M INISTRY OF EDUCATION AND TRAININGM INISTRY OF DEFENCE
108 IN STITU TE OF C LINI C A L MEDI C A L AN D P HA R MAC EU TI CA L SCI EN C ES
NGUYEN TO HOAI
RESEARCH ON RECTAL RESECTION LAPAROSCOPY
COMBINED PREOPERATIVE SHORT-COURSE
RADIATION TO TREAT RECTAL CARCINOMA
Speciality: Gastrointestinal Surgery
Code: 62720125
ABSTRACT OF MEDICAL PHD THESIS
Ha Noi – 2020
THE THESIS WAS DONE IN:108 INSTITUTE OF CLINICAL MEDICA L AND PHA RMACEUTICAL SCIENCES
Supervisor:
1. Ass.Prof.PhD. Trieu Trieu Duong
2. Ass.Prof. PhD. Le Ngoc Ha
Reviewer:
1. ...............................................................................
2. ...............................................................................
3. ...............................................................................
This thesis w ill be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences
Day Month Year 2020
The thesis can be found at:
Institute of Clinica l Medica l and 1. National Library of Vietnam 2. Library of 108 Pharmaceutical Sciences
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INTRODUCTION
Rectal cancer is a fairly common disease in the world and is on the rise in developing countries. According to Globocan statistics, in 2018 there were 704,376 cases of cancer, accounting for 3.9% of cancer diseases, of which 310,394 patients died, accounting for 3.2% of the total cancer deaths.
In the world, there have been many
studies on preoperativeshort-course radiation combined with total mesorectal excision to treat rectal cancer.Studies show that the regimen has a short duration of treatment, low treatment costs and is easy to apply while effectively reducing local recurrence rates by about 50% compared to the simple surgery group and the effectiveness of oncology to the equivalent of long-course.
Summary of studies in Vietnam, many previous studies on rectal cancer have not been indicated for neoadjuvant treatment. The current prevailing treatment before surgery is long-term radiation therapy, the total time of wa iting for surgery to be prolonged, expensive and difficult for patients to follow the regimen.
Based on
the advantages of preoperative short-course radiationsuch as short treatment time, low cost of treatment, ease of application and advantages of laparoscopic surgery with the desire to improve the quality and reduce the recurrence rate in the treatment of rectal cancer. We perform this study to:
1. Describe the stage of disease in patients with rectal carcinoma who received preoperative short-course radiation.
2. Evaluate the results of laparoscopic surgery combined with preoperative short-course radiation to treat rectal carcinoma.
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CONTRIBUTIONS OF THE THESIS
radiationtreatment short-course preoperative
This is the first thesis in Vietnam that fully describes the stage of disease and the results of laparoscopic rectal excision combined rectal carcinoma. - Stage of the disease: The stage of pre-surgery disease according to MRI meets stage II, III respectively 16.4% and 83.6%, according to the CT stage II, III respectively are 12.9% and 87, first%. The stage of postoperative disease stage I, II, III was respectively 14.3%, 64.3% and 21.4%. - Surgical results:LAR procedure was 74.3%, APR procedure was 25.7%. Ileostomy rate was 53.8%. Intraoperative complication was 5.7%, serious postoperative complication was 12,1%. Mean operative time was 134.1 ± 32.4 minutes. Mean postoperative time was 10,7±4,6 days. Complete and nearly complete mesorectum were 63.6% and 36.4% respectively. Mean distal resection margin was 24.5 ± 13.6 mm. Distal margin with negative was 98.0%. Circumferential resection margin with negative was 98.5%. Overall survival and disease-free survival were 26.7 ± 9.6 months and 25.2 ± 10.9 months respectively. Recurrence rate was 12.1%. Late toxicity of the preoperative radiotherapy common grade 3 was 12.9%.
The above-mentioned contributions are
realistic and practical, provide another option for surgeons in their treatment of rectal cancer. The research has provided new contributions, confirms the safety, feasibility and efficacy in reducing complication rates and ensuring oncologica l principles of laparoscopic rectal excision combined short-course radiation in treating rectal cancer. STRUCTURE OF THE THESIS
The thesis consists of 113 pages: 2-page questions, 33-page overview, 19-page research objects and methods, 27-page research results, 32-page discussion, 2-page conclusions, 1-page request. Research works, 34 tables, 9 charts, 18 images. 113 references, of which 13 are in Vietnamese and 100 are in foreign languages.
