Steven D. Wexner M.D., FACS, FRCS, FRCS(Ed)
Chairman, Department of Colorectal Surgery
Cleveland Clinic Florida, Weston, FL
Professor of Surgery, Ohio State University Health Sciences Center at the Cleveland Clinic Foundation
Clinical Professor, Department of Surgery, University of South Florida College of Medicine
Susan M. Cera, MD
Clinical Associate
Cleveland Clinic Florida
Objectives:
1.
Understand the short-term benefits of laparoscopy for colon cancer such as faster bowel function recovery, less post-operative pain, and shorter hospitalization based on data organized according to levels of evidence
2.
Understand the long-term benefits of laparoscopy for colon cancer with regard to recurrence and survival based on data organized according to levels of evidence

Introduction
The advantages of laparoscopy in the treatment of benign disease have been well demonstrated. Compared to laparotomy, laparoscopy is associated with a shorter hospital stay, less ileus, decreased postoperative pain, earlier return to work, and better cosmesis.
The role of laparoscopy for the treatment of gastrointestinal malignancy has been slower to evolve and the subject of much debate over the past decade. From 1991 through 2004, several concerns limited the widespread use of laparoscopy for the attempted cure of colorectal carcinoma. These technically demanding and time-consuming procedures presented prohibitive challenges during the development of laparoscopic approaches in some centers with a high volume of patients where operating room time is always at a premium. Concerns were also raised about the feasibility of adhering to oncologic principles. In particular, the adequacy of the lateral and distal margins, the ability to explore the abdomen, and subsequent impact on oncologic outcome (recurrence rates and survival) have been the source of controversy particularly in the hands of novice surgeons. Reports by some investigators of port site metastasis rate of up to 21% [1] deterred many surgeons from adopting laparoscopy for colon cancer. Furthermore, financial constraints posed significant obstacles to widespread adoption. The many retrospective and case-controlled studies that ensued demonstrated some benefits but were all conducted with potential bias towards laparoscopic groups. Because of these problems, the use of laparoscopy in the curative management of colorectal surgery had limited penetrance and led the American Society of Colon and rectal Surgeons to claim in
1994 in a consensus statement [2]:
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“…laparoscopic colectomy may be an alternative approach to traditional resection of benign colonic disease. The absence of 5year survival data makes it premature to endorse laparoscopic colon resection for cancer. If laparoscopic colon resection is performed it is important to follow traditional surgical principles and standards. It is appropriate to continue to perform all laparoscopic resections in an environment where the outcomes can be meaningfully evaluated.
The ASCRS encourages the development of randomized, prospective studies to evaluate the safety, efficacy and benefits of this alternative (2.5)”
More recently, Chapman et al published a representative report of growing concerns in a systemic review in 2001 that, after a decade of experience via an analysis of 52 studies on laparoscopy for colorectal cancer, little high evidence existed advocating laparoscopy for cancer [3]. They concluded that the approach was time-consuming, more expensive, and countered the advantages of early recovery from surgery and reduced post-operative pain.
As a result of these reports, several worldwide, prospective, randomized trials addressing the long-term recurrence rates and survival were initiated. The recent release of the largest multicenter, prospective, randomized trial to date from the Mayo Clinic marked the beginning of a new, minimally invasive age in colon cancer treatment [4].
This study was the first with sufficient statistical power to be able to conclusively detect any differences between these two procedures. The study revealed that, in experienced hands, laparoscopic colectomy offers the same oncologic outcomes as the open procedure with shorter hospital stay and less post-operative pain. With the report of these new results, laparosocopy has a more clearly established role in the surgical armamentarium for colorectal cancer.
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The current review aims to analyze the results several of the various studies published to date on short and long-term outcome of laparoscopy for colorectal carcinoma, based on levels of evidence (Table 1) [5]. From the least to the most convincing data, the hierarchy of study designs progresses through a spectrum from retrospective reviews to prospective series to case control, cohort, and ultimately randomized controlled trials.
