Therefore, while these studies justify the use of laparoscopy in rectal cancer, it is prudent to wait for the

final results of the larger COLOR II and ACOSOG Z6051 trials before endorsing laparoscopy as the

preferred surgical approach to LARC.

Table 68-9 Open versus Laparoscopic Rectal Resections: Results of the Most

Representative Series

Many surgeons currently perform a hybrid approach consisting of the laparoscopic lymphovascular

control and colon mobilization, and the open mesorectal dissection and anastomosis through a lower

abdominal transverse incision. The hybrid approach is aimed at facilitating the most technically

challenging portion of the operation: the dissection of the distal rectum and the creation of the

anastomosis. With this approach the size of the abdominal wall incision is smaller compared with a

totally open procedure, but larger than with a totally laparoscopic procedure. Although there is some

evidence of short-term advantages to this approach compared to open surgery,237 long-term benefits

compared to the totally open or laparoscopic approaches are unknown.

The robotic platform (da Vinci®) was introduced to the surgical armamentarium to facilitate the

minimally invasive approach to procedures such as prostatectomy, hysterectomy, and TME, which

require optimal visualization and dexterity in the narrow pelvic space. The experience accumulated thus

far – based on retrospective institutional case series – suggests that robotic TME is equivalent to

laparoscopic TME in terms of completeness of the mesorectal excision, CRM positivity, and short-term

oncologic outcomes. Conversion rates appear to be lower compared to laparoscopic TME, but hospital

charges are higher.238 A prospective, randomized study comparing laparoscopic and robotic TME – the

Robotic Versus Laparoscopic Resection for Rectal Cancer (ROLARR) trial – has completed accrual, but

the results are not available yet.239 However, as laparoscopy has not become standard in LARC, it is

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likely that the controversy regarding the benefit of robotic TME will continue for years.

The transanal–transabdominal proctectomy, or down-to-up TME, is a transanal, minimally invasive

approach for the dissection of the distal rectum in patients with a narrow pelvis.240,241 With this

approach, lymphovascular control, the entire colonic mobilization, and dissection of the upper rectum

are performed using conventional transabdominal laparoscopy. The dissection of the distal rectum is

performed through the anus, using either conventional transanal equipment for very distal tumors, or

endoscopic equipment (TEMS, TEO, TAMIS) for higher tumors. The rectal wall is incised

circumferentially, distal to the tumor, and the MRF is identified. The lumen of the colon is closed with a

purse-string suture to avoid contamination. The dissection is carried cephalad in the proper plane until

the abdominal field is reached. The specimen is then removed, and the anastomosis performed through

the anus. This approach is particularly useful for patients with very distal rectal cancers treated with

chemoradiation therapy, in which the surgeon has no anatomical cues about where to transect the

rectum in order to achieve a negative distal margin. The transanal approach allows the surgeon to

choose precisely the point for transecting the rectum while visualizing the distal edge of the tumor. The

benefit of the down-to-up approach for higher rectal cancers that could be treated with a conventional

transabdominal dissection and a double-stapled anastomosis are uncertain.

Adjuvant Chemoradiation for Locally Advanced Rectal Cancer

Several randomized, controlled trials conducted in the pre-TME era demonstrated that radiation therapy

(RT) given before or after surgery reduced the rate of LR, compared to surgery alone.242–244 However,

the relevance of these trials was later questioned, because surgery was not standardized and the LR

rates reported in the control arms – approximately 25% – were considered too high compared to that of

patients treated in later years with surgery alone according to TME principles.129 The efficacy of RT in

the setting of quality TME surgical resection was investigated in the Dutch Colorectal Cancer Group

trial, which randomized 1,861 patients with resectable disease to TME alone or short-course RT (SCRT)

(5Gy a day × 5 days, for a total dose of 25Gy), followed by TME within 2 to 7 days. The study showed

that SCRT reduced the rate of LR in resectable rectal cancer treated by TME, compared to TME alone;

however, SCRT did not provide a significant survival benefit.245 This trial proved that preoperative RT

decreases the rate of LR in LARC patients treated with TME surgery.

The benefit of combining chemotherapy with RT was proven by several randomized trials that

compared postoperative RT combined with 5-FU, administered as a bolus or as continuous venous

infusion (CVI), to postoperative RT alone, in patients with pathologic stage II and III rectal

cancer.246,247 The results proved that combined 5-FU and radiation was more effective than radiation

alone in reducing the risk of LR, and that CVI 5-FU was associated with lower toxicity compared to

bolus 5-FU.

The European Organization for Research and Treatment of Cancer (EORTC) protocol 22921 was

developed to assess the effect of adding CT to preoperative RT, and the subsequent value of

postoperative CT in rectal cancer patients.248 At the 5-year mark, LR was significantly lower in all three

arms receiving any CT (pre- or postoperative) compared to preoperative RT alone, indicating a benefit

of CT in reducing the risk of LR, regardless of when it was administered. The addition of CT to RT did

not impact survival. Additional work by the Federation Francophone de la Cancerologie Digestive

corroborated these findings.249 These studies showed that, similar to what was found using

postoperative radiation, adding CT to preoperative RT also reduced the rate of LR, compared to

preoperative RT alone.