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Chapter 1. OVERVIEW
1.1. Rectal anatomy 1.1.1. Rectum
The rectum is the continuation of the sigma colon to the anal canal, about 12 to 15 cm long. In women, the anterior of rectum is associated with the posterior vaginal and cervical wall. In men, rectum is located behind the bladder, vas deferens, seminal ves icles and prostate gland. 1.1.2. Atery
The blood supply enters the rectum posteriorly. The upper rectum is supplied by the superior rectal artery (SRA), a branch of the inferior mesenteric artery (IMA). The middle and lower rectum are supplied by the middle rectal artery and inferior rectal artery, respectively, which branch from the anterior division of the internal iliac artery and/or the pudendal artery 1.1.3. Venous and lymphatic drainage
The pathways for the lymphatic and venous drainage of the rectum are cephalad and lateral.The lymphatic drainage of the upper two-thirds of the rectum is along the pathway of the superior hemorrhoidal vein, cephalad to the inferior mesenteric nodes, and the paraaortic nodes. The lymphatic drainage of the lower third of the rectum is cephalad as well as lateral along the middle hemorrhoidal vessels to the internal iliac nodes. There are no communications between the inferior mesenteric and internal iliac lymphatics. In women, lymphatic drainage above the dentate line also includes the posterior wall of the vagina and reproductive organs. Below the dentate line, the drainage is along the inferior rectal lymphatics to the superior inguinal nodes and along the pathway of the inferior rectal artery. 1.1.4. Nerve
All branches of the pelvic region are located between the peritoneum and inner pelvis. The nerve branches may be damaged or severed during rectal removal. 1.1.5. Mesorectum
The fascia propria is an extension of the pelvic fascia and encloses the rectum, adipose tissue, blood, and lymphatic vessels. It
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is more pronounced laterally and posteriorly and forms the lateral ligaments of the rectum. In 25 percent of patients, the lateral ligaments contain branches of the middle rectal artery and venous plexus.
The rectum is not suspended by a true mesentery (ie, two layers of peritoneum that suspend an organ). The "mesorectum" is perirectal areolar tissue that is thicker posteriorly and contains the terminal branches of the inferior mesenteric artery 1.2. Pathology 1.2.1. Macroscopic Rectal cancer consists of 3 main types : fungating/polypoid,
ulcerfungating/ulceroinfiltrative, infiltrative 1.2.2.Microscopic
According to Halminton: 98% are adenocarcinoma. Less common are lymphoma (1.3%), carcinoid (0.4%) and connective carcinoma (0.3%). 1.3. Diagnosis 1.3.1. Clinical The first common symptom is a bloody stool. Another symptom of UTTT is natural anal bleeding or defecation.
Rectal examination in addition to determining the location and size of the tumor, can also assess the invasion of the tumor, and also check nearby organs such as sphincter, prostate, vagina ... 1.3.2. Subclinical 1.3.2.1. Colonoscopy
Colonoscopy is the most accurate diagnostic method for colorectal cancer. Proctoscopy can accurately determine the distance between the distal tumor margin, the top of the anorectal ring, and the dentate line.It also allows the tumor biopsy to be performed. 1.3.2.2. Imaging Valuable imaging diagnostics help assess local tumor lesions
and metastases help to indicate treatment. - Local imaging may include preoperative CT scan, MRI or endoscopic ultrasound. For some early stage adenomas (cT1) there is a risk of lymph node metastasis (<2%), according to patient assessment guidelines after excision.
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- Evaluation for distant metastases: According to 2016 NCCN Guidelines, CT with intravenous (IV) contrast, chest imaging are available to a ll patients when they are first diagnosed with cancer or PET-CT. 1.3.3. TNM Staging
Diagnosis of the rectal cancer stage is usually based on physical examination, biopsy and imaging tests such as CT scans, MRI and endoscopic ultrasound.
Assess according to the 2017 American Joint Committee on Cancer(AJCC) 2017, based on tumor lesions, lymph nodes and distant metastases (TNM). 1.4. Study the stage of disease of patients with rectal carcinoma who received short-course preoperative radiation 1.4.1. World studies using There have been many
short-course preoperative radiationcombined with surgery to treat advanced rectal cancer (invasive tumor level T3-4 or metastatic N1-2 lymph node) showing the effectiveness such as reducing local recurrence rates by more than 50% compared to surgery alone and in some studies have shown to help prolong life while reducing post-radiation toxicity, cost and duration of treatment.
Two randomized studies were Dutch TME and MRC CR07 conducted comparisons of short-course preoperative radiation thensurgery immediately with surgery alone with se lective treatment of traditional postoperative radiotherapy for patients at risk high. In the first report of Marijnen, the group short-course preoperative radiationwith TME surgery, there were 662 patients, the stage Iwas 34%, the stage II was 29% and the stage III was 37%. The MRC CR07 study included 1350 rectal cancer patients with stages I, II, III and IV, respectively 31%, 28%, 40% and 1%. Evaluation of results after 3 years after surgery showed that the radiation group improved the recurrence rate (5% with 11%).
In the phase 3 randomized study, Pas et al. (2013) had 412/699 patients in the laparoscopic surgery group who received short-course preoperative radiation. In the laparoscopic surgery group, preoperative staging I, II, III were 30%, 31% and 38%,
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respectively. Evaluation of postoperative results has the same stage I, II and III are 34%, 26% and 34%, respectively.
The study of Schiphorst et al (2014) on 86 patients who had laparoscopic surgery to TME had 51% the patients who had short- course preoperative radiation. Evaluation of postoperative stage in laparoscopic group met stage I was 26%, stage II was 20%, stage III was 42% and stage IV was 7%.
