Nghiên cứu ứng dụng phẫu thuật nội soi cắt gần hoàn toàn tuyến giáp điều trị bệnh basedow tt tiếng anh

Basedow disease Grave’s disease is a hyper function,hypertrophy and hyperplasia thyroid gland, which caused byantibodies stimulates the receptor of TSH lead to a high levels ofcirculatin

VIETNAM MILITARY MEDICAL UNIVERSITY

TRAN DOAN KET

RESEARCH APPLICATION OF ENDOCSOPIC SUBTOTAL THYROIDECTOMY IN TREATMENT

Science instructor:

1 Assoc.Prof Tran Ngoc Luong

2 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 UniversityAt:

The thesis can be found at:

1 National Library

2 Library of Military Medical University

Basedow disease (Grave’s disease) is a hyper function,hypertrophy and hyperplasia thyroid gland, which caused byantibodies stimulates the receptor of TSH lead to a high levels ofcirculating thyroid hormone

The disease is called in many different names: Hyperthyroidism,Graves' disease, Parry's disease, exophthalmos goiter, autoimmunethyroid 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 andyoung people.This is an autoimmune disease with a chronic tendencyand recurrence

In Europe, the incidence rate was 20 / 100,000 people per year, inthe US, the rate wasabout 40 / 100,000 people The disease occurredmainly in women, more than mengender from 4 - 10 times and mostlybetween the ages of 20 - 50 In England in Whickham region, it wasfound that 2.7% of the population had Grave’sdisease, the rate offemale 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 BachMai Hospital According to Ta Van Binh.at National Hospital ofEndocrinology, number of hyperthyroidism patients accounts for 40% ofpatients examined endocrinology and women accounted for 95%

Currently, there were 3 treatment options for Graves’ patient: internaltreatment,radioactive iodine therapy and surgery Each method with its ownadvantage, disadvantage and appropriate indication

Open surgery of Grave’s disease had developed strongly from the90s of the last century and achieved many results: cure rate was 95-97%, less complications However, scars in the anterior neck made thepatients lose confidence Today besides treatment, aestheticexpectation was also concerned The advent of thyroid endoscopicsurgery 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 theNational Hospital of

Endocrinology in 2003 and later developed in many majorhospitals in the country such as Military Hospital 103, Binh DanHospital, Nhan Dan Hospital Gia Dinh, Cho Ray Hospital,175Hospital and Endoscopic Thyroid Surgery have confirmed theadvantages such as: scarring is hidden in the shirt, avoiding the risk ofscarring and postoperative paresthesia in the neck, significantlyimproving cosmetic.

Endoscopic thyroid surgery was more significantly complex thanconventional surgery,but so far, there were no studies have adequatelyevaluated and systematized Clinical, subclinical examinations cansupport and help surgeon set up the best endoscopic surgery plan forGraves’ patient and help patient to stay stable soon with normalthyroid function We conduct research on this topic with two target:

1 Review some clinical, subclinical feature Grave’s diseases and indication of endoscopic surgery.

2 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, Parrydisease ., diffuse thyrotoxicosis, exophthalmos goiter or immunehyperthyroidism This is a common endocrine disease, especially forwomen in the age of working If patients are not treated well, it willcause many complications and affect to the working ability as well aspatient ‘s life

Surgical treatment of Grave ‘s disease (subtotal thyroidectomy)has clear and sustainable result, the duration of treatment is short butthe disadvantage is always to leave surgical scars They are located onthe anterior neck and always affect the aesthetics of patients, whilemost of them are women of the working age Therefore, the studyabout endoscopic surgery for treatment of Grave ‘s disease with theadvantage of leaving a small surgical scar in armpit has practical andscientific significance, responding to current treatment needs in ourcountry as well as in the world

New contributions of the thesis

The thesis determined the advantages of thyroid endoscopic surgerycompared 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 diseasewhich achieved good results, especially overcome the limitations ofopen surgery such as less invasion, aesthetic.

