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MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY NGUYEN MINH TRONG RESEARCH OF CIRCUMFERENTIAL RESECTION MARGIN BY MAGNETIC RESONANCE AND PATHOLOGY IN SURGICAL TREATMENT[.]
MINISTRY OF EDUCATION MINISTRY OF HEALTH AND TRAINING HANOI MEDICAL UNIVERSITY NGUYEN MINH TRONG RESEARCH OF CIRCUMFERENTIAL RESECTION MARGIN BY MAGNETIC RESONANCE AND PATHOLOGY IN SURGICAL TREATMENT OF RECTAL CANCER Major: Gastrointestinal surgery Code: 9720104 SUMMARY OF THE PhD DISSERTATION OF MEDICINE HA NOI – 2022 THE WORK IS COMPLETED AT HANOI MEDICAL UNIVERSITY Science instructors: Assoc Prof., PhD Nguyen Xuan Hung Assoc Prof., PhD Pham Hoang Ha Reviewer 1: Assoc Prof., PhD Trieu Trieu Duong Reviewer 2: Assoc Prof., PhD Nguyen Quoc Dung Reviewer 3: Assoc Prof., PhD Dang Viet Dung The dissertation is defended at the Dissertation Assessment Committee of Hanoi Medical University at on , 2022 The thesis can be found at: National Library Library of Hanoi Medical University LIST OF AUTHOR'S PUBLISHED PAPERS RELATED TO THE DISSERTATION Nguyen Minh Trong, Nguyen Xuan Hung, Pham Hoang Ha Comparison of results of evaluaton of stage of rectal carcinoma cancer between imagine VietNam medical journal 2020, N02- Octobner: 51-54 Nguyen Minh Trong, Nguyen Xuan Hung, Pham Hoang Ha et al Clinical and histopathological characteristics of rectal cancer patients VietNam medical journal 2021, N01- July: 35-40 Nguyen Minh Trong, Nguyen Xuan Hung, Pham Hoang Ha et al The early results of radical surgery in treatment of rectal cancer VietNam journal of Medicine 2021, Vol 62 N05: 16-21 INTRODUCTION Necessary Rectal cancer is a common malignancy of the gastrointestinal tract, with an increasing trend According to GLOBOCAN 2020, the incidence of colorectal carcinoma was 732,210 cases (accounting for 3.8% of new cancer cases) and 339,022 deaths (accounting for 3.4% of all cancer deaths) Circumferential resection margin (CRM) in colorectal cancer was first proposed by P Quick (1986) on pathology, determined by measuring the closest distance of tumor, lymph node metastasis to the mesenteric fascia rectal The rate of invasive circumcision is about 7.2-25% Magnetic resonance with the advantage of better evaluation of soft tissue has been the consensus of researchers and research associations on rectal cancer in assessing the extent of tumor invasion, the degree of lymph node metastasis, the degree of invasion of the circumcision area, the extent of vascular invasion of the rectal wall, Accuracy, sensitivity and specificity of rectal MRI in evaluating wall invasion are 85%, respectively, 87% and 75% In Vietnam, magnetic resonance has been indicated in the assessment of the stage of colorectal cancer before surgery, but currently there is no study that fully evaluates the circumcfrential resection margin by preoperative MRI and compares it with the pathological results after surgery to confirm the relationship in the diagnosis of circumferential resection margin between MRI and pathology in order to reach the goal of choosing appropriate treatment methods in colorectal cancer in order to improve treatment effectiveness and reduce the risk of local recurrence and increased overall survival time, so we carried out a study on the topic: “Study of circumferential section by magnetic resonance and pathology in surgical treatment of rectal carcinoma” Objectives - Determining the value of magnetic resonance in the diagnosis of wall invasion, lymph node metastasis, invasion of circumferential resection margin (CRM) and disease stage of rectal carcinoma - Evaluating the results of surgical treatment of rectal carcinoma in the group of patients with circumferential resection margin by magnetic resonance and pathology Meaning of the study The results obtained through the study contribute to the specialty on the characteristics of magnetic resonance imaging, histopathology in the diagnosis of rectal carcinoma and the results after radical surgery to treat rectal carcinoma The topic has scientific significance and practical value, contributing to improving the quality of diagnosis and treatment, saving patients’ lives, and improving survival time in patients with rectal carcinoma Structure of thesis The thesis has 126 pages, including the following parts: Introduction (2 pages), Chapter (Literature of