JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES Volume 21, Number 5, 2011 Mary Ann Liebert, Inc.

. DOI: 10.1089/lap.2010.0059

Full Reports

Effectiveness and Safety of Laparoscopic Resection Versus Open Surgery in Patients with Rectal Cancer: A Randomized, Controlled Trial from China
Xiaobo Liang, MD, Shenghuai Hou, MM, Haiyi Liu, MD, Yaoping Li, MM, Bo Jiang, MM, Wenqi Bai, MM, Guodong Li, BS (Med.), Wengyuan Wang, MM, Yi Feng, MM, and Juan Guo, BS (Med.)

Abstract

Background: The long-term survival and safety of laparoscopic surgery in patients with rectal cancer remain unclear. The aim of this trial was to assess the efcacy and safety of laparoscopic surgery for treatment of rectal cancer. Methods: We undertook a randomized, controlled trial in 343 patients with rectal cancer between May 2004 and April 2008. One hundred sixty-nine patients were randomly assigned to laparoscopic surgery and 174 patients to open surgery. The main endpoint was 3-year survival. Data were analyzed according to the intention-to-treat principle. Results: Laparoscopic surgery was associated with earlier recovery of bowel movement compared with open surgery. The average time to rst discharge, bowel movement, resumption of uid intake, and activity out of bed in laparoscopic surgery were shorter by 0.63, 0.32, 0.33, and 0.63 day, respectively (P < .001). The incidences of postoperative morbidities such as infectious complications, anastomotic leakage, anastomotic stenosis, and deep vein thrombosis have no differences. No differences were found in the comparison of long-term survival. Interpretation: Laparoscopic surgery for rectal cancer is as safe and effective as open surgery in terms of oncology outcomes. Long-term survival for patients with rectal cancer undergoing laparoscopic surgery were similar to those undergoing conventional open surgery, thus supporting the continued use of laparoscopic surgery in Chinese patients with rectal cancer.

Introduction

ectal cancer is one of the common digestive tract tumors, and the disease incidence rate rises by 2% per year continually in China. Surgical operation is the rst-choice method to treat rectal cancer. In 1991, Jacobs introduced for the rst time the laparoscopic technology in colorectal cancer surgical operation,1 which is considered a milestone-like progress in colorectal cancer treatment. Until now, the application of laparoscopic techniques in colorectal cancer has lasted for more than a decade. For the past few years, the practical effectiveness of laparoscopic surgery for colorectal cancer has been conspicuously enhanced because of the improvement of instruments and technique. Although laparoscopic colorectal resection has some merits such as tiny injury and superior cosmesis, as a kind of therapy for malignant tumor,

the safety of surgery (radical care or not), postoperative short-term outcomes, and the cancer-related long-term survival remain the focus of attention. There were several largescale, randomized, controlled trials comparing laparoscopic and open surgery for colorectal cancer to evaluate the feasibility of laparoscopic surgery. The radical resection of laparoscopic surgery for colorectal cancer was conrmed.24 National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (Version 2010) pointed out explicitly that the colon cancer laparoscopic surgery may be the conventional application in clinic; however, the rectal cancer laparoscopic surgery is not recommended outside of a clinical trial.5,6 The trial was designed to evaluate the clinical effectiveness and safety of laparoscopic surgery for Chinese patients with rectal cancer by comparing with open surgery.

Department of Colorectal Surgery, Shanxi Tumor Hospital, Taiyuan, China.