The German Rectal Cancer Group (CAO/ARO/AIO 94) compared preoperative versus postoperative

CRT in 823 patients with clinical T3–4/N+ rectal cancer.250 RT in this trial consisted of 50.4 Gy in 25

fractions with bolus 5-FU as a radiosensitizer. In the preoperative treatment group, surgery was

performed 6 weeks after completion of CRT. Both groups had surgery according to TME principles, and

received postoperative adjuvant CT. The preoperative CRT group had less toxicity and lower 5-year LR

rates compared to the postoperative CRT group (6% vs. 13%). This study found no differences in the

rates of DR, DSS, or OS. The NSABP R-03 study also compared the use of preoperative versus

postoperative 5-FU/LV, using 45 Gy in 25 fractions in T3/4, N+ patients, to evaluate differences in

DFS, LR, or OS.251 Despite stopping the study early due to limited accrual, the R-03 study reported

better DFS in the preoperative CRT group, compared to the postoperative group, with a near-significant

difference (p = 0.065) in OS and no difference in LR. The results of these two trials established

preoperative CRT as the preferred treatment for LARC in both Europe and the United States.

More recently, it has been shown that capecitabine is noninferior to infusional 5-FU as a

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radiosensitizer for LARC, in both the NSABP R-04 trial and the German Cancer Research Center multicenter trial.252,253 Several large, prospective trials have failed to prove that the addition of oxaliplatin to

a fluoropyrimidine (5-FU or capecitabine) is superior to fluoropyrimidine alone as a radiosensitizer in

patients with LARC.252,254–256 In fact, patients receiving the oxaliplatin plus a fluoropyrimidine had a

greater rate of adverse events, with similar or lower tumor response rates. Therefore, based on the

current evidence, oxaliplatin is not recommended as a radiosensitizer to a fluoropyrimidine in patients

with LARC.

In addition to the standard hypofractionation (180 to 200 cGy a fraction) commonly delivered during

the standard CRT, radiation therapy is also frequently delivered as short course (SCRT) using fewer,

larger fractions (5 Gy daily fractions for 5 consecutive days and a total dose of 25 Gy). In these patients,

surgery is performed within 7 days of completion of the radiation. Both schemes are biologically

equivalent in eradicating cancer cells, but SCRT has the potential benefits of shorter duration of

treatment, more efficient utilization of resources, and reduced cost compared to CRT. However, higher

dose per fraction increases the risk of delayed toxicity, and tumor regression is lower with SCRT. Two

prospective, randomized trials comparing SCRT with CRT have reported equivalent local tumor control

with both regimens, and the selection between CRT and SCRT is based on doctor and patient

preferences.257,258 In general, CRT is preferred in the setting of large tumors that may benefit from

maximal tumor regression before surgery.

Current guidelines recommend CRT with the aim of reducing the risk of LR for all patients with stage

II and III rectal cancer. However, the risk of LR is variable depending on the distance of the tumor from

the anal verge, the risk being lower for tumors located in the upper rectum compared to those in the

lower rectum. It is possible that some patients with high rectal cancers, specifically those with T3N0

tumors and a clear CRM, may not actually benefit from preoperative radiation but may simply be

exposed to radiation-associated toxicity. A current trial in the United States seeks to address this

question by comparing the outcomes of rectal cancer patients treated with neoadjuvant chemotherapy,

with or without radiation, before TME.259

Adjuvant Chemotherapy for Locally Advanced Rectal Cancer

In the past, LR was the dominant problem in patients with LARC, but in the modern era more patients

develop distant metastasis than LR. Consequently, patients with LARC treated with neoadjuvant CRT

and TME are recommended for postoperative adjuvant chemotherapy, with the aim of reducing distant

metastasis and improving survival. However, the data supporting this recommendation are limited, and

based heavily on experience using adjuvant therapy for resected colon cancers. The QUASAR study

discussed above showed that adjuvant chemotherapy has a modest effect in lowering recurrence and

improving survival in stage II/III CRCs following curative-intent surgery.153 However, the cohort was

not powered to demonstrate differences in the 29% of rectal cancer patients who were accrued, and the

association with better outcomes stems from subset analysis. In contrast, the 10-year update of the

EORTC 22921 trial showed no difference in OS or DFS with the addition of 5-FU–based postoperative

chemotherapy in rectal cancer patients treated with preoperative RT or CRT and TME.260 However,

these results have been criticized because the proportion of patients receiving the full dose of

postoperative adjuvant chemotherapy was only 43%, thus underestimating the therapeutic effect. A

meta-analysis of 21 controlled trials in patients receiving potentially curative surgery, including a total

of 4,854 patients randomized to surgery plus fluoropyrimidine-based postoperative chemotherapy, and

4,367 patients to surgery and observation, has shown a significant reduction in the risk of death (17%)

(HR = 0.83, CI: 0.76–0.91) and a reduction in the risk of DR (25%) (HR = 0.75, CI: 0.68–0.83) among

patients undergoing adjuvant chemotherapy, compared to those undergoing observation.261 Available

data were insufficient to investigate the effect of adjuvant chemotherapy separately in different TNM

stages. These data support the use of postoperative chemotherapy after curative-intent surgery in

patients with rectal cancer. Similar to colon cancer patients, patients with LARC treated with CRT and

TME are recommended to receive 5-FU or capecitabine plus oxaliplatin-based adjuvant chemotherapy.

