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Management and imaging of low rectal carcinoma
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Surgical Oncology 13 (2004) 55–61 www.elsevier.com/locate/suronc
Management and imaging of low rectal carcinoma Gisella Salernoa, Ian Danielsa, R.J. Healda, Gina Brownb,, B.J. Morana a
Pelican Cancer Foundation, Basingstoke, Hants, UK Department of Radiology, Royal Marsden Hospital, Downs Road, Sutton SM2 5PT, Surrey, UK
b
Abstract Large variations in recurrence rates have been reported with the best results following total mesorectal excision (TME) surgery for low and middle rectal cancers. However, the low rectal cancers still have higher rates of local recurrence (up to 30%) whether operated by low anterior resection or abdominoperineal excision (APE) due to high rates of circumferential margin involvement. The treatment of choice for low rectal cancers that encroach upon the potential circumferential resection margin is surgery combined with preoperative neoadjuvant treatment. Preoperative chemotherapy combined with long-term radiotherapy reduces recurrence rates and preoperative loco-regional staging can help to select the patients more likely to benefit from neo-adjuvant therapy. Surface coil MRI is the most promising modality for patient selection, which can provide good views of the circumferential resection margin especially the presence or absence of tumour encroaching the intersphincteric plane. r 2004 Published by Elsevier Ltd. Keywords: Rectal neoplasms/surgery; Preoperative staging; Radiotherapy; Magnetic resonance imaging
1. Introduction Low rectal cancer, defined as an adenocarcinoma with its lower edge arising less than 6 cm from the anal verge, represents a particular surgical challenge for both local tumour control and sphincter preservation. In published series, such tumours have a higher incidence of positive resection margins and poor survival [1]. This has been attributed to narrow surgical planes deep within the pelvis as the mesorectum becomes narrowed and tapered, becoming a bare muscle tube at the level of the anal sphincter complex. The lack of surgical planes is further limited in the male by the presence of the prostate lying anteriorly. The challenge for the surgeon is to undertake careful removal of a cylinder of tissue beyond the rectal wall without perforating tumour. In this review, we discuss the anatomic imaging of the lower rectum as visualised using MRI, the surgical aspects of treating a low rectal cancer and how MRI Corresponding author. Tel.: +44 208 661 3215; fax: +44 208 661 3506. E-mail address: [email protected] (G. Brown).
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based future strategies may improve outcome in these patients.
2. Anatomic and imaging considerations [2,3] The embryological development of the rectum starts with the division of the cloaca into the dorsal rectum and the ventral urogenital sinus by the urogenital septum. During the last 2 weeks of embryological development, the urogenital septum fuses with the cloacal membrane at the ectodermal anal pit and the anal portion of the cloacal membrane disappears at the mucocutaneous border of the anus, the dentate line. Although the in vivo anatomy of the anal canal has been well described using the endorectal coil [4,5] it is now possible to show similarly high-resolution anatomic detail using the phased array coil [6,7]. In the adult, the rectum is defined as the distal 15 cm of bowel above the anorectum. The rectum is enveloped by a distinct compartment comprising fatty tissue, connective tissue, vessels, draining lymphatics and
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nerves—the mesorectum. This mesorectal compartment is enveloped by a fascial covering down to the pelvic floor. This fascial layer is derived from visceral peritoneum—the mesorectal fascia. Between this layer and the parietal endopelvic fascia is loose areolar tissue which is relatively avascular representing the plane of bloodless excision in total mesorectal excision surgery [8]. In the upper third of the rectum, the lateral and posterior aspects of the rectum are surrounded by mesorectum, but anteriorly, the rectum is covered by peritoneum. In the lower third, the rectum is completely enveloped by mesorectum which begins to narrow caudally from the level of the origin of the levator muscles. Anteriorly the mesorectal fascia fuses with the remnant of the urogenital septum. This is a dense band of connective tissue in the male, Denonvilliers fascia, separates the prostate and seminal vesicles from the rectum. The corresponding structure in the female is the rectovaginal septum. For practical purposes, the lower third of the rectum can be considered on anatomical and imaging features as the area of rectum and mesorectum below the origin of the levators where the mesorectum tapers sharply, usually within 6 cm of the anal verge. This can be illustrated pictorially on coronal MRI scans (Fig. 1). The rectum is supported by: 1. The recto-sacral fascia, which is just above the pelvic floor at the anorectal junction at S4. MRI depiction
Fig. 2. Sagittal T2 weighted image showing the rectosacral fascia running from S4 to the rectal wall. The sagittal image best demonstrates the angulation of the anorectal junction produced by the puborectalis muscle sling (curved white arrow).
of the recto-sacral fascia is dependent on the thickness of the fascia, which is highly variable. When seen it is demonstrated as an oblique low signal intensity band that extends from the S3/S4 junction to the posterior wall of the rectum (Fig. 2). 2. The levator ani complex, which includes the puborectalis, pubococcygeus, ileococcygeus, and coccygeus muscles, covered by fat and parietal fascia. The muscles form a sheet that supports the pelvic floor and arise from various points of attachment at the bony pelvic sidewall: the spine of the ischium, the obturator fascia, the body of the pubis and the coccyx. The fibres of the levators muscles interdigitate in the midline posteriorly to form the anococcygeal raphe. The levator muscle sheet is best visualised by MRI on coronal images which depict the muscle sheet running obliquely toward the anorectal junction (Fig. 1). The rectum forms an acute anorectal angle with the anal canal and this is well demonstrated on in vivo MRI scans obtained in the sagittal plane (Fig. 2).
