.1µUI / l FT4 and T3 concentrations are higher than normal and patients have a diffuse goiter, rapid pulse, proptosis 1.6 Treatment There are basic treatments - Internal medicine: Treatment with synthetic anti-thyroid drugs - Surgical: perform subtotal thyroidectomy leave each 2-3 gram thyroid remnant in one side - Radiotherapy 1.7 Classical approach in treatment of Grave’s disease 1.7.1 Indication of surgery Surgical indication is a very important factor directly related to the outcome of surgery Today science has developed especially in medicine, surgical indications also always change to match the specific level of the medical facility in each area Indications of surgery in Grave ‘s disease also have changes and completed 1.7.1.1 Foreign authors  Guideline Association of German Endocrinology (2011): - Big goiter compress other local organs - Patient had complications when treated by anti-thyroid medicine - Children and adolescents with Grave ‘s disease - Failed medical treatment - Uncontrolled hyperthyroidism - Patient had severe eye complications  Guideline British Endocrinology Association (2013) - Children with Grave ‘s disease and failed medical treatment - in women who wish to, or may become, pregnant within two years of radioiodine treatment - Large goiter  Guideline American Thyroid Association (2016) - The aspiration of patients who want surgery for quick control hyperthyroidism, not want medical treatment, I 131 - Pregnant women (in first trimester) and during breastfeeding  Vietnam Endocrine Association - Diabetes (2016) - Medical treatment results limited, or relapse - Large goiter - Grave ‘s disease in children with medical treatment has no results - Pregnant women (3 - months) and during breastfeeding - No medical treatment conditions 1.7.1.2 Domestic authors designate surgery based on: Nguyen Khanh Du (1978): - Medical treatment for 3-6 months with little or no results - Age is not contraindicated - Pregnant women: The first months of pregnancy: preservation is the first choice and surgery when no results The last months of pregnancy: surgery when the disease tends to get worse - Patients have heart complications Dang Ngoc Hung and some other authors: - The 4-6 months medical treatment is unstable - Severe form in children under 10 years old, teenagers, children treated medical treatment has no results - Pregnant women and nursing mothers have no conditions for medical treatment - Patients have heart complications - Large goiter causing compression Kieu Trung Thanh: based on the following conditions - Socioeconomic - The possibility of medical treatment - Depends on each age group 10 - Tumor characteristics, disease patterns, disease severity - Experience of surgeon and treatment facilities - The choice of patients Nguyen Ngoc Trung: Patients with Grave ‘s disease indicated open surgery when the 3-6 month medical treatment have no results or loss of aesthetic or side effects of anti-thyroid drugs In summary, the domestic authors give the indication for surgery based on the factors: - Prolonged treatment of effects: work, childbirth, aesthetic and mentality - Patients with special circumstances - Allergy or non-response to thyroid resistance, or response but the results are not stable - Children and puberty should be medical treatment But treatment is too long, the patient is difficult to perform, the disease is difficult to stabilize or relapse - Pregnant women: Anti-thyroid drugs have an effect on the development of the fetus or birth of a tumor 1.7.2 Surgical principles 1.7.2.1 Control blood vessels Basedow disease was characterized by goiter of vessel, the surgical procedure had been mentioned by many authors with different surgical methods in Vietnam as well as many authors around the world At Military Medical Hospital 103 - Military Medical Academy From 1989, Dang Ngoc Hung and Ngo Van Hoang Linh The techniques were implemented: - Revealing the thyroid gland by a middle line between the infrahyoid muscles, without cutting the muscles - Tie the artery on the superior pole Then tighten small blood vessels close to the glands in the remaining glands Do not tie the inferior thyroid artery - Pinch clip parallel along the axis of each lobe (one branch penetrates the parenchyma) Cut the thyroid gland on this branch and then stitch remnant with a U-shaped thread - Stitch the incision with continuous subcuticular sutures With this