Minimally invasive approaches for the treatment of inflammatory bowel disease

Abstract

Despite significant improvements in medical management of inflammatory bowel disease, many of these patients still require surgery at some point in the course of their disease. Their young age and poor general conditions, worsened by the aggressive medical treatments, make minimally invasive approaches particularly enticing to this patient population. However, the typical inflammatory changes that characterize these diseases have hindered wide diffusion of laparoscopy in this setting, currently mostly pursued in high-volume referral centers, despite accumulating evidences in the literature supporting the benefits of minimally invasive surgery. The largest body of evidence currently available for terminal ileal Crohn’s disease shows improved short term outcomes after laparoscopic surgery, with prolonged operative times. For Crohn’s colitis, high quality evidence supporting laparoscopic surgery is lacking. Encouraging preliminary results have been obtained with the adoption of laparoscopic restorative total proctocolectomy for the treatment of ulcerative colitis. A consensus about patients’ selection and the need for staging has not been reached yet. Despite the lack of conclusive evidence, a wave of enthusiasm is pushing towards less invasive strategies, to further minimize surgical trauma, with single incision laparoscopic surgery being the most realistic future development.

INTRODUCTION

The past 20 years have seen dramatic improvements in the treatment of inflammatory bowel disease (IBD)[1]. Medical therapy, especially with the advent of biologics, has significantly increased efficacy of disease control, even if the actual reduction of the need for surgery is still debated, and concerns have been raised about potential negative impact on postoperative outcomes[2,3]. In this setting, the introduction and implementation of minimally invasive surgical techniques has substantially improved outcomes and quality of life in this particularly frail patient population[4,5]. After the first description of laparoscopic colectomy about 20 years ago, laparoscopic surgery slowly has gained wide acceptance for the treatment of colorectal diseases, showing several advantages in short-term outcomes over open surgery in randomized trials and meta-analysis, with comparable safety and long-term results[6-9]. However, the diffusion of laparoscopy for IBD is proceeding particularly cautiously, given the magnitude of the procedures required for the most complex cases and the difficulty in handling severely inflamed tissues, as proven by the high conversion rates observed even in the hands of surgeons with documented experience in IBD and laparoscopic surgery[10,11]. Cronh’s disease (CD) and ulcerative colitis (UC) represent real surgical challenges, due to thickened mesentery, strictures, abscesses, inflammatory masses, and enteric fistulae in CD, and intense inflammation leading to colonic distension and high risk of bleeding and accidental perforation in UC[12,13]. The quest for further reduction of surgical trauma is ongoing, and if the natural orifice transluminal endoscopic surgery has unsolved issues related to the violation of uninvolved hollow viscera, costs and specific training, single incision laparoscopic surgery (SILS) seems to be a reasonable approach capable of minimizing the overall trauma and extent of incisions, with benefits in short term outcomes and cosmesis[14-17].

The aim of this article is to provide a comprehensive review of the state of the art in minimally invasive approaches to IBD, highlighting the current standard of care, with a glance at the most promising future directions.