2.1. The anal canal [6] Fig. 1. Coronal T2 weighted image showing lateral mesorectal borders (black arrows). At the level of the levatororigins (open arrow), the mesorectum tapers and very little mesorectal tissue surrounds the lower rectal wall. The risk of surgical circumferential margin involvement in tumours arising below this level increases.
The anal canal is the distal 4 cm of the gastrointestinal tract. The components of the anal canal of relevance to surgical disease and treatment are described here and are well demonstrated on axial (Fig. 3), coronal (Fig. 4) and sagittal (Fig. 5) T2 weighted imaging of the anal canal.
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Fig. 3. Axial T2 weighted image in male and corresponding histology section showing external sphincter (open arrow), intersphincteric plane (narrow black arrow) and internal sphincter (broad black arrow). Fig. 5. Anorectal junction and anal canal detail shown in inset. The levator muscle fibres (white arrow) run forward and anteriorly to blend with the fibres of the external sphincter at the anorectal junction. The mesorectal fascia (open arrow) abuts the levator. The rectosacral fascia anchors the rectum and mesorectum to the sacrum running obliquely from sacrum to rectal wall (arrow heads). The dentate line is demonstrated on this sagittal image at the lower margin of the ridged anal columns.
rectum forming a U-shaped sling. This marks the point of the anorectal junction and the puborectalis sling pulls the rectum forward at the point resulting in 90–1151 of angulation between the rectum and anal canal. 2.3. The external anal sphincter (EAS)
Fig. 4. Coronal T2 weighted image in female showing low signal intensity external sphincter, and low signal intensity internal sphincter which is continuity with the muscularis propia. The bright high signal intensity layer between these two represents the intersphincteric plane.
2.2. The puborectalis sling and anorectal junction The anterior fibres of the levator give rise to the puborectalis sling which arches backward from the posterior surface of the pubis to sweep around the
The external sphincter comprises skeletal muscle fibres that blend with the puborectalis component of the levator ani to form a muscular ring. The sphincter is traditionally thought of as having 3 segments—deep, superficial and subcutaneous however, recent anatomic studies suggest that the external sphincter cannot be subdivided in this way and is incomplete anteriorly [6]. On in vivo imaging the sphincter is depicted as an almost complete ring of muscle. The superior margin of the external anal sphincter is defined by the lower edge of the puborectalis sling. Inferiorly, the fibres curve inwards just below the internal sphincter. 2.4. The internal anal sphincter (IAS) The IAS is formed by a very thickened segment of the circular muscle coat in the distal rectum. At the level of the top of the anal sphincter, fibres from the puborectalis slin join those of the outer muscle coat and together these form the conjoint longitudinal coat which forms a thin muscular layer between the IAS and EAS.
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2.5. The mucosa of the anal canal The mucosal layer of the anal canal comprises three distinctive zones. Its upper third is characterised by ridges of mucosal membrane that form the anal columns. Below this the mucosa is smooth surfaced and this point of transition is marked by the dentate line. Below this area, lies anal skin made up of keratinised stratified squamous epithelium. 2.6. Lymphatic drainage of the rectum and anus The anal canal and rectum have lymphatic drainage to nodes within the mesorectum following tributaries of the superior rectal lymphatics which mirrors the inferior mesenteric arterial supply and ultimately drain to the para-aortic nodes. The lower portion of anal canal and rectum also drain via the inferior rectal lymphatics to the internal pudendal lymphatics, which then drain to the internal iliac nodes in the pelvis. The lower anal canal drains to the superficial inguinal nodes. There is considerable overlap between these lymphatic drainages of the rectum and anus.
