MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE VIETNAMESE MILITARY MEDICAL ACADEMY PHAM VAN BINH THE STUDY IN APPLICATION OF LAPAROSCOPIC ABDOMINOPERINEAL RESECTION FOR TREATMENT OF LOW RECTAL CANCER Speciality: Gastrointestinal surgery Code: 62 72 01 25 Ph.D THESIS ABSTRACT HÀ NỘI - 2013 The thesis was completed in: Vietnamese Military Medical Academy Scientific supervisors: 1. Assistant Professor, Ph.D: Nguyễn Văn Xuyên 2. Assistant Professor, Ph.D: Nguyễn Văn Hiếu Thesis reviewer 1: Prof. HA VAN QUYET Thesis reviewer 2: Assoc Prof. PHAM DUC HUAN Thesis reviewer 3: Assoc Prof. TRIEU TRIEU DUONG The thesis was defended at the Council of Military Medical Academy at 13h30, 03/10/2013 Thesis can be found at: 1. National Library 2. Library of Military Medical Academy Introduction Rectal cancer is one of the common cancers, accounting for nearly a third of the colorectal cancer. Morbidity and mortality of colorectal cancer tend to increase on the world. Today, multidisciplinary treatment of rectal cancer includes surgery, chemotherapy and radiotherapy in which surgery plays an important role. For over two decades, laparoscopic surgery has clear advantages including less postoperative pain, faster recovery, shorter hospital stay. However, there are some questions: Could laparoscopic surgery achieve lymphadenectomy in oncologic principle? What is survival, recurrence, metastasis rate? At the present, studies on laparoscopic abdominoperineal resection under two aspects including lymphadenectomy and postoperative outcomes on the world as well as in Vietnam remain limited. Due to the above issues, we implemented the study "The study in application of laparoscopic abdominoperineal resection for treatment of low rectal cancer" with 2 goals: 1. Study lymphadenectomy in laparoscopic abdominoperineal resection for treatment of low rectal cancer. 2. Evaluate results of laparoscopic abdominoperineal resection (LAPR) for treatment of low rectal cancer and some factors associated with survival. New main scientific contribution of the thesis Thesis is done at K Hospital – Biggest Cancer Center in Vietnam for studying lymphadenectomy and evaluating the results of LAPR for treatment of low rectal cancer. The thesis reports lymphadenectomy results of laparoscopic surgery ensures oncology principles through analysis of number of harvested lymph-nodes. The average harvested lymph-nodes is 14.6 per patient. Among them, there are 5.5 mesenteric lymph nodes, 5.4 lymph nodes near tumor; 3.7 lymph nodes (LN) of 1 superior rectal artery. The overall rate of lymph node metastasis is 31.11%. Stage N1 is 17.78%, N2a is 2.22%, and N2b is 11.11%. Metastasis rate of 1 LN station was 14.1%, 2 LN stations is 9.6%, 3 stations is 7.4%. Patients treated with preoperative radiotherapy have less harvested lymph-nodes and lower rate of lymph node metastasis. Thesis reports early results in term of surgery: average duration of surgery is 133 minutes, average blood loss is 13, 6 ml, accident rate is 1.48%, complication rate is 2.8%, no open conversion surgery and no intraoperative and postoperative death. The long- term results in terms of oncology is good. Average postoperative survival rate is 33.3 months. There is no local recurrence and metastasis. Preoperative radiotherapy, lymph node metastasis, stage of disease and age are some factors related to postoperative survival rate. STRUCTURE OF THE THESIS The thesis consists of 123 pages: 2 introduction pages, 39 background pages, 19 pages for study methods, 24 pages for results, 37 discussion pages, 2 pages for conclusion. There are 37 tables, 16 diagrams, 24 pictures, and 149 references, including 30 in Vietnamese, 119 in foreign languages. CHAPTER 1 – OVERVIEW 1.1. Anatomy application in rectal cancer surgery 1.1.1. Anatomical landmarks: The rectum is the last segment of the gastrointestinal tract connecting with sigmoid colon at the third sacral vertebra and ending at the edge of the anus. 1.1.2. Mesentery of rectum: Mesentery of rectum, fat fiber tissue is located within the limits of the rectal muscle and visceral perineum of pelvis, covering 3/4 2 circumference of the rectum. 