Comment on the results of the method of visualization and sentinel lymph node biopsy in thyroid carcinoma by Methylene blue in Hanoi Medical University Hospital from 11/2014 to 9/2018 and analyze the some factors affecting the results of method. Evaluate the value of sentinel lymph node biopsy in the diagnosis of occult cervical lymph node metastasis.
Trang 1MINISTRY OF EDUCATION MINISTRY OF HEALTH
HANOI MEDICAL UNIVERSITY
NGUYEN XUAN HAU
RESEARCH THE VALUE OF SENTINEL LYMPH NODE BIOPSY IN THYROID CARCINOMA
Specialization :Oncology
SUMMARY OF DOCTORAL DISSERTATION
HANOI - 2019
Trang 2Spervisor: Assoc Prof MD Le Van Quang
Reviewer 1:Assoc Prof MD Le Ngoc Ha
Reviewer 2:Assoc Prof MD Ngo Thanh Tung
Reviewer 3:Assoc Prof MD Le Trung Tho
The thesis will be defended before the Examining Board at university level in Hanoi Medical University
At …… o’clock……… Date …… Month …… Year…
This thesis could be found at
- National Library
- Centre Medical Information Library
Trang 31 Nguyen Xuan Hau, Tran Thi Hau, Le Thi Hang (2017) Clinical, subclinical characteristics and histopathology of early thyroid cancer at Hanoi Medical University Hospital Vietnam Medical Journal, Number 1, volume 456
2 Nguyen Xuan Hau, Le Van Quang, Duong Chi Thanh (2017) The result of visualization of sentinel lymph node biopsy with Methylene Blue in thyroid carcinoma Vietnam Medical Journal, Number 2, volume 456
3 Nguyen Xuan Hau and Le Van Quang (2018) The role of sentinel lymph node biopsy in thyroid carcinoma and the factors affecting the value of the method Vietnam Medical Journal, Number 2, volume 472
4 Le Van Quang, Nguyen Van Hieu, Nguyen Xuan Hau, Nguyen Van Hung (2018) Role of sentinel lymph node biopsy in papillary thyroid carcinoma
in Vietnam International Journal of Hematology and Oncology, number 4, Volume 28
Trang 4INTRODUCTION
1 Reason to choose the thesis
Thyroid cancer is the most common disease in endocrine cancer, accounting for 3.6% of all cancers in general
Surgery is the most important treatment in thyroid cancer Thyroidectomy plus lymphadenectomy increase the rate of complications after surgery, but the disease recurrent mainly in cervical lymph node and lymphadenectomy is the first priority choice Surgery to remove central lymph node in recurrent thyroid cancer increase the risk of complications such as paralysis of the recurrent laryngeal nerve and hypoparathyroidism To limit systemic cervical lymph node dissection, finding a method to detect occult lymph node metastasis is necessary to determine the treatment strategy Sentinel lymph node is defined as the first lymph node in the lymphatic drainage area to be drained from the primary tumor, which reflects the condition of the remaining lymph nodes with or without lymph node This result contributes to the detection of metastatic lymph nodes that are smaller than 2-3 mm in diameter - difficult to detect by other techniques such as high resolution ultrasound In the world, there have been many studies on the sentinel lymph node of thyroid cancer, however, there has not been any research in this field in Vietnam Therefore, we carried out the thesis: "Research on the value of sentinel lymph node biopsy in thyroid cancer" with the following two objectives:
1 Comment on the results of the method of visualization and sentinel lymph node biopsy in thyroid carcinoma by Methylene blue in Hanoi Medical University Hospital from 11/2014 to 9/2018 and analyze the some factors affecting the results of method
2 Evaluate the value of sentinel lymph node biopsy in the diagnosis of occult cervical lymph node metastasis
2 New finding of the thesis:
- This is the first study in Vietnam, using Methylene Blue to detect
sentinel lymph node in thyroid cancer, to help determine the exact occult lymph node metastasis, thereby giving a strategy the cervical
Trang 5lymph node dissection with the same time reasonable
thyroidectomy
- The rate of sentinel lymph node detection with Methylene Blue is very high: 98.2%; Most lymph nodes are in the pre-tracheal group (group 6): 90.4%
- Percentage of non-metastatic lymph nodes on pathology: 55.7%; metastasis on pathology: 44.3%, the rate of occult cervical lymph node metastasis is very high: 51.5%
- Sensitivity, specificity, positive predictive value, negative predictive value, overall accuracy and false negative rate of the method are: 86%, 100%, 100%, 87,1%, 92.8% and 14% respectively