review 41 pages), Chapter (Subjects and methods 19 pages); Chapter (Results 30 pages); Chapter (Discussion) 32 pages; Conclusion pages The thesis has 43 tables, figures, 26 images and 165 references (28 documents in Vietnamese, 127 documents in English) CHAPTER LITERATURE OF REVIEW 1.1 Rectal anatomy and rectal circumferential resection margin 1.1.1 Rectal anatomy 1.1.2 Anatomy of the mesentery and rectal circumferential resection margin 1.1.2.1 Mesorectum The mesentery of the rectum is a compartment surrounding the rectum, located between the rectum and the mesenteric rectal fascia (the mesentery of the rectum) This compartment contains the superior rectal vessels, the superior rectal lymph node chain, and the nerves to the rectum from the inferior mesenteric plexus and loose fatty connective tissue Thus, the mesentery is a mass of fattyvascular-lymphatic tissue that surrounds the entire length of the rectum, is thick posteriorly and bilaterally, and is covered with a separate collagen fiber, known as the Mesorectal fascia (MRF), or in other words, the fascia propria 1.1.2.2 Some rectal fascia 1.1.2.3 Circumferential resection margin Circumferential resection margin (CRM) in rectal cancer was determined by measuring the proximal distance of tumor and lymph node metastasis to the mesenteric fascia, this concept was developed by P Quick et al (1986), at the University of Leeds, UK Many previous studies have recorded that the circumferential resection margin is positive when this distance is ≤ 1mm and has a worse prognosis than the circumferential resection margin > 1mm 1.1.2.4 Relating to anatomy and surgery in the treatment of rectal carcinoma * Anatomy of the posterior rectal wall * Anatomy of the lateral wall of the rectum 1.2 Diagnosis of rectal carcinoma 1.2.1 Clinical, subclinical characteristics 1.2.1.1 Clinical characteristics: 1.2.1.2 Subclinical characteristics * Colonoscopy: * Intrarectal ultrasound: * Computed tomography (CLVT): * Tests to detect cancer markers: 1.2.1.3 Magnetic resonance in the diagnosis of rectal cancer: - Tumor location: determined vertically from bottom to top (lower, middle or upper rectum) and according to the circumferential plane (according to the clock position), as well as length, relationship anterior peritoneal flexion and the distance from the lower border of the tumor to the anal margin to the anorectal junction, then, select the best surgical method Tumor locations were classified as lower third (0–5 cm from anal margin), middle third (>5–10 cm from anal margin) and upper third (>10 – 15 cm from the anal margin) - Tumor morphology: morphology of the tumor (nodule, ulcer, infiltration or infiltrative ulcer) Invasive diagnosis in situ (Wall invasion): The accuracy, sensitivity, and specificity of rectal MRI in the evaluation of wall invasion were 85%, 87%, and 75%, respectively Diagnosis of lymph node metastasis (N): Compared with the accuracy of MRI in diagnosing tumor invasion, the accuracy of MRI in assessing the degree of lymph node metastasis of rectal carcinoma is lower There were studies that suggest that lymph nodes measured on MRI with a size greater than mm had a high specificity in the assessment of lymph node metastasis To evaluate lymph node metastasis in rectal cancer, it is necessary to combine the evaluation of lymph node size characteristics and malignant morphological features including irregular border image (1), heterogeneous signal intensity (2), shape circle (3) When the lymph node size is mm in size, it is always considered to be suspected of lymph node metastasis Diagnosis of distant metastases (M): On MRI, distant metastases are graded as follows: M0: no distant metastasis; M1a: distant metastasis to an organ (liver, lung, ovary, non-regional lymph nodes ); M1b: metastasis more than an organ or peritoneal metastasis Diagnosing the circumferential margin: The circumferential margin, also known as the superior mesorectal fascia is best determined in the cross-sectional plane on magnetic resonance It presents as a low signal layer surrounding the rectum on T2-weighted images The mesentery of the rectum is composed of fatty tissue, blood vessels and lymphatic system, showing high signal in T2W phase of MRI 1.2.2 Pathology: 1.2.2.1 Macroscopic type: ulcer nodule, nodule, infiltration, besides, ulcerative, ring types 1.2.2.2 Microscopic