method, the operation was safe, the operation time was shortened, it reduced the complications after surgery with beautiful incisions 13 accounting for 3.2% Temporary hoarseness: cases, accounting for 0.8% Permanent hoarseness: case, 0.4% Hyperthyroidism: cases, accounting for 0% Death: case, accounting for 0.4% Tran Ngoc Luong operated on 200 patients at the National Hospital of Endocrinology from 2002 to 2004 (with unmodified method) results are as follows: performed total thyroidectomy on14 patients (7%), subtotal thyroidectomy and left superior pole on patients (4.5%), subtotal thyroidectomy and left posterior portion on 177 patients (88.5%) No patient had thyroid storm or tachycardia needed postoperative intervention There were cases (1.5%) had postoperative bleeding need a second operation for hemostatic cases had temporary hoarseness (1.5%), temporary hypocalcemia 19 cases (9.5%) Rate of postoperative euthyroid was 90.7% 1.8 Methods endoscopic surgery in treatment of Grave’s disease 1.8.1.History - Yamamoto M et al (2001) conducted hemithyroidectomy for 12 patients with hyperthyroidism (Grave ‘sdisease) - Sasaki A et al (2009) conducted a close cut endoscopic thyroid gland for treatment Basedow disease for 42 patients The author followed the chest approach, used forceps to enterthe subcutaneous layer of the chest through the right edge of the areola, creating space by pumping CO and split the subcutaneous layer of the chest neck area Place mm trocar on the bilateral areola Surgeons used Harmonic Scalpel, thyroid parenchyma around the ligament Berry was removed by moving the Harmonic Scalpel from inferior pole to superior pole - Pornpeera et al (2016) compared the results between trans-oral laparoscopic surgery and open surgery for Grave ‘s disease 49 patients undergoing open surgery and 46 patients undergoing trans-oral laparoscopic surgery, the author assumed 10 mm trocar in the center of the vestibule, trocars mm placed below the lower lip The surgery has the advantage of following natural holes There was no scarring, however, the patient had postoperative vestibular numbness Addition, the care of postoperative incisions was more difficult due to poor oral hygiene - Zhi Yu Li et al (2010) performed endoscopic subtotal thyroid surgery for 37 Grave ‘s patients from 2006 to 2009 The author followed the chest approach The author used 10 mm trocar at the central point 14 between nipples, and trocars on edges of the areolas Author used Harmonic Scalpel to cut parenchyma Thyroid gland was removed from lowerpole to the upper pole and left 2-3 grams - Hyungju Kwon and colleagues conducted robotic endoscopic surgery followbilateral breast axillary approach for 44 patients with Grave ‘s disease, the authors assumed the Da Vinci robot system, with the sides specialized endoscopic instruments Postoperative results show the rate of complications after surgery(hoarseness, numbness ) was not different compared to open surgery and had high aesthetic results - Tran Ngoc Luong used trocars to create working space on each side and CO2 insufflationabout liters / minute and pressure from 10 12mmHg He split up to the sterner notchand developed further laterally to deliver thyroid lobe Used Harmonic Scalpel to cut the upper, lower pole and most of tissue except a small remnant in situ on both sides.When cutting the thyroid organ, the author moved the active blade forward the inactive upper arm In this way, it cut simultaneous and cauterized tissues and avoided bleeding Dr Luong left the small remnant on each side about 3gam 1.8.2 Indications for laparoscopic surgery Indications have not been agreed upon among surgeons: - Akira Sasaki performed endoscopic of near total thyroidectomy for 41 Grave patients with the following criteria: Allergy to synthetic thyroid drug, patients not want to treat radioactive iodine, large goiter treated persistently with resistant synthetic thyroid hormone drugs, thyroid volume below 100 ml is measured by computerized tomography All patients must achieve euthyroid status before surgery and be treated with Lugol solution 7-10 days before surgery - Pornpeera Jitpratoom and partner when conducting oral endoscopic surgery for Grave ‘s disease treatment on 97 patients from 2014 to 2016 gave indications of Grave ‘s disease endoscopic surgical treatment including: Grave’s disease spread, multinodular toxic goiter, failure or relapse