3. Surgical aspects of low anterior resection (LAR) and abdominoperineal excision (APE) The Colorectal Research Unit in Basingstoke, led by Prof. R.J. Heald, initiated prospective data collection in 1978 and has continued to the present day. A policy of sphincter conservation was adopted and the oncologic principle applied was of accurate total mesorectal excision (TME) for all rectal cancers with the exception of less than 5% who had local excision of early tumours. Preoperative radiotherapy was only used for clinically fixed or tethered tumours. Sphincter preservation and reconstruction was facilitated by the use of the small PI 30TM (United States Surgical Corp., Norwalk, CT) linear stapler which can reach the depths of the narrow pelvis and be used for the ‘Moran triple stapling technique’ [9]. An independent audit of the Basingstoke data, by MacFarlane et al. [10], demonstrated that no case above 4 cm from the anal verge had undergone APE. In Basingstoke, Heald refuted Miles’ theory of inferior rectal node involvement and exploited the knowledge that rectal cancer is unlikely to spread distally down the muscle tube [11]. Similarly this disputed the ‘5 cm rule’ for the distal margin [12,13]. Further work has demonstrated that a distal margin of 1–2 cm is safe as distal intramural spread rarely exceeds 10 mm [14–16]. Other work suggests that distal intramural spread is not a feature of rectal cancer and thus not a factor in determining local recurrence of rectal cancer [17]. In Basingstoke, despite using a narrow distal margin, a
local recurrence rate of only 1% was seen in the ‘curative’ anterior resections (including 29 Dukes stage C), and 4% in all cases (including those with metastases). The 6-year cure rate was 76% for curative cases and 68% for all cases. However, in this series, patients undergoing APE (n=15) had a worse local recurrence rate of 33% [11]. This may represent the ‘Will Rogers Phenomenon’ where selectivity alters assessment [18]. Based on audit of abdominoperineal resections, the Norwegian surgeon Dr. J. Wiig (unpublished data) suggests that recurrence below the levators occurs in the wound or scar. A possible cause for these perineal recurrences could be the implantation of free tumour cells extruded through the imperfectly occluded anus. Another reason for poor outcomes in patients with lower rectal tumours may relate to a tendency for metastasis to the internal iliac nodes, thus escaping the surgical excision planes of a TME [19]. However, the most likely cause is through surgical technique, with the plane of excision involving the muscular rectal tube at the ano-rectal junction. When Low Anterior Resection (LAR) was first adopted, there were concerns that this would result in higher rates of anastomotic leakage and therefore higher incidence of local recurrence (ref). The leakage rate after anterior resection varies from 3% to 21% and usually results in serious morbidity requiring emergency surgery (ref). Mortality associated with anastomotic complications ranges from 6% to 22% and accounts for approximately one-third of all deaths following colorectal surgery [20]. Thus, the low anastomosis is regarded as a significant risk factor for anastomotic leak rate due to anatomical inaccessibility, a less than optimal blood supply, a tightly closed anal sphincter below the anastomosis and the possibility of a pelvic haematoma becoming infected near the anastomosis [21]. Rullier et al. [22] analysed the variables that were associated with anastomotic leaks in 272 consecutive anterior resections and found that the leak rate was 6.5 times higher in the 131 anastomoses situated below 5 cm from the anal verge. Small randomised studies have shown some benefit of a defunctioning stoma for low rectal anastomoses; with a 50% reduction in clinical leaks [23]. Although LAR may have better outcomes in terms of local recurrence and psychological benefits to the patients, there will always be cases where sphincterpreserving reconstruction with colorectal or coloanal anastomosis cannot be performed because of the proximity of the rectal cancer to, or its direct involvement of the anal sphincter or the levator. Therefore, in these cases, efforts are required to improve the local recurrence rate with meticulous APE surgery. Dehni et al. [24] reported n overall local recurrence rate of 10% after APE for all stages of rectal cancer. Two-thirds had surgery alone. They attributed this low LR to the surgical technique, which included a wide perineal
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dissection, where the levator ani was divided laterally at its bony insertion onto the pelvis. The abdominal dissection stopped above the tumour, taking care to avoid separation of the tumour from the underlying pelvic floor to reduce the risk of inadvertent tumour cell spillage. Morbidity was low and perineal wound healing occurred in 94% of patients where an omentoplasty was routinely performed to facilitate perineal healing, with the vascularity of the omentum preserved via the left gastroepiploic vessels. This contrasts with the historical series, where the reported frequency of perineal infections was up to 50% [25]. Perineal infection is one of the main causes of morbidity after APE resulting in prolonged hospital stay and a painful post-operative course. Furthermore a persistent perineal sinus was reported to remain in 7–10% of patients [26]. Good results were also reported by Volpe and co-workers [27] who also employed a wide perineal dissection. It is logical to assume, that an enhanced or radical quality of APE resection specimen is more likely when a wider cylindrical excision of tumour occurs. Margin positivity in APE specimens may be reduced when a cuff of levators is taken compared, with resections that cone on to the rectal wall by following the natural TME ‘Holy Plane.’ This technique of radical dissection, as compared to the current standard technique, needs to be formally addressed within a prospective clinical trial of surgical technique and macroscopic assessment of the quality of the excised specimen and the pathological assessment of the resection margins.