In the study of Stevenson et al (2015) in the group of TME laparoscopy there were 50% of patients received short-course preoperative radiation. Patients who were evaluated for invasive cT4 tumors by MRI or endoscopic ultrasound were excluded from the study. In the laparoscopy group, cT1, cT2 and cT3 were 8%, 29% and 63%, respectively. The lymph node status of cN0, cN1 and cN2 were 45%, 34% and 13%, respectively. Evaluation after surgery met pT0 (no tumor cells) was 14%. pT1, pT2, pT3 and pT4 were 10%, 28%, 44% and 5% respectively. Evaluation of postoperative lymph node metastasis to pN0, pN1 and pN2 were 62%, 28% and 10%, respectively. The average tumor diameter is 30 mm (20-40 mm).
In the study of Minama H et al (2017) on 28 patients, conducting short-course radiotherapy followedby laparoscopic TME for cStage II/III low rectal cancer. Preoperative staging had 35.7% in stage II, 28.0% in stage IIIa and 39.3% in stage IIIb. None of the patients had tumor in stage cT1/2, 89.3% in stage cT3 and 10.7% in stage cT4. Evaluation of lymph node metastases cN0, cN1, cN2 and cN3 were 39.3%, 21.4%, 7.1% and 32.1%, respectively. 1.4.2. Vietnam
In Vietnam, radiotherapy has been used for the treatment of rectal cancer for several decades and there are studies showing the improve clinical effectiveness of preoperative radiotherapy to symptoms. In study of Lam Viet Trung, 18.7% of patients received short-course preoperative radiationwith the results of the stage of postoperative I, II and III respectively 20.3%, 35.9% and 43, 6%. However, there has been no systematic study of the stage of disease in patients with rectal cancer who short-course preoperative radiation
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1.5. Research on the res ults of laparos copic resection surgery combined with short-course preoperative radiationto treat rectal carcinoma. 1.5.1. World
The study of Minama H et al (2017) short-course radiotherapy followedby laparoscopic TMEfor rectal cancer showed that the rate of completion of radiation treatment plan was 100%, no patients showed acute toxicity. About surgical method, 39.3% of patients had extremely LAR, 14.3% of patients had sphincterectomy, 32.1% had APR and 3.6% had Hartmann procedure. No patients had to undergo convertion to open surgery. The average operative time was 379 minutes (175-890 minutes). The average blood loss was 90 ml (0-1185 ml). The complication in 3-4 degrees is 10.7%. In the phase 3 randomized study, Pas et al. (2013) had 412/699 patients in the laparoscopic surgery group who received short-course preoperative radiation. The rate of LAR was 70%, the rate of diverting ileostomy was 35%. Intraoperative complication was 12%. The rate of convertion to open surgery was 17%. Patients in the laparoscopic group had an average blood loss less than the open surgery group (200 ml vs 400 ml; p <0.0001). However, the average operative time in the laboratory group was 240 minutes (184-300 minutes) lasted longer than the open surgery was 188 minutes (150-240 minutes). Postoperativey complications (if at least 01 complication) is 40%. In the study of Stevenson et al (2015), in the laparoscopic group, 50% of patients were given short-course preoperative radiation. LAR rate was of 89%. The rate diverting ileostomy was 68%. The average operation time is 210 minutes (163-253 minutes). The average blood loss was 100 ml (50-200ml). Complications at level 3 and 4 were 21%. The rate of convertion to open surgery was 9%. The average hospital stay was 8 days (6-12 days). The operative death rate was 0.6%. The study also showed that laparoscopic TME no more difficult in patients after short-course radiation therapy, large tumors or high BMI.
A study of Schiphorst et al (2014)had 51% of short-course preoperative radiation. The rate of LAR was 65%, the rate of diverting ileostomy was 57%. The blood loss were significantly
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lower in the laparoscopic group compared to open surgery (200 ml vs 457 ml; p <0.001). Average operative time did not differ significantly in the laparoscopic group compared with open surgery (146 minutes with 130 minutes; p = 0.06). The rate of complications was 27%. The rate of reoperation was 14%. The average hospital stay time was 7 days (3-141 days). Operative death has 1 patient. The oncology results of applying laparoscopic TME after short-course preoperative radiationalso showed very encouraging results.
The study of Minama H et al (2017), the radical rate was 100%. The average number of lymph nodes was 27 (12-71 lymph nodes). Response after radiation the author found that the grade 1 was 85.7%, grade 2 and grade 3 were 7.1%, respectively. Research by Pas et al. (2013) showed that the rate of complete mesorectum was 88% and the circumferential resection margin with positive was 10%. The average distal resection margin was 3cm. In a trial study in Australia (AlaCaRT), Stevenson et al reported that negative circumferential resection margin was 93%, the negative distal resection margin was 99%, the rate of complete mesorectum was 82%. In the study of Schiphorst et al (2014), the rate of circumferential resection margin with positive was 5%, the average number of lymph nodes was 13 (1-25 nodes). The follow-up results after 18 months, the recurrence rate in the radical group was 2.6%, the distant metastasis rate was 8% and the death rate from cancer was 5%. 1.5.2. Vietnam
In Vietnam, application laparoscopic surgery for rectal cancerfollowing the development trend of the world, from the early 2000s to the present, has been performed at many surgical centers across the country. However, there are very few reports on the application of laparoscopic TME combined with short-course preoperative radiationto treat rectal carcinoma.