The length of adjuvant treatment in rectal cancer is shorter compared to colon cancer (4 months vs. 6

months), given the use of sensitizing 5-FU or capecitabine during CRT.

A common criticism about the use of postoperative adjuvant chemotherapy after curative surgery in

patients with rectal cancer is low treatment compliance. In some series, up to 27% of eligible patients

never start treatment, and more than 50% require dose reductions or treatment interruptions or

delays.248,256 This is particularly relevant, as a systematic review of 10 studies – including more than

15,000 patients – evaluated the effect of timing on the efficacy of postoperative adjuvant therapy,

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Trendelenburg position during surgery are at risk of compartment syndrome, in particular obese

patients and those with peripheral vascular disease. These patients require monitoring of the peripheral

pulses, and position changes, to prevent compartment ischemia.

Principles of Total Mesorectal Excision

The principle of rectal cancer treatment is the eradication of the primary tumor and its lymphatic

drainage by en bloc removal of the rectum and the mesorectum, following well-defined anatomical

planes. This operation, known as total mesorectal excision, or TME, requires dissection under direct

vision along the areolar tissue plane situated between the MRF and the presacral fascia (Fig. 68-15). A

sharp dissection along this plane is associated with a higher probability of achieving a negative CRM,

lower risk of bleeding from inadvertent tearing of the presacral veins, and reduced risk of injuring the

hypogastric nerves.128

Adequate lymphadenectomy requires division of the lymphovascular pedicle at the origin of the

superior rectal vessels, caudal to the branching of the left colic artery from the inferior mesenteric

artery (usually defined as low tie). In patients with clinically suspicious nodes at the origin of the

inferior mesenteric artery, the lymphovascular control should be extended proximally by dividing the

inferior mesenteric artery close to the origin (high tie). In both cases the sigmoidal branches are

included in the surgical specimen; therefore, the proximal division of the bowel should ideally be

performed at the junction of the descending and the sigmoid colon, incorporating most of the sigmoid

colon in the surgical specimen.201 As distal tumor extension along the rectal wall is limited, a distal

margin of 2 cm of normal bowel wall is considered adequate for most tumors. However, distal spread in

the mesorectum may extend farther than intramural spread. Not infrequently, mesorectal deposits are

found 3 to 4 cm distal to the lower edge of the tumor. Therefore, for tumors of the upper rectum, the

mesorectal excision should be extended to 5 cm distal to the lower edge of the tumor. In these patients

the mesorectum should be divided perpendicular to the axis of the rectum. As some of the distal

mesorectum is left in the pelvis along with the distal rectal stump, this operation is known as tumorspecific TME (TSME), to distinguish it from the TME performed with dissection carried to the pelvic

floor, the rectum divided distal to the end of the mesorectum, and the entire mesorectum included in

the surgical specimen.123

Figure 68-15. Total mesorectal excision. A: APR specimen. B: ELAPE specimen. C: Planes of dissection for TME. D: Robotic TME.

Sphincter Saving Procedures

A TSME or a TME is compatible with sphincter preservation by anastomosing the divided end of the

descending or the sigmoid colon to the rectal stump. This operation is known as a low anterior resection

or LAR (Fig. 68-16). In this operation the rectum is divided distal to the tumor using a stapling device

that simultaneously staples and divides the rectum, leaving a short rectal stump. The anastomosis is

completed with a circular stapler that brings together the end of the colon to the rectal stump. The reestablishment of the large bowel’s continuity by suturing the colon to the anal canal, working through

the anus, is known as coloanal anastomosis or CAA (Fig. 68-17). The connection of the colon to the

rectum or anal canal can be performed by an end-to-end or a side-to-end connection, or with the

creation of a J-pouch reservoir (Fig. 68-18). A tension-free, well-vascularized low colorectal or coloanal

anastomosis requires a complete mobilization of the entire left colon with take-down of the splenic

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flexure, including division of the inferior mesenteric vein close to the ligament of Treitz. The blood

supply to the entire left colon is based on the left branch of the middle colic vessels through the

marginal artery.

Figure 68-16. A: Low anterior resection, section in the distal third of the rectum, candidate for colorectal anastomosis. B: Low

anterior resection, section above the sphincteric complex, candidate for coloanal anastomosis. C: Colorectal anastomosis.

Figure 68-17. Double stapling technique for low colorectal end-to-end anastomosis.