Short-term outcome
The short-term variables assessed for patients undergoing laparoscopic surgery for malignancy include the time until bowel function recovery, quality of life, and length of hospitalization. In addition, the cost-effectiveness of the technology has been evaluated.
Bowel Function (Table 1)
Laparoscopy has traditionally been associated with rapid bowel function recovery due to reduced surgical trauma as compared with laparotomy. However, because patients undergoing laparoscopy are usually fed earlier than patients who undergo laparotomy, it may be difficult to eliminate bias in the assessment of flatus passage and bowel movement.
Level 3 evidence from large retrospective and prospective series has revealed a mean time of bowel recovery of 2.5 days after surgery. [6-8]. Level 2 evidence from nonrandomized, case-controlled studies [9-14] revealed faster bowel function recovery in patients undergoing laparoscopy (mean 2.6 days) when compared to those patients
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undergoing laparotomy (mean 3.6 days); however, these studies are small and some did not reach statistical significance. The most definitive evidence comes from randomized trials (level 1 evidence) [15-18]. Milsom et al [15] published the first trial in the United
States comparing 54 patients who underwent laparoscopy with 53 who underwent laparotomy. All patients underwent screening laparoscopy prior to randomization and patients whose operations were converted were excluded. As part of the study design, diet was initiated on the third postoperative day for all patients. Patients in the laparoscopy group passed flatus earlier than patients in the laparotomy group (median, 3 vs. 4; p=0.006). Lacy et al [17] published a large randomized, controlled trial comparing
111 patients who underwent laparoscopy with 108 patients who underwent laparotomy.
Evidence of peristalsis was evaluated twice a day and oral intake began once peristalsis was detected. In an intention-to-treat analysis, the mean time of peristalsis initiation was
36 hours in the laparoscopic group and 55 hours in the laparotomy group (p=0.001).
Similar findings favoring laparoscopy in regards to bowel function recovery was demonstrated by two other smaller randomized trials. [16,18] The COST trial did not specifically report on the timing of bowel function recovery, although faster perioperative recovery was inferred by the shorter hospital stay (P<0.001) and briefer use of parenteral narcotics (P<0.001) and oral analgesics (P<0.001) [4]. Based on these data, the evidence that laparoscopy offers faster bowel function recovery than the traditional open approach may be considered high (Level I).
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Quality of Life (QOL) (Table 2)
Evaluation of quality of life has primarily focused on postoperative pain and intravenous analgesic requirements. While it may be expected that laparoscopy results in decreased pain and consequently less intravenous analgesic use, this assessment may be subject to bias in non-randomized trials since patients undergoing laparoscopy tend to start oral feeding/analgesics earlier. The few case control and cohort studies that have addressed postoperative pain have reported inconsistent results possibly due to the small number of patients in these studies. In contrast, randomized trials have shown laparoscopy to be associated with less pain at some point in the postoperative recovery period. [15, 18-21]
In the randomized trial published by Milsom et al [15], patients in the laparoscopy group used significantly less morphine on the first postoperative day than did patients who had laparotomy (0.78 + 0.32 vs. 0.92 + 0.34 mg/kg p=0.02); this difference was not significant in the subsequent postoperative days. Schwenck et al [21] conducted a small randomized trial including 30 patients in each group (study power > 80%) and found that patients who underwent laparoscopy required significantly less morphine up to postoperative day four than patients in the laparotomy group (median, 0.78 mg/kg vs.
