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MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENSE INSTITUTE OF CLINICAL MEDICAL SCIENCE 108 NGUYEN HONG NHUNG RESEARCH OF USING FREE LATERAL ARM FLAP IN SOFT TISSUE RECONSTRUCTION AFTER ORAL CANC[.]

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENSE INSTITUTE OF CLINICAL MEDICAL SCIENCE 108 NGUYEN HONG NHUNG RESEARCH OF USING FREE LATERAL ARM FLAP IN SOFT TISSUE RECONSTRUCTION AFTER ORAL CANCER REJECTION Major: Odonto Stomatology Code: 62720601 SUMMARY OF DOCTORAL THESIS HANOI – 2022 Thesis completed at: INSTITUTE OF CLINICAL MEDICAL SCIENCE 108 Supervisors: Associate Professor Le Van Son Associate Professor Vu Ngoc Lam Reviewers: The Thesis will be definded to Thesis grading committee at the Institute level Organized at Institute of Clinical Medical Science 108 Time: Date: The Thesis can be found at: Vietnam National Library Institute of Clinical Medical Science 108 Library INTRODUCTION According to the Union for International Cancer Control, oral cancer represents the sixth in the most common cancers More than 90% of oral cancers are squamous cell carcinoma and less responsive to radiotherapy and chemotherapy Extensive resection to remove the tumor is the most effective therapeutic option However, following surgery, the tumor frequently leaves huge organizational flaws and has a significant impact on vital processes including chewing, breathing, and communicating As a result, reconstructing and restoring the function of these areas of the mouth cavity are crucial Due to the fact that traditional techniques of reconstructing are not suitable for large defects, several authors utilize free flaps, such as the lateral arm flap (LAF), to form the oral cavity In Vietnam, a number of prominent medical institutes are employing LAF to reconstruc the head, neck, and oral cavity, with initial success in concealing anomalies as well as restoring some of the patients’ essential functions and improve their quality of life There have been no comprehensive studies on the use of LAF in the restoration of oral cavity defects after cancer resection to far, we decided to investigate the subject “Research of using free lateral arm flap in soft tissue reconstruction after oral cancer rejection” with these targets: Describe some anatomical characteristics of the lateral arm flap Describe clinical characteristics of oral cancer lesions Evaluation of the results of reconstructive surgery of soft tissue defects after surgical resection of oral cancer with the lateral arm flap URGENCY OF THE SUBJECT Although oral cancer rejection is the only successful method, it is required to reconstruct the organizational defects as well as restore the function of the lost organs after surgery The free lateral arm flap is an appropriate plastic material because of its same size, weight, and skin quality as the oral cavity In spite of the fact that there has been some research on the lateral arm flap, none have focused on the septocutaneous perforator of the lateral arm flap, which is one of the most important anatomical components for blood supply vessels formation for flap To satisfy the needs of employing flexible flaps in sculpting the oral cavity, it is vital to learn about perforating branches NEW PRACTICAL MEANINGS AND CONTRIBUTIONS 1.Anatomical contributions: It is the first study to determine the number, distribution, and diameter of perforating branches, demonstrating that the lateral arm flap has invariable pedicle, and rich distribution of vessels in flap, and that it can be divided into smaller flaps to allow surgeons to resurfacing defects due to tumor resection or trauma more flexibly Clinical contributions: The size, thichness, flexibility, and appropriate color of lateral arm are confirmed by its use in oral cavity reconstruction, which includes sculpting the tongue, the floor of mouth, and the buccal mucosa in a significant number of cases After tumor rejection, it is feasible to replace lost organs and components in both structure and function THESIS STRUCTURE Introduction; Chapter 1: Overview 31 pages; Chapter 2: Subjects and methods 27 pages; Chapter 3: Results 26 pages; Chapter 4: Discussion 31 pages; Conclusion pages; References: Vietnamese 17, English 116 Chapter OVERVIEW 1.1 OVERVIEW OF ORAL CANCER 1.1.1 Epidemiology of oral cancer 1.1.2 Diagnose 1.1.2.1 