Is laparoscopic colorectal cancer surgery equal to open surgery? An evidence based perspective

Abstract

Laparoscopic colorectal surgery (LCS) is an evolving subject. Recent studies show that LCS can not only offer safe surgery but evidence is growing that this new technique can be superior to classical open procedures. Fewer perioperative complications and faster postoperative recovery are regularly mentioned when studies of LCS are presented. Even though the learning curve of LCS is frequently debated when limitations of laparoscopic surgeries are reviewed, studies show that in experienced hands LCS can be a safe procedure for colorectal cancer treatment. The learning curve however, is associated with high conversion rates and economical aspects such as higher costs and prolonged hospital stay. Nevertheless, laparoscopic colorectal cancer surgery (LCCR) offers several advantages such as less co-morbidity and less postoperative pain in comparison with open procedures. Furthermore, the good exposure of the pelvic cavity by laparoscopy and the magnification of anatomical structures seem to facilitate pelvic dissection laparoscopically. Moreover, recent studies describe no difference in safety and oncological radicalness in LCCR compared to the open total mesorectal excision (TME). The oncological adequacy of LCCR still remains unproven today, because long-term results do not yet exist. To date, only a few studies have described the results of laparoscopic TME combined with preoperative adjuvant treatment for colorectal cancer. The aim of this review is to examine the various areas of development and

controversy of LCCR in comparison to the conventional open approach.

INTRODUCTION

Throughout the past decade, evidence is growing that laparoscopic colorectal surgery (LCS) can be superior to classical open procedures[1]. Fewer perioperative complications and a faster postoperative recovery resulting in shorter duration of hospital stay appear to be the main advantages[1]. The wide implementation of LCS in clinical practice made the limitations of these technically demanding procedures more clear. The learning curve in LCS is frequently debated when limitations of laparoscopy are reviewed[2-4]. An estimated 50 segmental procedures are necessary to gain sufficient proficiency in LCS[5]. Potential reasons for this prolonged learning curve in comparison to open surgery are exposure difficulties of the colonic anatomy and lack of tactile sense. The learning curve overall in laparoscopic techniques is associated with higher conversion rate, prolonged hospital stay, increased costs and higher morbidity[6]. In the early 1990s, an attempt was started to facilitate the transition from open surgeries to minimally invasive/minimal access surgery by introducing the hand-assisted laparoscopic surgical technique (HALS)[7]. The loss of pneumoperitoneum and impaired hand movements were the main obstacles encountered. For these specific reasons, hand-access ports were introduced[8,9].

The laparoscopic approach for colon resection is widely accepted but its definitive role in rectal tumors is still controversially debated due to technical difficulties and missing long-term results. Tumor size and volume and pelvic dimensions may influence intraoperative and/or immediate outcome[10,11]. Laparoscopic colorectal cancer surgery (LCCR) nevertheless offers several advantages in comparison to open procedures, including less postoperative pain, shorter duration of postoperative paralytic ileus, shorter hospital stay and less co-morbidity[12,13]. Furthermore, the good exposure of the pelvic cavity by laparoscopy and the magnification of anatomical structures seem to facilitate pelvic dissection laparoscopically[10]. Moreover, as advocated by Heald and Ryall, there is no compromise on the surgical radicality and safety while performing an adequate total mesorectal excision (TME)[14,15]. The oncological adequacy of LCCR still remains unproven today because long-term results over a time span of at least 10 years of LCCR do not yet exist. Potential concerns have arisen including port site recurrence and abdominal wall metastases when the suitability of LCCR is considered for colorectal cancer[16]. To date, only a few studies have described the results of laparoscopic TME (LTME) combined with preoperative adjuvant treatment for colorectal cancer[17,18].

Cost benefits of LCS is another area that is difficult to assess simply because total costs of a surgical procedure can be relatively easy to assess but the total economic costs are very difficult to measure because the earlier reintegration in the patient’s normal life cannot be “financially” measured by simple figures.

This review examines the various areas of development and controversy of LCCR in comparison to the conventional open approach.