Many patients undergoing a sphincter-saving procedure report high bowel frequency, urgency,

soiling, and inability to defer defecation for 15 minutes.202 This constellation of symptoms is commonly

known as low anterior resection syndrome (LARS).203 The frequency and severity of these symptoms is

variable and depends, to some degree, on the location of the tumor and the anastomosis, the patient’s

prior bowel function, and the use of neoadjuvant or adjuvant therapy.204 Pelvic irradiation, before or

after surgery, increases significantly the risk of bowel dysfunction.205,206 The anatomical and

physiologic factors that contribute to LARS are not completely understood. Anal sphincter pressures are

not different in patients with or without LARS. What appears to be different is an exaggerated anal

sphincter relaxation to even small volumes of stool within the neorectum.207 Surgeons have tried to

overcome this low capacitance of the neorectum – which results from an end-to-end anastomosis – by

creating a colonic reservoir: either a colonic J-pouch, or a side-to-end anastomosis. A number of studies

have compared the functional outcomes after straight end-to-end anastomosis and a colonic J-pouch. A

systematic review of reconstructive techniques after LAR identified 9 trials that randomized a total of

473 rectal cancer patients to either colonic J-pouch or straight end-to-end anastomosis, reporting that

short-term bowel function was better for J-pouch compared to straight anastomosis.208 Frequency and

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urgency were less prevalent in patients with a colonic J-pouch, but the rate of fecal incontinence was

similar in both groups. The only two trials that followed patients for more than 118 months found

minimal or no long-term differences between groups. Although the methodology of these studies was

very heterogeneous, they do indicate that a colonic J-pouch is associated with a short-term

improvement in frequency and urgency, but no apparent long-term benefit, compared to end-to-end

anastomosis. The same systematic review found no differences in anastomotic leak rate, or other

complications, between groups. Of note, almost one-third of patients with colonic J-pouches often

complained of long-term difficulty emptying the rectum, requiring use of laxatives or

suppositories.209,210 These symptoms are more prevalent when larger pouches are created; therefore,

pouch size should be limited to 5 to 6 cm.211,212

Figure 68-18. Reconstructive options after LAR. A: End-to-end anastomosis. B: End-to-side anastomosis. C: J-pouch anastomosis.

The side-to-end anastomosis (created by inserting the anvil of a circular stapler 3 to 4 cm from the

end of the mobilized descending colon) can also potentially increase the reservoir capacity of the

anastomosis. It has similar functional results, but is easier to construct than the colonic J-pouch;

although it, too, is associated with defecatory problems.213 The creation of a transverse coloplasty

proximal to an end-to-end anastomosis is another option used to increase the capacity of the neorectum,

but is associated with a higher anastomotic leak rate.208

In summary, colonic reservoirs are associated with a temporary improvement in bowel frequency and

urgency, but have the risk of long-term defecatory problems. In general, the author prefers an end-toend anastomosis using the larger descending colon, rather than the sigmoid colon, for creation of the

neorectum.

The integrity of the anastomosis should be tested intraoperatively with a pneumatic test, or by

endoscopy, with distension of the bowel while submerging the anastomosis in water. Air leaks thus

detected may be treated with suture repair, re-do of the anastomosis, and/or the creation of a proximal

diverting stoma. Testing the integrity of the anastomosis during surgery has been associated with a

lower risk of clinical postoperative anastomotic leak.214

Low colorectal and coloanal anastomoses have a risk of leakage ranging from 3% to 34%, depending

on the patient population, the use of neoadjuvant radiation, the distance of the anastomosis from the

anal verge, and the surgical technique.215,216 An anastomotic leak can cause pelvic sepsis, which may

not only preclude sphincter preservation, but has also been associated with an increased risk of local

recurrence and poorer survival217 (although more recent data have questioned this association).218,219

To prevent these possible complications, a diverting stoma is recommended for patients having a TME,

and for patients receiving neoadjuvant radiation.220 Diverting stomas do not prevent complications, but

mitigate the consequences of a leak and reduce the need for urgent reoperation in patients developing a

leak.221,222 A loop ileostomy is preferred over a transverse loop colostomy because it is easier to create

and close.223 However, loop ileostomies are associated with postoperative dehydration and electrolyte

abnormalities requiring hospital readmission.224 Prevention of these complications requires adequate

patient education and training about stoma management.

Abdominoperineal Excision

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For many cancers located in the distal rectum, particularly those infiltrating the levator muscles or the

anal sphincter, an oncologically safe circumferential and/or distal resection margin is not compatible

with sphincter preservation. In these patients an R0 resection requires a TME with en bloc excision of

the levator muscles and the anal canal, and the creation of a permanent end colostomy. This operation is

known as abdominoperineal excision of the rectum or APE (Fig. 68-19). As the name indicates, the APE

has two parts: an abdominal part and a perineal part. During the abdominal part, the proximal

lymphovascular control, division of the colon, and dissection along the mesorectal plane are similar to

those in LAR, except that the mesorectal dissection should stop at the upper level of the levators, to

avoid disturbing the portion of the rectum resting on the levator muscles. During the perineal part, the

anal canal with the sphincter complex and the levator muscles are dissected off the ischiorectal fat, all

the way to the apex of the ischiorectal fossa. The levators are divided close to their insertion in the

white line near the obturator internus and coccygeus muscles. The levator muscles are left attached to

the rectum, and the resulting surgical specimen has a cylindrical appearance; therefore, this procedure is

called cylindrical APE or extralevator APE (ELAPE) (Fig. 68-20).225 However, some surgeons question

the need to entirely remove both levator muscles in every rectal cancer patient, and recommend

removing only the portion of the levators required to clear the tumor. This operation has been called

the standard APE or SAPE.226 The choice between an ELAPE and SAPE is controversial. The potential

oncologic benefit of larger tissue removal needs to be weighed against the increased morbidity

potentially associated with a larger perineal defect, particularly in patients treated with neoadjuvant

therapy.227 A recent meta-analysis with 949 patients from one randomized trial, one prospective casecontrol study, and six retrospective case series, indicated that ELAPE is associated with lower

intraoperative rectal perforation, lower positive CRM, and lower risk of local recurrence, but with

similar complication rates, compared to SAPE.228 At the present time, the hypothetical benefit of the

ELAPE over the SAPE has not been proven conclusively. It is possible that both techniques – the total or

the tumor-specific excision of the levator muscles – may be equivalent as long as an R0 resection, with

an intact rectal specimen, is achieved.