1.37 mg/kg, p<0.01). Furthermore, pain with coughing and fatigue were significant less in the laparoscopy group up to postoperative day seven (p<0.01, and p<0.05, respectively). In the COST trial, patients in the laparoscopic group required 2 days of IV analgesia and 1 day of oral analgesia compared to 4 days and 2 days, respectively, in the open group [4]. Other randomized trials have shown significantly less postoperative pain after laparoscopy, despite the small number of patients enrolled. [18, 20]
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A broader assessment of QOL was conducted by Weeks et al [19] who reported the early results of the COST randomized trial conducted in the United States. Quality of life was assessed by three validated instruments including the Symptoms Distress Scale, the
Quality of Life Index and a single global rating score administered preoperatively and at two days, two weeks, and two months after surgery. In an intention-to-treat analysis, the authors found that patients in the laparoscopy group (n=221) had a significantly shorter duration of both oral and parenteral analgesia requirements while hospitalized than did patients in the laparotomyl group (n=228) (p=.03 and p<0.001, respectively). There were no differences in the other aspects of QOL, except that patients who underwent laparoscopy had a greater global rating score two weeks after surgery than did patients who had a laparotomy. Among patients assigned to laparoscopy, patients who required conversion (25.7%) reported slightly poorer QOL for all measures at baseline and every follow-up assessment than did patients undergoing laparoscopy. In addition, the superiority of laparoscopy in reducing pain during the same length of the postoperative period was evident (Level I). Other aspects of QOL however, warrant further investigation.
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Hospital stay
Length of hospital stay is a common variable assessed in most laparoscopic studies. It reflects the rapidity of physiologic recovery and has economic implications with regard to operative and hospital costs.
Results from numerous retrospective and prospective series demonstrate a mean duration of hospitalization of 10.5 days, with one series reporting a mean as high as 16.6 days.
[6,8,22,23-25] However, it is difficult to make sense of this data as the length of hospitalization is as significantly influenced by the healthcare system in which the patient is treated as by the condition of the patient himself. Results from 14 non-randomized, controlled studies reveal a mean of 9.6 days in the laparoscopy group and 13.7 days in the laparotomy group. [9,10,13,14,26-32] These findings are confirmed by randomized trial results. In the trial published by Lacy et al [17], the mean duration of hospital stay was 5.2 days for patients who underwent laparoscopy compared to a mean of 7.9 days for patients who had an open procedure (p=0.005). In the trial by Weeks et al [19], the length of hospitalization was 5.1 and 6.4 days for patients who underwent laparoscopy and laparotomy, respectively (p<0.001). The COST trial revealed a hospital length of stay of
5 days in the laparoscopic group and 6 days in the laparotomy group (<0.001) [4]. Similar results were reported in the smaller randomized trials [16, 18, 20-21] adding further proof of the benefits of laparoscopy for length of hospital stay since validity is stronger when the data is analyzed among patients within the same institution treated by the same surgeon rather than by various surgeons among different centers. The only study that did
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not find a significant difference in length of hospitalization between the two groups was that of Milsom et al [15], most likely due to the protocol design wherein all patients started a regular diet on the third postoperative day. Moreover, length of hospitalization was not a study endpoint. Thus, there is high evidence (Level I) that laparoscopy for malignancy is associated with an earlier discharge compared to laparotomy.
Costs
Experience with laparoscopy for the treatment of benign disease has suggested that the short term benefits gained with the laparoscopic approach may compensate for the higher costs related to a laparoscopic procedure. Several non-randomized studies have addressed the issue of cost of laparoscopic surgery for colorectal cancer, but the results are inconsistent , primarily because of differences in perspective and methodology. In a retrospective review, Khalili et al [26] found significantly higher operating room costs when compared to the open group ($21,000 vs. $12,000; p= 0.01). However, as a result of the shorter hospital stay, total hospital costs were similar for the laparoscopic and open groups ($14,800 vs. $14,200; p=0.48). Similarly, in a small non randomized study,
Psaila et al [27] found that although laparoscopy was associated with increased operating times and increased costs associated with disposable equipment, the total overall cost was less than for the open group (p=NS). The most convincing evidence comes from a recent prospective, randomized study, in which cost analysis was performed on a subset of patients (98 laparoscopic, 111 open) participating in the Swedish Colon Cancer
Laparoscopic or Open Resection (COLOR) trial [33]. The study period included 12 weeks after surgery and the analysis examined direct medical costs (hospital costs and
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cost of outpatient care) and indirect costs, such as loss of productivity because of time absent from work. The authors found that the total cost to society were similar for laparoscopic and open procedures but that the total cost to the healthcare system were significantly higher for the laparoscopic group. The main contributors of this higher cost included higher operating room costs, and costs resulting from complications and reoperations which occurred more frequently in the laparoscopic group. However, it is critical to note that in this study there was no difference in hospital length of stay to offset the higher costs of short-term care. However, early recovery resulted in less loss of productivity such that the two approaches did not differ in economic impact.