Results of studies on preoperative radiation treatment rectal cancer: Pham Quoc Dat evaluated the results of long-course radiotherapy combined with sugeryfor rectal carcinoma showed the advantages of preoperative radiotherapyas average survival was 70 months while preoperative and postoperative radiotherapy was 46.5
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months and postoperative radiotherapy was 36 months. Pham Van Binh (2017) studied 175 patients with 55 patients had preoperative radiotherapy found that the syndrome after rectal excition was 25.6% and radiotherapy was also one of the factors related to syndrome.
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Chapter 2. SUBJECTS AND METHODS
2.1. Studying subjects
The research was conducted on 70 patients rectal cancer stage II, III treated by laparoscopic rectal excision combined short- course radiation at 108 Military Central Hospital from August 2015 to February 2019. 2.1.1. Selective criterial - Patient was diagnosed with middle and lower 1/3 rectal carcinoma, based on clinica l, endoscopy, CT, MRI and histopathology. - Patients with rectal cancer stage II, III. - Patients were prescribed short-course preoperative radiation - Patient was patients were treated with laparoscopic total mesorectal excision, with or without preserving sphincter, at 108 Hospital. - Patients with ASA ≤ 3 and have no contraindications for laparoscopy. 2.1.2. Exclusive criterial - Patients with contraindications to radiation therapy. - Patient did not fully perform the Sshort-course preoperative radiation therapy. - Patients have complications during radiation therapy (bleeding, obstruction). - Patients with other cancers. - Patients with contraindications to general anesthesia or inoperative. - Patients do not agree to participate in the study. 2.2. Reseach methodology 2.2.1. Design and sample size - Prospective, interventional, follow-up. - The minimum sample size is calculated according to the formula for calculating a sample size for a ratio. With 95% confidence, the rate of conversion to open surgery in the literatures was 4%, the minimum sample size in the study is 60 patients. 2.2.2. Short-course preoperative radiation for rectal cancer 2.2.2.1. Indications - cT3, cN0, cM0 or any cT, cN1-2, MRF (-). 2.2.2.2. Planning
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- Imaging CT with injection and contrast medicine on Optima CT580 RT specialized simulation machine (GE, USA). Transfer the simulated CT image to the drawing computer and make treatment plan on Eclipse 10.0 software. 2.2.2.3. Treatment patients on Varian CX 2100 - Instruct patients to drink 600 ml of water 30 minutes before treatment. The patient on prone position on the treatment table using the Belly Board based on the markers on the - Treatment regimen 1 time / day x 5 days / week. 2.2.3. Laparoscopic total mesorectal excision
The patient was assigned a laparoscopic total mesorectal
excision within 10 days from the first radiation date. 2.2.3.1. Indications. - The patient was diagnosed with a middle, lower third, stage II, III had short-course preoperative radiation. - Patients with ASA 1-3. There are no contraindications for endotracheal anesthesia.. 2.2.3.2. Steps to perform surgery - Assess injury. - Lymphadenectomy along the IMA and cut artery about 1cm from origin. Cut IMV at the lower edge of the pancreas. The study did not require lateral pelvic lymphadenectomy. Total mesorectal excision. - In case of conservation of sphincter,we perform LAR - In case of failure to protect the sphincter, we perform APR. 2.2.4. Follow-up
Every 3 months for the first year, every 6 months for the 2nd year, determining local recurrence, distal metastasis and survival rate. 2.2.5. The patient’s data were recorded 2.2.5.1. Patient’s characteristics:Age, gender, medical history, physical condition, ASA, endoscopy and CEA. 2.2.5.2. Stage of disease Classification of stages according to AJCC 2010.
- Stage of preoperative: base on MRI 3.0 and CT-scan. - Pathology staging: base on pathology results. 2.2.5.3. The results of laparoscopic surgery TME
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time, operation Intraoperative: Average
- intraoperative complication, the average blood loss, the rate of conversion to open surgery, quality of mesorectum, distal margin, CRM. - Early results: Complications, the average hospital stay time after surgery. - Long-term results:Late toxicity, the recurrence rate, the overall survival and the disease-free survival 2.2.6. Data processment
The data is processed by medical statictic method with SPSS 22.0 software for Window.