Figure 68-19. Abdominoperineal excision of the rectum (APE).

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Figure 68-20. Cylindrical APE.

Many surgeons will perform both parts of the APE operation with the patient in modified lithotomy,

also known as the Lloyd–Davis position. It provides relatively good access to the perineum and allows

two teams to work simultaneously – one in the abdomen, and one in the perineum. Others perform the

abdominal part in the supine position, and the perineal part with the patient prone over a hip roll and

padding of the bony prominences. The prone position, also known as jackknife position, provides better

exposure of the perineum, and facilitates assistance and teaching. It requires turning the patient, which

takes time, and does not allow a two-team approach. Results seem to be similar with both approaches,

and the selection is based on the surgeon’s preferences.229

Minimally Invasive Surgery for Rectal Cancer

5 Open surgery for rectal cancer requires long abdominal incisions. An APE can be performed though a

midline infraumbilical or low transverse incision. Most sphincter-preserving procedures (SSPs) require a

long midline incision, extending from the epigastrium to the symphysis of the pubis, in order to permit

access to the entire left side of the large bowel from the splenic flexure to the lower rectum. These

abdominal incisions are a source of patient discomfort, and short- and long-term morbidity. The goal of

minimally invasive surgery in rectal cancer is to reduce the size of the abdominal incision, thus

expediting recovery, without compromising the completeness of the mesorectal excision or the

oncologic outcomes. However, the adoption of minimally invasive surgery for rectal cancer has been

slow due to the difficulty of working in the relatively deep and narrow pelvic space using long, rigid,

nonarticulated laparoscopic instruments. According to a number of retrospective case series and small

randomized controlled trials, laparoscopic TME is associated with less postoperative pain, less surgical

morbidity, and shorter length of hospital stay, but equivalent completion of the mesorectal excision,

CRM positivity, and even LR, compared to open TME.230–232 While these studies have shown that

laparoscopic TME is feasible, less than 20% of all rectal cancer operations are performed

laparoscopically in the United States.233

Three large multi-institutional prospective, randomized trials have compared open and laparoscopic

TME for rectal cancer (Table 68-9).234–236 A fourth prospective study conducted in the United States, the

ACOSOG Z6051, has completed accrual, but the results are not available yet. The combined experience

of these trials indicates that laparoscopic TME results in longer operative time, less blood loss, faster

bowel recovery, and shorter hospital stay compared to open TME. Operative mortality and

intraoperative and postoperative complications were not different between groups. The proportions of

patients having an SSP, a complete mesorectal excision, or a positive CRM were not different between

groups, nor was the number of lymph nodes retrieved. However, conversion and positive CRM rates in

the laparoscopic arms varied widely between different studies. These differences could be explained by

trial design, inclusion criteria, randomization, and use of neoadjuvant therapy. Only the CLASICC and

COREAN trials have reported 3-year oncologic outcomes. LR, distant metastasis (DM) and survival were

not different between groups. However, these results should be interpreted with caution, because the

CLASICC trial was not specifically powered to detect differences between treatment groups in rectal

cancer patients, and the COREAN trial allowed a 15% difference as the noninferiority margin.

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Figure 68-11. Anatomy of the rectum. A: Coronal pelvis. B: Sagittal pelvis.

The blood supply of the rectum comes primarily from the superior rectal artery, which is the terminal

branch of the inferior mesenteric artery after it gives off the left colic artery. The superior rectal vein

has a parallel course to its homonymous artery, and joins the left colic vein to form the inferior

mesenteric vein draining into the splenic vein. The lower portion of the rectum and the anal canal also

receive blood supply from the internal iliac vessels through the middle rectal artery, an inconsistent

branch of the inferior vesical artery; the inferior rectal artery is a branch of the pudendal artery. The

middle and inferior rectal vessels anastomose with the upper rectal vessels, supplying enough blood to

the entire rectum. As in other locations, the middle and inferior rectal veins follow the course of the

homonymous arteries, draining into systemic circulation through the internal iliac veins.

The anatomy of the autonomic pelvic nerve system is very important when operating in the rectum,

because of its proximity to the plane of dissection during different parts of the operation. Damage to

these nerves can result in urinary and/or sexual dysfunction. The hypogastric plexus, located in front of

the aorta, contains predominantly preganglionic sympathetic fibers originating from the lumbar

sympathetic trunk. The fibers of the hypogastric plexus converge at the level of the aortic bifurcation

into well-defined hypogastric nerves, which course laterally and anteriorly over the internal iliac vessels

toward the lateral pelvic sidewall. There they join the splanchnic pelvic nerves, containing primarily

postganglionic parasympathetic fibers from the anterior rami of S2, S3, and S4, to form the pelvic

plexus. Branches of the pelvic plexus provide innervation to the distal ureter, the vas deferens, the

seminal vesicles, urinary bladder, and prostate. Branches of the pelvic plexus also provide innervation to

the distal rectum, passing through the lateral rectal ligaments, or lateral stalks. Finally, distal to the

lateral rectal ligaments, the distal pelvic plexus forms the urogenital neurovascular bundles that pass

close to the posterolateral aspect of the seminal vesicles or the vagina, extending toward the apex of the

prostate and the neck of the bladder.