4. Neo-adjuvant therapy for low rectal carcinoma It is clear from variations in surgical results and local recurrence rates that surgical technique in low rectal cancers is a critical factor in determining the likelihood of local recurrence. The current treatment choices for patients with low rectal cancer include primary surgery alone without any pre- or post-operative adjuvant therapy, preoperative radiotherapy followed by surgery, preoperative neoadjuvant chemoradiotherapy or postoperative adjuvant chemoradiotherapy. Several trials have addressed the use of adjuvant and neoadjuvant therapy as a means of improving outcomes for patients with low rectal cancers with varying results and at present there remains no consensus for a treatment strategy using the combined modalities. The use of post-operative chemoradiation has been shown to produce superior survival compared to surgery [28] or radiotherapy alone [29], but no survival advantage has been demonstrated compared to chemotherapy alone [30,31]. There is now evidence to indicate that preoperative radiotherapy is more effective than postoperative radiotherapy in preventing local recurrence in patients with rectal cancer [32]. Similarly there is
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consensus agreement that adjuvant chemotherapy used in stages II and III rectal cancer improves survival compared to surgery alone [31,33]. The potential advantage of preoperative therapy resulting in sufficient tumour regression to achieve sphincter sparing surgery has prompted its investigation in low rectal cancers. Early experience in treating patients with preoperative radiotherapy alone 45–60 Gy over 412 to 6 weeks resulted in some improvements in the sphincter sparing surgery rates but unfavourable low rectal tumours still suffered high local recurrence rates (27%) [34]. In a later study high failure rates (53%) were also demonstrated for stage III (unfavourable) low rectal tumours treated by preoperative radiotherapy prior to APE [24]. Thus, although undoubted tumour regression was observed using radiotherapy alone, disappointing results for stages II and III rectal cancers prompted the investigation of preoperative chemotherapy in conjunction with preoperative radiotherapy. Several studies described an increase in sphincter sparing surgery, downsizing and downstaging of tumours following the administration of chemoradiotherapy. In one series of 32 patients with low rectal cancer, local recurrence at 2 years was 3% and distant failure 10% [35]. The potential advantages of using preoperative CRT include elimination of micrometastatic disease, increased radiosensitivity due to more oxygenated cells, lower incidence of acute toxicity compared with post-operative combined modality therapy and enhanced sphincter preservation. However, the potential disadvantage of preoperative CRT is overtreatment of patients due to overestimation of tumour depth by preoperative staging (estimated to be 18% in one randomised study [36]). When compared with endoluminal ultrasound the tendency to overstage tumours is significantly lowered using thin section MRI [37]. The technique offers an opportunity to assess low rectal cancers and select those tumours with invasion of the sphincter for preoperative therapy. The feasibility of using an MRI based preoperative strategy involving combination chemotherapy and chemoradiotherapy have recently been explored in two phase II trials. In the first study, neoadjuvant protracted venous infusion (PVI) of fluorouracil (5-FU) and mitomycin C (MMC) as a prelude to synchronous CRT could be administered with negligible risk of disease progression and low risk of systemic spread [38,39]. It produced considerable symptomatic response with associated tumour regression. This treatment strategy allowed sufficient tumour shrinkage for R0 (microscopically complete) resection in the majority of patients with locally advanced rectal cancer including those with initial CRM involvement. However, distant metastasis was the most frequent cause of treatment failure occurring in 28% of patients after a median follow-up of 15 months. A more effective approach
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Fig. 6. Oblique axial image shows a low rectal tumour before (left-hand image) and after (right-hand image) chemoradiotherapy. The pretreatment axial image shows early T3 invasion through the rectal wall and into the intersphincteric plane. The potential resection margins are considered threatened as there is very little space in this plane and there is a risk of cutting on to tumour during the resection. Following preoperative chemoradiotherapy, tumour has been replaced by very low signal intensity fibrotic material thus lowering the risk of a positive circumferential margin.
would be incorporation of newer chemotherapy agents for neoadjuvant chemotherapy. Oxaliplatin and infused 5-FU/leucovorin (LV) has shown considerable antitumour activity in randomised phase III studies [40,41]. Therefore, MMC and PVI 5-FU were replaced by oxaliplatin and capecitabine as the neoadjuvant chemotherapy with administration of capecitabine during the chemoradiation phase of this preoperative treatment schedule [42]. Preliminary analysis showed universal radiological tumour response. Moreover, rapid symptomatic relief occurred with a median of 23 days after commencement of oxaliplatin and capecitabine. Tumour regressed away from the potential CRM allowing R0 resection to be achieved in all patients undergoing surgery. For tumours arising below the levator ani, involving at least the full thickness of the muscle coat, chemoradiotherapy appeared effective at preventing positive circumferential margins. Pre- and post-treatment MRI images of low rectal cancers, that have received EXPERT Trial chemoradiotherapy, and their corresponding histopathology sections show the potential of this approach to improve outcomes for such potentially difficult resections (Fig. 6) [43]. Ultimately, a multi-disciplinary approach to the problem of low rectal cancers is important in reducing the rate of local recurrence, by providing optimal preoperative staging, neoadjuvant therapy and careful planning of surgery [44].