Long-term outcome
Comparison of long term outcome among the various studies may be impaired due to the lack of homogeneity in patient selection, radiation therapy, site and stage of the tumor, time of follow-up, and violation of the “intent-to-treat principle” in some trials, which can impact recurrence and reported survival rates. Additionally, most of these studies are non-controlled, non-randomized trials with a short-term follow-up and/or a small number of patients.
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Recurrence Rates (Table 5)
Several large retrospective and prospective series have reported recurrence rates after curative resection. [8,25,34-36] These studies have had a mean/median follow-up time from 16 to 71 months; recurrence rates varied from 7.2 % to 16.1 %, including local recurrences from 1.5% to 4.1%, and distant recurrences from 6.1% to 10.3%. In contrast to earlier reports, port/extraction site recurrence rates do not seem to surpass 1% after curative resection in the majority of recent studies. [17,37]
Comparative studies have found equivalent recurrence rates between laparoscopy and laparotomy with an overall rate of approximately 4.6% and 20% for both groups. Local recurrences have reached up to 14.8% and 26% and distant recurrences up to 15% and
18.6% in the laparoscopic and open groups, respectively. [10,11,13,27-40]
The results from the randomized, controlled trial by Lacy et al included a median followup of 43 (27-85) months [17]. One hundred six patients who underwent laparoscopy and
102 who underwent open resection for non-metastatic colon cancer were available for follow-up. Postoperative adjuvant therapy was routinely given to all suitable patients with stage II or III disease with no differences between the two groups. The overall recurrence rate was not statistically significant between the 2 groups, 17% (n=18) in the laparoscopic group and 27% (n=28) in the open group (p=0.07). The type of recurrence, time to recurrence, and number of patients who had curative reoperation were also similar in both groups. The probability of remaining recurrence-free was significantly higher in the
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laparoscopic group (p=0.01). This benefit was due to the overwhelming superiority of laparoscopy over laparotomy in patients with stage 3 disease. These findings confirmed the same suggestion from a cohort-comparison study by Lord et al [29].
In the COST trial involving 872 patients, the cumulative incidence of recurrence over a
4.4-year period in patients treated with the laparoscopic procedure did not significantly differ from that for patients who underwent open colectomy for any stage of cancer [4].
In particular, the one-sided P value for the time to recurrence in favor of the open procedure was 0.83, satisfying the criteria to declare that the laparoscopic procedures did not differ significantly from that for patients who underwent open colectomy. No differentiation between local or distant recurrence was made in this particular study.
However, port site recurrences were similar in both groups with 2 occurring in the laparoscopic group (0.5%) and one in the open group (0.2%). In addition, the time to recurrence was not significantly different. The estimated difference in the 3-year recurrence-free rate was 2.4% in favor of laparoscopy. The authors concluded that the laparoscopic approach did not present any additional oncologic risk with regard to recurrence since recurrence was equivalent in both groups. Unfortunately, although laparoscopy may be superior to laparotomy, the COST trial was not designed to detect this finding.
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Survival
Several studies have reported three to five year survival (Kaplan Meier curve) data.