Clinical Staging of Rectal Cancer

The preoperative evaluation of the rectal cancer patient follows the same principles as that of the colon

cancer patient, but the wider spectrum of therapeutic options for rectal cancer patients requires accurate

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information about the location and stage of the tumor. The clinical stage is important in making

treatment decisions, such as the intent of the treatment (palliative or curative), the need for

neoadjuvant therapy, or even the extent of the surgery (LE vs. TME).

Figure 68-12. Endorectal ultrasound. Role in rectal cancer staging.

Patients with rectal cancer should undergo a complete colonoscopy because synchronous polyps are

present in up to 30% of patients, and synchronous cancers in up to 5.3% of patients. They also require a

CT scan of the chest, abdomen, and pelvis to exclude distant metastasis, which is present in 20% of

patients at the time of diagnosis.

The preoperative locoregional staging of rectal cancer follows the clinical TNM system, based on

depth of tumor penetration in the rectal wall and the presence of regional lymph nodes. However, the

preoperative assessment of rectal cancer goes beyond determination of clinical tumor stage; it includes

the distance of tumor from the anal verge, its relationship to the sphincter complex and the levator

muscles, the proximity of tumor to the MRF, and the presence of extramural venous invasion (EMVI).

This information is essential in planning treatment and surgery. Gross morphologic features such as size,

morphology, and ulceration have been associated with prognosis. However, when stratified by stage,

these characteristics have not appeared to contribute independently to oncologic outcomes, and

therefore they are not incorporated into treatment decisions.

3 DRE and proctoscopy provide the surgeon with the first direct impression of the tumor. Tumor

mobility on DRE provides a gross estimation of the tumor depth of invasion. There is a four-category

clinical classification of rectal tumors, based on mobility on DRE, which supposedly corresponds to the

four T categories of the TNM system. However, the correlation between the clinical and pathologic T

classifications is not very accurate, and varies significantly with the experience of the examiner. In

general, DRE is able to distinguish between mobile tumors, most likely limited to the bowel wall, and

tethered or fixed tumors, likely penetrating beyond the bowel wall. However, DRE fails to identify

more than 50% of pathologically proven involved nodes.157 Finally, only very distal tumors are within

reach of the examining finger. Therefore, pretreatment clinical staging requires imaging studies;

namely, ERUS, multidetector CT (MDCT) scan, and MRI.

Ultrasound with an endorectal rotating probe is the imaging modality that best depicts the different

layers of the bowel wall, and it is most useful for staging early rectal cancer (Fig. 68-12).158 But ERUS

has a relatively short focal range, and cannot depict important anatomical structures such as the MRF.

MDCT scans provide accurate images of the rectum, adjacent pelvic structures, and even the MRF, but

have lower tissue resolution compared to MRI. A CT scan of the chest, abdomen, and pelvis should be

performed in every rectal cancer patient to exclude distant metastases. MRI with a surface phased-array

coil has become the preferred imaging modality for locoregional staging of rectal cancer. Using various

sequences and multiple planes, MRI provides high-tissue resolution and excellent anatomical depiction

of the rectum, the mesorectum, the MRF, the levator muscles, and other pelvic structures, relative to

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tumor location (Fig. 68-13).159 The addition of new contrast agents and advanced functional sequences

such as diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE) permit the

quantification of tumor biologic processes such as microcirculation, vascular permeability, and tissue

cellularity. While still experimental, these images are potentially useful for early assessment of rectal

cancer response to neoadjuvant therapy.160,161

Comparative studies suggest that ERUS is at least as accurate as MRI and more accurate than CT scan

in assessing the depth of tumor penetration in the bowel wall. The accurate detection of involved

mesorectal lymph nodes remains a challenge for all three techniques, however. Two meta-analyses of a

number of case series assessing the accuracy of these three techniques reported a wide range of

sensitivities and specificities for each, reflecting not only differences in technology, but also wide

variation in the criteria used to define malignant lymph nodes.162,163 However, the older studies

included in these analyses were conducted before MRI techniques for rectal cancer staging were fully

developed. At this time, MRI with a rectal cancer protocol provides the most useful information in a

majority of rectal cancer patients, and has great utility for surgical planning, while ERUS is most useful

for staging early-stage tumors.

Figure 68-13. Magnetic resonance imaging. Role in rectal cancer staging.