3 The structure of the thesis:
The thesis conclude 122 pages, with 4 main chapters: Introduction
2 pages, Chapter 1 (Overview) 40 pages, Chapter 2 (Subjects and Research Methods) 18 pages, Chapter 3 (Research results) 29 pages , Chapter 4 (Discussion) 30 pages, Conclusion and Recommendations
3 pages The thesis has 33 tables, 7 pictures and 5 charts, 155 references (26 Vietnamese references, 129 English references)
Chapter 1: OVERVIEW 1.1 Introduction
Sentinel lymph node is defined as the first lymph node in the lymph nodes receiving lymph nodes from primary tumors Since the past 19 years, approved sentinel lymph node biopsy is a technique to determine the metastatic presence of melanoma cancer and early breast cancer Recently, sentinel lymph node biopsy has been proposed for use in other cancers, including thyroid cancer The role
of this method is being clarified by the authors The results of lymph node biopsy help the surgeon make a decision right away in terms of regional lymphadenopathy and appropriate management or systemic behavior
1.2 Sentinel lymph node biopsy in thyroid carcinoma
1.2.1 Technology
Trang 6Blue dye is an injection used most often with methylene blue, isosulphan blue This method involves injecting a blue indicator into sites with the same lymphatic drainage system with the tumor then a certain period of time will be performed to detect lymph nodes by direct observation of the pathways Blue lymphatic drainage leads to lymph node All blue dyes disappear during the process of making the specimen and do not affect histological analysis
About radioisotopes, different forms of 99m-Technetium The lymph nodes in these cases are detected by skin markers for lymph nodes or it can be detected by radioactive signals using a gamma probe during surgery
After exposition of the thyroid gland, four quadrants around the tumor were injected with a total of 1ml of methylene blue with tuberculosis syringe At this time, stop the operation for one minute
to allow diffused dye The lymphatic pathways catch a blue stain (the stain of the blue dye, then continue into the central cavity and the blue stain nodes are taken and sent to frozen section
1.2.2 Factors affecting the results of the method
Although the studies have shown that the rate of visualization of the sentinel lymph node with Methylene blue is very high, there is still a small proportion of not showing the lymph nodes when
perform the method
To explain the absence of this sentinel lymph node, many studies suggest that the lymph node system from the tumor to the lymph node is disrupt during the process of thyroid disclosure, the lymphatic pathway is blocked by invasive tumors or The main lymphatic vessels that were not detected after injecting the color indicator may be that it is behind the esophagus or after the thyroid site
When studying other factors affecting the results of sentinel lymph node such as age, sex, tumor position in lobe, tumor size, tumor stage, multifocality, all studies showed that there was no the relationship between the above factors with the result of the sentinel lymph node
Trang 7Chapter 2: OBJECTIVES AND METHODOLOGY
2.1 Research subjects
The patient was diagnosed with thyroid cancer and surgery at the Oncology-Palliative Care Department, Hanoi Medical University Hospital from November 2014 to September 2018
2.1.1 Sample size
Sample size is determined by the formula:
n = Z21-α/2
p(1 – p) (pε)2
Where
n: Minimum sample size in the study
Z 1-α/2 : coefficient of confidence with a probability of 95% ( ε=
0.05) → Z = 1.96
Select ε: deviation of p, limit of 10% (ε = 0.1)
p: percentage of lymph nodes without metastasis (p = 0.7) according to Cabrera's study (2014)
From the above formula, we selected 170 patients
2.1.2 Criteria for selecting research subjects
- Patients diagnosed with thyroid cancer based on clinical, ultrasound and cytology Cases of unknown cancer in cytology and / or ultrasound will be frozen section in surgery
- Diagnosis of clinical stage T1,2,3,4; N0; M0 classified by AJCC
2010
- Injection of methylene blue around the tumor
- Surgical removal of selective lymph nodes group VI and group II, III, VI on both sides
- Results of postoperative pathology are differentiated thyroid carcinoma