Precancerous signs + Leukoplakia + Erythroplakia 1.1.2.2 Diagnose Oral cancer diagnose is based on the history of risk factors, clinical examination, laboratory tests, and pathological results 1.1.2.2.1 Clinical symptoms Initial stage: Ambiguous clinical signs that are easy to dismiss Period of illness: Symptoms: increasing and spreading pain, hoarseness, speaking and swallowing difficulty, mobility, tooth loss Signs: types of lesions: vegetation, ulcer, and infiltrate 1.1.2.2.2 Tests Radiology: determine the location, size, infiltrate, and regional as well as distant metastasis lymph nodes + X-ray + CT Scan + MRI + PET/CT Pathology: determine diagnosis, malignance, and infiltrates 1.1.3 Treatment 1.1.3.1 Chemotherapy 1.1.3.2 Radiotherapy 1.1.3.3 Surgical treatment of oral cancer 1.1.3.3.1 Rejection For the treatment of oral cancer, this is the most effective choice It is feasible to remove the entire tumor at the first time In late- stage cases, to improve outcomes, surgery is combined with radiotherapy and chemotherapy The resection area more than cm from the edge of the lesion is deemed entirely tumor-free 1.1.3.3.2 Lymphadenectomy + Selective cervical lymphadenectomy + Functional cervical lymphadenectomy + Absolute cervical lymphadenectomy + Modified absolute cervical lymphadenectomy 1.2 TREATMENT METHODS FOR SOFT TISSUE RECONSTRUCTION AFTER ORAL CANCER REJECTION The classic methods are direct suture, skin grafting, local or adjacent flaps; however, these are ineffective for large tissue deffects Free flaps including scapular - parascapular flaps, lateral forearm flaps, anterolateral thigh flaps, deep inferior epigastric perforators flap, ect are used to reconstruct the oral cavity Advantages of these flaps: can be taken with a large area, attached to muscles Disadvantages of these flaps: rough skin, dense subcutaneous tisse, and some hairy flaps make it less suited for the oral cavity 1.3 OVERVIEW OF LATERAL ARM FLAP 1.3.1 Research situation of lateral arm flap anatomy The lateral arm flap was first described by Song in 1982 The artery supplying the flap is the posterior radial collateral artery The flap drainage has the superficial vein system as the head veins, the deep vein system as the vena comitants The flap may include the inferior lateral cutaneous nerve of arm and the posterior forearm cutaneous nerve The average length of the pedicle is 7.8cm, the average diameter of the artery is 2mm, the average diameter of the vein is 2.5mm, and the average size is 12x9cm The flap has 2-4 branches through the skin wall, the application is to split the flap in half In addition, there is an anastomosis between the ending branch of posterior radial collateral artery with the reversing branch of posterior interosseous, which expands the flap area In Vietnam, Truong Uyen Cuong (2008), Vu Minh Hiep (2014), Nguyen Huy Canh (2015) mainly researched the vascular pedicle, pedicle composition, and the blood supply area There are no studies on septocutaneous perforators 1.3.2 Application situation of lateral arm flap in clinical practice Lateral arm flap has been frequently employed by surgeons all over the globe to shape small and medium-sized organizational flaws in the head, neck, arm and leg, especially in reconstruct oral cavity after rejection, with success rates ranging from 95.2 to 100% In Vietnam, the lateral arm flap is utilized to shape soft tissue deformities of the wrist, head, and neck, in which 17 cases of tongue reconstruction after tumor resection However, this is only an initial report with a limited number of flaps, the evaluation is incomplete, and there are still some questions regarding the anatomy of the septocutaneous perforators in Vietnamese and specifically the applications of flaps in reconstructing the oral cavity after surgery that need to be answered CHAPTER SUBJECTS AND METHODS 2.1 SUBJECTS 2.1.1 Anatomical research Over 20 specimens of Vietnamese adult corpses 2.1.1.1 Criteria for specimen selection - Vietnamese adult corpses - No injury or deformity on the arm and forearm 2.1.1.2 Place Department of Anatomy, University of Medicine and Pharmacy Ho Chi Minh City 2.1.1.3 Time From October, 2018 to October, 2019 2.1.2 Clinical research Oral cancer patients 2.1.2.1 Criteria for patient selection - Pathological result is squamous cell carcinoma - Eligible for major surgery - No injury