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Study design
Rectal cancer patients
Selective criterial Exclusive criterial. Clinical examination. Laboratory features: endoscopy, pathology, MRI 3.0, CT, CEA
Rectal cancer patients entered the study
Short-course preoperative radiation
Recording toxicity
Laparoscopic surgery TME (LAR or APR)
Assess surgical results Clinical staging Pathology staging
Conclusion
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Chapter 3. RESEARCH RESULTS
3.1. Characte ristics
70 patients rectal cancer with 62.9% male. Mean age was 59.6 ± 10,48. Mean BMI was 20.5 ± 2.6. Low rectal cancer was 50,0% and mild rectal cancer was 50.0%. CEA level was 8.3 ± 28.0 ng/ml 3.2. Stage of dise ase Table 3. 5. Stage of disease base on MRI
cT
cN
Stage cT3 cT4 cN0 cN1 cN2 II III n = 61* 58 3 10 29 22 10 51 % 95.1 4.9 16.4 47.5 36.1 16.4 83.6
*: There were 9 patients contraindicated MRI Conclusion: 100% invasive tumor lesions in T3, T4. In which T3 accounts for 95.1%. The number of patients with lymph node metastases in N1 and N2 accounted for 83.6% is also corresponding to the number of patients in the stage III. Table 3. 6. Stage of diseasebase on CT
cT
cN
Stage cT3 cT4 cN0 cN1 cN2 II III n = 70 64 6 9 34 27 9 61 % 91.4 8.6 12.9 48.6 38.5 12.9 87.1
Conclusion: - On CT-Scaner showed 91.4% of patients had invas ive tumor in T3.
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lymph node metastasis incidence of cN0
- The is 12.9% corresponding to patients in stage II and metastasis of lymph nodes cN1 and cN2 is 87.1% corresponding to patients in stage III.
Table 3. 7. Pathology res ults n = 70 %
pT
pN
Stage
pT1 pT2 pT3 pT4 pN0 pN1 pN2 I II III 1 9 59 1 55 13 2 10 45 15 1.4 12.9 84.3 1.4 78.6 18.6 2.8 14.3 64.3 21.4
Conclusion:Invasive tumors in pT3 accounted for 84.3%. The rate of metastatic lymph node was 21.4%. Stage I has 14.3%, stage II was the highest rate (64.3%).
Table 3.9. Invasive tumors and lymph npde on MRI and CT compare with pathology res ults
Correct Overstage Downstage
n (%) n (%) n (%)
MRI T 49 (80.3%) 12 (19.7%) 0
(n=61) N 17 (27.9%) 42 (68.9%) 2 (3.3%)
CT T 56 (80.0%) 14 (20.0%) 0
N 20 (28.6%) 50 (71.4%) 0
(n=70) Conclusion: - For tumor, most of them are correct (about 80%) and there are no cases of downstage. - For lymph nodes, most are overstage (about 70%).
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3.3. The res ults of laparos copic surgery TME 3.3.1. Intraoperative
Table 3. 12. Specification of laparoscopy surgery
Trocar (n=70) 4 trocar 5 trocar
Diverting Ileostomy(n=52)* Milddle (n=35) Low (n=17) n 59 11 28 16 12 (%) 84.3 15.7 53.8% 45.7% 70.6%
*: 52 patients had LAR procedure. Conclusion:Using 4 trocar was 84.3%. The patients had diverting ileostomy in LAR group was 53.8% (of which the lowof rectal cancer was 70.6%). - Conversion to open surgery rate was 5,7%. - Mean operative time was 134,1 ± 32,4 minutes. Table 3. 11. Results of mesorectal excision n (%)
Macroscopic assessment (n=66) Distal resection margin(n=49*)
63.6 42 24 36.4 24.5 ± 13.6 mm 98.0 48 2.0 1 98.5 65 1.5 1
Complete Nearly complete Mean (SD) Negative Positive Negative CRM (n=66) Positive *: 4 patients were convertedto open surgery (of which 3 in 52 patients LAR group and 1 in APR group). Conclusion:Complete mesorectal excision was 63.6%. Most of patients had negative distal resection marginand negative CRM(98.0% and 98.5%, respective). - The total number of lymph nodes collected was 397 lymph nodes. There are 27 metastatic lymph nodes accounting for 6.8%. The
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average number of lymph nodes on 66 patients with laparoscopic surgery was 6.0 ± 3.4 nodes. 3.3.2. Early results - The rate of mild complications was 21.1%. Severe complications was 12.1%. - The meanpostoperative hospital stay time was 10,8 ± 5,1 days.
Table3.19. Early results
Good Medium Least n= 66 44 14 8 % 66.7 21.2 12.1
Conclusion: The good result was 66.7%. 3.3.3. Long-term res ults - Local recurrence rate was 12.1%. - Late toxicity mainly encountered degree 3 was 12.9%
Table3.23. Recurrence rate and some related factors
p (Fisher’s exact test)
Procedure >0,05
CEA >0,05
Tumor size >0,05
>0,05
Recurrence(%) n = 66 8 (16.3%) 0 (0%) 6 (12.8%) 2 (10.5%) 0 (0%) 4 (11.8%) 4 (14.3%) 0 (0%) 6 (14.3%) 2 (13.3%) LAR APR ≤ 5 > 5 < 2 cm 2-3 cm >3 cm I II III
Pathology stage Conclusion: - The APR group did not have any recurrence cases, the LAR group had 8 recurrent cases, accounting for 16.3%. This difference is not statistically significant with p> 0.05.
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- Considering the relationship between local recurrence and CEA, tumor size and stage found no significant difference (p> 0.05).
