Trattamenti

EMR, ESD, TEM

Piecemeal mucosectomy, submucosal dissection or transanal microsurgery for large colorectal neoplasm

Although smaller colonic polyps are removed by snare polypectomy or Endoscopic Mucosal Resection (EMR), there is evidence from the British Bowel Cancer Screening Programme that many larger lesions are referred for surgical resection. However, there is a significant morbidity and mortality associated with the surgical treatment, with 30 day mortality rates varying between 1% and 8% [1].

In addition, surgery is expensive. In the UK, the surgical treatment of colonic lesions accounts for more hospital in-patient expenditure than any other site. In contrast to surgical resection, endoscopic resection allows colonic lesions to be removed with a minimum of cost, morbidity and mortality [2-4]. The recognition and removal of precancerous lesions are important to reduce the risk of subsequent colorectal cancer [5]. Furthermore, many likely early colonic cancers are considered for removal by endoscopic resection such as EMR or Endoscopic Submucosal Dissection (ESD) [6]. EMR is now a well-established technique worldwide for the treatment of colorectal neoplasms with minimal invasiveness [7-9]. However, it entails a high frequency of local recurrence after piecemeal EMR for large lesions [10,11]. ESD was conceived in Japan with the aim to avoid this problem, allowing en bloc resection of larger colorectal lesions. Despite its longer procedure time and higher complication rate, ESD result in a higher en bloc resection rate compared to that seen with conventional or piecemeal EMR [12-14]. Nevertheless, the use of ESD for colorectal lesions is not yet fully established as a standard therapeutic method for colorectal lesions worldwide. In this review manuscript we discuss the therapeutic strategies available to manage non-polypoid early cancers of the colon and rectum, with particular regards to the different position of Eastern and Western endoscopists.

EMR or ESD for Colorectal Neoplasms? The Western position

Several methods of EMR have been described. The most common the “strip biopsy method”. With this technique a solution is injected into the submucosa below the lesion creates a “cushion” to carry out the snare polypectomy. Different EMR solutions have been described. In general, more viscous solutions such as succinylated gelatine, hydroxy-propyl-methyl-cellulose [16], hyaluronic acid [17] or dextrose [18] are preferred as they last longer. In most cases, a small amount of adrenaline is added for a 0.5% solution together with indigo carmine to achieve a light bluish solution. The adrenaline reduces immediate oozing from small veins during the procedure but does not reduce the risk of delayed bleeding [15]. Dye is added to the solution to allow the extent of lift to be ascertained.], The “pull within the snare” (“grasp and snare”) technique less commonly used. It requires a double channel endoscope as it uses a grasping forceps to pull the lesion into the snare. This technique allows otherwise unresectable or poorly lifting lesions to be removed. However, the “pull within the snare” technique has been associated with a higher risk of perforation [19]. Whereas ESD has the clear advantage of achieving a single specimen, allowing for more accurate histological assessment and lower risk of recurrence, the general perception in the western scientific community is that ESD is a more complex technique, requiring greater experience, longer procedure times, higher risk of complications, the need for admission and the availability of specialised equipment including carbon dioxide insufflation and, usually in the West, general anaesthesia with all that this entails. A recent comparative study [20] demonstrated that the higher en bloc resection rate of 83.5% with colorectal ESD compared with 48.1% for lesions removed by EMR. However in this study, ESD was associated with greater risk of perforation than when lesions were removed by EMR (5.9% vs 0%). This was confirmed in an analysis of 17 case series (n= 1858) in which the overall risk of perforation complicating an EMR was found to be 0.2% [21]. The largest ESD experience published in Europe [22] reports perforation rates up to 18%. Furthermore, the equipment used in ESD’s are expensive, nowadays of increasing concern in the management of National Health Care Systems in Europe.