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Surgical Oncology 13 (2004) 55–61 www.elsevier.com/locate/suronc
Management and imaging of low rectal carcinoma Gisella Salernoa, Ian Danielsa, R.J. Healda, Gina Brownb,, B.J. Morana a
Pelican Cancer Foundation, Basingstoke, Hants, UK Department of Radiology, Royal Marsden Hospital, Downs Road, Sutton SM2 5PT, Surrey, UK
b
Abstract Large variations in recurrence rates have been reported with the best results following total mesorectal excision (TME) surgery for low and middle rectal cancers. However, the low rectal cancers still have higher rates of local recurrence (up to 30%) whether operated by low anterior resection or abdominoperineal excision (APE) due to high rates of circumferential margin involvement. The treatment of choice for low rectal cancers that encroach upon the potential circumferential resection margin is surgery combined with preoperative neoadjuvant treatment. Preoperative chemotherapy combined with long-term radiotherapy reduces recurrence rates and preoperative loco-regional staging can help to select the patients more likely to benefit from neo-adjuvant therapy. Surface coil MRI is the most promising modality for patient selection, which can provide good views of the circumferential resection margin especially the presence or absence of tumour encroaching the intersphincteric plane. r 2004 Published by Elsevier Ltd. Keywords: Rectal neoplasms/surgery; Preoperative staging; Radiotherapy; Magnetic resonance imaging
1. Introduction Low rectal cancer, defined as an adenocarcinoma with its lower edge arising less than 6 cm from the anal verge, represents a particular surgical challenge for both local tumour control and sphincter preservation. In published series, such tumours have a higher incidence of positive resection margins and poor survival [1]. This has been attributed to narrow surgical planes deep within the pelvis as the mesorectum becomes narrowed and tapered, becoming a bare muscle tube at the level of the anal sphincter complex. The lack of surgical planes is further limited in the male by the presence of the prostate lying anteriorly. The challenge for the surgeon is to undertake careful removal of a cylinder of tissue beyond the rectal wall without perforating tumour. In this review, we discuss the anatomic imaging of the lower rectum as visualised using MRI, the surgical aspects of treating a low rectal cancer and how MRI Corresponding author. Tel.: +44 208 661 3215; fax: +44 208 661 3506. E-mail address: [email protected] (G. Brown).
0960-7404/$ - see front matter r 2004 Published by Elsevier Ltd. doi:10.1016/j.suronc.2004.09.013
based future strategies may improve outcome in these patients.
2. Anatomic and imaging considerations [2,3] The embryological development of the rectum starts with the division of the cloaca into the dorsal rectum and the ventral urogenital sinus by the urogenital septum. During the last 2 weeks of embryological development, the urogenital septum fuses with the cloacal membrane at the ectodermal anal pit and the anal portion of the cloacal membrane disappears at the mucocutaneous border of the anus, the dentate line. Although the in vivo anatomy of the anal canal has been well described using the endorectal coil [4,5] it is now possible to show similarly high-resolution anatomic detail using the phased array coil [6,7]. In the adult, the rectum is defined as the distal 15 cm of bowel above the anorectum. The rectum is enveloped by a distinct compartment comprising fatty tissue, connective tissue, vessels, draining lymphatics and
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nerves—the mesorectum. This mesorectal compartment is enveloped by a fascial covering down to the pelvic floor. This fascial layer is derived from visceral peritoneum—the mesorectal fascia. Between this layer and the parietal endopelvic fascia is loose areolar tissue which is relatively avascular representing the plane of bloodless excision in total mesorectal excision surgery [8]. In the upper third of the rectum, the lateral and posterior aspects of the rectum are surrounded by mesorectum, but anteriorly, the rectum is covered by peritoneum. In the lower third, the rectum is completely enveloped by mesorectum which begins to narrow caudally from the level of the origin of the levator muscles. Anteriorly the mesorectal fascia fuses with the remnant of the urogenital septum. This is a dense band of connective tissue in the male, Denonvilliers fascia, separates the prostate and seminal vesicles from the rectum. The corresponding structure in the female is the rectovaginal septum. For practical purposes, the lower third of the rectum can be considered on anatomical and imaging features as the area of rectum and mesorectum below the origin of the levators where the mesorectum tapers sharply, usually within 6 cm of the anal verge. This can be illustrated pictorially on coronal MRI scans (Fig. 1). The rectum is supported by: 1. The recto-sacral fascia, which is just above the pelvic floor at the anorectal junction at S4. MRI depiction
Fig. 2. Sagittal T2 weighted image showing the rectosacral fascia running from S4 to the rectal wall. The sagittal image best demonstrates the angulation of the anorectal junction produced by the puborectalis muscle sling (curved white arrow).
of the recto-sacral fascia is dependent on the thickness of the fascia, which is highly variable. When seen it is demonstrated as an oblique low signal intensity band that extends from the S3/S4 junction to the posterior wall of the rectum (Fig. 2). 2. The levator ani complex, which includes the puborectalis, pubococcygeus, ileococcygeus, and coccygeus muscles, covered by fat and parietal fascia. The muscles form a sheet that supports the pelvic floor and arise from various points of attachment at the bony pelvic sidewall: the spine of the ischium, the obturator fascia, the body of the pubis and the coccyx. The fibres of the levators muscles interdigitate in the midline posteriorly to form the anococcygeal raphe. The levator muscle sheet is best visualised by MRI on coronal images which depict the muscle sheet running obliquely toward the anorectal junction (Fig. 1). The rectum forms an acute anorectal angle with the anal canal and this is well demonstrated on in vivo MRI scans obtained in the sagittal plane (Fig. 2).