CD

Approximately 70% of patients with a diagnosis of CD will eventually require a surgical treatment, due to failure of medical therapy, septic complications, recurrent intestinal obstruction, and malnutrition[18]. The treatment of CD has traditionally represented a challenge even in open surgery, with just two prospective randomized trials comparing laparoscopic vs standard approach published to date[19,20], and with the long-term results of these studies only recently available[21,22]. The panintestinal involvement and inflammatory complications, along with the additional risk for postoperative complication, increased by the aggressive medical management, make CD patients particularly poor laparoscopic candidates[23]. Concerns have been raised about missing occult segments of disease and critical strictures due to the lack of tactile sensation, technical difficulty due to inflamed bowel mesentery and the presence of adhesions, fistulas, and abscesses[24]. In order to overcome this issues, some authors have advocated the use of laparoscopic-assisted or hand-assisted laparoscopic surgery procedures, with the rationale that an incision is needed for specimen extraction, and the handling of inflamed Crohn’s tissue is easier and safer when an assisted method is used, while maintaining the advantages of a minimally invasive approach[25]. The intrinsic difficulty of this surgery is further confirmed by a study by Hamel at al[26], that showed no differences in morbidity or conversion between the earlier and the latter time periods of the experience, thus negating the effects of the learning curve. Alves et al[27] looked at the risk factors of conversion in a prospective study on 69 patients undergoing primary laparoscopic ileocecal resection, observing a conversion rate of 30%, with recurrent CD, intra-abdominal abscess and fistula independent risk factors on multivariate analysis. Even if minimally invasive surgery for CD is technically complex, requiring specific training and longer operating time[28], data in the literature confirm the safety and efficacy of this approach in terms of postoperative pain, cosmesis, return to normal activity, and, more importantly, surgical recurrence rates[29]. Despite this evidence, in a recent study by Lesperance et al[30] on 49 609 patients admitted for CD that required surgical treatment from the 2000-2004 Nationwide Inpatient Sample, only 2826 cases (6%) underwent a laparoscopic resection, demonstrating that the vast majority of CD patients are still undergoing open conventional surgery, with a minimal invasive approach mostly reserved for patients who are younger (< 35 years old), female, admitted to a teaching hospital, with ileocecal, uncomplicated disease. The increased adoption of the laparoscopic approach for the treatment of CD in teaching hospitals confirms the peculiar technical complexity of minimally invasive procedures in this setting, requiring more skilled colorectal surgeons, as can be found in referral centers where specific laparoscopic training programs are implemented.

Terminal ileal CD

The small samples size and selection bias explain the conflicting results in the initial published series of ileocolonic CD treated by laparoscopic surgery[28,31-34]. In our series of selected consecutive patients with elective, complex and even recurrent terminal ileal CD, laparoscopic patients had faster postoperative recovery - partially related to less postoperative pain and consequent decreased need for intravenous narcotics - and similar operating times compared to the open cohort, without increased complication and recurrence rates, with potential overall cost savings[35]. In regards to the issue of costs associated with laparoscopy, Young-Fadok et al[36], in a case match study comparing 33 cases of laparoscopic ileocolic resections with 33 open, showed significantly lower direct and indirect costs in the laparoscopic group.

The strongest evidence available comes from the only two prospective randomized trials present in the literature, both conducted on small samples of highly selected patients. Although such populations might be far from the reality of a tertiary referral center, it is the only way to randomize CD patients given the panintestinal, relenting nature and often unpredictable presentation of the disease. In the trial by Maartense et al[19], patients with a fixed palpable inflammatory mass, prior median laparotomy, earlier bowel resection, or pregnancy were excluded. In this study, the laparoscopic approach showed longer median operating time, shorter hospital stay, lower 30-d post-operative morbidity, but no differences in quality of life, the primary endpoint of this study. After a median follow-up of 6.7 year, there were no differences in recurrence rate and need for reoperation between open and laparoscopic group, with a 58% relapse free rate and no patients in the laparoscopic group requiring a reoperation for incisional hernia or adhesive small bowel obstruction[21]. Even if a minimal invasive approach did not impact the overall quality of life, body image and cosmesis scores were significantly higher after laparoscopy[21]. These data differ from the previous observation by Thaler and colleagues, that found long-term quality of life significantly reduced in patients with CD compared to general healthy population, irrespective of the surgical approach, with recurrence identified as the only significant predictor of poor quality of life[37]. In the other randomized trial, Milsom et al[20] included only patients with isolated Crohn’s disease of the terminal ileum with or without cecal involvement. The results of this study demonstrated that laparoscopy offers faster recovery of pulmonary function, fewer minor complications, and a trend towards shorter length of stay compared with conventional surgery, even if no differences in the amount of morphine equivalents, return of bowel function and length of stay were found. After a mean follow-up of 10.5 years there were no significant differences between groups with regard to use of medications to treat CD and recurrence rates, both clinical and surgical. Furthermore, two laparoscopic patients underwent lysis of adhesions while none did in the open group, with an incidence of incisional hernia repair of 4% in the laparoscopic group vs 14% in the open (both differences were not statistically significant)[22]. Recently, Dasari et al[38] conducted a meta-analysis of the aforementioned trials, and found that laparoscopic patients had a trend towards less wound infection and shorter hospital stay, with comparable incidence of other postoperative complications, duration of postoperative ileus, incidence of anastomotic leak and intraabdominal abscess, 30-d reoperation rate, and actuarial disease recurrence rates. To date, three meta-analysis comparing laparoscopic and open surgery for ileocolonic CD have been conducted, all demonstrating that laparoscopic surgery is associated with prolonged operative time, shorter duration of postoperative ileus, shorter hospital stay and lower incidence of early postoperative complications[39-41]. Other significant findings from these studies also include similar intraoperative blood loss and complications[41], with a trend toward lower overall costs with laparoscopic surgery[39], and no differences in the rate of disease recurrence[40]. With regard to the long-term outcomes, the study from Washington University, comparing 63 CD patients treated laparoscopically with 50 open ileocolic resections, found that the two groups had a recurrence rate of 9.5% and 24%, respectively (difference not statistically significant), with the laparoscopic group having shorter mean follow-up, thus confirming the non-inferiority of the laparoscopic approach. Interestingly, 50% of the recurrences in the laparoscopic group and 33% in the open group were able to be retreated laparoscopically[29].

