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Jourrnal of military pharmaco-medicine n09-2019 THE ROLE OF ENDOSCOPIC ULTRASOUND IN THE STAGING OF RECTAL CANCER Vu Hong Anh1; Nguyen Thuy Vinh1 SUMMARY Objectives: To evaluate the value of endoscopic ultrasound in the diagnosis of rectal cancer stage. Subjects and methods: Prospective, cross-sectional description study on 75 patients diagnosed with rectal adenocarcinoma by histopathology after surgery. Result: - Image of endoscopic ultrasound: Most tumors invaded the muscle layer (34.7%) and serosa (38.7%). There were 13.3% of tumors invading the fat layer. 34.7% at T2; 52% of tumors were in stage T3 and T4; 34.7% had lymph node. - Evaluation of invasion: Sensitivity, specificity and accuracy of endoscopic ultrasound were 83.3%; 92.8% and 92%, respectively. - Assessment of lymph node metastases: Sensitivity, specificity and accuracy of endoscopic ultrasound were 68.4%; 78.6% and 77.3%, respectively. Conclusion: Endoscopic ultrasound is a good method to diagnose, follow-up and evaluate the stage of rectal tumors quickly, safely and accurately. * Keywords: Rectal cancer; Histopathology; Endoscopic ultrasound. INTRODUCTION Evaluation of the stage of rectal cancer with endoscopic ultrasound (EUS) was first reported by Hildebrandt U and Feifel G in 1985 [8] and is now accepted as a method of initial selection to diagnose, follow-up, evaluate the stage of rectal tumors quickly, safely and accurately [9]. According to studies by foreign authors, the accuracy of EUS in diagnosing invasive levels (T - according to TNM classification) of rectal cancer is 80 - 95% compared with CT (65 - 75%). and MRI (75 - 85%); In determining lymph node metastasis of rectal cancer is about 70 - 75% compared with CT (55 - 65%) and MRI (60 - 70%) [6, 7]. Implementing a small needle biopsy (FNA) under the guidance of EUS increases the effectiveness of diagnosis of early stage T cases and suspects lymph nodes around the pot. Studies in Vietnam on EUS to diagnose the stage of rectal cancer are few and not systematic. Therefore, we conducted this study with the aims: Evaluation of the value of endoscopic ultrasound in the diagnosis of rectal cancer stage. SUBJECTS AND METHODS 1. Subjects. 75 rectal adenocarcinoma patients diagnosed by histopathology after surgery, treatment at the E Hospital from January 2013 to January 2019. 1. E Hospital Corresponding author: Vu Hong Anh (anhvh1979@gmail.com) Date received: 10/10/2019 Date accepted: 28/11/2019 281 Jourrnal of military pharmaco-medicine n09-2019 - Patient had no surgical treatment. * Standard selection: - Patient with rectal tumor was colonoscopy and biopsy to diagnose rectal adenocarcinoma by histopathology. - Patient was previously treated (surgery, radiation, chemicals). - Patients who did not agree to participate in the study. - Performed colorectal endoscopic ultrasound before surgery. 2. Methods. - Surgical treatment at the E Hospital. Cross-sectional descriptive study. - Results of postoperative histopathology were rectal adenocarcinoma. - Patients with bleeding/coagulation disorder. * Research targets: Characteristics of images of rectal EUS, assessment of tumor invasion, lymph node metastasis with postoperative histopathological results. - Patients with acute and chronic diseases contraindicated to colonoscopy. Data were processed by SPSS software 20.0. * Exclusion criteria: RESULTS 8([VALUE]%) 13([VALUE]%) 54([VALUE]%) Hypoechoic Hyperechoic Isoechoic Figure 1: Echogenic characteristics of tumors by EUS. Mostly tumors had hypoechoic (54 patients accounted for 72.0%). * Tumor invasion characteristics on EUS: Submucosa layer: 10 patients (13.3%); muscle layer: 26 patients (34.7%); serosa and subserosa: 29 patients (38.7%); fat layer: 10 patients (13.3%). 282 Jourrnal of military pharmaco-medicine n09-2019 Table 1: Characteristics of lymph node on EUS. Characteristics of lymph node metastasis Lymph node metastasis No of lymph node No. of patients Ratio (%) No 49 65.3 Yes 26 34.7 Total 75 100.0 1 node 5 19.2 2 nodes 7 26.9 3 nodes 8 30.8 3 - 6 nodes 6 23.1 Total 26 100.0 0.97 ± 0.17 cm (0.58 - 1.25) Size of node EUS detected 26 cases (accounting for 34.7%) of lymph nodes around the rectal, in which 20/26 cases of lymph node ≤ 3. Table 2: Classification of TNM stage by EUS. Classification of TNM stage T N No. of patients (n = 75) Ratio (%) T1 10 13.3 T2 26 34.7 T3 29 38.7 T4 10 13.3 Total 75 100.0 N0 49 65.3 N1 20 26.7 N2 6 8.0 Total 75 100.0 52% of tumors had invaded the serosa and subserosa (T3 and T4); lymph node metastasis also accounted for 34.7%. Table 3: Comparison of invasion level in EUS with pathology after surgery. Pathology Localized Invasion around Total p EUS n % n % n % Localized 64 92.8 1 16.7 65 86.7 Invasion around 5 7.2 5 83.3 10 13.3 Total 69 100.0 6 100.0 75 100.0 < 0.001 (*: Test of Fisher’s 2-side) Sensitivity, specificity and accuracy of EUS in diagnosis of tumor invasion levels were 83.3%, 92.8% and 92%, respectively. 