ROLE OF LTME

Since the early 1970s, low anterior resection (LAR) has been the main surgical procedure to surgically treat rectal cancers[19]. Even in experienced hands the local recurrence has averaged about 30% and 5-year survival rates ranged from 27% to 42%[20,21]. Furthermore, the risk of damaging the autonomous pelvic nerve plexus resulting in a high incidence of sexual and bladder dysfunction was regularly encountered in LAR[22]. Local control and survival has been dramatically improved by the introduction of the TME first described by Heald et al[14] in 1982. TME includes the routine excision of the intact mesorectum by precise dissection in the tissue plane between the visceral and parietal layers of the pelvic fascia. Importantly, pathological studies by Reynolds et al[23] emphasized the widespread distribution of metastases within the boundaries of the mesorectal fascia. This was a strong argument for the complete resection of the mesorectum that includes uninvolved circumferential margins. Nevertheless, TME yields a considerably lower local recurrence rate[24], better function of the sphincter[25], longer survival[26] and reduction in the need for abdominoperineal amputation[27] (Miles procedure). A recent study of open TME has described local recurrence rates of 4% to 8% and cancer-specific survival rates of 70% to 80% at 5 years[28]. A prospectively randomized study of 622 patients with rectal cancer by Law et al[29] demonstrated the outcomes of the TME and of partial mesorectal excision (PME). The reported local recurrence rate in the study group undergoing anterior resection with mesorectal excision was reported as 9.7% and the cancer specific survival was 74.5%[29]. They performed TME in mid and distal rectal cancer and PME for proximal rectal cancer when a 4 to 5 cm mesorectal margin could be achieved. They reported a comparable mortality and morbidity rate whereas a significantly longer median operating time with more blood loss and a prolonged hospital stay occurred in the TME group due to the higher complexity of the TME itself compared to PME. They concluded that local control and survival of patients requiring TME is comparable to those with proximal rectal cancers where adequate clearance can be achieved by PME[29].

A major problem that limits the broad acceptance of laparoscopic cancer surgeries is the significant skepticism about LCS for cancer although laparoscopy is very popular in the treatment of many intra-abdominal disorders. The potential benefits of the laparoscopic technique must in fact be weighed against the potential for limited oncological outcomes due to inadequate resection, potential occurrence of port site metastases or metastatic spread[30-32]. Moreover, surgeons are fearful that laparoscopic surgery could be more harmful to cancer patients than open procedures[33]. To address certain important issues of laparoscopic surgeries in rectal cancer surgery, Leroy et al[19] described the application of LTME following the principles of open TME in an unselected population of patients. This study demonstrated not only that LTME is feasible and safe, but also achieved a level of cancer control at least comparable to that reported in open TME. Interestingly, they did not report a single port site metastasis of the entire study population of 98 individuals[19]. Several limitations nevertheless have been discussed by the authors. First, the study did not include a group of patients operated on by conventional surgical methods in the same period of time. Second, all surgeries were performed by only one surgeon which makes overall interpretation of data difficult because the results might not be reproducible in other hands.

Laparoscopy is relatively new and recent studies reporting randomized trials comparing open vs laparoscopic surgeries[34] have been criticized because of the high risk of bias due to surgeons operating within the early phase of the learning curve[35] and the associated effect on the treatment group.

Morbidity of the laparoscopic approach

The reported anastomotic leakage rate after LTME was 17% but only 65%[19] of these patients required a reoperation for drainage or diversion. These numbers are according to leakage rates that are reported to be as high as 10%-20% in open TME[36,37] although some series have reported rates as low as 5% after TME[38]. To prevent the risk of anastomotic leakage, some authors suggested temporary protective colostomies or ileostomies in analogy to open surgery, side-to-end anastomoses or pouches to prevent clinically apparent leakage.

Modern concepts in pouch formation

In recent years improved functional results were achieved while introducing modern concepts for rectal replacements after LAR. The colon J-pouch-anal and -low rectal anastomosis was developed by Parc et al[39] and Lazorthes et al[40]. The superiority of J-pouches over straight coloanal anastomosis has been demonstrated in multiple randomized trials and is rarely contested[41-43]. Complications of large colon J-pouches (8-10 cm) can occur by manifestations of defacatory dysfunctions with further medical necessities of suppositories, medication and enemas in about 25% to 37% of patients[44,45]. Therefore surgeons tend to construct shorter pouches with a limb length of about 5 to 6 cm[46]. Shorter J-pouch formations have improved functional results which have been confirmed in randomized controlled studies[47,48]. A modern concept of a transverse coloplasty pouch was explored by Z’graggen et al[49] where 37 patients underwent low anterior rectal resection with TME for rectal cancer and 4 for benign pathology. Total intraoperative complications occurred in 7% of patients and all were unrelated to the transverse coloplasty pouch. Furthermore, apart from nonexistent hospital mortality, the total complication rate was 27%. An anastomotic leakage rate was recorded as 7%. Furthermore, dysfunction such as stool urgency, fragmentation and incontinence grade 1 and 2 were regularly observed within the initial 6 mo; thereafter the incidence decreased significantly. None of the patients had difficulties in pouch evacuation. The authors concluded that the transverse coloplasty pouch can be safely used for reconstruction after sphincter-preserving rectal resection[49]. The early function of this small-volume reservoir is favorable and can be compared to other colonic reservoirs. Furthermore, long-term problems of pouch evacuation can be avoided with this concept of a transverse coloplasty[49]. Whether there is a clinical significant difference in pouch formation performed in open vs laparoscopic surgery, or long term function of these pouches is not compared today and potentially assumed to be equal.

