F. Otto and M. P. Lutz (eds.). Early Gastrointestinal Cancers II: Rectal Cancer. Recent Results in Cancer Research
1. Оценка и обоснование решений по лечению раннего ректального рака
Total mesorectal excision for invasive rectal cancer guarantees removal of the primary tumour and its draining lymph nodes in an enclosed package and is associated with <3% risk of local recurrence if no preoperative adverse features are identified and is regarded as a standard of care for malignant lesions arising at a height of 6 cm or more. For low rectal polyps, the additional morbidity and loss of quality of life associated with an ultralow anastomosis or permanent stoma formation means that the options of alternative approaches to enable sphincter preservation while not compromising oncological outcomes increases in importance from the patient’s perspective. Precise preoperative staging by imaging and histopathology is essential to enable a balanced risk assessment if more radical surgery is to be avoided.
If local excision or TEM is being considered—preoperative staging of early rectal cancer should enable surgical planning that avoids the risk of subsequent recurrence caused either by tumour perforation beyond the mesorectal envelope or of leaving viable metastatic disease within the mesorectum. In assessing early rectal cancer it is important for radiologists to recognise early stage rectal cancer that is potentially amenable to local excision. Equally, it is important for lesions detected at endoscopy to be staged prior to removal to ensure definitive treatment of high risk early stage rectal cancers for avoidance of piecemeal removal of polyp cancers. MRI or endorectal ultrasound performed prior to a biopsy is likely to be more accurate as oedema/inflammation may distort the submucosal and muscularis propria layer interfaces resulting in potential overstaging.
2. Стадийная классификация раннего рака прямой кишки
Early rectal cancer can manifest as either a polyp characterised by a rounded or polypoidal mass associated with a fibromuscular stalk or a sessile (flat) lesion. In polyp cancers, tumour spread extends into the stalk and then into the submucosa and beyond.
The principle of staging polyps and sessile lesions is based on knowledge that the deeper and more extensive the tumour spread is into the rich lymphatic and vascular plexuses of the mid and lower thirds of the submucosa, with a higher risk of spread into the lymphatic and venous channels beyond the confines of the rectal wall and into mesorectum.
Pedunculated polyps were originally classified by Haggitt (2008) on a 1–5 point scale to describe the level of polyp invasion and associated risk of metastatic spread to lymph nodes or vessels within the mesorectum. For sessile or flat lesions—the Kikuchi classification describes the depth of submucosal invasion. The Kikuchi classification divides the submucosa into thirds to classify T1 spread as sm1, sm2 and sm3. The upper third of the submucosa is relatively devoid of venous and lymphatic channels and the risk of nodal metastatic disease for sm1 tumours was originally reported by Kikuchi as 0%. For increasing submucosal invasion, a higher rate of nodal metastatic disease is seen—rising to 10% for sm2 and 25% for sm3 and sm3 is considered equivalent to Haggitt level 4 in terms of nodal risk spread.
Further risk factors for nodal spread have since been identified: resection margin <1 mm (high risk), 1–2 mm (risk factor), poor differentiation, mucinous or signet ring morphology, tumour budding, intramural lymphatic or vascular invasion. These factors, when incorporated into histological staging of polyps form the basis of a risk stratification that enables counselling of patients with regard to the need for definitive surgery or to consider adjuvant therapy following the local excision of an early rectal cancer.
3. Эндоректальная ультрасонография
Since Dragsted et al. (1983) introduced ERUS as a method for rectal tumour evaluation, the method has been increasingly accepted as an essential part of the preoperative evaluation regime. Reviews and meta-analyses have indicated that the overall accuracy of ERUS rectal tumour staging is in the range of 80–90% (Bipat et al. 2004; Puli et al. 2009; Hunerbein 2003). However, a number of papers evaluating the method have been published over the last two decades (see Table 1), demonstrating accuracies ranging from 55 to 97%. This relatively wide range can, at least in part, be explained by heterogeneity in methods, study design, prevalence of different pT-stages and degree of observer experience. Multi-centre studies tend to report lower accuracies than single-centre studies from high-volume institutions. Studies have also shown that the accuracy of ERUS can be improved from low as 50% to as high as 90% with training (Orrom et al. 1990; Badger et al. 2007; Kav and Bayraktar 2010; Li et al. 2010; Morris et al. 2011). Development in ultrasound technology, such as strain elastography, may also contribute to improved staging of ERC (Waage et al. 2011)
4. MRI техника и качество
The accuracy of MRI in assessing depth of spread into or beyond the rectal wall, its ability to precisely assess the risk of CRM involvement and local recurrence on baseline and post treatment scans—was based on high quality MRI scans performed according to standardised protocol and images interpreted according to agreed diagnostic criteria, which were standardised through 1 day training workshops. When applied in the multi-centre setting at non-specialised and tertiary referral institutions alike the results were found to be reproducible and consistent. The key to improvements in diagnostic and prognostic accuracy from preoperative MRI assessment of rectal cancers was specialist gastrointestinal radiologists who worked closely with their surgeons, oncologists and pathologists in the MDT setting. The participating radiologists were responsible for reviewing and reporting all newly diagnosed rectal cancers in the MDT meetings at their respective institutions. Participation in the MERCURY studies showed that with only a minimal investment in training and support development of radiologists—it was possible to harmonise the standards of cancer staging preoperatively.