Fig. 3.4. Overall survival
Conclusion:The overall survival rates after 1, 2 and 3 years were 97.1%, 95.7% and 95.7%, respectively.
Fig. 3.7. Disease-free survival
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Conclusion: The disease-free survival ratesafter 1, 2 and 3 years were 92.9%, 91.4% and 88.6% respectively.
Chapter 4. DISCUSSION 4.1. Characte ristics
The study showed that the mean age of patients was 59.6 ± 10.48 years. This result is similar to other authors. Understanding gender, the statistics of domestic and foreign authors show that men meet more often (about 60-70%). The results showed that male patients accounted for 62.9%. CEA is commonly used in colorectal cancer. Research by several authors shows that a high CEA at the time of diagnosis has an adverse effect on the survival time independent of the tumor stage. If this indicator decreases after surgery is associated with increased disease-free survival. CEA levels> 5 ng / ml at the time prior to radiotherapy were associated with poor tumor response. Concentrations of CEA <5ng / ml are associated with increased clinical and anatomic complete response rates. The research results have mean CEA before surgery is 8.3 ± 28.0 ng / ml.
Rectoscopy can assess tumor size, macroscopic of the tumor. In addition, rectal examination allows an assessment of the patient's anal sphincter function, which is an important consideration when considering whether a patient is suitable for performing LAR. Research of Pas found that tumors in the lower third position accounted for 29%, the middle third accounted for 39% and the upper third was 32%. The statistics show that in this study the tumor was located in the middle 1/3 and lower 1/3 with 50%. 4.2. Stage of dise ase 4.2.1. Preoperative staging There are a variety of facilities available to assess the preoperative staging including endoscopic ultrasound, CT Scaner and MRI. For large tumors invading the mesorectal fascia, surrounding organs and the pelvic wall, the evaluation by CT and MRI is better. The tumors invaded of anal sphincter and anal lift muscles use MRI for a clearer image than CT - Scaner. Results of research on rectal cancer patients in stage II and III on MRI and CT were mainly with cT3, 95.1% and 91.4% respectively. Results of Stevenson met cT1 was 8%, T2 was
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29% and T3 was 63%. In study of Minama H et al (2017) cT3, cT4 were 89.3% and 10.7%, respectively.
Identifying metastatic lymph nodes on diagnostic imaging is difficult. Some authors evaluate metastatic lymph nodes based on size (> 8mm). However, some authors believe that the standard size> 8mm is unconvincing because pathological studies have shown that about 60% of metastatic lymph nodes have a diameter of less than 6 mm. In other words, the sensitivity of diagnostic imaging methods based on size to diagnose metastatic lymph nodes is usually low (50 - 70%). The histopathological features of the lymph node metastatic in addition to size also have other characteristics such as shape, border irregularity, and heterogeneous signal. However, diagnostic lymph node metastases remains a challenge. In the study of rectal cancer in Germany, stage evaluation was based on rigid endoscopy, endoscopic ultrasound and pelvic CT scan. A review of patients with cT3-4 and / or cN + found that the clinica l stage was not significantly associated with survival. This suggests that the pre-treatment evaluation was inaccurate, especially metastatic lymph nodes.
Study results of pre-operative lymph node metastasis on MRI: cN0, cN1 and cN2 were 16.4%, 47.5% and 36.1%, respectively. On CT: cN0, cN1 and cN2 were 12.9%, 48.6% and 38.6%, respectively. In the study of Kang, the rate of metastatic lymph node was 65.3%. The study of Stevenson: N0, N1 and N2 were 45%, 39% and 16%, respectively. The study of Minama H et al (2017) found that cN0, cN1, cN2 and cN3 were 39.3%, 21.4%, 7.1% and 32.1%, respectively. 4.2.2. Postoperative staging The results showed that pT2 was for 12.9% and pT3 was for 84.3%. Compared with MRI and CT, the accuracy were 80.3% and 80.0%, respectively. Research by Stevenson at al found that the ratio of cT1 or cT2 compare pT1 or pT2 after surgery reached 86%, the ratio of cT3 / pT3 reached 79%. A meta-analysis of nearly 5000 rectal cancer patients comparing the accuracy of assessing tumor invasion between MRI, CT and endoscopic ultrasound showed an accuracy of 84%, 73% and 87%, respectively. There is a correlation between postoperative tumor invasion and lymph node metastasis.
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The study results met pN0 was 78.6%, pN1 was 18.6% and pN2 was only 2.8%. The study results obtained statistically equivalent of Kang found 79.4% of lymph nodes were not metastatic, pN1 was 10.6% and pN2 was 10%. Comparison with MRI results showed that 27.9% was evaluated correctly and this result when compared with CT was 28.6%.