Retrospective and prospective reviews have demonstrated a five-year survival rate ranging from 72% to 80.9 % after curative resection with better outcomes associated with early stage carcinomas. [6,22,36,39-41]
Comparative case control and cohort studies have not demonstrated any differences in five-year survival between patients who underwent laparoscopy and those individuals who had laparotomy with rates ranging from 64% to 93% in both groups.
[10,13,14,26,32,37,42-46]. Lujan et al. [44] published one of the largest non-randomized studies. Data from 102 consecutive patients who underwent laparoscopic colorectal resection were reviewed and compared to 641 patients who had an open procedure at the same institution and with the National Cancer Data Base (NCDB) including 36,947 patients during a similar time period; complete five-year survival data were attained for
93% of the laparoscopically treated patients. Overall, the mean follow-up time was 64.4 months; patients who died were excluded. The five-year relative survival rates in the laparoscopic group were 73% for Stage I, 61% for Stage II, 55% for Stage III, and 0% for
Stage IV disease. These results were comparable to the open group and the NCDB data which showed a survival rate of 75% and 70% for Stage I, 65% and 60% for Stage II,
46% and 44% for Stage III, and 11% and 7% for Stage IV disease, respectively. Finally, the overall Kaplan-Meier fiver-year survival curve for patients treated by laparoscopy was 54% including all stages of disease and 64% for Stage I to III disease.
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Another large prospective non-randomized trial was published by Patankar et al [46] who attempted to eliminate some confounding factors such as combined analysis of different tumor sites and effect of radiation therapy. The laparoscopic group was comprised of 161 patients and the open group included 174 patients. A separate five-year survival analysis between tumors in the colon and rectum did not reveal any differences between laparoscopy and laparotomy. Analysis between survival of patients with Stage I and II colon cancers and Stage I rectal cancers was separately performed, with no differences between the two groups. Overall observed Kaplan-Meier five-year survival rate for all stages was 69% for the laparoscopy group vs. 64% for the open group (p=0.23).
The most important information with regard to survival and the effects of laparoscopy on disease-specific outcome is provided by prospective, randomized trials initiated in several countries. The COLOR group in Europe [47] reported preliminary results demonstrating short-term (less than two years of follow-up) survival rates of 95% for Stage I, 98% for
Stage II and 93% for Stage III carcinomas. There was no cancer-related death for patients with Stage I disease. The trial by Curet included survival data with outcome ranging from 2.5 to 6.3 years (mean 4.9 years). Six of 18 (67%) cancer related deaths occurred in the open group while 4 of 18 (78%) cancer related deaths occurred in the laparoscopic group [14] The randomized trial by Lacy et al [17] demonstrated no difference in survival rates between patients who underwent laparoscopy and laparotomy
(82% vs. 74%). However, the cancer-related survival rate was significantly higher in the laparoscopic group (91% vs. 79%; p=0.02). When stratified by stage, the probability of being recurrence-free, overall survival, and cancer-related survival was superior in the
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laparoscopic group, which, like recurrence, was due to the results obtained in patients with Stage III tumors (freedom from recurrence, p=0.04; overall survival, p=0.02; cancer related survival, p=0.006). The authors postulated that these findings may result from the decreased surgical stress and consequent reduced impact on immunity from laparoscopy.
This benefit may be critical for patients with Stage II tumors who are at greater risk for tumor dissemination, compared to Stage I or II disease. Anecdotally, other surgeons have confirmed these findings (48).
In summary, there may be no significant differences between laparoscopy and laparotomy for either recurrence or survival rates. Since three of the studies were prospective and randomized, the level of evidence is considered high. However, there may indeed be superiority in favor of laparoscopy for patients with Stage III disease. As techniques improve to better preoperatively stratify disease stage, we may be able to better counsel patients and guide them towards laparoscopic resection. Alternatively since the benefits of less pain, shorter hospitalization, improved cosmesis, and lower morbidity can be applied to all patients, there is certainly no harm in advocating laparoscopic resection even for patients with stage II or stage III disease.