Therapeutic strategy for early rectal neoplasm

There is no doubt that an initial attempt of removing an early colonic lesions should always be done endoscopically, due to the invasiveness of colonic resection even when done laparoscopically. On the other hand, the treatment of rectal lesions may benefit from a further therapeutic option (i.e. transanal surgery). Looking at the literature and analyzing recent data collected at the Department of Surgery of the University of Torino, neither pit-pattern classification, nor EUS, nor biopsy histology, nor lifting sign verification, nor digital examination allow a specificity of more than 75% of suspected adenomas or early rectal cancer. In particular different EUS studies [34,35] including a considerable number of patients from a multitude of centers revealed a uT-pT correspondence of less than 65%, demonstrating that, in daily routine use, the diagnostic accuracy of transrectal ultrasound in staging rectal carcinoma does not attain the good results reported in the literature. Assumed that the vertical depth of tumor infiltration is the most important predictive parameter for lymph node metastases [36], the goal of a local excision of a rectal neoplasm should be that one to allow a correct pathology examination of the specimen, when possible. Almost 30 years ago, transanal endoscopic microsurgery (TEM) revolutionized the technique and outcomes of transanal surgery, first becoming the standard of treatment for large rectal adenomas [37-39], then offering a possibly curative treatment for early rectal cancer [40], and finally generating discussion on its potential role in combination with neoadjuvant therapies for the treatment of more invasive cancer [41-43]. TEM afforded the advantage of combining a less invasive transanal approach with low recurrence rates thanks to magnified visualization of the surgical field, which allows more precise dissection. Today performed routinely under spinal anaesthesia, and with the aid of standard laparoscopic instrumentation, in combination with a dedicated rectoscope 7 or 15 cm in length (Karl Storz GmbH Tuttlingen, Germany), it allows excellent exposure of the rectum and minimal invasiveness, as opposed to conventional surgical techniques [44-46], besides, lower recurrence rates [47]. Originally developed for the treatment of large villous adenomas, over a few years TEM gained consideration as a suitable curative treatment for early rectal carcinoma, thus contributing to the identification of pathology risk factors for invasiveness and recurrence [48]. The technique was initially described to achieve a submucosal dissection or partial-wall excision. However, the, the difficulty in preoperatively recognizing malignant lesions, together with the need of reaching disease-free dissection margins lead to the development of full-thickness excisions.. Even the opening of the peritoneum which was considered, in former times, a good reason to perform only partial-wall excision to avoid intra-operative complications, is now considered routine [49]. TEM may be considered a potential platform towards the abdominal cavity for Natural Orifices Transluminal Endoscopic Surgery (NOTES) procedures [50]. The accurate histological assessment of depth of invasion relies on an en-bloc resected specimen. Ideally this should be a R0 resection, with both lateral and deep resection margins free of neoplasia. In the absence of comparative studies, we have recently performed a single-arm meta-analysis of case series [51]. We defined strict inclusion criteria, limiting the analysis to lesions >2 cm according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines [52], suspected non-invasive by preoperative assessment and excluded all TEM series including preoperatively assessed malignant lesions and not performed full-thickness. We could demonstrate an R0 resection achieved by ESD in 74% of patients compared to 89% by TEM. This probably reflected on the consistently higher need of further abdominal surgery in the ESD group, as high as 9% of patients, despite the rate of unpredicted invasive cancers treated in the two groups was comparable.

Conclusions

In Western countries, many units have concluded that piecemeal resection of rectal lesions is no longer acceptable. This is the reason why many surgical colleagues are favouring trans-anal single fragment resection over piece-meal EMR. One could assert that if “single-fragment resection” is the correct procedure in the rectum, it must also be the correct way to proceed elsewhere in the gastrointestinal tract. In truth, it all depends on which therapeutic alternatives you can offer the patient. Currently in many institutions, the only alternative would be a major surgical colonic resection. In the rectum, surgery may offer a better alternative to radical surgery, truly minimally invasive, such as the transanal approach.. Supporters of piecemeal resections, even in the rectum, affirm that in the case of larger lesions, endoscopic resection is quicker, safer and cheaper than surgical resection. The advantage of ESD is that a single fragment resection potentially allows for a more confident histological diagnosis. However, similarly to laparoscopic resections, ESD is a technique which is a more prolonged with higher cost and greater hazards than the standard approach. As was the issue with laparoscopic resections some years ago,, training is a crucial issue. Naturally, moving from EMR to ESD would have far reaching implications. As the risk of lymph node metastases is very low with T1 colorectal cancers, a move to ESD means that all small colorectal cancers would first be resected endoscopically. Then, lesions which after histological analysis are found to contain lymphovascular invasion, poor differentiation or extensive tumour budding would then proceed to colectomy. In Eastern countries, supporters of ESD consider it is an ideal method to provide “en bloc resection” even for large colorectal lesions. However, the prevalence of lesions with a “definite indication for ESD” among all colorectal neoplasms is small. Colorectal ESD should be performed by experienced or well-trained endoscopists. In contrast, it is crucial for trainee endoscopists to master more fundamental techniques (e.g. cold or hot snare polypectomy, conventional EMR, single block or piecemeal EMR) and have knowledge of surveillance strategy after endoscopic treatment. Furthermore, characteristic colonoscopic findings obtained by magnifying chromoendoscopy are useful for determination of the invasion depth of early stage colorectal cancers, which is an essential factor in selecting a treatment modality between endoscopic treatment and surgery. As the therapeutic techniques are developed, preoperative endoscopic diagnosis will become increasingly important. The rectum offers the further option of transanal endoscopic surgery. Differently from colectomy, that even when done laparoscopically represents a major surgery, TEM entails the true concept of minimally invasiveness. In a comparison of techniques, we performed a systematic review of published series, and we could demonstrate an advantage of TEM compared to ESD in achieving an R0 resection, probably reflected by the consistently higher need for further abdominal surgery in the ESD group.

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