Oncological outcomes and adequacy of lymph node dissection

One aspect of great concern is whether laparoscopy provides a radicality of resection equivalent to that of the open procedure in terms of oncological outcomes. For a successful cancer operation several objectives must be achieved: adequate tumor margin, adequate lymph node dissection and prevention of the spillage of cancer cells into the peritoneal cavity or the adjacent lumen of the bowel[19]. Only two recent studies reported superior recovery of distal margins during open right colectomy[50], whereas Lord et al[51] similarly reported superior recovery of distal margins during laparoscopic-assisted anterior resection for colorectal cancer. Leroy et al[19] demonstrated that all laparoscopically operated patients had negative margins although these results were not prospectively assessed. The mean tumor free margin was 3.46 cm[19]. However, a limitation of this study was that the impact on local recurrence as well as on overall survival could not be determined. With regard to lymph node dissection, two randomized trials[52,53] compared the outcomes of LCCR with the standard open procedure. In terms of recovered lymph nodes, none of the mentioned studies found a significant difference between the laparoscopic or the standard open procedure[52,53]. Despite these results, Leroy et al[19] debate whether the harvest of lymph nodes per se is an appropriate measure of the adequacy of a technique because the number of lymph nodes identified in a specimen is not only dependent on the surgeon but also on the diligence of the pathologist. The relevance of lymph node assessment as an outcome measure is probably not adequate because the pathologic result is often not included as a primary endpoint of the study.

Local recurrence and port side metastases

The local recurrence rates reported by Enker et al[54] of 6% are comparable with a published series of open TME. In a long-term study by Heald et al[55] an overall 6% rate of local recurrences at 5 years post surgery and 8% after 10 years was found. Another study by Hainsworth et al[56] reported an overall recurrence rate of 11% that was stage dependent i.e. 0% for Duke’s A stage, 8% for Dukes B and 30% for Dukes C. Advanced lymph node disease (N2) as well as perineural invasion and positive lateral margins were reported as risk factors for local recurrence[56,57]. Because of the relatively low number of local recurrence after either open or LCS, future prospective randomized trials have to be adequately powered to gain further information about this crucial issue.

Even though port side metastases occur, they seem to be only a minor obstacle that occurs during laparoscopic colectomy. A recent review of 20 laparoscopic colectomy studies performed between 1994 and 1998 found 30 port site metastases of about 1% after a mean follow-up of 10-33 mo[58].

Long-term survival in LTME

The overall 5-year survival rate published by Leroy et al[19] was 65% and the overall cancer specific 5-year survival rate was 75%. These numbers are potentially in favor with previously reported results of open surgery. A multicenter study by Havenga et al[59] found 5-year survival rates of overall survival and cancer-specific survival of 62%-75% and 75%-80% respectively[59]. Variations in survival rates

between studies can be related to differences in the makeup of the study population. In this regard, important factors such as the inclusion of patients undergoing palliative resection, acceptance of screening colonoscopies in the population, differing definitions of curative surgery and a mix of different stages makes it almost impossible to judge common outcomes objectively and this can impact on the study results. Multicentric studies with clearly defined inclusion and treatment criteria may contribute to a better comparison of study results and also potentially influence further study groups to maintain certain “gold” standards. Therefore, the comparability of studies might become more transparent and the interpretation of their results more obvious.