type: World Health Organization (WHO) 2010 classification of rectal cancer 1.2.3 Stages of rectal cancer: 1.2.3.1 Invasive classification according to Dukes 1.2.3.2 TNM classification 1.2.4 Histopathology of mesorectal fascia and circumferential resection margin 1.3 Research of circumferential resection margin 1.3.1 History and concepts of circumferential resection margin In 1986, Quirke and colleagues at the University of Leeds - UK, in a study analyzing 52 surgical specimens for rectal cancer, introduced the concept of lateral resection margin when measuring the interval Tumors, lymph nodes closest to the cutting area ≤ 12mm The results of the analysis showed that the local recurrence rate was 85% in the group of patients with lateral resection and 3% in the non-invasive group The article was published in the Lancet (November 1986) 1.3.2 Methods of evaluating the circumferential resection margin 1.3.3 The role of circumferential resection margin in the treatment of rectal carcinoma In magnetic resonance imaging, the circumferential area can be determined by measuring the shortest distance between the rectal tumor and lymph node metastasis to the Mesorectal Fascia (MRF) MRF (+) when the distance is ≤ 1mm, and there is a risk when this distance is in the range of 1-2mm 1.4 Surgical treatment of rectal cancer 1.4.1 Principles of radical surgery - Resection of rectum with tumor and extensive mesenteric: for upper rectal cancer, it is at least cm below the tumor, with at least cm for middle and lower rectal cancer and the whole mesentery Cut over the tumor at least cm - Extensive lymphadenectomy: Dissect the mesenteric lymph nodes up to the base of the superior mesenteric artery or the inferior mesenteric artery and the iliac lymph nodes if there is evidence of metastasis - Repeat gastrointestinal circulation if indicated to ensure quality of life for the patient 1.4.2 Radical surgical method * Abdominoperineal resection: * Anterior resection * Abdominal-anal rectal surgery * Intersphincteric resection: * Hartman surgery: * Total mesenteric resection: This is considered the standard technique in surgical treatment of rectal cancer, total mesenteric resection for middle and low rectal cancers, and at least 5cm lower mesenteric resection below the tumor for upper rectal cancer is the standard designation 1.4.3 Results of radical surgical treatment 1.4.3.1 Close results after radical surgery * Anastomic leakage * Other accidents and complications: Some accidents and complications have been recorded in rectal cancer surgery such as: vascular damage, ureteral damage, bladder injury, vaginal injury, peritonitis, surgical site infection 1.4.3.2 Distant results after radical surgery * Anal sphincter dysfunction; Bladder dysfunction; Sexual function results: * Survival time, recurrence and metastasis after rectal cancer surgery: The ability to diagnose early and surgical treatment techniques as well as adjuvant treatment measures before and after surgery have actively contributed to prolonging the survival time after surgery as well as improving the quality of life of the patients Studies have shown that the survival rate after years, years of patients with rectal cancer undergoing radical surgery has increased significantly, the rate of local recurrence and distant metastasis after surgery has been much reduced CHAPTER SUBJECTS AND METHODS 2.1 Subjects Including patients diagnosed with rectal cancer with preoperative MRI scan, radical surgery treatment at Viet Duc Friendship Hospital and post-operative anatomical assessment, from October 2016 to May 2019 2.1.1 Criteria of selection - The patient was diagnosed with primary rectal carcinoma, determined based on the postoperative pathology results and the tumor location determined by flexible laparoscopy ≤ 15cm from the anal margin - Preoperative pelvic magnetic resonance imaging, classification of TNM stage and circumferential resection margin; radical rectal surgery + lymph node dissection and pathological examination, classification of TNM stage and circumferential resection margin - The patient consented to participate in the study 2.1.2 Criteria of exclusion - Have no rectal carcinoma or have other cancer from or more locations or distant metastases: liver, bone, lung Incomplete postoperative pathology results, assessment of TNM classification and