Laparoscopy in complicated/recurrent CD

In complicated CD laparoscopy is even more challenging. Seymour and Kavic analyzed their series of 17 patients managed with laparoscopic approach for complicated CD (defined as for the presence of fistulas, multiple or long-segment disease, abscesses and previous operations). In this study, conversion to open procedures was not always required, but operative time and postoperative hospital stay were longer compared to laparoscopic ileocecal resections for uncomplicated disease, with major complications occurring in 18% of patients[42]. In the literature, surgical recurrence rates are reported as high as 70% to 90%, and multiple procedures are required in more than 30%[12]. In a recent study from France, of 62 reoperations for CD recurrence in 57 patients, 29 were performed laparoscopically. While no differences between the two groups were observed in terms of use of a temporary stoma, mean operating time, postoperative mortality (nil in both groups), overall morbidity rate, severe complications, median hospital stay, and conversion rates, a higher number of intraoperative intestinal injuries was reported in the laparoscopic group (5 vs 0) (P = 0.01). The occurrence of fistulizing disease was a risk factor for conversion, and conversion did not seem to affect complication rate[43]. A study from Japan looked at 16 laparoscopic procedures for CD recurrence at the anastomotic site out of 61 attempted laparoscopically by experienced surgeons in 52 patients. The result of this study showed that while the operating time was significantly longer in the recurrent group, there were no differences in the rates of postoperative complications and hospital stay, with the repeated laparoscopic operations performed using the same small incision as that of the primary operation. The advantage of a minimally invasive primary approach are supported by the fact that the operating time was shorter and blood loss was less in patients who underwent the primary procedure laparoscopically[44]. Finally, in the experience by Goyer et al[45] on 54 complex CD (defined as recurrent or complicated by abscess and/or fistula) compared with 70 patients with uncomplicated CD, the complex group had increased operative time, conversion rates and use of temporary stoma. Conversely, no differences were noted in overall postoperative morbidity, including major surgical postoperative complications and hospital stay, leading to the conclusion that complex CD should not be considered an absolute contraindication to a laparoscopic approach in experienced hands.

Crohn’s colitis

In contrast with the data available on minimally invasive surgery for terminal ileal CD, very few series have been published on CD of the colon. The feasibility and safety of a laparoscopic approach to subtotal colectomy for CD was addressed by Hamel et al[46], who observed a higher rate of intraoperative complications compared to ileocolic resection, while hospital stay and postoperative complication rate did not differ between the two groups. Contrasting results come from a recent case match study by the Cleveland Clinic group on 27 laparoscopic and 27 open cases, with a conversion rate of 26%. In this series, laparoscopic colectomies took longer with similar blood loss and postoperative complications, along with a trend towards shorter time to first bowel movement and length of stay, which became statistically significant in favor of laparoscopy when overall length of stay included 30-d readmissions[47]. In our own personal experience on 125 patients who underwent colectomy for CD, 44% by a laparoscopic approach, the conversion rate was 10.9%, median operative time, blood loss, return of bowel function and length of post-op stay were reduced in the laparoscopic group, while postoperative complications and disease recurrence rates were similar, suggesting that a laparoscopic approach for CD of the colon is safe and feasible in the hands of experienced surgeons[48].

