“Down-to-Up” transanal NOTES Total mesorectal excision for rectal cancer: Preliminary series of 9 patients

Abstract

BACKGROUND:

Applications for natural orifice translumenal endoscopic surgery (NOTES) to access the abdominal cavity have increased in recent years. Despite potential advantages of transanal and transcolonic NOTES for colorectal pathology, it has not been widely applied in the clinical setting. This study describes a series of nine patients for whom we performed transanal retrograde (“Down-to-Up”) total mesorectal excision for rectal cancer.

MATERIALS AND METHODS:

Under IRB approval, informed consent was obtained from each patient with rectal adenocarcinoma. Rectosigmoidectomy with total mesorectal excision was performed using low rectal translumenal access to the mesorectal fascia and subsequent dissection in a retrograde fashion. This was achieved using either a single port device or flexible colonoscope with endoscopic instrumentation and laparoscopic assistance. This was followed by transanal extraction of the specimen and hand-sewn anastomosis.

RESULTS:

Mean operative time was 311 min. Mean hospital stay was 7.56 days. Complications occurred in two patients, and consisted of one anastomotic leakage with reoperation and one intraoperative conversion to open surgery because of impossibility to dissect the specimen. TME specimen integrity was adequate in six patients.

CONCLUSION:

This series suggests that a retrograde mesorectal dissection via a NOTES technique is feasible in patients with rectal adenocarcinoma. This technique may act as a complimentary part of operative treatment for rectal cancer alongside other minimally invasive strategies. Long-term follow up will be needed to assess oncological results.

INTRODUCTION

Natural orifice translumenal endoscopic surgery (NOTES) has emerged in recent years as a promising new alternative to open and laparoscopic access for abdominal surgery. Potential benefits in avoiding the complications of surgical incisions encouraged the first successful series of clinical applications for transvaginal and transgastric NOTES.[1,2]

Access via the anal canal in the form of transrectal or transcolonic NOTES appears to be an attractive option for treating both colorectal and other abdominal diseases.[3,4,5,6,7] In fact, full thickness rectal wall excision extending into the peritoneal cavity with hand-sewn closure by transanal endoscopic microsurgery (TEM) is not a new concept.[8] Technical obstacles such as the risk of infection, safe entrance into the abdominal cavity and reliable closure of the bowel wall have been inhibiting factors that have prevented the progress of transrectal and transcolonic applications in particular. Our institution has developed innovative techniques in transanal perirectal access in animal studies and subsequently in human subjects. Access via this method, Perirectal NOTES Access (PNA), allows access to the mesorectal fascia and therapy in the retroperitoneal space and ultimately the abdominal cavity if needed. Total mesorectal excision (TME) with high lymphadenectomy is the standard of care for curative resection of rectal cancer[9,10] and there is good evidence showing that minimally invasive surgery has equivalent oncological outcomes.[11] This study describes our first series of transanal Down-to-Up TME NOTES for patients with rectal cancer.

MATERIALS AND METHODS

The study was approved by the local institutional review board for NOTES clinical trials. The multidisciplinary research group had access to a veterinary hospital facility where technical methods could be tested. This involved solving problems of spatial orientation, insufflation, and instrument development over a period of 14 months.

The study protocol for human clinical applications was designed for patients with rectal adenocarcinoma located in the middle and lower rectum that were amenable for TME and low anastomosis. Selection criteria excluded patients with T4 tumours, and patients with poor clinical condition. Patients were referred and informed about transrectal NOTES surgery, laparoscopic surgery and open surgery, and were free to choose or exclude any of the methods available. Laparoscopic assistance was required as a prerequisite, as high ligation of IMA would not be possible using the transrectal access due to instrumental limitation.

Between November 2009 and June 2010, nine patients who were ASA I or II with biopsy-proven rectal adenocarcinoma and suitable for elective low anterior resection were offered participation in the study. Each patient underwent fully informed consent. All patients had staging computed tomography and attempted colonoscopy in addition to local assessment with digital rectal examination and rigid rectosigmoidoscopy. Five patients presented with obstructive type symptoms and passage of the endoscope was not possible through the tumour. These cases did not receive bowel preparation. Four patients received preoperative neoadjuvant chemoradiotherapy. Transanal retrograde NOTES TME using rigid or flexible endoscopic techniques were employed with laparoscopic assistance and all relevant perioperative data were prospectively collected. The operating team was composed of a general and a colorectal surgeon, a gastroenterologist who was fully competent in advanced endoscopic techniques and two surgical residents.