2.1. The anal canal [6] Fig. 1. Coronal T2 weighted image showing lateral mesorectal borders (black arrows). At the level of the levatororigins (open arrow), the mesorectum tapers and very little mesorectal tissue surrounds the lower rectal wall. The risk of surgical circumferential margin involvement in tumours arising below this level increases.
The anal canal is the distal 4 cm of the gastrointestinal tract. The components of the anal canal of relevance to surgical disease and treatment are described here and are well demonstrated on axial (Fig. 3), coronal (Fig. 4) and sagittal (Fig. 5) T2 weighted imaging of the anal canal.
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Fig. 3. Axial T2 weighted image in male and corresponding histology section showing external sphincter (open arrow), intersphincteric plane (narrow black arrow) and internal sphincter (broad black arrow). Fig. 5. Anorectal junction and anal canal detail shown in inset. The levator muscle fibres (white arrow) run forward and anteriorly to blend with the fibres of the external sphincter at the anorectal junction. The mesorectal fascia (open arrow) abuts the levator. The rectosacral fascia anchors the rectum and mesorectum to the sacrum running obliquely from sacrum to rectal wall (arrow heads). The dentate line is demonstrated on this sagittal image at the lower margin of the ridged anal columns.
rectum forming a U-shaped sling. This marks the point of the anorectal junction and the puborectalis sling pulls the rectum forward at the point resulting in 90–1151 of angulation between the rectum and anal canal. 2.3. The external anal sphincter (EAS)
Fig. 4. Coronal T2 weighted image in female showing low signal intensity external sphincter, and low signal intensity internal sphincter which is continuity with the muscularis propia. The bright high signal intensity layer between these two represents the intersphincteric plane.
2.2. The puborectalis sling and anorectal junction The anterior fibres of the levator give rise to the puborectalis sling which arches backward from the posterior surface of the pubis to sweep around the
The external sphincter comprises skeletal muscle fibres that blend with the puborectalis component of the levator ani to form a muscular ring. The sphincter is traditionally thought of as having 3 segments—deep, superficial and subcutaneous however, recent anatomic studies suggest that the external sphincter cannot be subdivided in this way and is incomplete anteriorly [6]. On in vivo imaging the sphincter is depicted as an almost complete ring of muscle. The superior margin of the external anal sphincter is defined by the lower edge of the puborectalis sling. Inferiorly, the fibres curve inwards just below the internal sphincter. 2.4. The internal anal sphincter (IAS) The IAS is formed by a very thickened segment of the circular muscle coat in the distal rectum. At the level of the top of the anal sphincter, fibres from the puborectalis slin join those of the outer muscle coat and together these form the conjoint longitudinal coat which forms a thin muscular layer between the IAS and EAS.
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2.5. The mucosa of the anal canal The mucosal layer of the anal canal comprises three distinctive zones. Its upper third is characterised by ridges of mucosal membrane that form the anal columns. Below this the mucosa is smooth surfaced and this point of transition is marked by the dentate line. Below this area, lies anal skin made up of keratinised stratified squamous epithelium. 2.6. Lymphatic drainage of the rectum and anus The anal canal and rectum have lymphatic drainage to nodes within the mesorectum following tributaries of the superior rectal lymphatics which mirrors the inferior mesenteric arterial supply and ultimately drain to the para-aortic nodes. The lower portion of anal canal and rectum also drain via the inferior rectal lymphatics to the internal pudendal lymphatics, which then drain to the internal iliac nodes in the pelvis. The lower anal canal drains to the superficial inguinal nodes. There is considerable overlap between these lymphatic drainages of the rectum and anus.