Laparoscopy has a role also in creating diverting stomas for severe perianal CD, reducing the number of incisions to few trocars and the ostomy site. In a study by Liu et al[49] on 80 patients who underwent laparoscopic stoma creation over a 10-year period (ileostomy 30, colostomy 49, conversion 1), the overall morbidity rate was 11% with five major complications requiring reoperation, and no further stoma complications recorded within a 1-year follow-up.

UC

Despite significant advances in the medical treatment of UC, surgery remains definitive cure for these patients after failure of medical management or diagnosis of neoplastic degeneration[50,51]. A restorative procedure with the creation of an ileal pouch anal anastomosis (IPAA) is universally considered the standard of care. The earliest reports of a laparoscopic approach to ulcerative colitis was published in 1992 by Peters et al[52], who described the technique of laparoscopic proctocolectomy for two UC patients. The same year, Wexner and colleagues reported the first case-controlled series on the outcome of laparoscopic-assisted proctocolectomy with IPAA, showing a longer operative time compared to open procedure, and comparable postoperative ileus and hospital stay, with no shot-term benefits in favor of laparoscopy[53]. Since then, numerous series have been reported both in the adult and pediatric patient populations[54-56], but only from single institutions with short follow-ups[5,57]. Universally, these initial studies showed that laparoscopy took longer, with the exception of the series published by Araki et al[58]. In these studies only the colonic mobilization was performed laparoscopically, with vessel transection and rectal mobilization carried out through a mini laparotomy[53,58-61], with the exception of the series reported by Marcello et al[55], where a totally laparoscopic techniques was adopted, reserving a mini laparotomy only for specimen extraction. Subsequently, in a study from the Netherlands, 60 patients were randomized for hand assisted or laparoscopic restorative proctocolectomy with IPAA. The results from this study failed to show statistically significant differences in terms of morbidity, postoperative stay, quality of life at 3 mo after surgery, and overall costs, but the operative time for laparoscopy was significantly longer[62]. In a subsequent study, Polle et al[63] observed that female patients reported higher body image and cosmesis scores compared to open group, while there were no differences in functional outcome, morbidity, and overall quality of live. Similarly, Dunker et al[59] compared 16 patients who underwent restorative surgery with laparoscopic technique with 19 open patients. The authors found that laparoscopic patients showed significantly higher satisfaction with the cosmetic results and better body image, but once again functional outcome and quality of life were similar between groups. It seems evident, as it may have been expected, that laparoscopic IPAA offers significant advantages over the open conventional procedure in terms of body image and cosmesis, important factors in the acceptance of surgery in this young patient population, while conflicting results have been reported in terms of postoperative recovery. Faster return of bowel function after laparoscopy and decreased use of narcotics have been reported by some authors, not always translating into shorter hospital stay[57,62]. On the other hand, concerns have been raised regarding the duration of surgery often noted to be longer than open surgery even by very experienced laparoscopic surgeons, often resulting in higher costs. In regards to long-term pouch function, quality of life and complications, very few studies are available with adequate follow-up[5,57,62,63,59]. These observations were confirmed in a Cochrane review on 607 patients from 12 studies, only one randomized, which did not found any significant differences in complications, readmission, reoperation rates and mortality. However, once again, it showed that laparoscopic IPAA is associated with a significantly longer operating time, along with the inability to confirm conclusively the presumed short-term benefits of laparoscopy, with length of follow-up too short for evaluating long-term outcomes[64]. Similar results were obtained in a subsequent meta-analysis on 16 studies, only one randomized, by Wu et al[13]. Postoperative fasting time and hospital stay were shorter for laparoscopy, and overall complication rates were higher after open surgery. Once again, laparoscopy took significantly longer and no advantages were demonstrated in terms of recovery of bowel function, postoperative septic complications, anastomotic leakage, postoperative bowel obstruction, blood loss, and mortality[13]. In our personal experience with 73 laparoscopic IPAA with a mean follow-up of 24 mo, the minimally invasive approach offered a statistically significant earlier return of flatus and resumption of diet, less intraoperative blood loss, and lower incidence of incisional hernias compared to 106 open IPAA, with no differences in overall complication rate, pouch function and quality of life[65].