on the arm 2.1.2.2 Place At 108 Military Central Hospital and National Hospital of Odonto-Stomatology 2.1.2.3 Time From October, 2014 to December, 2020 2.2 METHODS 2.2.1 Anatomical research method Observational and descriptive research 2.2.1.1 Purpose - Improve flapping skills - Determine the composition and diameter of the vessels of the pedicle flap - Determine the number of septocutaneous perforators 2.2.1.2 Procedure - Flap dissection procedure: + The specimen was placed on the back, arms crossed over the chest + Design of flap axis: draw a straight line going from the attachment point of deltoid muscle to the lateral condyle of the humerus Flap dissection steps: + Incise the skin in a parallel line 3.5 cm posteriorly from the deltoid-condylar line, dissecting below the fascia of the triceps + Expose the pedicle including the radial lateral artery, the vena comitants, and the lateral cutaneous nerve of arm + Incise the skin in a parallel line 3.5 cm anteriorly from the flap axis, dissecting to the external intermuscular septum + Determine the origin: the position of the radial artery dividing the anterior radial artery and the posterior radial artery + Color injection: thread the needle No 18 into the lumen of the posterior radial collateral artery at the origin Irrigate the lumen with 70o alcohol, then inject 20-30 cc of oil-based brush ink into the lumen Measurement: + Pedicle length: from the origin of posterior radial collateral artery to MX1 + Count the number of septocutaneous perforators MX1, MX2, MX3, MX4… + Distance from the deltoid muscle attachment point to the septocutaneous perforators MX1, MX2, MX3, MX4… + Distance from humerus lateral epicondylitis to MX1, MX2, MX3, MX4… + Measure the flattended diameter of the artery, veins of the pedicle at the origin + Measure the flattened diameter of the artery of the septocutaneous perforators MX1, MX2, MX3, except MX4 because the diameter is too small and far from the center of the flap + True diameter is calculated by the formula: D=C/ (D: diameter, C is times the measurement of flat blood vessel, =3,14) 2.2.2 Clinical research method Prospective study, clinical intervention, no control group 2.2.2.1 Sample size Sample size: calculated by the formula n: sample size : : confidence coefficient at the probability level 95% (=1,96) p: patient success rate 95,2% following Marques Faria (2008) - p: failure rate 4,8% d: is the desired accuracy 95% (0,05) The minimum sample size calculated was 36 patients In this study, we selected 61 patients 2.2.2.2.1 Patient preparation - Examination and assessment of the general condition and tumor pathology - Surgical plan development - Explain to the patients and their family about the surgical method 2.2.2.2.2 Procedure - Pre-operative design + Draw the lymphadenectomy line and the approaching line into the oral cavity 11 + Survival or death status of the graft + Healing results - Long-term results after grafting Assessed by periods: after 3, 6, 9, 12 and 24 months - Regarding speech, swallowing, and flap aesthetics + Speech function: very good: clear pronunciation, clear words; good: speak understandably; moderate: a lot of lisp, difficult to understand; poor: unable to speak + Swallowing function: very good: eat food normally; good: eat soft food; moderate: eat liquid food; poor: eat through sonde + Aesthetic function: very good: soft flap, well-proportioned shape, similar to the healthy side; good: relatively balanced shape, quite similar to the healthy side; moderate: morphologically similar, size inconsistent; poor: shape is not the same, size is not suitable, and there is a lot of stretch Evaluate long-term at donating flap: + Very good: soft scars, no sequelae; + Good: soft and stretchy scars, reduced or disturbed sensation + Moderate: hypertrophic scars, reduced sensation of the lateral arm + Poor: keloid scars, loss of sensation on the lateral arm 2.4 DATA PROCESSING - Research data was processed by medical statistical algorithm using SPSS 20.0 software 2.5 RESEARCH ETHICS - The patients all agreed to take part in the study - Personsal information about patients is kept private - The patient had given his or her permission for images to be used in reports 12 CHAPTER RESULTS 3.1 ANATOMICAL CHARACTERISTICS OF LATERAL ARM FLAP - Pedicle composition: 100% flaps have artery and vena comitants - Origin: 100% is