1.1.3. Nerve, blood vessels of the rectum: The rectum is supplied by 3 main vessel bundles: superior rectal, middle rectal, and inferior rectal artery. Autonomic nerve control rectal secretions, motor nerves control movement of anal sphincter. 1.1.4. The lymphatics of the rectum: * Lymphatics of mesentery of rectum * Lymphatics of ischiorectal cavity * Lymphatics of rectal wall peritoneum. Lymphatic drainage: * Lymphatic vessels from superior half of rectum drain to para rectal nodes and from there to inferior mesenteric and lumbar nodes * Lymphatic vessels from the inferior half of the rectum Travel with the middle rectal vessels to the internal iliac nodes Anastomose with the lymphatics of the anal canal 1.2. Histopathology of rectal cancer 1.2.1. Gross appearance: ulcers, infiltration and other type. 1.2.2. Micro appearance: Classification by the World Health Organization (WHO 2000): Adenocarcinoma accounting for over 98%, carcinoid tumors, lymphoma, mesenchymal tumors, GIST, Kaposi Sarcoma. 1.2.3. The natural progression of colorectal cancer: Cancer cells spread along the gastrointestinal tract into the submucosal layer. From primary tumor, cancer cells can spread to regional lymph nodes and distant metastases to the liver, lungs, brain as well as invade nearby organs. 3 1.2.4. Evaluating stage of rectal cancer E. Dukes offer the common, simple staging system. In 1954, the AJCC established TNM system for stage evaluation for most cancers. 1.3. Diagnosis of rectal cancer 1.3.1. Signs and Symptoms: Abdominal pain, bowel habit change. Digital rectal examination is important to assess rectal tumors. 1.3.2. Investigations: * Colorectal endoscopy: biopsy to identify histopathology. * Diagnostic Imaging: X-ray of the colon with radio-contrast agent has switched to endoscopy, abdominal ultrasound to find out liver, peritoneal metastasis. Endorectal ultrasound assess T stage and N stage. CT scanner is accurate for T stage from 50% to 90%, for N stage from 70% to 80%. Pelvis magnetic resonance imaging (MRI) evaluate T stage and N stage with a sensitivity of 95%, a specificity of 90%. PET-CT find out early postoperative recurrence and distant metastasis. * CEA: Monitoring local recurrence and distant metastasis. 1.4. Treatment of rectal cancer 1.4.1. Surgery 1.4.1.1. Principles of radical surgery (R0) * Remove entire primary rectal tumor. * Remove invaded organs as well as metastatic lesions. * Lymph nodes dissection. 1.4.1.2. Surgical types: depend on disease stage, patient condition, the ability of the surgeon. According to the nature of the treatment, the type of surgery: * Radical surgery 4 * Pelvic exenteration surgery * Palliative surgery 1.4.1.3 The open surgery of rectal cancer: * Transanal tumor resection * Low anterior resection * Abdominoperineal Resection * Surgery for complications of rectal cancer 1.4.1.4. The laparoscopic surgery of rectal cancer: Today, with the perfection of surgery skills and endoscopic equipment, all open surgery of rectal cancer is switched to laparoscopic surgery. * Laparoscopic low anterior resection. * LAPR. * Hartmann Surgery. * Sphincter preservation surgery. 1.5. Adjuvant treatment for rectal cancer: * Chemotherapy: improving survival. * Radiotherapy: reducing the incidence of local recurrence and improving disease free survival, so multidisciplinary treatment have become the standard treatment in rectal cancer. 1.6. Study situation of LAPR on the world and inVietnam 1.6.1. On the world The number of LAPR studies are limited. * In 2005, Aziz.O review literature from 1993 to 2004. There are 22 studies with 2071 patients, only 8 studies mentioned laparoscopic lymphadenectomy in LAPR. * According to major report by Wiley Publishers in 2008, there are 33 clinical trials from 1988 to 2007 on 46 medical journals, among them 6 studies on 5 lymphadenectomy in LAPR, 12 studies on 5 year survival in LAPR with 3346 patients. * Lourenco.T, Health Research Institute of Britain in 2008 review laparoscopic surgery compared with open surgery on 4500 patients from 1997 to 2005 on the world. 