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Conclusion
Laparoscopy for colorectal cancer has shown to be superior to laparotomy in regard to short-term benefits including pain, length of ileus, length of hospitalization, cosmesis, morbidity, and disability. When performed by appropriately skilled surgeons in properly selected patients, these short-term benefits are almost always demonstrated. Since the publication of the COST trial, it appears that laparoscopic colectomy and conventional open colectomy have similar long-term outcomes. Fundamental differences exist between the Lacy trial and the COST trial. The former study included patients all of whom were operated upon by a single highly skilled surgeon with a team devoted to laparoscopic resection. The latter study included a myriad if surgeons with a wide range of backgrounds entering a variable number of cases per surgeon. The COST trial may therefore better reflect the typical community standard than the Lacy trial. However, the
Lacy trial which found superiority relative to recurrence and survival in favor of laparoscopy suggests that, in the hands of skilled laparoscopic surgeons performing a high volume of this technique in the setting of a dedicated team, laparoscopy may be superior to laparotomy. The fact that this difference was not detected in the COST trial may be due more to study design than to case selection. In addition, other benefits, may be conferred by laparoscopy including reduced rates of ventral incisional hernia and bowel obstruction. Unfortunately, none of the randomized, controlled trials to date have included these variables for analysis. In conclusion, the COST trial prompted the
American Society of Colon and Rectal Surgeons and the Society of American
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Gastrointestinal Endoscopic Surgeons to jointly endorse an approval statement on laproscopic colectomy for curable cancer[49]. That statement claims:
“Laparoscopic colecotmy for curable cancer results in equivalent cancer related survival to open colectomy when performed by experienced surgeons. Adherence to standard cancer resection techniques including but not limited to complete exploration of the andomen, adequate proximal and distal margins, ligation of the major vessels at their respective origins, containment and careful tissue handling, and en bloc resection with negative tumor margins using the laparoscopic approach will result in acceptable outcomes. Based upon the COST
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trial, prerequisite experience should include at least 20 laparoscopic colorectal resections with anastomosis for benign disease or metastatic colon cancer before using the technique to treat curable cancer. Hospitals may case credentialing for laparoscopic colectomy for cancer on experience gained by formal graduate medical educational training or advanced laparoscopic experience, participation on hands-on training courses or outcomes.”
More recently, Abraham and coworkers performed a meta-analysis of randomized clinical trials comparing the short term outcomes of laparoscopy with those of laparotomy for colorectal carcinoma[50]. The outcomes of 2512 procedures from 12 trials were analyzed. The authors tabulated specific percentage benefits for each individual category comparing laparoscopy to laparotomy. Specifically, although laparoscopic resections took on the average 32.9% longer to perform, the average time to passage of first flatus was reduced by 33.5%, to tolerance of solid diet by 23.9%, to 80% recovery of peak expiratory flow by 44.3%, early narcotic analgesia requirements by
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36.9%, pain at rest by 34.8%, pain during coughing by 33.9%, and hospital stay by 20.6%.
In addition, the odds ratio for wound infection rate was significantly lower at 0.47. All of these findings were in the context of no significant differences in perioperative mortality or oncologic clearance. Those authors concluded that “laparoscopic resection for colorectal cancer is associated with lower morbidity, less pain, a faster recovery, and a shorter hospitalization than with open resection, without compromising oncological clearance”.
Fortunately, the slow measured growth of laparoscopy for the attempted cure of malignancy has resulted in appropriate evolution of the technique. Surgeons gained sufficient expertise working with benign conditions while medical students and residents were weaned on laparoscopic methods and instrumentation. Manufacturers have improved the technology and patients became more aware of the benefits. Costs were brought under some control and protocols were adapted to minimize hospital stay in all cases. All of these factors converged to, after 13 years, allow the widespread adoption of this technique for patients with colorectal cancer. Had adoption of the technique been explosive 13 years ago, the result relative to morbidity, mortality, recurrence, and survival may have indeed been quite different.