283 Jourrnal of military pharmaco-medicine n09-2019 Table 4: Comparison of detection of lymph node by EUS and pathology after surgery. Pathology EUS Lymph node no cancer Lymph node cancer Total p n % n % n % Non-detected lymph node 44 78.6 5 26.3 49 65.3 Lymph node 12 21.4 14 73.7 26 34.7 56 100.0 19 100.0 75 100.0 Total 0.001 Sensitivity, specificity and accuracy of EUS in diagnosis of lymph node metastasis were 68.4%; 78.6% and 77.3%, respectively. DISCUSSION 1. Echo-density of tumors. In our study, mostly tumors had hypoechoic property (72.0%). On EUS, tumors often appear as a hypoechoic block. It is difficult to determine the degree of tumor invasion when it develops to the junction between the two layers of the colon wall, for example: when the tumor is adjacent between the submucose and the muscle layer (between T1 and T2) or between muscle and fat surround the rectum. A deep lesion at T1 stage may show abnormalities and the thickening of the submucosal layers on ultrasound causes difficulty when distinguishing from the surface of the tumor at stage T2. Explaining this, the authors suggested that the high resolution of the ultrasound probe can be detected but it is not possible to correctly distinguish the image of the hypoechoic inflammation around the tumor or whether it is a tumor. In addition, this also occurs when the tumor image is on a straight line twice or sharp corners create a tangent image. This difference is most common for stage T2, but on EUS the tumor may appear as at stage. 284 2. The extent of the tumor invasion. Evaluation of tumor invasion by endoscopic ultrasound is based on the extent of invasion of the tumor compared to the rectal wall. When conducting endoscopic ultrasound for 75 cases of rectal tumors, we found that only 10 patients accounted for 13.3% of the tumor invaded the submucosal layer; and most tumors invaded the muscle (34.7%) and serosa (38.7%). 8.0% of tumors invaded fatty tissue and 5.3% of tumors invaded the surrounding organs. Thus no cases of tumors were localized in the mucosa and muscularis, which means that no patients had indicated mucosal surface resection treatment by endoscopy, but all had indications for thorough cutting surgery treatment. Based on the determination of the extent of invasion of the tumor through the layers of rectum wall along with the use of a high frequency probe 5 - 12 MHz, it is possible to evaluate the stage of cancer on ultrasound according to phase TNM: + Stage of T0 tumor: There was no image of injury on ultrasound. + Stage T1 tumor: Limited lesions of the mucosa and submucosa, equivalent Jourrnal of military pharmaco-medicine n09-2019 to the period of Tis and T1, on ultrasound images, small tumors were often separated from the muscle layer. + Stage T2 tumor: Tumor invaded the rectal muscle layer equivalent to T2. + Stage of T3 tumor: Tumor invaded through muscle layer, equivalent to T3. + Stage of T4 tumor: Tumor invaded the surrounding organization equivalent to T4. Combining the above factors, when dividing the invasion level of tumor by TNM stage, we found that most tumors had invaded to the serosa and overcome serosa (T3 and T4), accounting for 52%; 34.7% of tumors were in stage T2 and 13.3% of tumors were in stage T1. Results of assessment of invasive levels of tumors in 75 cases, we found sensitivity, specificity and accuracy of EUS in the diagnosis of tumor invasion level were 83.3%, 92.8% and 92%. Our research results were consistent with many other studies. Ta Van Ngoc Duc et al (2018) [1] studied EUS before surgery in 30 patients with rectal cancer, the results showed the value of EUS in assessing the level of invasive tumors (stage T) compared with histopathology had a sensitivity of 96.15%, specificity 96.46%, accuracy of 93.33%. In a meta-analysis of de Jong E.A et al (2016) [5] in forty-six studies included 2,224 patient. Results showed that the gross accuracy for tumor invasion assessment was 75% for MRI, 82% for EUS and 83% for CT. If the T4 period was evaluated separately, the accuracy of EUS was 94%. Waage J.E et al (2015) [11] studied 120 cases of rectum cancer to give results of sensitivity, specificity and accuracy (with 95%CI) in the diagnosis of adenocarcinoma respectively 0.96 (0.90 - 0.99), 0.62 (0.40 - 0.80) and 0.90 (0.83 - 0.94). Badger S.A et al [2] conducted research from October 1999 to May 2004, 95 rectal cancer patients were assessed for cancer stage according to TNM before EUS treatment by 1 doctor who performed EUS only. The results showed that the overall accuracy of the T-stage evaluation was 71.6%. Sensitivity, specificity, positive predictive value and negative predictive value of EUS rated the T3 period were 96.6%, 33.3%, 70.4% and 85.7%, respectively. Zammit M et al [12] studied 78 patients with rectum cancer without difficulty in the implementation of EUS, the accuracy in diagnosis of stage T was 80% and 77% for stage N. While at 39 patients when implementing EUS, there were difficult problems such as causing rectal stenosis (23 patients), uncomfortable patients (8 patients), preparing patients before performing poor surgery (6 patients) and postoperative scarring (2 patients), the accuracy of the T-stage evaluation was 68%. 