12 studies mentioned lymphadenectomy but did not regard to LAPR. Some larger ongoing study on LAPR: * Study of Japan Cancer Research Group will finish by 2014. * European Colorectal Cancer Research Group will finish by 2017. * Study of United States Cancer Surgeon Association is going to report in 2013. 1.6.2. In Vietnam From 2003 to 2012, mainly focusing on perfecting surgical techniques such as removal of entire mesentery of rectum, preservation of nerves and urogenital fuction. Recently there have been some researches on LAPR. But these has not really focused on the role of lymphadenectomy and postoperative results. Thus LAPR still need further studies to confirm that LAPR is a standard option in the treatment of low rectal cancer. CHAPTER 2 - SUBJECTS AND METHODS 2.1. Study subjects: Patients with low rectal cancer at K Hospital from 01/01/2009 to 31/12/2011 underwent curative LAPR, follow up to 30/06/2012. 2.2. Research Methodology 2.2.1. Methods: prospective descriptive study (cross-sectional non-control). 2.2.2. The formula for calculating sample size: The minimum sample size was calculated as following: 6 n = (1.96) 2 x 0.056 x 0.944 / (0.05) 2 = 81.2 patients According this above formula, minimum sample size are 82 patients. 2.3. The study targets: the clinical, pathological, investigation characteristics 2.3.1. The clinical characteristics 2.3.2. The pathological, investigation characteristic 2.4. LAPR and lymphadenectomy process 2.5. Assessment results 2.5.1 Lymphadenectomy results * Total number of harvested lymph-nodes on 135 patients. * The average number of lymph nodes per 1 patient (mesenteric lymph nodes, lymph nodes near tumor, lymph nodes of superior rectal artery). * Overall rate of lymph node metastasis, metastasis rate of LN stations, LN stages. * The average number of lymph nodes per 1 patient and lymph node metastasis rate of patients with and without receiving preoperative radiotherapy 2.5.2 Early Results * Operation time, estimated blood loss. * The surgical complications: bleeding, urinary, intestinal damage. * The postoperative complications: bleeding, intestinal obstruction, infection, abscesses, bladder paralysis * Time using IV or IM algenesthesia, bowel peristalsis, and length of hospital stay. 7 * Mortality due to surgery: in 30 days after surgery. 2.5.3. Delayed results and some related factors 2.5.3.1 The postoperative survival by Kaplan-Meier Postoperative follow up every 3 months for first year, followed by every 6 months in next 2 years, and every year from the fifth year. Results of treatment at the end of the study: * Number of alive patients, died patient. * Rate of local recurrence, distant metastasis, trocar holes recurrence. * The median survival. * The average survival at 6 months, 12 months, 24 months, 36 months. 2.5.3.2. Analysis on factors related to survival * Age ≤ 60 years and> 60 years old. * Disease stage. * N stage. * Preoperative Radiotherapy. 2.6. Data Analysis: Data were collected from medical records. All the data is analyzed by Excel 5.0 and SPSS 15.0. Evaluating postoperative survival rate by Kaplan-Meier method. Compare the differences between quantitative variants by T test, and categorical variants by chi-square test with 95% accuracy (p <.05). CHAPTER 3 – RESULTS 3.1. General Characteristics * Age, sex: 135 patients with mean age 55.3. 69 male, 66 female. Rural: 98 - Urban: 37. 8 [...]... rectal artery : 4.2 nodes) and lymph node metastasis rate was 37.9% 19 4.4 Results of LAPR 4.4.1 Early Results * The duration of surgery: reflecting the skill of the surgeon, the operating time will decrease when the level of technical perfection increases According to Soper (2009) surgeons specializing in colorectal laparoscopic surgery spend 120278 minutes in LAPR The largest study as COLOR in the. .. the surgery history of low rectal cancer Laparoscopic TME that we do in our study showed the same advantages as described by foreign authors Pelvic lymphadenectomy is still debate on the world today Japan is the first one in