Таблица 1. Точность — либо сообщенная полная uT-стадийная точность, либо точность, вычисленная на основании информации, предтавленной в этой статье
5. Предоперативная оценка нодального распространения
It is now well understood that nodal metastatic spread cannot be reliably excluded using preoperative imaging since a significant majority of metastases measure <0.3 mm in diameter and well beyond the resolution of modern imaging techniques (Landmann et al. 2007). It is also understood that measuring the size of nodes is futile since benign reactive nodes are seen in many patients with and without nodal metastatic disease and reactive nodes can enlarge to any size (Dworak 1991). Therefore, measuring lymph nodes as a means of assessing the likelihood of malignancy is highly inaccurate and is not recommended as good practice in the preoperative assessment of rectal cancer (Brown et al. 2003). The positive identification of nodal or extramural disease relies on resolving tumour signal within a node and its effect on the node, which can manifest as nodal heterogeneity or penetration of the nodal capsule by tumour resulting in nodal border irregularity; this is best seen on high resolution imaging with a minimal voxel resolution of 1.1 mm3 (Brown et al. 2004).
Таблица 2. Критерии опухоли, измеренные по следующим характеристикам, были включены при изучении опухоли на MRI
Таблица 2. Критерии опухоли, измеренные по следующим характеристикам, были включены при изучении опухоли на MRI
6. MRI техника
A 1.5T or 3T system is used with phase array coils. The first series is the sagittal T2-weighted fast spin echo sequence to identify the primary tumour. The second series is the large field of view axial sections of the whole pelvis and the third and subsequent series consists of the high resolution images through the rectal cancer and adjacent tissues. For patients with low tumours, high spatial resolution coronal imaging will optimally show the levator muscles, the sphincter complex, the intersphincteric plane and the relationship to the rectal wall. A sagittal high resolution series will also enable multiplanar assessment of anteriorly located polyps or sessile lesions. Finally, the examination is completed by undertaking further high resolution axial imaging from the upper most border of the tumour to the L5/S1 junction to enable assessment of mesorectal nodes, venous deposits and pelvic sidewall nodes at high resolution.
7. Оценка лимфатических узлов таза
Nodal assessment with imaging takes place in two settings:
- The initial assessment of the mesorectum prior to resection/local excision/ TEM or preoperative therapy.
- Following preoperative therapy.
- During follow up surveillance of the mesorectum if primary radical surgery has been avoided.
In all three scenarios—it is important that the entire mesorectum above the primary tumour is imaged at high resolution, and that this covers the mesorectum to the L5/S1 sacral junction.
The absence of any visible nodes within the mesorectum is strong reassurance that there is an absence of nodal metastatic disease. The natural history of nodes containing micrometastatic disease is unpredictable and is not necessarily associated with adverse outcomes. Clearly, the absence of nodal recurrence in many patients on long-term follow up suggests that the patient’s own immune system with and without the use of adjuvant chemoradiotherapy in some high risk cases results in long-term cures. The precise mechanisms for this are poorly understood—however, this favours the possibility that nodal micrometastatic disease— at least in some patients does not necessarily equate to viable metastatic disease in the long term. Thus, surveillance of nodes is relevant and the lack of progressive change in the morphology of a node is reassuring. On the other hand, a node that changes from smooth bordered and uniform signal to a mixed signal or irregular node should be diagnosed as malignant and such patients can be successfully salvaged by surgery.
8. The anatomy of the rectum and mesorectum at high resolution
The first demonstration of the layers of the rectal wall using a high resolution MRI technique was achieved by Schnall et al. in a study of 12 patients undergoing endorectal MRI. In this paper, the authors elegantly showed how high resolution imaging depicts the layers of the rectal wall. This has been reproduced using the high resolution pelvic phased array MRI (Fig. 3).