after years of treatment with synthetic thyroid drug, localized symptoms, allergic patients with thyroid resistance drug - Hyungju Kwon and partner gave an indication for robotic endoscopic surgery on Axillary breast surgery for relapse after treatment of anti-thyroid drugs, localized tendency symptoms, patients wishing to treat surgery as initial treatment, allergy to synthetic thyroid drug- Tran Ngoc Luong and partner reported the results of laparoscopic surgery of 2194 cases including: nodular in isthmus lobe: 49 patients, 1thyroid lobe: 1755 patients, thyroid lobe : 275 patients, 15 Grave ‘s disease: 89BN, thyroid cancer: 26 patients The largest tumor size measured on ultrasound is cm, the largest thyroid volume of Grave ‘s disease is 120 ml 1.8.3 Result of endoscopic thyroidectomy 41 patients underwent endoscopic thyroidectomy (Sasaki A and Nitta H) The mean operative time was 227 minutes, the mean blood loss was 76 ml, the excised thyroid volume was 49,9 grams There were a case of transient laryngeal nerves injury and hypocalcemia There was a case of permanent hypocalcemia There were cases with hyperthyroidism and case with hypothyroidism After 92 months of surgery, patients felt dysphagia, patient found paresthesia in anterior chest However, these symptoms disappeared after 36 months Author Li ZY, Wang P patients with hypocalcemia among 37 patients accounted for 7.5% Operation time was at least 84.7 minutes The mean blood loss was 138.3ml Transient hypocalcemia 13.5%, hospital stay of 3.4 days, case of relapse after 13 months According to Tran Ngoc Luong, 40 patients after 12 months: the mean operative time: 97 minutes, the mean blood loss is 24.1ml, there were patients with hypothyroidism (5%), hyperthyroid patient (2.5%) Kwon H, Koo by H, Choi JY, Kim E, Lee KE, Youn YK, 30 patients underwent robotic surgery: the mean operative time was 190 minutes (range: 105-298), the mean blood loss was 229 ml (range: 50550 ml) The mean excised thyroid volume was 36,6 grams (range: 7.8-123) There were 3.3% of hypocalcemia Chapter 2: SUBJECTS AND METHODS 2.1 Research object Patients withGrave ‘s disease are examined and treated inpatient at National Hospital of Endocrinology from January 2005 to May 2017 Selection criteria: Patients who have received medical treatment for at least 3-6 months, achieved euthyroid before surgery Age between 14 and 50 Goiter is big at grade Ib or grade II (according to WHO classification 1995) Wishing to endoscopic surgery and agreed with participated in the study Exclusion criteria: Grave ‘s patients had not been euthyroid, accompanied chronic disease without indications of endoesophular anesthesia, there were diseases of blood coagulation, bleeding, old surgery on the neck area, or inflammation in the neck area or the chest area 2.2 Research methods 2.2.1 Research design: Describe retrospective from 2005 to 2011 and 16 research progress from 2011 to 2017 Sample size of study: Convenient sample from January 2005 to May 2017 met the research standards 2.2.2 Research indicators - Clinical examination: + History: age, gender, duration of disease + Thyroid examination: clinical size, density, thyroid classification according to WHO goiter classification - 1995 + Eye specialist examination: evaluated injury of both eyes (According to NOSPECS classification of the Association American- 1969) - Subclinical examination: Measurement of thyroid volume, number of vascular spots, heartbeat, thyroid hormone T3, FT4 and hormone TSH of pituitary gland, TRAb, blood calcium concentration; blood PTH levels 2.2.3 Assess the results of treatment + Good result: easy dissection, blood loss < 30ml No complications: bleeding must be reoperated, hoarseness, hypocalcemia Stable on thyroid function, beautiful surgical scar, patients are very satisfied + Pretty result: Hard dissection, blood loss 30-50ml Complications: hoarseness or temporary hypocalcemia, stabilization of thyroid function, nice surgical scar, patients are satisfactied + Medium result: difficult dissection, blood loss 50-100ml, complications: bleeding, hoarseness and temporary hypocalcemia, recurrent disease, normal surgical scar, patients are satisfied or feel normal + Bad result: very hard dissection, blood loss > 100ml, complications: convert open operation, hoarseness or permanent hypocalcemia, recurrent disease, normal surgical scar, patients are dissatisfied 2.3 Endoscopic