3. Surgical aspects of low anterior resection (LAR) and abdominoperineal excision (APE) The Colorectal Research Unit in Basingstoke, led by Prof. R.J. Heald, initiated prospective data collection in 1978 and has continued to the present day. A policy of sphincter conservation was adopted and the oncologic principle applied was of accurate total mesorectal excision (TME) for all rectal cancers with the exception of less than 5% who had local excision of early tumours. Preoperative radiotherapy was only used for clinically fixed or tethered tumours. Sphincter preservation and reconstruction was facilitated by the use of the small PI 30TM (United States Surgical Corp., Norwalk, CT) linear stapler which can reach the depths of the narrow pelvis and be used for the ‘Moran triple stapling technique’ [9]. An independent audit of the Basingstoke data, by MacFarlane et al. [10], demonstrated that no case above 4 cm from the anal verge had undergone APE. In Basingstoke, Heald refuted Miles’ theory of inferior rectal node involvement and exploited the knowledge that rectal cancer is unlikely to spread distally down the muscle tube [11]. Similarly this disputed the ‘5 cm rule’ for the distal margin [12,13]. Further work has demonstrated that a distal margin of 1–2 cm is safe as distal intramural spread rarely exceeds 10 mm [14–16]. Other work suggests that distal intramural spread is not a feature of rectal cancer and thus not a factor in determining local recurrence of rectal cancer [17]. In Basingstoke, despite using a narrow distal margin, a
local recurrence rate of only 1% was seen in the ‘curative’ anterior resections (including 29 Dukes stage C), and 4% in all cases (including those with metastases). The 6-year cure rate was 76% for curative cases and 68% for all cases. However, in this series, patients undergoing APE (n=15) had a worse local recurrence rate of 33% [11]. This may represent the ‘Will Rogers Phenomenon’ where selectivity alters assessment [18]. Based on audit of abdominoperineal resections, the Norwegian surgeon Dr. J. Wiig (unpublished data) suggests that recurrence below the levators occurs in the wound or scar. A possible cause for these perineal recurrences could be the implantation of free tumour cells extruded through the imperfectly occluded anus. Another reason for poor outcomes in patients with lower rectal tumours may relate to a tendency for metastasis to the internal iliac nodes, thus escaping the surgical excision planes of a TME [19]. However, the most likely cause is through surgical technique, with the plane of excision involving the muscular rectal tube at the ano-rectal junction. When Low Anterior Resection (LAR) was first adopted, there were concerns that this would result in higher rates of anastomotic leakage and therefore higher incidence of local recurrence (ref). The leakage rate after anterior resection varies from 3% to 21% and usually results in serious morbidity requiring emergency surgery (ref). Mortality associated with anastomotic complications ranges from 6% to 22% and accounts for approximately one-third of all deaths following colorectal surgery [20]. Thus, the low anastomosis is regarded as a significant risk factor for anastomotic leak rate due to anatomical inaccessibility, a less than optimal blood supply, a tightly closed anal sphincter below the anastomosis and the possibility of a pelvic haematoma becoming infected near the anastomosis [21]. Rullier et al. [22] analysed the variables that were associated with anastomotic leaks in 272 consecutive anterior resections and found that the leak rate was 6.5 times higher in the 131 anastomoses situated below 5 cm from the anal verge. Small randomised studies have shown some benefit of a defunctioning stoma for low rectal anastomoses; with a 50% reduction in clinical leaks [23]. Although LAR may have better outcomes in terms of local recurrence and psychological benefits to the patients, there will always be cases where sphincterpreserving reconstruction with colorectal or coloanal anastomosis cannot be performed because of the proximity of the rectal cancer to, or its direct involvement of the anal sphincter or the levator. Therefore, in these cases, efforts are required to improve the local recurrence rate with meticulous APE surgery. Dehni et al. [24] reported n overall local recurrence rate of 10% after APE for all stages of rectal cancer. Two-thirds had surgery alone. They attributed this low LR to the surgical technique, which included a wide perineal
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dissection, where the levator ani was divided laterally at its bony insertion onto the pelvis. The abdominal dissection stopped above the tumour, taking care to avoid separation of the tumour from the underlying pelvic floor to reduce the risk of inadvertent tumour cell spillage. Morbidity was low and perineal wound healing occurred in 94% of patients where an omentoplasty was routinely performed to facilitate perineal healing, with the vascularity of the omentum preserved via the left gastroepiploic vessels. This contrasts with the historical series, where the reported frequency of perineal infections was up to 50% [25]. Perineal infection is one of the main causes of morbidity after APE resulting in prolonged hospital stay and a painful post-operative course. Furthermore a persistent perineal sinus was reported to remain in 7–10% of patients [26]. Good results were also reported by Volpe and co-workers [27] who also employed a wide perineal dissection. It is logical to assume, that an enhanced or radical quality of APE resection specimen is more likely when a wider cylindrical excision of tumour occurs. Margin positivity in APE specimens may be reduced when a cuff of levators is taken compared, with resections that cone on to the rectal wall by following the natural TME ‘Holy Plane.’ This technique of radical dissection, as compared to the current standard technique, needs to be formally addressed within a prospective clinical trial of surgical technique and macroscopic assessment of the quality of the excised specimen and the pathological assessment of the resection margins.