9. Preoperative evaluation of primary early rectal cancer
Assessment of polypoidal and sessile lesions
Preoperative evaluation of polypoidal lesions is aimed at firstly determining the site of the stalk and then assessing the extension of tumour into the fibromuscular stalk and beyond. Sessile or flat lesions are characterised by lateral raised rolled edges, which are the non-invasive portions of the lesions, and the central depressed portion, which forms the advancing edge of the tumour. Preoperative assessment of sessile lesions requires detailed evaluation of the central depressed portion of the tumour and the degree of preservation identifiable in the submucosa and muscularis propria at the advancing edge. Multiplanar assessment is essential and if submucosa is evident on any single view at the base of the stalk or at the central invasive base of a sessile tumour—then this enables the confident diagnosis of a T1 lesion amenable to a local excision approach. Assessment of the depth of T stage tumour depth within and beyond the rectal wall is achieved by assessing the extent of the intermediate signal intensity tumour and its extent of spread into the submucosa, muscularis and beyond. The precise depth of extension into submucosa should be attempted, but crucially a measurement of the thickness of preserved submucosa is relevant with a thickness of [1 mm in any plane increases the likelihood of detection of an Sm1 or Sm2 lesion, which could be cured by a local excision approach. The lack of any measurable high signal intensity layer on any plane imaged between the advancing edge of the tumour and the low signal intensity of the muscularis suggests a high probability of a T1sm3 or early T2 tumour. It should be emphasised that the distinction between a T1sm3 and an early T2 is prognostically and clinically irrelevant since it means that a local excision without removal of the full thickness of the underlying muscularis propria will result in a positive deep margin of <1 mm.
In selecting patients for local excision, it is currently understood that T1 sm1 can be safely removed without further therapy since the likelihood of local relapse and tumour recurrence is low in these patients. The current gold standard for patients with T1 tumours sm2 or greater is TME surgery. This is considered a good and safe option for patients amenable to TME surgery with sphincter conservation. However, for low rectal polyps and early stage tumours within 10 mm of the puborectalis sling, surgery most often requires either an abdominoperineal excision or an ultralow intersphincteric anastomosis—both result in significant impact on patient’s quality of life due to impairment or loss of sphincter function. Thus, despite the ideal recommendation being definitive surgery many patients opt for the alternative of chemoradiotherapy and surveillance following local excision or TEM of an early stage lesion. Thus, identification of patients with low lying tumours amenable to sphincter preserving approaches is becoming increasingly important.
In order to judge the safety of TEM preoperatively careful documentation of the advancing edge of the tumour is needed, and therefore precise documentation of both the quadrant (clock position) and height of tumour. Certain interfaces may limit the extent for TEM excision: the anterior rectal wall and the prostate, the tumour height and the relationship to levators, distal TME plane and the peritoneal reflection.
Алгоритм для стадирования рака прямой кишки ранних стадий, используя MRI и ERUS
The goal of preoperative imaging in early stage rectal cancer, whether by EUS or MRI, is to determine the safety and feasibility of potentially less radical options such as local excision and TEM. A policy of assessing lesions prior to attempted removal would appear justified if high rates of piecemeal excision or unexpected cancers in locally excised lesions are to be avoided. It is crucial that for both MRI and EUS that appropriately trained expertise and equipment is used to optimally assess early rectal cancer. In this way, patients can be presented with a comprehensive assessment of staging findings and options for treatment, which could range from local exicision, TEM, or primary TME surgery with and without sphincter preservation and with or without preoperative therapy.
In future studies will need to assess ongoing controversies
What are the documented patterns of recurrence? When do patients relapse after local excision, defining an ideal follow-up schedule and imaging appearances of early relapse. What is the long-term prognostic importance of nodal micrometastatic disease. What is the role of adjuvant chemoradiotherapy and chemotherapy in high risk T1 disease following local excision.
Суммарные показания для MRI оценки раннего ректального рака
- To assess bulky polyps >5 mm thick.
- Initial assessment of disease remote from the lumen within entire mesorectum.
- Identification of pelvic sidewall disease.
- Road-mapping for surgical planning—identify site location of stalk or invasive border and relationship to puborectalis sling, peritoneal reflection, mesorectal or intersphincteric border.
- Identification of high risk patients with extramural venous invasion.
- Ongoing surveillance of high risk cancer patients opting for conservative approach.
Суммарные показания для ERUS
- High frequency EUS to assess flat or depressed lesions <5 mm thick.
- Limited assessment of disease remote from the lumen—therefore for low risk polyp assessment.
- Assisting with planned ESR—identify site location of invasive border.
- Early stage tumours can be usefully evaluated using high resolution MRI and high frequency ultrasound for superficial lesions.
- Technique is important.
- Options to consider especially for low lying early stage tumours: results from current trials awaited.
- Follow up if less radical therapy is given: MRI surveillance is also important to enable early detection of salvageable regrowth/recurrence (Table 2).
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