The controversy about the safety of a single-stage procedure has not been resolved yet. Since long-term functional outcomes after IPAA are threatened by the occurrence of pouch-related septic complications, every effort should be made to reduce such complications and to identify patients at risk for pouch-related sepsis[66]. In a study by Marcello et al[67] on 59 patients who underwent laparoscopic proctocolectomy for UC, where only 9 patients received a diverting stoma at the primary procedure, 9 patients, all on high dose immunosuppressors or elevated body mass index, required a secondary ileostomy for postoperative complications. Better results were reported by Ky et al[68], with only one out 32 patients with an anastomotic leak requiring secondary diversion after one-stage laparoscopic restorative proctocolectomy. It is hard to analyze these data since these results can be influenced by patients’ selection; pelvic sepsis is reported to occur in up to 23% of patients after IPAA for UC, especially after the introduction of biologic therapy for IBD, in most cases secondary to an anastomotic leak[66,69-72]. In a recent study on 118 UC patients treated with a minimally invasive approach, we compared a 3-stage approach (laparoscopic abdominal colectomy followed by pouch surgery with a diverting loop ileostomy, 50 patients) with a 2-stage approach (laparoscopy colectomy with IPAA and diverting stoma at the initial operation, 68 patients). We observed a significant higher rate of septic complications in the 2-stage group (38.2% vs 21%, P < 0.05), despite 3-stage patients had been receiving a more aggressive medical therapy in the immediate preoperative period[73].

The role of laparoscopy for the treatment of ulcerative colitis in the emergency setting has been investigated by two studies. In the study by Bella and Seymour, 18 patients underwent laparoscopic-assisted restorative proctocolectomy for fulminant colitis, reporting a postoperative complication rate of 33%, with a length of stay of 5.0 d, which was shorter compared to the 8.8 d reported for the 6 open cases analyzed in the study[74]. The other study, by Marcello et al[67], reviewed the data from 19 laparoscopic and 29 conventional total colectomies with end ileostomy and mucous fistula buried within subcutaneous tissue for acute, not fulminant, UC, demonstrating longer operative time (210 vs 120 min) but lower complication rates (16% vs 24%), earlier return of bowel function (1 vs 2 d) and shorter length of stay (4 vs 6 d) for the laparoscopic group.

SILS IN IBD

During the last few years an increasing number of reports and case series on SILS colorectal resections for both benign and malignant diseases have been reported. Few studies have been published comparing SILS to standard laparoscopy, showing potential for improved short-term outcomes[75-78]. Besides the obvious cosmetic advantage resulting from a reduced number and size of scars - particularly important in a young IBD patient population - limiting the incisions seems to result in less postoperative pain, less use of narcotic pain medications, with consequent faster recovery and earlier discharge, along with a lower incidence of wound-related complications[17,76,78-80]. These data are still preliminary, with only few cases of SILS for UC published to date[4,16,17,75-78,81-92]. We believe that particularly for total abdominal colectomy (TAC) the SILS approach is a very attractive option in this patient population, representing a true “scarless” procedure, with the only access to the abdominal cavity at the site of the future stoma. Our preliminary results with the adoption of a well-standardized SILS approach to TAC confirm the potential of this technique in improving the postoperative recovery in selected patients, without significant increases in operative time and costs[93].

CONCLUSION

During the past three decades the evidence has been accumulating in favor of a minimally invasive approach to IBD. Crohn’s disease is probably one of the most challenging diseases to treat laparoscopically for the colorectal surgeons, especially when the disease is located in the colon and involves multiple segments, thus explaining the fact that in the United States the majority of CD patients are still approached with open surgery. Laparoscopic IPAA for UC has been shown to be feasible, but to date the evidence present in the literature is still not conclusive. Current data suggest a shorter length of stay, shorter ileus, faster recovery and less postoperative pain, along with better cosmesis with minimally invasive surgery. On the other hand, significantly longer operative times with laparoscopy are universally reported. Our goal and responsibility is to explore new avenues for a true minimally invasive approach to IBD and to train the next generation of surgeons to facilitate wide spread acceptance of laparoscopy.