In
the study, compared postoperative staging versus preoperative staging found that a reduction staging. This was explained by the low sensitivity and specificity of imaging when evaluating lymph node metastases. The postoperative staging met stage I surgery was 14.3%, the stage II was 64.3% and the stage III was 21.4%. Research by Schiphorst et al (2014) assessed the postoperative stage in laparoscopy group stage I was 26%, stage II was 20%, stage III was 42% and stage IV was 7%. 4.3. The res ults of laparos copic surgery TME 4.3.1. Intraoperative
The study results showed that all patients with middle 1/3 rectal cancer were performedLAR. The rate of LAR and APR procedure were 74.3% and 25.7% respectively. Understanding this rate in Kang study, the rate of APR procedure was 11.2%, the LAR rate was 88.8%. Research has shown that short-course preoperative radiationdoes not affect the choice of LAR or APR. Minami H et al (2017) suggested that
the diverting ileostomyreduces the incidence of leakage and reduces the severity of the anatomosis fistula. The risks of a anastomosis fistula are described by a number of study such as : low anastomosis, male patient, progressive or metastatic disease, smoking, low albumin rate, diabetes, old age, patients have to undergo blood transfusion in surgery and surgical techniques. Neoadjuvent has not been shown to increase the risk of anastomosis. In the practice of treatment, it is difficult for the surgeon to predict which group of patients is at high risk factor for diverting ileostomy. The rate of diverting ileostomyin Kang's study with laparoscopic surgery group was 91.4% and open surgery was 88.4%, the difference between laparoscopy and open surgery was not statistically significant (p = 0.386). Fleshman at al do diverting ileostomyin most cases. In study of Stevenson, the rate of diverting ileostomywas 68%. The study results had the rate of
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diverting ileostomy was 53.8%. This result was similar to the Stevenson but lower than the Kang and Fleshman.
Laparoscopy
technical, requiring is considered highly experienced surgeons. The authors suggest that the more experienced the surgeon is, the lower the incidence of the intraoperative complication. In the study results intraoperative complication was 5.7%. The complications such as bleeding, damage to the ureters. There was no difference in the rate of intraoperative complication in the two groups (LAR and APR). The study of Pas at al had 12% complications in the laparoscopic surgery group, including 3% bleeding, tumor rupture <1%, anastomosis complications were 1%, ureter injury 1%. Other complications were 6%. Res ults of mesorectal excision Research on rectal cancer specimen found that there were cancer cells in the mesenteric mesenteric range within 4 cm from the lower edge of the tumor. In the wall of the rectum, the spread is from 1 cm to 1.5 cm and if there are cancer cells w ithin the range of 1-1.5 cm from the lower edge of the tumor, it is considered a bad prognosis factor with distant metastases. Kang's study had a median distal resection margin was 2.0 cm (1.0-3.5 cm). Pas's study had a median distal resection margin was 3 cm. Fleshman's study had a median distal resection margin was 3.2 ± 2.6 cm and the negative distal resection margin was 98.3%. Stevenson's study had median distal resection margin was 26 mm (15 - 45 mm) and negative distal resection margin was 99%. The study results in the LAR group, the median distal resection margin was 24.5 ± 13.6 mm, without negative distal resection margin was 98.0%. One of the main advantages of MRI is to enable accurate evaluation of mesorectal fascia. This is the radical of TME procedure. Research by Bipat at al found that the use of MRI in the evaluation of positive CRM helped to reduce 35% of patients undergoing preoperative. Kang's study had a positive CRMwas 2.9% and negative CRMwas 97.1%. In the Pas study, the percentage of positive CRM was 10%, and this rate did not differ in the laparoscopic and open surgery group. The results of Bonjer's study showed that the rate of positive CRM in laparoscopic surgery group was 10%. In which, the upper , middle and lower were 9%, 10% and 9% respectively. Fleshman at al had the results in the laparoscopic
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surgery group, the negative CRMwas 87.9%. The study of Stevenson had negative CRMwas (≥ 1mm) was 93% in laparoscopic surgery group. The study results showed that the negative CRMwas 98.5%. Interpretation of this result is possible in our study, mainly in patients with tumors were ypT1, ypT2 and ypT3, accounting for 98.5% and the carefulness in operation. 4.3.2. Early results
In the study results, complications were 33.3%. In which, minor complications were 21.2%, urinary tract infection and all are successfully treated internally. Severe complications were 12.1% such as bleeding, leakage of anastomosis and early bowel obstruction. Kang's study had complications of 21.2%, of which the highest rate was urinary retention, accounting for 10.0%, having to leakage was 1.2%, surgical site re-urinate sonde, anastomotic infection 1.2%. The study of Pas at al had 40% complications, in which, anastomotic leakage was 13%, abscess 7%, surgical site infection 4%. Study results of Fleshman met complications in laparoscopic surgery group was 57.1%, of which serious complications (Clavien-Dindo level 3-5) were 22.5%. The study of Minama H et al (2017) showed that there were 2 patients with anastomotic leakage, abscess in 3 patients, and urinary retention in 1 patient.The complication degree 3-4 were 10.7%.