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24

III
I
II-1
II-2
II-3
Table 1. Levels of evidence 3
Evidenced obtained from at least one properly randomized controlled trial
Evidenced obtained from well-designed controlled trials without randomization
Evidenced obtained from well-designed cohort or case control analytic studies, preferable from more than one center or research group
Evidence obtained from comparisons between times or places with or without the intervention with or without intervention; dramatic results in uncontrolled experiments were also included in this category
Opinion of respected authorities based on clinical experience, descriptive studies, or reports of expert committees
25

Table 2. Bowel Function Recovery
Author, year Year N of patients
Prospective
Morino
6
Tsang 25
Retrospective
Melotti 7
Schiedeck
8
Zhou
23
1999
2000
2003
2003
2003
Case-control/Cohort
Seow-Choen 9 1997
Ramos
11
Goh 12
1997
1997
Schwandner
10
Hartley
13
Champault
14
1999
2001
2002
Randomized
Milsom
15
Curet
16
Lacy 17
Hasegawa
18
Bold; p<0.05
1998
2000
2002
2003
Lap
163
399
82
100
44
16
18
20
32
21
74
54
18
111
29
11
18
20
32
22
83
53
18
108
30
Open
-
-
-
-
-
2
1.9
3
4.1
3
1.4
3
2.7
1.5
2
Bowel function
( mean/median n of days)
Lap Open
2.9
3
1-2
2.9
2
-
-
-
-
-
2.5
3.0
3
5.1
4
3.2
4
4.4
2.3
3.3
26

Table 3. Postoperative pain
Author, year Year
Case-control/Cohort studies
Seow-Choen
9
Ramos
11
Goh 12
1997
1997
1997
Psaila
27
Schwandner
10
1998
1999
Randomized
Stage 20
Schwenk
21
Milsom
15
Weeks
19
Hasegawa
18
Nelson 2
1997
1998
1998
2002
2003
2004
N of patients
Lap
Less pain/ analgesic requirement
(days)?
Open Lap p value
16
18
20
29
32
15
30
54
168
29
435
11
18
20
25
32
14
30
53
No
Yes
No
Yes
No
Yes
Yes
Yes
221 Yes
30 Yes
425 Yes
-
<0.005
-
0.002
-
<0.05
< 0.01
0.02
0.03
0.0022
<0.001
27

Table 4. Hospital Stay
Author
Case series
Melotti 7
Schiedeck
8
Zhou 23
Year
1999
2000
2003
Prospective series
Yamamoto
24
2002
Anderson
22
Morino
6
Tsang
25
2002
2003
2003
Case-control/cohort studies
Lord
29
Franklin
37
1996
1996
Seow-Choen 9
Ramos
11
1997
1997
Goh 12
Khalili
26
Psaila
27
Schwandner
10
Fleshman
28
Leung 32
Hartley
13
Baker
30
Anthuber
21
Champault 14
1997
1998
1998
1999
1999
2000
2001
2002
2002
2002
Randomized
Stage
20
Schwenk
21
Milsom
15
Curet
16
Lacy
17
Weeks 19
Hasegawa
18
Nelson 2
1997
1998
1998
2000
2002
2002
2003
2004
N of patients
Lap Open
163 -
399 -
82 -
70 -
100 -
100 -
44 -
32 32
224 224
16
18
20
80
29
11
18
20
90