COST EFFECTIVENESS

In times of financial restrictions when health insurance rates are increasing every year, the cost effectiveness of a new medical procedure needs to be addressed carefully. Today there is no doubt that laparoscopic procedures are more costly compared to open surgeries if only direct medical costs such as materials, salaries and infrastructure are considered. What remains unclear is whether laparoscopy is as cost effective in terms of overall costs compared to open surgery. This assessment includes non-hospital related economic costs including cost reduction to the social health care system where patients are perhaps re-integrated earlier in their normal social and professional lives.

There are however, studies that compared the cost effectiveness of HALS and LCS. Targarona et al[60] described the total costs for HALS and laparoscopic-assisted colectomies (LAC) surgery including operating room costs, salaries of personnel and costs of disposable and non-disposable materials. They did not find a significant difference in total costs for surgery between LAC and HALS group.

Polle et al[61] on the other hand described costs for surgery and hospital admission. In their study, overall costs for surgery were significantly higher in the LAC group[61] due to the higher costs of disposable materials such as trocars and the longer operating time required for LAC. However, the total costs for LAC were lower (by € 1864) compared to the HALS group. This reduction in total costs was not statistically significant and was explained by the earlier discharge of patients that underwent LAC.

POTENTIAL ADVANTAGES OF THE LTME

Every new surgical technique faces hurdles, initial weaknesses and limitations. The development of refined instrumentation combined with a set of specific surgical skills has tremendously aided the implementation of advanced laparoscopy in colorectal surgery. Whereas laparoscopy is considered as the method of choice for cholecystectomies, laparoscopic approaches are still under debate for colorectal surgeries. Multiple studies and centers have proven that advanced surgical procedures such as laparoscopic pancreaticoduodenectomy[62], laparoscopic-assisted esophageal cancer operations[63], laparoscopic subtotal gastric cancer operations[64] and others are technically feasible though not necessarily beneficial even when practiced in specialized centers.

While many considerations have been placed on the potential negative impact of LCS on patient outcomes, little attention has been paid to discovering the potential of laparoscopy in helping to improve those outcomes. Greater patient comfort and earlier hospital discharge while ensuring the oncological radicality as detailed in recent studies, display potential benefits of laparoscopic procedures in colorectal surgery.

A major advantage of laparoscopic surgery lies in the magnification that is offered by the endoscopic camera which enables greater surgical precision and better identification of tissue structures such as the presacral nerve plexus. Preservation of this plexus is an important quality measurement of every rectal cancer operation independent of the approach. The dissection of this plexus may be particularly demanding in a narrow deep pelvis. Furthermore, to perform deep pelvic dissection with full preservation of the presacral nerves in full view and magnification offered by the laparoscope will undoubtedly improve and accelerate the teaching of colorectal cancer surgery. This important step may potentially lead to greater standardization of the surgical approach and technique.

To address the importance of a standardized procedure, it is pertinent to note that a major problem of published studies on adjuvant therapy in the treatment of rectal carcinoma is that the surgical procedures have not been strictly standardized in these studies. Therefore, the unbiased effect of adjuvant therapies in rectal cancer is difficult to assess. The only way to study the effect of neoadjuvant treatment in colorectal surgery would be when strictly standardized and quality-controlled procedures are performed[65]. In this type of approach lies another important advantage of LCS. Laparoscopy per se enables the operation to be recorded and differences in operative technique to be documented. Standardization processes become easier to manage and may improve the quality of studies significantly. Documented videos can be used to prove that adherence to the strict oncological criteria was maintained.

The possibility that laparoscopy will lead to an improved platform for expanded opportunities for instructions have a particular relevance in rectal surgery. Despite the improvements gained through the implementation of adjuvant and neoadjuvant treatments, the individual skills of the surgeon remains an important factor in tumor control and the reduction of disease and morbidity[66,67]. Local recurrence rates after rectal surgeries can be decreased by over 50%; this impressive improvement was achieved by a surgical teaching initiative in the county of Stockholm[68] and shows the effectiveness of adequate teaching and standardization in surgical techniques. Calculations have demonstrated that if optimal TME surgery could be widely implemented, the outcome improvement in terms of decreased local recurrence rates and better survival would be about four times greater than that achieved by adjuvant therapy - and at a fraction of the cost[69]. More refined computer simulations of surgical procedures and virtual reality training systems may further improve the practice of laparoscopic surgery for various fields such as rectal cancer[70-72].