Evaluation of early results based on the rate of complications affecting quality and prolonging the day of treatment, the study results were 12.1% at a poor result due to severe complications. At a good result and average resultwere 87.9%. 4.3.3. Long-term res ults Late toxicity
Toxicity in the small intestine has decreased when replacing postoperative radiotherapy with preoperative radiotherapy. Ngan SY et al (2012) studied comparing the results of short-course preoperative radiation versus long-coursepreoperative radiationon 326 patients with rectal cancer T3N0-2M0, follow up on average 5.9 years. There was no significant difference in the incidence of late side effects at level 3-4 (5.8% versus 8.2%). Krajcovicova I at al (2012) found late toxicity in long-coursepreoperative radiation group in short-course preoperative were 16 patients (29%) and
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of the rectal bleeding anastomotich,
radiationgroup were 23 patients (24%) with no statistics significant difference (p = 0.48). The study results showed that the rate of late toxicity was 3-4.1% with symptoms such as intestinal obstruction, stenosis requiring hospitalization. Local recurrence Local recurrent withsymptomsc such as pain, bleeding or constipation. Treatment of recurrent rectal cancer has so far been difficult and treatment options were limited to patients who had previously received radiation therapy. Recurrent cancer without surgery has a 5-year survival rate of less than 4% and overall survival about 8 months. The main risks of local recurrence in rectal cancer are the circumference invasion and the location of the tumor from the anal verge. In patients who undergo surgery to TME the lymph nodes does not help to predict local recurrence but remains a risk factor for metastases as far as the invasive depth of the tumor. The study results showed a recurrence rate of 12.1% with the mean follow-up time of 27.7 months (14 - 43 months). Local recurrence rate and some related factors
The risk of local recurrence is increased with advanced disease and unfavorable pathological characteristics such as poor differentiation, signs of invasive vascular and nerve, low tumors, patients with obstruction, invas ive organ around. The CRM is considered to be a prognostic factor independent of local recurrence and survival. Understanding the relationship between recurrence rate and related factors such as surgery method, CEA, tumor size and stage of disease, the study results did not show any significant difference. This may be due to the small number of patients in this study. In other studies, surgeons experience to varying degrees has an effect on the incidence of local recurrence. A study comparing loca l recurrence rates after rectal cancer surgery in surgical groups in Canada showed that those with standard experience or training had a loca l recurrence rate of 13% compared to 34% in the normal surgeon group. Survival
The study had overall survival rates after 1, 2 and 3 years were 97.1%, 95.7% and 95.7%,respectively. The disease-free
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survival rates after 1, 2 and 3 years were 92, 9%, 91.4% and 88.6%, respectively. In study of Bonjer et al (2015) at 3 years had disease- free survival rate was 74.8% and overall survival rate was 86.7%. Jeong's study followed the 3-year follow-up with the disease-free survival in the laparoscopic surgery group was 79.2%.
CONCLUSION
1. The stage of dise ase of patients with rectal carcinoma who is given short-course preoperative radiation - Clincal staging: cT3 tumor on MRI and CT was 95.1% and 91.4% and metastatic lymph nodes on MRI 3.0 and CT-Scaner were 83.6% and 87.2%, respectively. Stage III accounts for over 80%. - Pathology staging: pT3 tumor was 84.3%, with accuracy compared to before 80%. Evaluation of lymph nodes met pN0 is 78.6%, with an accuracy of about 30% compared with before surgery. The pathology staging I, II and III were 14.3%, 64.3% and 21.4%, respectively. 2. The res ults of laparoscopic surgery TME combined short- course preoperative radiationfor rectal carcinoma - Intraoperative: Average operation time was 134.1 ± 32.4 minutes. Intraoperative complication was 5.7%. The average blood loss was 20.0 ± 12.6 ml. The rate of conversion to open surgery was 5.7%. Complete mesorectum were 63.6%. Distal margin with negative was 98.0%. Circumferential resection margin with negative was 98.5%. - Early results: Complications 33.3%. There was no deaths. The average hospital stay time after surgery was 10.8 ± 5.1 days. Good results account for 66.7%. - Long-term results:(average follow-up time of 27.7 months): Late toxicity of the preoperative radiotherapy met 22.7%. The recurrence rate was 12.1%. The overall survival rates after 1, 2 and 3 years were 97.1%, 95.7 and 95.7%, respectively. The disease-free survival after 1, 2 and 3 years was 92.9%, 91.4% and 88.6%, respectively. There was no significant differencein overall survival and in disease-free survival at different stages of disease and tumor size groups (p> 0.05).
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REQUEST
1. The study should be further studied with a larger number of patients and a longer follow-up time to be able to evaluate the distant results and related factors.
LIST OF PUBLISHED ARTICLE RELATING TO THESIS
1. Nguyen To Hoai, Nguyen Anh Tuan, Trieu Trieu Duong and Nguyen Van Du (2020). " Study on characteristics of stage in rectal cancer patients were treated with laparoscopic total mesorectal excision after preoperative short-course radiation". Jounal of 108 – Clinical Medicine and Pharmacy, (15), pp 87-91.
2. Nguyen To Hoai, Nguyen Anh Tuan, Trieu Trieu Duong and Nguyen Van Du (2020). "Evaluation the results of laparoscopic total mesorectal excision after preoperative short-course radiation for rectal cancer". Jounal of 108 – Clinical Medicine and Pharmacy, (15), pp 73-79.