Surgical Procedures * Indications of laparoscopic surgery -Failed medical treatment -Allergy with anti-thyroid drugs -Disease relapses many times -Goiter at grade Ib and II -The patient had no conditions of internal medicine treatment * Preparing patients and preoperative instruments: - Patients must reach euthyroid and be treated with a solution 1% 17 Lugol before surgery (1-2 weeks) -Surgical instruments: Harmonic Scalpel Ace; Unipolar; KarlStorz endoscope; Endoscopic surgical instrument * Surgical technique: + Stage 1: Incision, place the trocar and create the working compartment: 10mm incision in the right armpit if done on the right side, forward the trocar to the sterner notch, pull out the trocar and pump CO2 with 12mmHg pressure, flow liters / minute Place one 5mm trocar on the right shoulder and mm in the areola at o'clock if surgeon the right side or 10h if it's on the left, to create a compartment with vacuums and hook Dissected gradually forward to the suprasternal notch The area of the dissection is horizontal to the thyroid cartilage and the outer border of the sternocleidomastoid muscle + Stage 2: dissect to deliver thyroid gland: Dissection of the sternocleidomastoid muscle and the sternothyroid muscle, omohyoid muscle: Identify the omohyoid muscle, this muscle located above the outside of sternocleidomastoid muscle, with the tendon between the belly muscle is at the level of the sternocleidomastoid muscle, separating from this inferior border of muscle by hook Splits the sternothyroid muscle with hook, deliver thyroid lobe + Stage 3: Subtotal thyroidectomy: Cut superior pole: this pole is closely related to the upper larynx nervesand superior parathyroid glands so the surgeon must be very careful to avoid damaging these components and to control the upper arteries well Cut inferior pole: Take the clip applicator clamp under the pole or lift it lightly, use itultrasonic knife or hook that separates the pole from the surrounding organization Separation of the posterior portion of the lobe: the blood vessels of the posterior are oftensmall, so the surgeon should be very delicate and cautious because the recurrent nerve locates behind thyroid lobe and closely relates with trachea Cut the thyroid with an ultrasonic knife or hook: Lift the lobe, cut from the outside into the length of the lobe, leaving the posterior portion by: Using the distance between two arms of the Harmonic Scalpel (= 1.5cm), measure the length of - 3cm, the width about 1.5 - 2cm, height about 1cm; thus, the volume of remnant about - 6g Cut the gland parallel to the surface of the trachea, from the outer to the trachea, cut the isthmus 18 Check the hemostasis of the section of tissue Doing the same protocol with the opposite lobe, surgeon can use the third trocar to lift thyroid when cutting Put the plastic bag through the 10mm trocar hole to remove the part of the thyroid Can set drain + Stage 4: Check the hemostasis and stitch the trocar holes: Stitch the trocar holes with interrupted nonabsorbable suture 2.4 Data processing The results are recorded in the follow-up form The data processed and analyzed by SPSS 16.0 statistical software 2.5 Research ethics Research was accepted by the research object and approved by Scientific Council of the Hospital and accepted by the National Hospital of Endocrinology All information of patients is kept confidential RESEARCH DIAGRAM Retrospective group (n=36) Research group (n=40) Selected object Selected right subject Research medical record Import data Features Surgery Postoperative Examination Surgery P After surgery: 3,6,12 months Postoperative After surgery: 3,6,12 months Result Conclusion CHAPTER III: RESULT 3.1 Features Table 3.1: Age distribution of 76 patients ( n=76) 19 Age ≤ 20 21 - 30 31 - 40 41 - 50 Total Number 12 47 16 76 Rate % 15.8 61.8 21.1 1.3 100 X Min (14 ) Max(46 ) ± SD 26.38 ± 6.02 Group of patient from 21 to 30 was biggest (61.8%) Mean Table 3.2: Duration of illness (n=76) Min Max X ± SD Time (months) 132 50,85±37,06 3.2 Clinical and subclinical features  Clinical features Table 3.3 Goiter grading classified accoding to WHO Grade Number 67 76 Rate % 11.8 88.2 100 Ib II III Sum  Subclinical features Table 3.4: Volume of thyroid gland on ultrasound (n=76) Volume Minimum Maximum Average ml 12.5 65 30.48 ± 1.15 Table 3.5: Number of vessels before and after lugol treatment(n=76) Vessel Min Max Mean Before 