systematic pelvic lymphadenectomy, but the rate of genitourinary complications such as in the study of Takahashi at Tokyo Institute of Cancer are up to 40% But the European-American... LIST OF PUBLICATIONS SHOWING OF THESIS RESULTS 1 Pham Van Binh, Nguyen Van Hieu, Nguyen Van Xuyen (2012) “Lymphadenectomy in LAPR for treatment of low rectal cancer at K Hospital”, Vietnam Journal of Medicine, (1), p.11 – 13 2 Pham Van Binh, Nguyen Van Hieu, Nguyen Van Xuyen (2012) “Complications of laparoscopic surgery for colorectal cancer in our series of 377 cases at Hospital K”, Vietnam Journal of. .. Almost studies in Viet Nam and on the world analyze overall metastatic rate without detailed analysis on metastasis lymph nodes classified according to stations and stage How preoperative radiotherapy influenced the rate of lymph node metastasis in low rectal cancer is the subject of major concern in the world cancer conference The large study in Europe, Japan, the United States show the number of harvested... 5.5), lymph nodes of superior rectal artery was 3.7 This result is similar to the foreign authors Lymph node metastasis in rectal cancer also follow the principle of lymphatic metastasis in cancer from the primary tumor to near stations and go further Our results also follow this principle, Metastasis rate of 1 LN station was 14.1% , 2 stations is 9.6%, 3 stations is only 7.41%, there is no skip metastasis... 4.3.1 The number of harvested lymph nodes Laparoscopic lymphadenectomy in LAPR has not been emphasized According to AJCC-2010, the number of harvested lymph nodes must be at least 12 new lymph nodes for evaluating N stage Among 135 patients with low rectal cancer in this study, the number of harvested lymph nodes are 1977, the average number of lymph nodes per 1 patient is 14.6 (preoperative radiotherapy... different in 2 groups Today, the cancer surgeon as Bleday at the University of Texas, Garcia-Aguilar in California and Milsom have consensus to tie off at division of superior left colon artery that is enough for LAPR Our technique also follows this principle 1982 Heald introduced the concept of Total mesorectal excision (TME) that reduced relapse rate from 15% - 30% to 4% This is an important change in the. .. without radiotherapy is16) 4.3.2 Metastasis lymph nodes classified according to stations There is a century history of rectal cancer surgery, but maps of lymph node metastasis still have been studied Galandiuk in 2005, Pirro in 2008 reported 80% of lymph nodes in rectal mesentery In this study, we obtained an average number of mesorectal lymph nodes was 10.9 (lymph nodes near tumor was 5.4 and mesorectal... will be lower In this study, patients in stage III group is also in the group of lymph node metastasis, so overall survival in 2 groups is the same This 21 means that the median overall survival in group with stage III was 28.42 months lower than group with stage II (33.06 months) There is no signigficant statistical differences (p > 0.05) * Preoperative radiotherapy: Rectal cancer is a typical for multidisciplinary... cancer is a typical for multidisciplinary treatment in cancer Almost studies confirm the role of preoperative radiotherapy in improving overall survival and reducing local recurrence rate In our series of 135 patients, the median overall survival in group with preoperative radiotherapy was 33.34 months higher than those without preoperative radiotherapy (30.74 months) The difference is statistically significant . lymphadenectomy in laparoscopic abdominoperineal resection for treatment of low rectal cancer. 2. Evaluate results of laparoscopic abdominoperineal resection (LAPR) for treatment of low rectal cancer. limited. Due to the above issues, we implemented the study " ;The study in application of laparoscopic abdominoperineal resection for treatment of low rectal cancer& quot; with 2 goals: 1. Study lymphadenectomy. MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE VIETNAMESE MILITARY MEDICAL ACADEMY PHAM VAN BINH THE STUDY IN APPLICATION OF LAPAROSCOPIC ABDOMINOPERINEAL RESECTION FOR TREATMENT OF