It performed a pre-operative procedure and surgery in a unifiedway It evaluated results in and after surgery with strict, scientificresearch criteria, and the following up duration was up to 36 months

Thesis layout

The thesis consists of 127 pages (except appendix) Background:

2 pages;Chapter 1: Overview: 37 pages; Chapter 2: Objects andmethods research: 18 pages; Chapter 3: Results: 29 pages; Chapter 4:Discussion: 39 pages Conclusion: 2 pages In this thesis, there are 36tables and 6 charts, 12 illustrations, diagram 1 Reference: 116 (45Vietnamese 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 byantibodies stimulates the receptor of TSH lead to a high levels ofcirculating 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 andyoung people This is an autoimmune disease with a chronic tendencyand recurrence It is involved a combination of environmental factorsuch as: stress, injury, infection, …

In white people, Grave’s disease is related to B8 and DR3 antigen, however in each race are associated with different HLA forexamples DR5 in Japanese, DR9 in Chinese and DR5 / DR8 in Korean.White people carry HLA-DR3 at risk 7 times higher than people

HLA-do not have this antigen

The cause is due to the appearance of autoantibodies thatstimulate the Receptorof TSH (TRAb), resulting in continuousstimulation of thyroid cells synthesis and excretion of T4 and T3

- The structure of TRAb has been clearly studied, it is a antibodyhas a high specificity, the nature is IgG1 only in humans There are 3types of structures of TRAb and also have three different ways ofattaching 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 cycledisorders in women During the examination, the patient was sittingrestless, irritabilities, or bulging eyes

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 inupright 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 firstmanifestation of the diseaseand patients always have palpitations Frequent tachycardia with heart beat always more than100 timesper minute, even ifrest If patients work or are emotional, heart beatcan be faster Hear the heart can feel systolic murmur

Blood pressure: Systolic blood pressure increases, diastolic bloodpressure 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’sdisease 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 manycases without proptosis.

In addition, there are a number of other symptoms such as:pretibial myxedema,digestive disorders

1.4.2 TSH receptor antibody (TRAb)

TRAb is an autoantibody that affects the receptor of TSHreceptors on the surfacethyroid cells

Normal value of TRAb <1.5 U /l This index increases inhyperthyroidism

1.4.4 Ultrasound of the thyroid gland

Based on thyroid Doppler ultrasound assesses the number ofvascular spots / 1cm2

1.4.5 ECG

Often seen with sinus tachycardia, such arrhythmias can bedetectedextrasystole, branch block, atrial fibrillation

1.4.6 Thyroid scan

Record thyroid scintigraphy with Technetium 99 or I131

Grave’s diseaseoften causes increase radiation of the lobes

- Hyperthyroid syndrome: Fatigue, nervousness, tremor, heat,digestive disorder: diarrhea, weight loss

- Diffuse goiter, soft density, systolic sound, classify goiteraccording to WHO in 1995

- Tachycardia, frequent heartbeat > 100 times per minute evenwhenrest

- Eye disease; lid retraction, lid lag, protosis, ….according toNOSPECS classification

Of American Thyroid Association (1969)

- Hand tremor with small amplitude and fast frequency

- Subclinical feature: Thyroid hormone quantification (T3, FT4increased), pituitary hormone (TSH decrease), TRAb increased,thyroid color Doppler ultrasound, thyroid ultrasound, ECG

According to the American Medical Association, Australia and theEuropean Thyroid Association, the diagnosis of Grave’ s diesae ismainly based on the concentration of hormones in the blood whenTSH is present below or equal to 0.1µUI / l FT4 and T3concentrations are higher than normal and patients have a diffusegoiter, rapid pulse, proptosis

1.6 Treatment

There are 3 basic treatments

- Internal medicine: Treatment with synthetic anti-thyroid drugs

- Surgical: perform subtotal thyroidectomy leave each 2-3 gramthyroid remnant in one side

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 twoyears of radioiodine treatment

- Large goiter

 Guideline American Thyroid Association (2016)

- The aspiration of patients who want surgery for quick controlhyperthyroidism, do 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 - 4 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 isthe first choice and surgery when no results

The last months of pregnancy: surgery when the disease tends toget 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, childrentreated medical treatment has no results

- Pregnant women and nursing mothers have no conditions formedical 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

- Tumor characteristics, disease patterns, disease severity.