3,42 ± 0,87 After 0,5 3,5 1,89 ± 0,74 Table 3.6: Thyroid and Pituitary Hormone test before surgery(n=76) Hormone Min Max Mean Normal T3 (nmol/l) 0.86 2.9 1.55 ± 0.39 1.0 – 3.0 20 - FT4 (pmol/l) 10.22 21.72 17.25 ± 2.73 9.0 – 25.0 TSH (μIU/ml) 0.03 3.5 1.13 ± 0.92 0.3 – 5.5 TRAb (U/l) 1.0 21.0 10.48 ± 3.85 1- 1.58 3.3.Classified indication of endoscopic surgery (n = 76): - Failed medical treatment: 04 patients (5.3%) - Goiter caused swallowing problems: 09 patients (11.8%) - Eye complications: 09 patients (11.8%) - Relapse after medical treatment: 54 patients (71.1%) 3.4 Assess surgical result 3.4.1 Result in surgery Table 3.7: surgery time and blood loss Min Max Mean Surgery Time 40 180 98,81 30,95 Blood loss 15 100 27,46 12,49 The average surgery time for patients was 98.81 ± 30.95 minutes In which, the shortest surgery took 40 minutes, the longest surgery took 180 minutes - Average blood loss was 27.48 ± 11.07ml In which, the operation had at least 15ml blood loss, the operation had the most blood loss of 100ml Table 3.8 The amount of thyroid tissue left (ml) Volume of remnant Min Max Mean Amount(ml) 3,0 10,0 6,19 0,97 The average amount of thyroid parenchyma left was 6.19 ± 0.97 ml The case of leaving the amount of parenchyma at least was3.0ml, the case of leaving the amount of parenchyma at most was 10.0ml 3.4.2 Result and complications after surgery Table 3.9 Complications immediately after surgery (n = 76) Complication Number of patient % none 68 89,6 bleeding 3,9 numbness 3,9 Hoarseness 2,6 Total 76 100 There were patients accounting for 10.4% with complications after surgery, including: bleeding, hematoma (3.9%); numbness (3.9%) and hoarseness (2.6%) 21 Table 3.10 Postoperative hospital stay Hospital Stay Min Max Mean Day 12 6,05 1,42 The average length of hospital stay after surgery was 6.07 ± 1.49 days In it, at least days, at most 12 days 3.4.3 Evaluate results after 3, 6, 12 and 36 months of laparoscopic surgery Table 3.11 Postoperative complications After After After After 36 months months 12months months (n=74) (n= 73) (n=72) (n = 55) n % n % n % n % Numbness in neck 4,0 2,73 1,38 0,0 Numbness 2,7 2,73 1,38 1,8 Hoarseness 1,35 0,0 0 0,0 Total 8,1 5,5 2,8 1,8 p p 0.05 - Thyroid function after surgery: 22 Table 3.13 Postoperative thyroid function Thyroid Function months (n=74) n % 70 94.6 2.7 2.7 Euthyroid Hypothyroid Hyperthyroid months (n=73) n 70 % 95.8 2.8 1.4 12 months (n=72) n % 69 96.1 2.6 1.3 The rate of euthyroid reached over 90% and fluctuated insignificantly over time after surgery: months (94.6%), months (95.8%), 12 months (96.1%), 36 months ( 96.4%) There were patients with hypothyroidism at the postoperative time 3, 6, 12 months After months of surgery, there were patients with hyperthyroidism At other times, there was only patient with hyperthyroidism and patient with hypothyroidism Table 3.14 Assess the results of treatment Result of surgery Very good good Medium Bad Total n 49 3 55 Rate % 89.0 5.5 5.5 100 CHAPTER 4: DICUSSION 4.1 Clinical, subclinical features of patients with Grave ‘s disease undergoing endoscopic subtotal thyroidectomy -Grades of goiter: According to Do Trung Quan goiter in Graves’ disease was a diffuse goiter, grade II occupied 70.62%, Grade III occupied 13.03% Clinical Examination of the thyroid’s sizeand ultrasonography evaluated thyroid volume as one of the factors determining the surgical decision Authors often indicated open surgical treatment for Graves’ disease with goiter in Grade II and Grade III However, when the endoscopic surgery was performed in patients with too large goiter would be more difficult because of many limitations, so we chose goiters in grade Ib and grade II Classification size of the clinical tumor was based on the WHO classification (1986) In our study, we had patients (11.8%) in grade 23 Ib,grade II (67 patients) 88.2% - Duration of internal treatment: Nguyen Ngoc Trung average internal treatment time was 17.0 ± 3.1 months Nguyen Huu Binh: 20.3 ± 3.5 months The shortest duration of illness in our study was months, the longest one was 132 months -Volume of goiter measured on ultrasound: thyroid volume was determined by conventional thyroid ultrasound, ultrasound was a necessary test and increasingly applied in clinical specialties, especially in diagnosis of thyroid disease Ultrasound could measure volume and thyroid morphology and help surgeons decide to indicate an