the posterior radial collateral artery, a branch of the radial collateral artery - Pedicle length: the shortest is 4.50 cm, the longest is 8.00 cm, the average is 5,81± 0.96 cm - Diameter: the smallest artery is 1.13 mm, the largest is 1.51 mm, the average is 1.36± 0.09 mm; the average diameter of the first vein is 1.52± 0.04 mm; the average diameter of the second vein is 1.41± 0.09 mm - Number of perforatories: 75% has perforatories, 25% has perforatories - Distance to the deltoid muscle attachment point: MX1 5.81 ± 0.96 cm, MX2 7.97 ± 0.78 cm, MX3 10.09 ± 0.70 cm, MX4 12.15 ± 0.77 cm 3.2 CLINICAL CHARACTERISTICS OF ORAL CANCER 3.2.1 Epidemiological characteristics: - Sex: Male 46/61 patients - 74,5%; Female 15/61 patients - 24,6% - Age: Minimum: 23 years old; Maximum: 73 years old; Average: 52.16 ±10 years old Age: 50 – 70 years old accounting for 80,32% 13 3.2.2 Clinical signs: Table 3.10: Clinical signs (n=61) Clinical signs Number (n) Rate (%) Pain, burning 52 85.2 Increased salivation 40 65.6 Long-healing ulcer 39 63.9 Vegetation 35 57.37 Bleeding 17 27.9 Bad breath 41 67.21 Eating difficulty 39 63.93 Pain, burning and increased salivation were the most common, initial, abnormal signs, accounting for 85.2% and 65.6%, respectively 3.2.3 Characteristics of tumor 3.2.3.1 Location of tumor Table 3.11: Location of tumor in oral cavity (n=61) Location Number (n) Rate (%) Tongue tip 4.9 Tongue lateral border 44 72.1 Tongue root 3.3 Floor of mouth 11.5 Buccal mucosa – posterior mandibular 8.2 Total 61 100 Tongue cancer accounted for the most (49 patients - 80.3%), of which tongue lateral border cancer was 72.1%, tongue root cancer was rare 14 3.2.3.2 Morphology of tumor Table 3.12: Morphology of tumor (n=61) Morphology Number (n) Rate (%) Ulcer 28 45.90 Vegetation 25 40.98 Infiltration 13.11 Total 61 100 Morphology of tumor was mainly ulcer (45.90%) and vegetation (40.98%), and infiltration was 13.11% 3.2.3.3 Characteristics of pathology Pathologic result: 100% of cases were squamous cell carcinoma with different histology 3.2.3.4 Classification according to TNM Tumor size: T2 80.32%, T3 14.75% T4 4.93% Regional lymph nodes: N0 68.9%, N1 16.4% N2a 14.8% Metastatic lymph nodes: Mo 90.2%, M1 9.8% Stage: II 60.65%, III 26.22%, 13.12% 3.3 SURGICAL RESULTS 3.3.1 Results of lymphadenectomy, tumor rejection Table 3.14: Related to lymphadenectomy and disease stage (n=61) Disease stage II III IV Total, Rate (%) Unilateral 36 59.0% 12 19.7% 6.6% 52 85.2% Bilateral 1.6% 6.6% 6.6% 14.8% Total 37 60.7% 16 26.2% 13.1% 61 100.0% Lymphadenectomy P P=0.001 The rate of unilateral lymphadenectomy was 85.2%, bilateral lymphadenectomy was 14.8%, of which most patients in stage II with unilateral lymphadenectomy Table 3.15: Area of organizational defects after rejection (n=61) 15 Area Number Rate (%) 1/3 tongue 3.27 ẵ tongue 28 45.90 ắ tongue 17 27.86 All 3.27 Floor of mouth 11.47 Buccal mucosa – 8.19 posterior mandibular Total 61 100 Tongue defect accounted for 77.50%, of which half tongue defect accounted for the most 45.9% 3.3.2 Results of taking lateral arm flap 3.3.2.1 Size of flap - Width: cm - cm, average 5.84 ± 0.41 cm - Length: 8cm - 18 cm, average 13.52 ± 1.74 cm - Area: minimum 31.4 cm², maximum: 84.8 cm² average 62.27 ± 10.75/ cm² - Pedicle length: minimum cm, maximum cm average 5.67 ± 0.87 cm 3.3.2.2 Types of flaps - Fasciocutaneous: 56/61 flap (91.80%) - Myocutaneous: 5/61 flap (8.20%) 3.3.2.3 Results of donating flap area preparation - Direct closure 85.24% - Complementary skin grafts accounted for 14.75% 3.3.3 Results of grafting 3.3.3.1 Receiving arteries - Superior thyroid artery 70.49% - Facial artery 29.51% 3.3.3.2 Receiving veins - Superior thyroid vein 52.45% - Facial vein 29.50% 16 - External jugular vein 18,50% 3.3.3.3 Anastomosis results - Artery: 100% patent - Vein: 98.36% patent, 1.63% occlusion 3.3.3.4 Types of reconstruction - Tongue 1.67% - Tongue and floor of mouth 65.57% - Floor of mouth: 6.5% and buccal mucosa posterior mandibular 8.19% 3.3.3.5 Initial results after grafting - Complete flap survival 98.36% - Complete flap necrosis 1.63% 3.3.4 Results of healing In both donating and receiving flap areas, wound healing in the first period accounted for the majority (91.80% and 90.16%), longhealing cases (8.19%) owing to stretch marks, cases (6.55%) that had a wound leak healed after weeks 3.3.5 Initial