2.1.3 Exclusion criteria
- Metastatic lymphoma of the lymph nodes clearly clinical, distant metastasis
Trang 8- There is a history of allergy to Methylene blue
- Thyrois cancer is not the epithelial cell type
- Patient was undergoing thyroid surgery at the other hospital
- Patients disagree to participate in the study
2.2 Research Methods
2.2.1 Research design
Descriptive research study
2.2.2 Research Methods
2.2.2.1 Exploiting clinical and subclinical information
2.2.2.2.Technical process of visualization and sentinel lymph node
- Endotracheal anesthesia, antiseptic neck area down through depressions, above the chin
- Incision skin across the lower neckline, about two fingers away from the noch of breastbone, cutting the platisma muscle, dissection the two skin flaps up and down Open along the neck fascia before the trachea, clearly showing the thyroid lobe containing the tumor
- Find and protection the parathyroid glands and recurrent laryngeal nerves before injecting Methylene Blue, avoiding difficulties in finding later
- Inject 1 ml of Methylene Blue into 4 positions around the tumor: 3 hours, 6 hours, 9 hours and 12 hours Be careful not to let Methylen around the operation space to avoid confusion when making a judgment
If gauze and gloves are slotted with a color indicator, they must be replaced to avoid penetrating the surrounding organization
- Gently massage the thyroid lobe that is injected within 1 minute with the fingertip Dissection around the thyroid lobe to detect blue lymphatic drainage This process should be carried out gently, meticulously, hemostatic to facilitate maximum observation Follow all the detected
Trang 9lymphatic pathways to the stain lymph nodes (lymph nodes) Take all the stain lymph nodes and record the sentinel lymph node in separate groups
- Duration is 10 - 15 minutes from the injection of color indicator Past that time, if the lymphatic or lymphatic channels are not detected, the procedure is classified as not recognizing the lymph node
- Total thyroidectomy and neck lymphadenectomy selected at the center neck group and lateral neck group or lobe thyroidectomy plus isthmusectomy and combined with selective neck lymph nodes remove are conducted according to modern surgical standards for thyroid cancer
- Detection rate = Number of detected cases with sentinel lymph node / total number of cases performed
- Sensitivity = Number of sentinel lymph node (+) / Number of patients with lymph node metastasis on final pathology= a / (a + c)
- Specificity = Number of sentinel lymph node (-) / Number of patients with no lymph node metastasis on final pathology = d / (b + d)
- Total accuracy = (frozen section positive positive lymph node + true negative frozen secton) / Number of lymph nodes detected = (a + d) / (a +
b + c + d)
- The rate of false negative = Number of sentinel lymph node (-) / Number
of patients with lymph node metastasis on final pathology = c / (a + c)
2.3 Data analysis
Data were collected and statistically processed with SPSS 16.0
software according to research criteria
The statistical method used includes:
- Descriptive statistics: average, standard deviation
- Comparison of the ratio: test χ2, statistical significance level was established when P <0.05 or Fisher’s exact test
Trang 10- Univariate evaluation method, Logistic multivariate regression model
Chapter 3: RESEARCH RESULT
3.1 Results of the method of visualization the sentinel lymph node biopsy with methylene blue in thyroid cancer and factors affecting the results of the method
3.1.1 Patient characteristics
Age: Average age: 40.3 ± 10.64 (20 - 68) years old
Gender: The disease is mainly seen in women, the rate of women
/ men: 7.5 / 1
Clinical tumor characteristics: The percentage of tumor
palpation on clinical examination is highest, accounting for over 60% Most patients have tumors in a thyroid lobe, accounting for nearly 90% The majority of tumors have a firm density, accounting for 81.9%, and mobility is easily accounted for over 95%
Results of thyroid ultrasound:
- The position of tumors in one of the most common lobes accounts for nearly 90%, evenly distributed in both right and left lobes About 4% of the tumors are located in the isthmus and 7% are