381

382 Materials and Methods Patients Between May 2004 and April 2008, we undertook a randomized, controlled trial comparing laparoscopic resection with conventional open surgery in 343 patients with rectal cancer meeting the selection criteria. Inclusion criteria were as follows: (1) rectal cancer patients diagnosed by pathologic examination; (2) written informed consent was obtained. Exclusion criteria were as follows: (1) liver or lung metastases assessed by computed tomography, magnetic resonance imaging, or ultrasonography; (2) body mass index (BMI) of >30 kg/m2; (3) acute intestinal obstruction; (4) serious infection; (5) previous abdominal surgery; (6) patients had received neoadjuvant chemotherapy. All the operations were done by the same surgeon team. Randomization was done on the day before surgery through sealed opaque envelopes containing surgical method. The study was approved by the institutional ethics research committee. No differences existed in the preoperative examination measures and preparation of intestinal tract between the two groups. Radicality principles of malignant tumor and total mesorectal excision were followed strictly during the operation. Resection modalities included lower anterior resection (LAR) and abdominoperineal resection. Indication of each resection modality was not different between the two groups. After the operation, patients were requested abrosia and no drinking for 23 days until rst discharge. During the period, gastrointestinal decompression and parenteral alimentation were performed. Liquid diet could be taken by patients who had evacuated, if no abdominal distention was observed, and semiliquid diet could be taken soon after. Low-residue diet could be taken till 2 weeks after the surgery. The patients were encouraged to be out of bed as soon as possible if their strength allowed. Primary and secondary outcomes The primary endpoint of the trail was 3-year survival. Secondary endpoints were number of lymph nodes removed, length of specimen, distance between inferior border of tumor and incised margin in LAR operation, time to rst discharge, bowel movement and uid intake, infectious complications, anastomotic leakage, anastomotic stenosis, deep vein thrombosis, and 1-year survival. Follow-up Patients were assessed for complications at the time of hospital discharge by a single reviewer who was unaware of patients treatment assignments. Follow-up visits were at 1 and 3 months after surgery, then every 3 months for the rst 2 years, and every 6 months afterward, including physical examination, abdominal and pelvic part ultrasonography, chest radiography, examination of alimentary tract tumor markers, and colonoberscope examination. Conrmation of recurrence required imaging or pathological evaluation. Statistical analysis We compared the differences of categorical data using w2 test or Fishers exact test and of continuous data using twosample t-test. KaplanMeier curve was used to estimate the
346 eligible

LIANG ET AL.

3 patients opted out of the trial

169 allocated to laparoscopic surgery; 1 converted to open surgery 2 patients lost to follow-up; 167 patients assessed for primary endpoint

174 allocated to open surgery

2 patients lost to follow-up; 172 patients assessed for primary endpoint

FIG. 1. Trial prole.

distribution of survival, and the log-rank test was used to compare survival between the two groups. All hypothesis tests were at the 0.05 signicance levels (two-sided). Statistical analyses were performed using SPSS version 13.0. Data were analyzed according to the intention-to-treat principle. Results Characteristics of the patients and tumors One hundred sixty-nine patients were randomly assigned to receive laparoscopic surgery and 174 patients to conventional open surgery. One patient in the laparoscopic surgery group was converted to open surgery because of severe ankylenteron (bowel adherence) (Fig. 1). There were no differences in the baseline characteristics such as gender, age, BMI, TNM (topography, lymph node, metastasis) stage, and resection modality between the two treatment arms (Table 1). Data associated with surgical intervention and morbidity Duration of surgery in the laparoscopic group was significantly longer than that in the open surgery group by 19.5 minutes. The percentages of patients who needed blood transfusion in the two groups were not different. The tumor size,

Table 1. Baseline Characteristics Laparoscopic surgery (n 169) Median SD (year) Male BMI (kg/m2) T1-2N0M0 T3-4N0M0 TxN1-2M0 APR LAR 57.34 14.13 104 21.45 9 72 88 83 86 Open surgery (n 174) 57.36 13.08 92 22.31 7 84 83 70 104 P value .990 .127 .223 .616 .329 .450 .065 .051

BMI, body mass index; APR, abdominoperineal resection; LAR, lower anterior resection.

LAPAROSCOPIC VERSUS OPEN SURGERY FOR RECTAL CANCER Table 2. Data Associated with Surgical Intervention and Morbidity Laparoscopic surgery (n 169) Duration of surgery (minutes) Number of patients who needed blood transfusion Number of lymph nodes removed Length of specimen (cm) Tumor size (cm) Distance between the inferior border of tumor and the incised margin in LAR operation (cm) First activity out of bed (day) First discharge (day) APR LAR First bowel movement (day) APR LAR First resuming of uid intake (day) APR LAR 138.08 23.79 4 7.05 5.05 19.11 2.20 4.26 1.301 3.22 0.738 3.50 0.832 2.96 0.889 2.98 0.826 2.95 0.961 3.90 0.850 3.86 0.857 3.93 0.852 5.71 1.716 5.49 1.735 5.95 1.681 Open surgery (n 174) 118.53 21.989 8 7.44 4.89 18.97 2.25 4.17 1.288 3.03 0.684 4.13 0.983 3.28 0.780 3.19 0.778 3.35 0.785 4.24 0.788 4.07 0.739 4.34 0.808 6.34 1.618 6.03 1.592 6.78 1.573

383

P value .000 .380 .469 .574 .530 .154 .000 .000 .104 .002 .000 .100 .001 .001 .031 .002

number of lymph nodes removed, length of specimen, and distance between inferior border of tumor and incised margin were similar in both groups. The average time to rst discharge, bowel movement and uid intake, and time to rst activity out of bed in the laparoscopic surgery group were shorter by 0.63, 0.32, 0.33, and 0.63 day, respectively (P < .001) (Table 2). Postoperative complications There were no signicant differences between the groups in the rates of postoperative complications, including infectious complications, anastomotic leakage, anastomotic stenosis, deep vein thrombosis, and death (Table 3). Long-term survival Two subjects from each group were lost to follow-up. The median length of follow-up was 44 months (range: 172). There was no evidence to support a difference in 1-, 2-, and 3-year survival between the two groups. No port site or wound metastasis was seen in the laparoscopic surgery group thus far (Table 4, Fig. 2).