Surgical Technique

Technique 1: Transanal Down-to-Up (retrograde) NOTES TME using a single port device

Single Port devices suited for umbilical surgery have a simple adaption when inserted transanally, allowing for intralumenal insufflation of CO₂, avoiding gas leaks and getting a good view and angle for dissection of the rectum especially above 4cm from the anal verge [Figure 1]. We used a Triport (Olympus, Japan) with a 10mm 30^o laparoscope, a standard laparoscopic grasper and either ultrasonic shears (Ultracision, Ethicon Endosurgery, Cincinatti, Ohio) or semiflexible monopolar hook (Novare, California) for performing rectal dissection. Other standard laparoscopic instruments (Karl Storz, Germany) were used for the laparoscopic assistance.

Figure 1.

Down-to-Up transanal perirectal NOTES Access (PNA) for total mesorectal excision for rectal cancer

Patients were positioned in the Lloyd-Davies position under general anaesthesia. Antibiotic prophylaxis was given at induction using 400 mg ciprofloxacin and 500 mg metronidazole intravenously. An anoscope was inserted and the rectum was disinfected using iodine irrigation. The single port was inserted and CO₂ insufflation to a pressure of 8-10 mmHg was used [Figure 2a and 2b].

Figure 2a.

Technique 1: The single port device (Triport, Olympus, Japan) is transanally inserted, and the presacral space is reached and the rectum is sectioned 4-5cm below the distal margin of the tumour, allowing TME progression in a retrograde manner

Figure 2b.

Transanal Insertion of single port device and transrectal insufflation with CO₂

The distal limit of the tumour was easily identified by the single port visualisation in all cases. After the level of the circumferential resection line was identified, a 2-0 Vicryl purse string suture was placed below the tumour to avoid potential cell spillage and subsequently to maintain pressure of CO₂ insufflation to the retroperitoneal space during dissection. In patients with lower tumours with difficult exposition, the purse-string suture is positioned about 1.5 cm above the dentate line and a first circular incision with monopolar cautery and perirectal dissection is performed (for further coloanal anastomosis) until there is sufficient room to place the port. Fixation of the port was achieved with 4 Vycril 2.0 sutures from the perianal skin to the external part of the port. In some patients, the method didn't promote an adequate fixation with significant gas leak. After the closure above the limit of rectal resection, the distal rectum was disinfected using topic Betadine irrigation. A transverse incision was made posteriorly in the planned line of rectal resection using monopolar cautery or ultrasonic shears [Figure 2c]. Once a full thickness rectal wall incision is made, the anatomical plane between the pelvic floor and the mesorectal fascia becomes apparent. Developing this plane laterally and circumferentially allows a retrograde TME to evolve [Figure 2d]. Sharp dissection progressed until the peritoneal reflection was breached anteriorly.

Figure 2c.

Intraluminal view of the initial circumferential incision of the rectal wall

Figure 2d.

Anterior progression of TME dissection to the posterior wall of the vagina (arrows)

High vascular ligation has not yet been possible in our series using transanal access. Therefore, using a standard 3 trocar transabdominal technique [Figure 3a] this was achieved under 30° laparoscopic surveillance using a 2.0 Prolene double ligature of the inferior mesenteric artery at the level of aorta. Laparoscopic mobilization of the left colon and splenic flexure allowed liberation of the proximal colon and upper rectum.

Figure 3a.

Laparoscopic ligation and division of inferior mesenteric artery at the level of aorta using 2.0 polypropylene ligatures.

The specimen was then grasped transanally and fully delivered through the anus [Figure 3b]. The exposed colorectum was resected at an appropriate level in preparation for the anastamosis. For low tumours with limited rectal wall remaining, a hand-sewn coloanal anastamosis was performed. For cases with more than 30 mm of bowel wall above the dentate line, a low stapled anastamosis was possible. The anvil of a circular stapler was inserted into the proximal colon with or without a colonic pouch. The prepared proximal colon was reinserted transanally into the pelvis. Closure of the rectal stump was performed using an anal retractor and a 2.0 Prolene pursestring suture which was then tightened over the spike of the circular stapler. Transanal stapled anastomosis was performed under laparoscopic surveillance. A defunctioning stoma was performed to protect the low anastomosis and a pelvic drain inserted. The resected specimen was assessed for the quality of the mesorectal resection and adequacy of the distal margin from the tumour.

Figure 3b.