Improved future technology will make laparoscopic instruments even more suitable for robotic control and video images are well suited for transmission. This will make it possible to perform laparoscopic surgeries even from remote distances[73]. This enables an expert surgeon to teach or monitor the performance of an advanced or new technical approach by real-time intervention. Such long-distance communication and teaching has the potential to blunt the learning curve and improve teaching and training. Finally, this could lead to an improvement in greater (and perhaps global) standardization of surgical procedures.

In times of financial restrictions, the overall costs of surgical procedures are of great importance. Although the overall costs are considered to be generally higher for laparoscopic procedures than open surgeries, the benefits of an early return to work and a reduction in intra-abdominal adhesions could offset these higher costs in the long run. Certain studies, including randomized controlled trials[13], have documented a number of advantages of laparoscopy in the short term including earlier hospital discharge, less pain and use of narcotics, improved and earlier bowel function and earlier resumption of a normal diet[52,53]. In terms of quality of life (QoL) outcomes, a recent multicenter study showed a significant reduction in the postoperative requirement for analgesia and a shorter hospital stay was reported in laparoscopic surgery. But despite these facts, the short-term QoL benefits for laparoscopic procedures were only minimal compared to open surgery[34].

Other studies have demonstrated that LCS is more expensive and time consuming than open procedures[74]. The mean operative time reported by Leroy et al[19] for LTME was 202 min. This figure compared favorably with other data presented by Heald et al[55] who described a mean operative time of about 4 h for open TME. Traditionally the laparoscopic approach has been associated with longer operating times than open surgeries. It can be assumed that the improved technology over the past decade (i.e. enhanced magnification and improved visualization of the narrow pelvis) coupled with the broad implementation of new laparoscopic techniques and improved technical expertise may explain the strides made in LTME as described by Leroy et al[19].

The laparoscopic rectal resection with anal sphincter preservation for rectal cancer is laparoscopically feasible and safe and offers short- and long-term outcomes comparable to conventional surgery[75,76]. Dulucq et al[75] suggested that elective LTME with anal sphincter preservation for rectal cancer is safely performed in expert hands and gives excellent short-term as well as long-term results. Jayne et al[76] reported that laparoscopic-assisted surgery for colon cancer is as effective as open surgery in terms of oncological outcomes and preservation of the QoL. Furthermore, they supported the continued use of LCS because also the long-term outcomes of patients undergoing LCCR were comparable to those with open surgery[76]. Another randomized study by Basse et al[77] demonstrated in 60 patients that the functional recovery after colonic resection is rapid with a multimodal rehabilitation regimen. There were no differences reported in the open vs the laparoscopic operation technique[77].

The presented studies show that the standards of correct rectal cancer resection including high ligation of the inferior mesenteric artery, a complete lymph node dissection and a complete resection of the mesorectum with an intact visceral pelvic fascia can be met laparoscopically. To further clarify whether the laparoscopic approach is potentially advantageous in certain aspects such as cost effectiveness and potentially in the QoL in comparison to the open surgical procedure, a controlled randomized study is needed. In such a trial, a large number of patients from the same collective should randomly be evaluated for either the LTME or the open TME.

CONCLUSION

The Basingstoke experience of TME has clearly demonstrated that open TME can cure rectal cancer by surgical therapy alone in 2 of 3 patients in all stages and in 4 of 5 patients having curative resections. Within this progress in treating this life threatening disease, a new concept of laparoscopic cancer surgery has evolved and is measured by the impressive achievements and criteria of open TME. LTME is technically feasible and has evolved into a trusted concept in experienced hands. Although certain limitations and shortcomings including insufficient long-term results remain, the technical progress has dramatically improved over the last decade and is no longer considered a major obstacle to safely perform LTME. Surgical and oncological limitations such as port site metastasis and oncological incomplete resections are no longer considered to affect the LTME in terms of oncological correctness and potential harm to patients. Although many studies have shown the benefits of laparoscopy for colorectal cancer including reduced postoperative complications, decreased surgical trauma, faster postoperative recovery, survival rates and long-term survival similar to those of open surgery[76-80], only a few studies have reported advantages of laparoscopy for rectal cancer[19,81]. A primary reason for this could be the lack of consensus regarding laparoscopy in the treatment of rectal cancer as well as the high levels of technical skills that are necessary. Future controlled randomized studies, comparing LTME vs TME are necessary to answer not only questions such as long-term outcomes, cost effectiveness, oncological correctness and radicality but also patient safety in terms of morbidity, mortality and QoL.