in both lobes In the lobe, tumors in the most common middle third account for over 55% On ultrasound, hypoechoic is the most common accounts for over 80%, microcalcifiation accounts for 54.1%, angiogenesis accounts for 34.7%, unknown boundaries account for only over 25%
- Most patients are classified TIRADS 4-5 on ultrasound, accounting for more than 98% Among them, the most common TIRADS 4b accounts for more than 40% However, 1.2% of thyroid cancer on ultrasound is TIRADS 3 image
- Most patients on ultrasound have only 1 tumor accounting for over 77%, 22.4% of patients have more than 1 tumor on ultrasound,
of which 7% have 3 tumors
- Most patients have tumor size <2 cm, accounting for 88.8%, tumor size> 4 cm accounts for only 1.2%
Cytology: 100% of patients were performed fine needle
aspiration before surgery The results of cytology diagnosed with
Trang 11cancer or suspected of cancer account for 93% only about 7% of thyroid cacner but benign cytology results
Frozen section: More than 85% of patients have the frozen
section tumor intraopetatively, 100% of results are cancer
Procedure of thyroid surgery: The patient had total
thyroidectomy, accounting for 89.4%, lobe thyroidectomy plus isthmusectomy accounted for 10.6%
Pathology result of thyroid tumors: Papillary adenocarcinoma
accounts for the majority of cases over 99% Follicular carcinoma accounted for only 0.7%
Thyroid inflammation enclosed: Among patients with thyroid
cancer, more than 11% of patients had thyroiditis with cancer
T stage: Clinically, the majority of patients diagnosed with T1 stage account for about 90% However, on pathlogy, the proportion of T1 patients accounted for only over 52%, the rate of T3 stage tumors increased to 37.6%
3.1.2 The results of the method of visualization the sentinel lymph nodes biopsy by methylene blue and the factors affecting the results
of the method
The rate of detection of sentinel lymph nodes with methylene blue:
The rate of detection of sentinel lymph nodes with methylene blue is very high, accounting for 98.2%
Some factors affecting the result of sentinel lymph node
Table 3.1 Some factors affecting the result of the method
Trang 12* 7 tumors on the isthmus cases; SLN: sentinel lymph node
Comment: The percentage of sentinel lymph node result of the
position of the middle third tumor has a 100% compared to the group
of patients with tumor position in uper third of 95.8% and lower third 95.8 %, this difference is not statistically significant p = 0.145 The patients at T1 and T2 stage had a lower incidence of sentinel lymph node than patients in the T3 and T4 stage (97% versus 100%), this difference was not statistically significant p= 0.27
The number of sentinel lymph nodes detected: The average number
of sentinel lymph nodes 3.4 ± 1.99; The maximum number of nodes
is 12, at least 1 Most patients detected more than 1 lymph node accounted for more than 85%
The position of the lymph node: Sentinel lymph node detected in the
pretracheal group (group 6) is the most common, accounting for
Trang 13more than 90% (150/167) There were 6.0% (11/167) patients with sentinel lymph nodes found in the both pretraheal and lateral group, while the percentage of sentinel lymph nodes detected in the ipsilateral group: 3.6% (6/167)
The position of the sentinel lymph node in the pretracheal group:
In the pretracheal group, the highest percentage of sentinel lymph node was detected in the recurrent chain group above 85% The rate
of detection of sentinel lymph node in the group pretracheal is only about 5%, prelaryngeal (Denphien lymph nodes) only accounts for about 1% There were 3.7% of sentinel lymph node detected in both groups of the recurrent chain group and the prelaryneal
The number of cervical lymph nodes: The average number of
cervical lymph nodes were 21,89 ± 9.09 nodes, the highest is 64 nodes, at least 4 nodes
3.2 The value of sentinel lymph node biopsy in diagnosis of cervical lymph node metastasis
3.2.1 Status of sentinel lymph node metastasis on frozen section Table 3.2 sentinel lymph node metastasis status on frozen section
Comments: In 167 patients with senetinel lymph node detected by
methylene blue, all these lymph nodes were sent to prozen section The rate of SLN metastasis accounts for 39.5%, 60.5% of the SLN negative on frozen section
3.2.2 Status of sentinel lymph node metastasis on pathology