accidents and complications - Donating flap area: There were disturbances and partial loss of sensation in the superior and lateral forearms in 58 patients (95.08%) Receiving flap area: There was case of venous occlusion causing flap necrosis (1.68%) and case opened wound after surgery to remove tumor and reconstruct the floor of the mouth (1.68%) 3.3.6 Long-term results after surgery Duration from to 77 months, average 39.13 ±21.08 months 3.3.6.1 Survival status of the patients after surgery - Survival: 47 patients, 77.0% with an average postoperative follow-up of 46.25 months - Death: 14 patients, 27.0% with an average postoperative follow-up of 16.78 months Relating to survival and disease stage - Stage II: survival 37/37 patients, 100% - Stage III: survival10/16 patients, 62,5% - Stage IV: there were no survivors 17 3.3.6.2 Results of oral reconstruction Table 3.33: Overall functional and aesthetic results (n=47) Functional and aesthetic results Overall Classification Grafts results Speech Swallowing aesthetics 39 39 39 38 Very good 83.0% 83.0% 83.0% 80.9% 6 Good 8.5% 12.8% 12.8% 10.6% 2 2 Moderate 4.3% 4.3% 4.3% 4.3% 2 Poor 4.3% 0% 4.3% 47 47 47 47 Total (100%) (100%) (100%) (100%) In general, the majority of patients achieved very good results after surgery with the rate of 80.9% 5/47 patients achieved good results (10.6%) Moderate and poor results were found in only patients (4.3%) 3.3.7 Results of donating flap area condition Table 3.33: Condition of donating flap area during the follow-up period (n=47) Follow-up period (months) Evaluation criteria 12 24 13 15 37 37 Very good 27.65% 31.91% 78.7% 78.7% 19 22 9 Good 40.42% 46.80% 19.1% 19.1% Scar at 15 10 1 donating Moderate 31.91% 21.27% 2.1% 2.1% flap area 0 0 Poor 47 47 47 47 Total 100% 100% 100% 100% 26 37 47 47 Normal 55.31% 78.72% 100% 100% 16 10 Sensory 0% 0% disturbances 34.04% 21.27% 0 Arm Loss of 10.63% 0% 0% 0% function sensation 0 0 Paralysis 47 47 47 47 Total 100% 100% 100% 100% 18 Scars at donating area improved over time, at months after surgery, 27.65% of scars were assessed as very good, at 12 months, it was 78.7% Hypertrophic scars evaluated after months was 31.91%, by the 12th month, it decreased to 19.1% Arm function 12 months after surgery in all 47 patients (100%) was functioning normally, with no sensory disturbances CHAPTER DISCUSSION 4.1 ANATOMICAL CHARACTERISTICS OF LATERAL ARM FLAP The lateral arm flap was discovered by Song R in 1982 and then comprehensively studied by many authors In Vietnam, Truong Uyen Cuong (2008), Vu Minh Hiep (2014), Nguyen Huy Canh ( 2015) also had similar studies on Vietnamese adults In our study, 100% of the flap arteries were posterior radial collateral arteries and had 3-4 perforating vessels, the average pedicle length was 5.81 ± 0.96 cm cm, the average arterial diameter was 1.36 ± 0.09 mm, equivalent to the results of studies by domestic authors 4.2 CLINICAL CHARACTERISTICS OF ORAL CANCER In our study, patients were aged from 23 to 73 years old, on average 52.16 ± 10.18 years old, the most common was from 50 to 70 years old, accounting for 80.32% The male/female ratio was 3/1 This is consistent with the comments of authors around the world about the increasing trend of disease in young people Regarding the clinical signs, the patients often showed signs of pain, burning and increased salivation, accounting for 85.2% and 65.6%, respectively Long-healing ulcers and vegetations were also the reasons that brought patients to the clinic, accounting for 63.9% and 57.3% Regarding the location of the lesion, in our study we encountered more mobile tongue lesions, in which lateral border was 72.1%, tip of the tongue was 4.9%; followed by 7/61 cases of floor of ... oral cavity 9 + Design lateral arm flap + Check septocutaneous perforators with doppler LifeDop - Anasthesia Endotracheal anesthesia under controlled respiration - Performing surgery: Two surgical... and poor results were found in only patients (4.3%) 3.3.7 Results of donating flap area condition Table 3.33: Condition of donating flap area during the follow-up period (n=47) Follow-up period... vein first, and then artery with 10/0 non-traumatic suture - Closing incision suture 10 + At the donating flap place: close the skin directly if the flap is ≤6 cm wide and cm wide, then close the

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