- Experience of surgeon and treatment facilities

- The choice of patients

Nguyen Ngoc Trung: Patients with Grave ‘s disease indicatedopen surgery when the 3-6 month medical treatment have no results orloss of aesthetic or side effects of anti-thyroid drugs

In summary, the domestic authors give the indication for surgerybased on the factors:

- Prolonged treatment of effects: work, childbirth, aesthetic andmentality

- Patients with special circumstances

- Allergy or non-response to thyroid resistance, or response but theresults 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 tostabilize or relapse

- Pregnant women: Anti-thyroid drugs have an effect on thedevelopment 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 surgicalprocedure had been mentioned by many authors with different surgicalmethods 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 techniqueswere implemented:

- Revealing the thyroid gland by a middle line between the infrahyoidmuscles, without cutting the muscles

- Tie the artery on the superior pole Then tighten small blood vesselsclose to the glands in the remaining glands Do not tie the inferiorthyroid artery

- Pinch clip parallel along the axis of each lobe (one branch penetratesthe parenchyma) Cut the thyroid gland on this branch and then stitchremnant with a U-shaped thread

- Stitch the incision with continuous subcuticular sutures

With this method, the operation was safe, the operation time wasshortened, it reduced the complications after surgery with beautifulincisions

1.7.2.2.The amount and location of remnant

The appropriate amount of thyroid parenchyma must be ensured tominimize the rate of recurrent hyperthyroidism and the rate ofpostoperative hypothyroidism Excessive thyroid tissue would lead tohyperthyroidism, otherwise small remnant would lead tohypothyroidism About the amount of remnant, there were manydifferent views between the authors Some authors left the amount ofparenchyma more or less depending on the size of the goiter, the age

of the patient, the other authors argued that depends on the level ofthyrotoxicosis, the age of the patient Some authors suggested that thethyroid gland should be remove totally

1.7.2.3.The approaching and surgical method

There are many methods of subtotal thyroidectomy in Grave ‘sdisease

- O V Nicolaev: Skin incision by Kocher line He performedthyroidectomy in both sides

- Surgery of Kocher (1902): After tying the superior and inferiorarteries, removed subtotal 2 lobes and isthmus, left bilaterally a smallremnant behind

- Surgery of De Quervain: After tying the superior and inferiorarteries, performedthyroidectomy according to the wedge shape(without isthmus) The rest of thyroid gland was quite big

- Ngo Van Hoang Linh studied improving some details in subtotalthyroidectomy techniquebased on OV Nicolaev method as follows:+ Reveal the thyroid gland follow midlinethrough interior border ofsternohyoid muscle and sternothyroid muscle, avoid destroying any muscle+ Tightening the superior thyroid arteries Then tighten the small blood

in the rest of the gland Do not tighten the inferior thyroid arteries

+ Blood grip clamps placed parallel along the axis of each lobe (apiercing branch in the parenchyma) Cut the thyroid gland on thosepinces and sew the cape cut with a U-shaped suture

+ Stitching the incision skin by continuous subcuticular suture.With this improved method, the operation is safe, the surgery time

is shortened,reduce complications after surgery, beautiful incisions,keep aesthetic for the diseasemultiply

1.7.2.4.Results of open surgery

Sugino et al (2008) summarized from 1989 to 1998 on 1897patients with Grave ‘s disease who underwent subtotal thyroidectomyand were followed up after surgery 2-3 years: 630 patients with left

remnant about 7 grams, relapse rate was 14.1%; 587 patients with lefttissue about 6 grams, recurrence rate is 12.6%; 620 patients left tissueabout 5 grams, relapse rate was 10.9% According to other authors,surgeon should leave the amount of remnant from 3 to 4g) to avoidrecurrent hyperthyroidism Also according to the author, the amount ofthyroid remnant in women (4,3 ± 1,2) was smaller than that of men(4.8 ± 1.3) but the rate of hyperthyroidism relapses was higher inwomen than in men.