Tumor distance from the MRF – the CRM when performing TME surgery – has prognostic

implications for local recurrence and patient survival, and has become one of the most important

parameters in the preoperative evaluation of rectal cancer patients.164 MRI is the most accurate imaging

modality in determining the distance of the tumor to the MRF, and predicting CRM involvement. The

MERCURY trial, a prospective observational study assessing the accuracy of MRI in predicting a

curative resection in rectal cancer, reported 92% specificity in predicting a negative CRM.165 Other

important tumor features accurately assessed by MRI, and associated with patient outcomes, are

extramural spread, EMVI, involvement of the peritoneal reflection, and distance of tumor from the

levator muscle and sphincter complex.166,167 Using information on these parameters for patients

registered to the MERCURY trial, clinicians are able to stratify rectal cancer patients with good

prognosis (e.g., clear CRM, no evidence of EMVI, T2 or T3 <5 mm and not involving the

intersphincteric plane) with a 3% LR rate and an 85% 5-year DFS after treatment with surgery alone.168

In European and Scandinavian countries, the information gained from imaging, rather than clinical TNM

staging, is used to determine treatment in patients with rectal cancer.169

4 Tumor response to neoadjuvant therapy has prognostic value, and re-staging after neoadjuvant

1790

therapy is becoming increasingly important in reassessing treatment options and planning the surgical

procedure. Some patients with a clinical complete response are now offered alternatives to rectal

resection, such as “wait-and-see,” in the context of clinical trials.170,171 However, endoscopy and DRE

tend to underestimate tumor response to CRT.172 Morphologic imaging modalities such as ERUS and CT

provide a rough estimate of tumor regression, but cannot reliably distinguish post-treatment edema,

fibrosis, and necrosis from residual tumor.173 Similarly, MRI assessment of tumor response based on the

reduction of signal intensity relative to pre-treatment images, that occurs when tumor is replaced by

fibrosis, correlates poorly with pCR.174 Functional studies such as FDG-PET with or without

simultaneous CT, are valuable in assessing partial tumor response, but are not sensitive enough to

identify pCR.175 MRI dynamic sequences such as DWI and DCE, which provide an estimate of tissue

perfusion and cellularity, are currently under investigation in assessing rectal cancer response to CRT.176

Local Excision for Early-Stage Rectal Cancer

Selected patients with stage I rectal cancer, those with tumors localized to the bowel wall (T1 or T2)

and without involvement of the mesorectal nodes (N0), can be hypothetically cured with a LE of the

portion of the rectal wall containing the tumor. This operation spares most of the mortality, morbidity,

and bowel, urinary and sexual dysfunction associated with TME. However, the success of LE requires

meticulous patient selection. With LE, the mesorectum is not inspected for pathologic nodal staging.

Therefore, LE should only be offered to patients with a low risk of nodal metastasis. The selection

criteria for LE include: tumor size smaller than 3 cm, involving less than 30% of the circumference of

the rectum, mobile on DRE, localized to the submucosa on ERUS, without evidence of metastatic lymph

nodes on ERUS and CT or MRI, and no high-risk histologic features (i.e., grade 3 or 4, lymphovascular

or perineural invasion).177

In the past, only tumors located in the distal rectum could be treated with conventional transanal

excision (TAE), and LE was recommended only for tumors located within 8 cm from the anal verge.

With the use of endoscopic instrumentation and large operating proctoscopes (TEMTM, Richard Wolf

Medical Instruments Corp., Vernon Hills, IL; TEOTM, Karl Stortz Corp., El Segundo, CA) or single-port

devices (TAMIS, Trans-Anal Minimally Invasive Surgery), LE can now be easily performed for tumors

located in the mid and upper rectum. However, the benefit of LE is more significant for very distal

tumors that otherwise would require a low anastomosis or a permanent stoma. The real benefit of LE

for tumors located in the upper rectum is a matter of debate.

Independent of the approach, a full-thickness excision of the portion of the bowel wall involved by

tumor, with a 1-cm negative margin is required to avoid local recurrence (Fig. 68-14). The final decision

regarding the suitability of LE is made after the pathologic evaluation of the surgical specimen. If the

resection margins are positive, depth of invasion is beyond the submucosa (T stage ≥2), or the

histology reveals high-risk features (grade 3 or 4, lymphovascular or perineural invasion), the patient

should be offered immediate salvage TME.

Even in patients with tumors meeting all selection criteria, LE is associated with a higher rate of LR

compared to TME. The recurrence rates for T1 tumors treated with LE have been described as up to

23%.178–180 While some patients who develop LR after a failed LE are candidates for salvage TME, only

half of these patients are ultimately cured of their tumors. Recurrences after LE generally present as

more advanced tumors, often requiring extended pelvic dissections.181,182 The oncologic outcome for

these patients is worse than those treated originally with TME; this reinforces the importance of patient

selection for this strategy.

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Figure 68-14. Local excision of early rectal cancer. A: Marking resection margins. B: Incision up to mesorectal fascia. C: Resection

lodge. D: Defect closed with interrupted absorbable sutures.

A number of retrospective case series have compared the results of LE versus radical surgery (RS) for

patients with early-stage rectal cancer. A cohort study from the National Cancer Database (NCDB)

reported a 12.5% LR rate for LE, versus 6.9% for T1 tumors treated with RS (p <0.001). Five-year

overall survival was 77.4% for LE versus 81.7% for RS (p = 0.09).183 Other series have reported similar

results.184 However, comparisons between LE and RS are limited by selection bias, since patients having

LE tend to be older, have more comorbid conditions, and lower-lying tumors; whereas patients having

RS tend to be younger and healthier with higher-lying – but usually larger – tumors.