Discussion Whether a new surgery technology can be promoted in clinic needs to be evaluated from six aspects, namely, technical feasibility, repeatability, security, effect, costbenet analysis, and whether the technique can become the gold standard. The technical feasibility and repeatability of laparoscopic surgery have not been questioned. But, in the decade of its development and promotion, dispute on the security, clinical effect, and especially the long-term effectiveness has not stopped. The patients characteristics such as gender, age, BMI, TNM stage, and resection modality equilibrated between the laparoscopic surgery group and the open surgery group, and thus, a comparable baseline was established for comparison of the other data. From the data of WHO, the world standard BMI ranges from 18.5 to 24.9 kg/m2. It was dened as overweight when the BMI exceeded 25.0 kg/m2 but was lower than 30 kg/m2. However, the optimal BMI range of Chinese people was from 20.0 to 22.0 kg/m2, and overweight was dened as ranging from 24.0 to 28.0 kg/m2. The median BMI of patients in the trial were ecumenic in Chinese people. The most apparent improvement of laparoscopic surgery for colorectal cancer compared with open surgery was its tiny wound: minimal intervention to the bowels, blood vessels, and nerves, application of ultrasound knife in the laparoscopic surgery for colorectal cancer, decrease in blood loss, and fewer transfusions required during the operation. The fact that laparoscopic surgery causes tiny injury was acknowledged extensively and thus laparoscopic surgery has become the

Table 3. Postoperative Complications Laparoscopic Open surgery P surgery (n 169) (n 174) value Infection Wound infection Abdominal abscess Respiratory tract Urinary tract Anastomotic leakage Bowel obstruction Deep vein thrombosis Anastomotic stenosis Death within 30 days after surgery 14 9 2 2 1 4 1 0 0 0 12 8 1 2 1 6 2 1 0 0 .686

Table 4. Long-Term Endpoints .215 .751 .545 .867 .991 .991 Laparoscopic surgery 1-year survival 2-year survival 3-year survival Port site or wound metastasis 94.0% 82.6% 76.0% 0 Open surgery 95.3% 91.2% 82.8% 0

384 basic surgery method of nonmalignant abdominal tract disease. The trial data adequately proved the dominance of laparoscopic surgery for rectal cancer. The average time to rst discharge, bowel movement and uid intake, and time to rst activity out of bed in the laparoscopic surgery group were shorter than that of the open surgery group. Laparoscopic surgery had more large space for operation and a specic magnifying video of laparoscopy, so that broader visual eld was supplied to the operator, the anatomic structure was more easily identied, the tissue diastem was more easily captured, and scavenging boundary and extent were identied clearly. As long as tumor-free principles were strictly followed by the operator during the operation, the curative resection could be reached unquestionably by laparoscopic surgery theoretically. No differences were found in the length of specimen, tumor positive of incisal edge, and number of lymph nodes removed between laparoscopic and open surgeries for colorectal cancer in several trials previously reported.2,7 In the trial, length of specimen, tumor size, distance between inferior border of tumor and incised margin in LAR operation, and number of lymph nodes removed were not different signicantly, and the result proved that laparoscopic surgery for rectal cancer could reach a radical resection. However, it was regretful that the radiation margin was not detected in the pathology analysis. Laparoscopy has microsurgery features such as superordinary illumination equipments, megascopic operative visual eld, and simultaneous limitations such as stereoscopic vision loss, loss of nger-touch sensation, and strictly relying on equipment and instruments. The difculty of laparoscopic surgery was obviously raised and demands on surgeons technique were accordingly increased. Thus, it was apprehensible and construable that the duration of laparoscopic surgery was much longer than that of open surgery. Of course, more experiences with laparoscopic surgery would lead to shorter operation time. Braga et al.8 reported that laparoscopic surgery for colorectal cancer caused a similar rate of complications to that of open surgery. Lacy et al.9 and Frasson et al.10 reported that the postoperative total rate of complications of laparoscopic surgery for colorectal cancer decreased when compared with open surgery. The comparison of infectious complications,
Survival Functions 1.0