circumferential resection margin; - The patient did not consent to participate in the study 2.2 Reaserch method The study was carried out by a descriptive prospective study All patients were staged by 1.5 Tesla preoperative magnetic resonance and compared with postoperative pathological results 2.2.1 Research indexes 2.2.1.1 General information - Age (years), sex (male/female) - Time from clinical symptoms to hospital admission - Clinical symptoms on admission - Physical symptoms: - Flexible colonoscopy: 2.2.1.2 Research on rectal cancer magnetic resonance imaging - Tumor location: - Distance of tumor to the anal margin: determined from the position of the lower border of the tumor to the edge of the anus, the unit is cm: - Tumor size: - Tumor thickness: - The extent of invasion of the rectal lumen of the tumor: - Physical features - Tumor enhancement properties Diagnosis of locally invasive (T) staging Characteristics of lymph node metastasis, degree of lymph node metastasis (N) Diagnosis of distant metastasis (M) Diagnosis of rectal carcinoma staging on MRI Invasive assessment of the CRM of rectal cancer on MRI 2.2.1.3 Research on the pathology of rectal cancer - Assessing tumor shape - Evaluation of the upper and lower section - Evaluation of the size of the rectal cancer - Assess the degree of invasion in the rectal lumen - Evaluation of the stage of rectal cancer according to TNM: based on AJCC 7th (American Joint Committee on Cancer) 2010 - Assess the integrity of the mesentery: based on the classification of Quirke et al (2009), divided into: complete, little integrity and incomplete - Evaluation of the CRM 10 3.1.2 Clinical characteristics Table 3.2 Characteristics of rectal digital examination Number (n) Rate (%) 17 15.60 No feel tumor 43 39.45 1/3 lower (≤ cm) Distance 1/3 middle (n=109) 43 39.45 (>5 – ≤ 10 cm) 5.50 1/3 upper (> 10 cm) 18 19.57 No mobility 44 47.83 Mobility (n=92) Mobile restrictions 30 32.60 Mobility 2.17 ≤ 1/4 circumference > 1/4 – ≤ 1/2 52 56.52 Degree of circumference invasion of the > 1/2 – ≤ 3/4 rectal lumen 37 40.22 circumference (n=92) Whole 1.09 circumference 7.61 Polyp 1.09 Ulcer Macroscopy 82 89.12 Nodule (n=92) 1.09 Infiltration 1.09 Ulcer – nodule Comment: The distance between the tumor and the anal margin was mainly in the lower 1/3 and the middle 1/3 The majority of rectal tumors had limited mobility with 47.83%, with no mobility with 19.57% Rectal digital examination revealed that rectal tumors invaded mainly from > 1/4 - 1/2 of the rectal lumen (56.52%), from > 1/2 - 3/4 of the rectal lumen circumference (40.22%) Mainly rectal tumors were in the form of nodule, accounting for 89.12% 11 3.2 Value of magnetic resonance in the diagnosis of wall invasion, lymph node metastasis, circumferential resection margin and disease stages of rectal carcinoma Table 3.3 Correlation of the degree of invasion of the rectal lumen between magnetic resonance and pathology Degree of invasion of the rectal lumen Pathology MRI ≤1/4 >1/4 – ≤1/2 (50.00) 31 (81.58) >1/2 – ≤3/4 (0.0) Whole Total (0.0) (15.79) (2.63) (5.56) (1.84) 38 (34.86) 54 (49.54) 15 (13.76) 109 (100) ≤1/4 (50.00) >1/4 – ≤1/2 (0.0) >1/2 – ≤3/4 (0.0) (12.96) 44 (81.48) Whole (0.0) (0.0) (60.00) Total (0.92) 39 (35.78) 59 (54.13) (40.00) 10 (9.17) * (Chi-square test) Comments: Magnetic resonance imaging was related to pathology in determining the extent of occupying the rectal lumen (p 1/4 - 1/2 of the rectal lumen had Se (79.49%), Sp (90.00%), PPV (81.58%), NPV (88.73%), Acc (86.24%) The extent of accounting for > 1/2 - ≤ 3/4 of the rectal lumen had Se (74.58%), Sp (80.00%), PPV (81.48%), NPV (72.73%), Acc (77.06%) The extent of occupying the entire rectal lumen was Se (60.00%), Sp (90.91%), PPV (40.00%), NPV (95.74%), Acc (89.07%) 12 Table 3.4 Diagnostic correlation of tumor invasion to the rectal wall between magnetic resonance and pathology Degree of invasion of the rectal wall Pathology MRI T1 T2 T3 T4 Total (0.00) (0.00) (0.00) (0.00) (0.00) T1 10 18 (22.22) (22.22) (0.00) T2 (55.56) (16.51) 10 67 84 (1.19) (7.15) T3 (11.90) (79.76) (77.06) T4a (0.00) (20.00) (60.00) (20.00) (4.59) T4 (0.00) (50.00) (50.00) (1.84) T4b (0.00) 21 75 109 (4.59) (7.33) Total (19.27) (68.81) (100) * (Chi-square test) Comment: Magnetic resonance imaging was related to pathology in determining the degree of wall invasion (p