Full transanal extraction of the specimen and colorectal sutured or stapled anastomosis

Technique 2: Transanal retrograde NOTES TME using a flexible endoscope

Retrograde NOTES TME can also be achieved by using flexible endoscopy and this was performed in two patients [Figure 3c]. We used an Olympus 130 single channel videocolonoscope (Olympus, Japan) and a standard laparoscopic set (KarlStorz, Germany). An anoscope was inserted and the rectum was closed by a circumferential purse-string suture of Vicryl 2.0 under direct vision as described above. Again, incision of the rectal wall started posteriorly and progression of TME dissection to the lateral and anterior aspects was achieved with sharp dissection using monopolar scissors. The peritoneal cavity was breached at the left lateral aspect of the dissection. At this point, loss of pressure in the retroperitoneal space occurred making further progress difficult. Vascular ligation, laparoscopic proximal bowel mobilization, specimen extraction and anastomosis were performed as described above. One patient received a hand-sewn anastomosis and the second a stapled anastomosis.

Figure 3c.

Technique 2: The flexible endoscope is inserted directly in the presacral space 3 cm above the dentate line, allowing flexible dissection in the mesorectal plane from below

RESULTS

Down-to-Up TME using transanal NOTES was achieved in seven of nine patients (Table 1). In one patient, a bulky and high tumour (10 cm from the anal verge and extending proximally for 8 cm) required conversion to laparoscopy and then to open surgery to mobilize the rectum. In a second patient, the tumour was high located (12 cm) and complete liberation and circumferential resection was not possible. The mean operative time was 311 min and mean intraoperative blood loss was 95.6 millilitre. One patient had metastatic disease with multiple liver implants. Anastomosis was performed using double stapling technique in five patients and a hand sewn coloanal anastomosis in four. Three patients had a colonic J-pouch.

Table 1.

Prospective data of intra- and postoperative parameters after NOTES transanal retrograde TME

Patients were started on an oral diet and initiated bowel movements on the second or third postoperative day. One patient complained of transient parasthesia of both feet due to intraoperative positioning. Satisfactory TME specimens were obtained [Figure 3d]. Mesorectal integrity after TME resection was inadequate in three patients: patient #3 due to T4 tumour with inadequate circumferential margins, and patients #7 and #8 with intraoperative partial tumour rupture before extraction.

Figure 3d.

Intact mesorectal specimen with mesorectal integrity

The mean hospital stay was 7.56 days and infectious complications were recorded only in one patient during the 30 day postoperative period. A 52-year-old female patient, Type II diabetic, and obese (BMI=42Kg/m2) in her 6th postoperative day, presented fever, vomiting and distension, with higher white blood count, and the diagnosis of anastomotic leakage was stated by computer tomography. Open surgery was indicated, and necrosis of the border of proximal colon was found, with limited local abscess [Figure 4]. The anastomosis was turned to an end colostomy. The patient had a postoperative stay of 28 days and recovered. Pathological examination of the specimens revealed a mean lymph node harvest of 13. All patients with a T3 status or positive nodes were referred for adjuvant radiochemotherapy.

Figure 4.

Postoperative anastomotic leakage after rectal resection. Notice necrotic proximal colon due to ischemia

DISCUSSION

The revolution of minimally invasive surgery over the last two decades continues to move forward. Since the first clinical descriptions of NOTES[1,12,13,14,15,16,17] there has been a concerted effort to refine the techniques of this exciting field because the potential benefits to patients are manifold. Despite the potential benefits of NOTES, to date there have not been any large studies demonstrating clear benefit over standard laparoscopy. Experimental and clinical studies still demonstrates that above all else, evolution of technology is needed to expand the application of NOTES, allowing safety and efficacy to be demonstrated.

Since 2007 many units have described human trials involving NOTES techniques. There were 1169 human cases worldwide independently reported to date and two important multicentric studies 362 cases enrolled in the International Multicenter Trial for NOTES (IMTN)[18] and the results of the German study D-NOTES[19] were published in 2010, mostly describing low complication rates.

Application of NOTES for cancer surgery has been described using transgastric access to evaluate pancreatic cancer[20] and a transvaginal approach to perform liver, peritoneal, greater omental and ovarian biopsies to evaluate carcinomatosis.[21] The former demonstrated the feasibility of transgastric endoscopic cavity exploration and showed a 90% accuracy in predicting possible resection. In the small series on NOTES for assessment and treatment of cancer, natural orifice tumour implantation has not been described, although this must be a potential concern in these cases.