endoscopic or open surgery In our study of 76 patients, the patient had a minimum volume of 12.5 cm3 and a maximum of 65 cm3, with an average of 30.48 cm3 If the volume was too large, the operation time would be longer -Number of vessel spots: number of vessel spots was determined by thyroid Doppler ultrasonography We performed thyroid Doppler Ultrasound to evaluate vessel spots and thyroid blood flow The smallest number of spots in our study was 1.0 spots and the largest was spots After a 7-day treatment with lugol, the smallest number of spots was 0.5 and the largest was 3.5 We founded that the higher number of vessel spots, the more the thyroid blood flow was, the more difficult the surgery was , and the more bleeding - Thyroid hormone test results and serum TSH: All 76 patients in the study group were tested for serum T3, FT4 and TSH levels before surgery All patients had T3 levels, FT4 was within normal limits, two cases TSH were higher than normal and cases were lower than normal but T3 and FT4 were within the normal range, accompanied by clinical symptoms without manifestations of hyperthyroidism or hypothyroidism This could be explained by the thyroid hormone TSH secreted by the anterior pituitary gland, which regulates T3 and FT4 production in the thyroid without directly causing clinical manifestations of thyroid gland function Hence, the TSH level always were fluctuated to remain production of thyroid hormones flat Thus, all patients in our study were clinically normal - TRAb antibody test: Cappelli C showed that Graves’ disease was an autoimmune disorder, characterized by the presence of autoantibody TRAb that stimulates the thyroid gland TRAb had a role in the diagnosis and follow-up of treatment based on disease It helped identified the 24 patients who are likely to be cured for short-term treatment, who should continue to maintain anti-thyroid drugs longer and who need optimal interventions such as surgery or radioiodine TRAb was an antibody against TSH receptor of thyroid cells, which had a diagnostic value as it is elevated and had a prognostic value in the treatment of disease, recurrence, and surgical indication in the Graves’ disease 4.2 Results of output surgery results 4.2.1 Indications for surgery Our patients were indicated surgery due to recurrent disease many times after medicine treatment accounted for 71.1% Indications for surgery depended on compression of goiter or aesthetics, we consider appointing surgery In this research, we operated with the goiter at grade Ib and II, which was also a medium goiter The largest volume was 65ml, the smallest one was 12.5ml and the average was 30.48 ± 1.15 4.2.2 Surgical technique We chose subtotal thyroidectomy We cut the superior and inferior pole, then remove most of gland except a small posterior portion on both side Volume of remnant left each side was about cm3 to cm3 4.2.3 Results of laparoscopic surgery - Operation time: the shortest surgery time was 40 minutes and the longest time was 180 minutes The case that lasts up to 180 minutes was done with a goiter had the volume was 35.4 cm 3, the number of vascular spots was 2.5 spots The goiter was soft and easy to bleed Operation time depends on the volume of thyroid, number of vascular spot, preoperative medical treatment , If thyroid volume or number of vascular spots were high, the surgery time would be longer -The amount of blood loss: The least amount of blood loss was15ml and the mostamount was 100ml, the medium was 27.48ml No patients needed blood transfusions during and after surgery The patient lost most amount of blood(100 ml) had a soft goiter, which had various vessel and on color doppler ultrasound, number of vessel was - The amount of thyroid tissue left: There were many different views between authors about how much thyroid tissue should be left Many authors who leftthe amount of thyroid tissue more or less depends on the size of the goiter, age of the patient Some other authors based on the level of thyrotoxicosis and patient ‘sage The amount of thyroid parenchyma left in endoscopic surgery was more difficult to estimate.It was determined 25 by the 1.5cm distance between two arms of the ultrasonic knife Size of remnants were usually 1.5x1,5x1cm The volume of the smallest remnant in this study was cm3, the largest was 10 cm3,the average was 6.19 ± 0.97 cm3 Author Tran Ngoc Luong: 32 patients undergoing laparoscopic