Author Hermann M and CS (1998) operated on 215 patients Theresults of the study show that the weight of thyroid parenchyma is clearlyrelated postoperative recurrence rate The group underwent subtotalthyroidectomy (leaving from 6 - 8 grams) recurrence rate was 23.8%; inthe group with remnant from 2 - 4g, the recurrence rate was 9.4%

Nikolayayev (1993) left 2 - 6 grams; Farrar W.B (1983) left 2 – 4grams; Orgiazzi J (1983) left 3 - 10 grams; Simus J.M and Talbot C.H(1983) left 6 grams

Author Nguyen Hoai Nam and Nguyen Khanh Du: among 245patients were performed subtotal thyroidectomy from 1992 - 1998with the amount of left issue about (3 - 6g), the rate of relapse ofhyperthyroidism was 4%

The author Agarwal A operated for 72 patients with the amount oftwo sides remnant about 3-5g: No deaths or postoperative stormsthyrotoxicosis, no cases of permanent injury of recurrent nerves orhypoparathyroidism; 8 patients (11.1%) were temporarily hoarse, 4patients (5.5%) had temporary hypocalcemia

Dang Ngoc Hung et al operated on 2916 patients met the rate ofearly stage complications such as:

Bleeding 21 cases, accounting for 0.71%.Tetani 43 cases,accounting for 1.45% Respiratory failure: 3 cases, accounting for0.44% Temporary hoarse 26 cases, accounting for 0.87%.The stormhyperthyroidism 2 cases, accounting for 0.87%.1 case of death,accounting for 0.03%

Nguyen Hoai Nam et al had rate of complication during and aftersurgery on 245 Grave ‘s patients as follows: Bleeding in surgery 4cases, accounting for 1.6% Postoperative bleeding 5 cases, accountingfor 2% Hypocalcemia temporary: 30 cases, accounting for 12%.Permanent hypocalcemia: 0 cases, accounting for 0% Subcutaneoushematoma: 12 cases, accounting for 5% Surgical infection: 8 cases,

accounting for 3.2% Temporary hoarseness: 2 cases, accounting for0.8% Permanent hoarseness: 1 case, 0.4% Hyperthyroidism: 0 cases,accounting for 0% Death: 1 case, accounting for 0.4%.

Tran Ngoc Luong operated on 200 patients at the NationalHospital of Endocrinology from 2002 to 2004 (with unmodifiedmethod) results are as follows: performed total thyroidectomy on14patients (7%), subtotal thyroidectomy and left superior pole on 9patients (4.5%), subtotal thyroidectomy and left posterior portion on

177 patients (88.5%) No patient had thyroid storm or tachycardianeeded postoperative intervention There were 3 cases (1.5%) hadpostoperative bleeding need a second operation for hemostatic 3 caseshad 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 12patients with hyperthyroidism (Grave ‘sdisease)

- Sasaki A et al (2009) conducted a close cut endoscopic thyroidgland for treatment

Basedow disease for 42 patients The author followed the chestapproach, used forceps to enterthe subcutaneous layer of the chestthrough the right edge of the areola, creating space by pumping CO2

and split the subcutaneous layer of the chest neck area Place 5 mmtrocar on the bilateral areola Surgeons used Harmonic Scalpel, thyroidparenchyma around the ligament Berry was removed by moving theHarmonic Scalpel from inferior pole to superior pole

- Pornpeera et al (2016) compared the results between trans-orallaparoscopic surgery and open surgery for Grave ‘s disease 49 patientsundergoing open surgery and 46 patients undergoing trans-orallaparoscopic surgery, the author assumed 10 mm trocar in the center ofthe vestibule, 2 trocars 5 mm placed 2 below the lower lip The surgeryhas 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 oralhygiene

- Zhi Yu Li et al (2010) performed endoscopic subtotal thyroidsurgery for 37 Grave ‘s patients from 2006 to 2009 The author followedthe chest approach The author used 1 10 mm trocar at the central point