3. The value of EUS in the diagnosis of lymph node metastasis. Regional lymph node injury is one of the important factors in prognosis, so the treatment regimen will depend on lymphadenopathy. The problem is how to diagnose lymphadenopathy before surgery to build the best treatment regimen for patients. Methods such as rectal examination 285 Jourrnal of military pharmaco-medicine n09-2019 and endoscopic examination cannot assess lymphadenopathy. Diagnosis of anatomy is performed only after surgery, so it is valuable for retention. Lymph nodes appear as rounded or oval-shaped structures hypoechoic compared to fat around the rectum. Although metastatic lymph nodes tend to be larger than normal lymph nodes with a diameter of 3 - 5 mm, up to 50% of metastatic lymph nodes identified in histopathology may be less than 5 mm; up to 8% may be less than 2 mm [4]. In our study on endoscopic ultrasonography, 26 cases accounted for 34.7% with lymph nodes surround the rectum, in which 20/26 cases of lymph node number ≤ 3. The results of our study in 75 patients, after comparing with the histopathological results, showed that sensitivity, specificity and accuracy of EUS in diagnosis of lymph node metastasis were 68.4%; 78.6% and 77.3%. The results of our research were consistent with the research of other authors. Ta Van Ngoc Duc et al (2018) [1] studied EUS before surgery in 30 patients with rectal cancer, the results showed the value of EUS in assessing the level of invasive tumors (stage N) compared with histopathology had 85.04% sensitivity, 88.04% specificity, 91.1% accuracy. In a meta-analysis of de Jong E.A et al (2016) [5] in forty-six studies included 2,224 patients. Results showed that the accuracy for predicting the presence of lymph node metastasis was 72% for MRI, 72% for EUS and 65% for CT. The study by Badger S.A et al [2] was conducted on 95 rectal cancer patients 286 who were evaluated for cancer stage according to TNM before EUS treatment by a single EUS doctor. The results showed that the overall accuracy of the N-stage evaluation was 68.8%. Sensitivity, specificity, positive predictive value and negative predictive value of EUS assessing metastatic lymph nodes were 73.2%, 62.2%, 74.5% and 60.5%, respectively. Landmann R.G et al’s study [10] conducted EUS in 938 rectal cancer patients, of which 134 patients were treated with thorough removal surgery, without treatment of accompanying radiation. The results showed that the accuracy and specificity of EUS in the evaluation of stage N was 70%. EUS is more likely to not detect small metastatic lymph nodes. The size of metastatic lymph nodes and the accuracy of EUS are related to stage T. Early rectal damage is more likely to have small metastatic lymph nodes but EUS is undetectable, which partly explains the reason why is the high recurrence rate of rectal cancer patients only treated for surgical removal of the merely tumor. Zammit M et al [12] studied the role of EUS in assessing invasive tumors in patients with rectum cancer before to surgical treatment. EUS is conducted by a single ultrasound doctor. The results showed that the accuracy of EUS in 78 patients was not difficult to implement EUS was 77%. Meanwhile, in 39 patients who performed EUS, they had problems such as rectal stenosis (23 patients), uncomfortable patients (8 patients), preparing patients before performing the procedure not good (6 patients), and postoperative scarring (2 patients) accuracy in the N-stage evaluation is only 67%. Jourrnal of military pharmaco-medicine n09-2019 The study of Bali C et al [3] conducted over a period of 4 years in 33 rectal cancer patients, who was assessed the pre-operative TNM stage and compared with the postoperative pathology results. The results showed that the accuracy of EUS in assessing the N stage was 59%. CONCLUSION Endoscopic ultrasound is a good method to diagnose, monitor and evaluate the stage of rectal tumors quickly, safely and accurately. REFERENCE 1. Ta Van Ngoc Duc, Nguyen Ngoc Tuan, Tran Quang Trinh et al, Value of ultrasonography in assessing stage of rectal cancer on 30 patients undergoing rectal resection surgery at Binh Dan Hospital (01 - 2017 to 07 - 2017). 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