25
32 32
152 33
59 34
21 22
28 61
101 334
74 83
15
30
54
14
30
53
18 18
111 108
168 221
29 30
435 425
Bold; p<0.05
Hospital stay (days)
Lap Open
10.9
14
8
-
-
-
8
8.3
16.6
8
5.8
5.7
6.5
7.4
5
6.2
10.7
15.3
7.4
16
13.5
13
14.4
8.2
5
10.1
6
5.2
5.2
5.6
7.1
5
-
-
-
-
8.2
9.7
8
12.9
5.5
8.2
17.8
21.9
8.7
25.5
15
18
19.9
12.3
8
11.6
7
7.3
7.9
6.4
12.7
6
28

Table 5: Recurrence
Author, year N of patients
Lap
Mean/media n follow-up
Open
(months)
Recurrence (%)
Overall
Lap Ope n
Local
Lap
Retrospective
Huscher, 96
34
Schiedek, 00 18
146
399
Prospective
Lumley, 02
35
Anderson, 02
32
Scheidbach,
02
36
154
100
206
Case control/Cohort
Franklin, 96
37
Ramos, 97
11
Khalili, 98
26
165
16
76
Schwandner,99
10
32
Santoro, 99
38
Lezoche, 00
39
Hartley, 01
13
Feliciotti, 02
40
Randomized
Curet, 00 16
Lacy, 02
15
Nelson, 04
2
40
99
21
74
18
106
435
-
-
-
-
-
16
30
71
43
25.2
212 60
16
82
32
43
22
75
18
20
21/18
33.1/32.1
24-60
109 32.2/34.2
38
48.9
59
102 44/43
425 53
11.7
7.2
13.6
16.1 -
11.6 -
12.2
12.5
13.1
15.6
20
16 20.2 3
5
12.7
0
-
-
-
22
25
18.3
15.6
23
4.5
13.3
6
4.1
1.5
1.9
-
3.4
-
6.2
3
3.1
2.5
5
1.3
-
17 27 6.6
17 20 -
-
-
-
-
-
Ope n
Distant
Lap Ope n
6.1
6.2
-
-
10.3 -
-
8.2
-
-
- -
18.7 6.2
6
0
10
-
6.2
11
12.5 15.6
2.3 15
9.2 11
4.5 5
18.6
11
0
2.7 10.8 10.7
- -
6.6 8.8
- -
-
13.7
-
29

Author, year N of patients Mean/media
Lap Open n follow-up
(months)
Retrospective
Fleshman, 96 41 372 - 22.6
513 - - Color trial,
00
47
Poulin, 02
42
Lechaux, 02 43
Prospective
Scheidbach,
02
37
Anderson, 02
22
70
166
214
100
-
-
-
-
31
65
25.2
40.3
45.7
Surviva l
Overall Survival (%)/
TNM Stage or Dukes’ classification
Lap
3 year I:93; II- 72; III-53 -
+ 2 year I- 95; II- 98; III-93 -
5-year 72.1
3 year 79
5-year 80.9
Open
-
-
-
5-year A-100; B-76; C-
51
-
5-year I- 92; II-79; III-67 - Morino, 03
6
Schwandner,99
10
70 -
Case control/Cohort
Franklin, 96
37
165 212
Leung , 97
32
50 50
Khalili, 98 26 76 82
32 32
Santoro, 99
38
Leung, 00
45
Hartley, 01
13
Lujan, 02 44
40
19
21
43
24
22
102 641
34/4.8
32.8
21
33.1
24-60
30/28
38
64.4
60
5 year 89.7
5-year 67.2
5-year
3-year
5-year
87.5
93
4-year 84.2
3-year 71
92.4
64.1
85
93
5-year I-73; II-61; III-55 I- 75; II-65; III-
46
5year
73.2
75.8
70.1
77.8
77
74.2 Champault,
02
14
Pantakar, 03
46
62 66
161 174
Randomized
Curet, 00
16
Lacy, 02
15
Nelson, 04
2
18
106
18
102
435 425
Table 6: Survival
52
59
44
53
5 year
5-year
5 year
I-76; II-68; III-53
78
90*
4.4-year 79
I-80; II-64; III-50
66
79*
78
Bold = *p<0.05
30