surgery had tissue left was 4.79 ± 0.97cm - Hospital stay: The period of hospital stay after surgery is at least days, at most: 12 days, average :6 days Hospitalized patients days after surgery was the young patient who had no postoperative complications, the surgery process was convenient A patient ‘shospitalization 12 days after surgery had postoperative tetani, we treated with calcium - Postoperative complications: There are patients after surgery (3.9%), patients with numbness limbs (3.9%), patients with hoarseness (2.6%) After 36 months, only patient (1.8%) remained numbness, this patient takes extra calcium twice a week for every 500mg once According to Li Zy 6.6% patients had temporary hypocalcemia Author Kwon H, Koo H operated with Robot has 3.3% of hypocalcemia - 36 month postoperative thyroid function: We followed up 55 patientswith the results as follows: Euthyroid in 53 patients accounted for 96.4%,1 patient with hypothyroidism (1.8%) was treated with a dose of 50 mg / day thyroxin and case with hyperthyroidism (1.8%) is being treated for low-dose of anti-thyroid drug Currently, thyroid hormone levels in these patients within normal limits CHAPTER V CONCLUSION Research on 76 patients with Grave’ s disease underwent endoscopic subtotal thyroidectomy, we have some conclusions: Clinical, subclinical features of patients with Grave ‘s disease has indicated endoscopic surgery The period of pre-operative medical treatment averages 50.85 ± 37.06 months Patients with goiterat grade II mainly accounted for 88.2% Soft tumor density accounts for a high proportion (57.9%), a solid tumor (42.1%) The average heart rate was 78.37 ± 5.91 26 Eyes without injury (88.2%), lesions (11.8%) The average thyroid volume was 30.48 ± 1.15ml The average number of vascular spots was3.42 ± 0.87 spots / cm2 - Average T3 in serum: 1.55 ± 0.39nmol / l - Average FT4 in serum: 17.25 ± 2.73pmol / l - Average serum concentrations of TRAb: 10.48 ± 3.85IU / L Evaluate the results of endoscopic surgery for Grave ‘sdisease treatment - The average surgery time was 98.81 ± 30.95 minutes - Average blood loss was 27.48 ± 11.07ml - The rate of complications in surgery was 10.4% (bleeding, hematoma 3.9%; numbness 3.9% and hoarseness 2.6%) - The average length of hospital stay after surgery was 6.07 ± 1.49 days - 100% of patients hadbenign histopathology results - The rate of postoperative complications decreased with time: after months (8.1%), after6 months (5.6%), after 12 months (2.8%), after 36 months (1.8%) - Concentrations of T3, FT4, TSH, PTH and blood calcium average before and after surgery 3, 6, 12, 36 months were within normal limits - 100% of postoperative patients had no injury to the vocal cords - Proportion of postoperative euthyroid reached 94.6% - 96.4% - The volume of thyroid tissue left was about 5.59 - 6.4ml - 89.0% of patients achieved good treatment results (after 36 months) - Eye complicationswas cure completely on patients, decreased on patients - 92.7% of patients satisfied laparoscopic surgery results Through the results obtained, it is possible to confirm thattrans axillary-breast endoscopic surgery ensures a subtotal thyroidectomy for treatment of Grave ‘s disease with goiters at grade I - II safely and effectively, aesthetic results and satisfaction of patients after surgery was very well LIST OF RESEARCH WORKS HAS BEEN DISCLOSURE OF THE AUTHOR RELATED TO THE THESIS Tran Đoan Ket, Tran Ngoc Luong, Kieu Trung Thanh (2018), "An analysis of clinical, subclinical features of graves' patients before endoscopic thyroid surgery", Iournal of military pharmaco-Medicine 43(8): 199 – 203 Trần Đoàn Kết, Trần Ngọc Lương, Kiều Trung Thành (2018), "Đánh giá kết phẫu thuật nội soi điều trị bệnh Basedow" Tạp chí Y học Việt Nam 471(2): 150 - 154 ... 199 – 203 Trần Đoàn Kết, Trần Ngọc Lương, Kiều Trung Thành (2018), "Đánh giá kết phẫu thuật nội soi điều trị bệnh Basedow" Tạp chí Y học Việt Nam 471(2): 150 - 154 ... compression Kieu Trung Thanh: based on the following conditions - Socioeconomic - The possibility of medical treatment - Depends on each age group 10 - Tumor characteristics, disease patterns, disease... conditions 1.7.1.2 Domestic authors designate surgery based on: Nguyen Khanh Du (1978): - Medical treatment for 3-6 months with little or no results - Age is not contraindicated - Pregnant women: The

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