4. Neo-adjuvant therapy for low rectal carcinoma It is clear from variations in surgical results and local recurrence rates that surgical technique in low rectal cancers is a critical factor in determining the likelihood of local recurrence. The current treatment choices for patients with low rectal cancer include primary surgery alone without any pre- or post-operative adjuvant therapy, preoperative radiotherapy followed by surgery, preoperative neoadjuvant chemoradiotherapy or postoperative adjuvant chemoradiotherapy. Several trials have addressed the use of adjuvant and neoadjuvant therapy as a means of improving outcomes for patients with low rectal cancers with varying results and at present there remains no consensus for a treatment strategy using the combined modalities. The use of post-operative chemoradiation has been shown to produce superior survival compared to surgery [28] or radiotherapy alone [29], but no survival advantage has been demonstrated compared to chemotherapy alone [30,31]. There is now evidence to indicate that preoperative radiotherapy is more effective than postoperative radiotherapy in preventing local recurrence in patients with rectal cancer [32]. Similarly there is
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consensus agreement that adjuvant chemotherapy used in stages II and III rectal cancer improves survival compared to surgery alone [31,33]. The potential advantage of preoperative therapy resulting in sufficient tumour regression to achieve sphincter sparing surgery has prompted its investigation in low rectal cancers. Early experience in treating patients with preoperative radiotherapy alone 45–60 Gy over 412 to 6 weeks resulted in some improvements in the sphincter sparing surgery rates but unfavourable low rectal tumours still suffered high local recurrence rates (27%) [34]. In a later study high failure rates (53%) were also demonstrated for stage III (unfavourable) low rectal tumours treated by preoperative radiotherapy prior to APE [24]. Thus, although undoubted tumour regression was observed using radiotherapy alone, disappointing results for stages II and III rectal cancers prompted the investigation of preoperative chemotherapy in conjunction with preoperative radiotherapy. Several studies described an increase in sphincter sparing surgery, downsizing and downstaging of tumours following the administration of chemoradiotherapy. In one series of 32 patients with low rectal cancer, local recurrence at 2 years was 3% and distant failure 10% [35]. The potential advantages of using preoperative CRT include elimination of micrometastatic disease, increased radiosensitivity due to more oxygenated cells, lower incidence of acute toxicity compared with post-operative combined modality therapy and enhanced sphincter preservation. However, the potential disadvantage of preoperative CRT is overtreatment of patients due to overestimation of tumour depth by preoperative staging (estimated to be 18% in one randomised study [36]). When compared with endoluminal ultrasound the tendency to overstage tumours is significantly lowered using thin section MRI [37]. The technique offers an opportunity to assess low rectal cancers and select those tumours with invasion of the sphincter for preoperative therapy. The feasibility of using an MRI based preoperative strategy involving combination chemotherapy and chemoradiotherapy have recently been explored in two phase II trials. In the first study, neoadjuvant protracted venous infusion (PVI) of fluorouracil (5-FU) and mitomycin C (MMC) as a prelude to synchronous CRT could be administered with negligible risk of disease progression and low risk of systemic spread [38,39]. It produced considerable symptomatic response with associated tumour regression. This treatment strategy allowed sufficient tumour shrinkage for R0 (microscopically complete) resection in the majority of patients with locally advanced rectal cancer including those with initial CRM involvement. However, distant metastasis was the most frequent cause of treatment failure occurring in 28% of patients after a median follow-up of 15 months. A more effective approach
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Fig. 6. Oblique axial image shows a low rectal tumour before (left-hand image) and after (right-hand image) chemoradiotherapy. The pretreatment axial image shows early T3 invasion through the rectal wall and into the intersphincteric plane. The potential resection margins are considered threatened as there is very little space in this plane and there is a risk of cutting on to tumour during the resection. Following preoperative chemoradiotherapy, tumour has been replaced by very low signal intensity fibrotic material thus lowering the risk of a positive circumferential margin.
would be incorporation of newer chemotherapy agents for neoadjuvant chemotherapy. Oxaliplatin and infused 5-FU/leucovorin (LV) has shown considerable antitumour activity in randomised phase III studies [40,41]. Therefore, MMC and PVI 5-FU were replaced by oxaliplatin and capecitabine as the neoadjuvant chemotherapy with administration of capecitabine during the chemoradiation phase of this preoperative treatment schedule [42]. Preliminary analysis showed universal radiological tumour response. Moreover, rapid symptomatic relief occurred with a median of 23 days after commencement of oxaliplatin and capecitabine. Tumour regressed away from the potential CRM allowing R0 resection to be achieved in all patients undergoing surgery. For tumours arising below the levator ani, involving at least the full thickness of the muscle coat, chemoradiotherapy appeared effective at preventing positive circumferential margins. Pre- and post-treatment MRI images of low rectal cancers, that have received EXPERT Trial chemoradiotherapy, and their corresponding histopathology sections show the potential of this approach to improve outcomes for such potentially difficult resections (Fig. 6) [43]. Ultimately, a multi-disciplinary approach to the problem of low rectal cancers is important in reducing the rate of local recurrence, by providing optimal preoperative staging, neoadjuvant therapy and careful planning of surgery [44].
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