LIANG ET AL. anastomotic leak, anastomotic stenosis, deep vein thrombosis, and death within 30 days after surgery between the laparoscopic surgery group and the open surgery group demonstrated that laparoscopic surgery was safe and feasible. The incident of complications in laparoscopic surgery was denitely related to the operators experience and learning curve.11 For the purpose of reducing the incidence of morbidity maximally, we should combine the perfect technique of open surgery, skilled laparoscopic technique, careful dissection according to tumor-free principle during the operation, and careful supervision after operation. Port site or wound metastasis was a focus point of the dispute of laparoscopic surgery. Original literature reported that laparoscopic surgery for colorectal cancer could lead to high incidence of port site or wound metastasis8 and this has been a reason that laparoscopic surgery for colorectal cancer has frequently been in question in the clinical application. The followup period has been 172 months at present in our trial, and no port site or wound metastasis has yet occurred. As a kind of therapy for malignant tumor, the cancer-related long-term survival is still a main focus for patients and surgeons. At the time of analysis, the follow-up data of the trial conrmed that the technique of laparoscopic surgery could reach radical resection in the therapy of rectal cancer. No differences were found in the comparison of long-term survival. In summary, our study indicates that laparoscopic surgery for rectal cancer was as safe and effective as open surgery in terms of oncology outcomes. Moreover, laparoscopic surgery reduced the patients pain and hospital stay. Thus, this surgical approach can be used in Chinese patients with rectal cancer. Acknowledgments The authors thank all the friends who had helped during the study, Professor Gui-feng Liu from the Statistics Research Institute of Shanxi Medical University for her helpful suggestions and instructions, and Yan Wang from Shanxi Medical University for her direction in the use of statistic software. Disclosure Statement No competing nancial interests exist. References
1. Jacobs M, Vere ja J, Goldstein H. Minimally invasive colon resection. Surg Laparosc Endosc Percutan Tech 1991;1: 144150. 2. The Clinical Outcomes of Surgical Therapy Study Group. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med 2004;350:20502059. 3. Guillou PJ, Quirke P, Thorpe H, et al. Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): Multicentle, randomized controlled trial. Lancet 2005;365: 17181726. 4. Veldkamp R, Kuhry E, Hop WC, et al. Laparoscopic surgery versus open surgery for colon cancer: Short-term outcomes of a randomized trial. Lancet Oncol 2005;6:477484. 5. NCCN Clinical Practice Guideline in Oncology, Colon Cancer, V.2. 2010. National Comprehensive Cancer Network, updated Feb. 8, 2010 (last accessed February 15, 2010). www.nccn.org/ professionals/physician_gls/PDF/colon.pdf.

0.8
Cum Survival

0.6
laparoscopic surgery and open surgery
open surgery laparoscopic surgery

0.4

0.2

open surgerycensored laparoscopic surgerycensored

0.0 0 20 40 60 Survival Curve (Log Rank, P=0.462) 80

FIG. 2. Survival curve.

LAPAROSCOPIC VERSUS OPEN SURGERY FOR RECTAL CANCER

6. NCCN Clinical Practice Guideline in Oncology, Rectal Cancer, V.2. 2010. National Comprehensive Cancer Network, updated Feb. 8, 2010 (last accessed February 15, 2010). www.nccn.org/professionals/physician_gls/PDF/rectal.pdf. 7. Bouvet M, Manseld PF, Skibber JM, et al. Clinical, pathologic, and economic parameters of laparoscopic colon resection for cancer. Am J Surg 1998;176:554558. 8. Braga M, Frasson M, Vignali A, et al. Laparoscopic vs. open colectomy in cancer patients: Long-term complications, quality of life, and survival. Dis Colon Rectum 2005;48:22172223. 9. Lacy AM, Garcia-Valdecasas JC, Delgado S, et al. Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: A randomised trial. Lancet 2002;359:22242229. 10. Frasson M, Braga M, Vignali A, et al. Laparoscopic-assisted versus open surgery for colorectal cancer: Postoperative

385

morbidity in a single center randomized trial. Minerva Chir 2006;61:283292. 11. Paraskeva PA, Aziz O, Darzi A. Laparoscopic surgery for colon cancer. Surg Clin North Am 2005;85:4960.

Address correspondence to: Xiaobo Liang, MD Department of Colorectal Surgery Shanxi Tumor Hospital No. 3 Zhigongxinjie St. Taiyuan 030013 China E-mail: liangxiaobo@medmail.com.cn

Copyright of Journal of Laparoendoscopic & Advanced Surgical Techniques is the property of Mary Ann Liebert, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.