Whereas most investigators have chosen to gain peritoneal access via a transvaginal or transgastric route, few have investigated the transcolonic route.[3,4,5,6,7] This approach has several theoretic advantages over the transgastric route. By eliminating the need for scope retroflection for upper abdominal surgery it allows a more direct route to the area under scrutiny and the anorectum allows passage of larger diameter instrumentation and retrieval of larger specimens.[22] Certainly, for natural orifice specimen extraction (NOSE),[23] the transanal and transvaginal routes are preferred because larger organs like the spleen, kidney and colon can be retrieved avoiding an unnecessary abdominal incision. These techniques have showed good results with few complications reported.[24,25,26,27,28,29] NOTES transvaginal colectomy assisted by minilaparoscopy was first described in a patient with sigmoid cancer by Lacy et al., naming the technique as MA-NOS.[30] Hybrid transvaginal right hemicolectomy has also been reported.[31]

Transanal NOTES using rigid platforms has been the subject of recent experimental cadaveric studies where radical sigmoid colectomy, transanal specimen extraction and primary anastomosis have been possible. The main obstacles for the use of rigid systems in human transanal NOTES are the acute angle created by the sacral promontory and the limited reach of current instruments.[32] Rigid transanal resection of the colon has been achieved in a series of 14 non-survival and cadaveric animal experiments. Leroy et al. described a combined technique using flexible and rigid transrectal and flexible transgastric accesses to perform sigmoidectomy in a porcine model.[33] This totally NOTES technique resulted in survival of all five animals and no signs of peritonitis or intra-abdominal abscess were found 2 weeks postoperatively. Velhote and Velhote described the technique for transanal pull through for megacolon in children using rigid laparoscopy.[34] Sylla et al., described the first case of successful transorificial rectal resection using TEM technology with mini-laparoscopic assistance allowing adequate oncologic resection.[35] Our group described experimental studies in a swine model in a period of 10 months before human applications using flexible transrectal dissection, resection and anastomosis with survival, and human casuistic starting in 2009.[36,37,38] Differences of our technique of transanal retrograde NOTES TME to these previous works is the absence of use of TEM devices and the employment of flexible dissection and single port access platform, thus allowing freedom for more creative dissection methods. Single access devices are also universally available and promotes an easy learning curve because its similarity with laparoscopic manipulation, in contrast to flexible dissection and TEM.

Developed and described by Buess et al., in the early 1980s, TEM is a widely used minimally invasive alternative for a range of benign and early malignant lesions of the rectum.[8] The concept of installing a transanal platform to perform colorectal surgery was initially reserved for resection of tumours located below the peritoneal reflection in order to avoid perforation into the peritoneal cavity. In fact, this practice does not appear to increase infectious postoperative complications.[39] Larach coined the term TAMIS (Transanal Minimally Invasive Surgery) in case series on transanal surgery using a specific transanal device.[40]

TME with high vascular ligation is currently the gold standard for curative resection of rectal adenocarcinoma. As described by Heald in 1982, a precise plane of dissection has allowed improved oncological outcome.[9,10] The present study has shown that an adequate TME with preservation of the mesorectal envelope can be achieved in most cases using a rigid and flexible retrograde transanal NOTES technique.

Transrectal access into the peritoneal cavity raises concerns about infection and still requires the need for secure closure of the colorectum.[41] The luminal closure and subsequent low entry point as described in this study allows for a relatively isolated field that can be adequately disinfected avoiding the need for full bowel preparation. In addition, this technique allows easy entrance and closure under direct view. PNA via retroperitoneal insufflation and retroperitoneoscopy also represents a novel method to perform transrectal retroperitoneal lymph node biopsies and even pancreatic, renal or adrenal surgery. PNA also allows relatively fast and easy access to the peritoneal cavity. The advantage of transanal colorectal surgery is the avoidance of breaches to other uninvolved hollow organs. Standard endoscopy is a helpful technology to perform transanal NOTES techniques but future flexible platforms with fully articulating instruments will undoubtedly allow these NOTES techniques to be disseminated into widespread practice.

Transanal Down-to-Up NOTES TME represents an innovation in current patient care, as it might represent easier access to the distal part of the mesorectum that can be so difficult to dissect under direct vision in both open and laparoscopic low anterior resection, especially in men. The goal for transanal access in colorectal surgery is the performance of totally NOTES transanal resections of all those procedures performed today. Overcoming the technical limitations of the current instruments available and making sure that any advances are safe, both in the short and long term will require patience and advanced training for those wishing to pursue this exciting field.

The described new NOTES access for rectal cancer opens a wide range of possibilities of future applications of transanal NOTES for colorectal surgery. Despite potential advantages over existing laparoscopic and open methods, no firm conclusions can be made regarding outcome in this small feasibility study; however, the concept of rigid or flexible transanal NOTES colorectal operations seems promising.