A recent systematic review of one small randomized trial and 12 observational studies, including a

total of 2,855 patients with T1N0M0 rectal cancer treated by LE (TAE/TEM-TEO) versus RS, showed

that LE was associated with lower perioperative mortality (relative risk 0.31, 95% CI 0.14–0.71), major

postoperative complications (relative risk 0.20, 95% CI 0.10–0.41), and need for a permanent stoma

(relative risk 0.17, 95% 0.09–0.30). The LR rate was higher for patients treated with LE, and overall

survival significantly lower, compared to patients treated with RS. The relative risk of dying after LE

was 1.46 (95% CI 1.19–1.77), which corresponds to 72 more deaths per 1,000 patients at 5 years. Metaregression showed that the difference in overall survival observed between groups could be explained

by the higher use of LE for tumors located in the lower third of the rectum, which is associated with

worse prognosis. Survival was similar between groups when only tumors located in the distal rectum

were included in the analysis.185

A number of studies have compared the outcomes of different techniques – conventional transanal

excision, TEMS, TEO, and TAMIS – for LE of rectal cancer, with most comparisons limited to

conventional TAE and TEMS. A recent meta-analysis of 6 retrospective case series including 927

procedures, reported that TEMS was associated with less specimen fragmentation, less positive resection

margins, and lower LR rates. No difference was observed in complication rate.186

In summary, the literature suggests that LE may be an alternative to TME for patients with small,

distal T1N0 rectal cancers, without high-risk histologic features, that would otherwise require a CAA or

an APE. Transanal endoscopic techniques may be superior to conventional transanal excision. Patients

considering LE should be informed about the potential gains in improved quality of life, but also about

the higher risk of LR and the need for salvage surgery.

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Patients with T2N0 tumors are not candidates for treatment by LE alone, independent of tumor

histologic features. The rate of LR for these patients when treated with LE alone ranges from 13% to

47%, significantly higher compared to similar stage tumors treated with TAR. Five-year overall survival

is also significantly lower for patients with T2N0 tumors treated with LE (65% to 67.6%) compared to

TAR (76.7% to 81%).183,187 A recent survey of the NCDB found that patients with T2N0 tumors treated

with LE alone had a higher hazard ratio for death compared to similar patients treated with TAR (1.535,

95% CI 1.283–1.835).188 Similar results have been reported in an independent cohort from the SEER

database.189 Based on this evidence, LE alone cannot be recommended as an alternative to RS for

patients with T2N0 tumor treated with curative intent.

Radiation therapy has been used to reduce the rate of LR in patients with T2N0 rectal cancer treated

with LE. A number of retrospective case series have reported 15% to 21% LR rates and 66% to 76.1% 5-

year survival rates with LE followed by radiation or chemoradiation for T2N0 tumors.190–193 The CALGB

8984 trial investigated the role of LE followed by 5-FU-based adjuvant chemoradiation for patients with

T2N0 cancers, reporting a 66% (95% CI, 51% to 84%) overall survival and 64% (95% CI, 51% to 80%)

DFS.194 The trial compared the survival curves of patients with similar stage tumors treated with TME,

concluding that LE and postoperative chemoradiation may be an alternative for patients with T2N0

tumors. However, 32% of the patients initially accrued for this trial were ultimately excluded from

analysis due to tumor size, inaccurate staging, surgical specimen fragmentation, high-grade histologic

features, or involved resection margins. Therefore, the conclusion is applicable only for properly staged

early rectal cancers penetrating only into the muscularis propria (pT2), with full-thickness excision

negative resection margins, and no high-risk histologic features.

The results of several retrospective studies have suggested that chemoradiation before LE reduces the

risk of recurrence to rates similar to those observed in similar stage patients treated with TME

alone.195,196 However, these studies are limited by small sample size, variable clinical staging criteria

and imaging modalities, and the use of different CRT regimens. A retrospective study using the SEER

database showed that patients who had undergone neoadjuvant CRT and LE had equivalent oncologic

outcomes compared to patients who had a major resection.189 One prospective trial found that patients

with ERUS-staged T2N0 rectal cancer treated with neoadjuvant CRT had similar recurrence and survival

rates when randomized to LE or RS. More than one in four patients in the RS arm required a permanent

colostomy, and a similar number required a temporary ileostomy.197 The ACOSOG Z6014 trial, a single

arm study investigating the use of 5-FU and oxaliplatin-based neoadjuvant CRT and LE in T2N0 tumors,

recently reported a complete pathologic response in 44% of patients.198 Only 2 (3%) patients had

developed recurrence after 4 years of follow-up. The 3-year DFS was 87%, with a 3-year OS of 90%. At

the end of the follow-up 70 of 72 patients treated with this approach had organ preservation.199 In

summary, the optimal treatment of T2N0 rectal cancer is TME; LE alone is not an alternative to radical

resection in patients treated with curative intent. Postoperative CRT may be an alternative to TME in a

patient with a distal clinical stage T1N0 cancer who is unexpectedly found to have a T2 tumor after LE

and is interested in preserving the rectum. Neoadjuvant CRT followed by LE may be an alternative for

patients with very distal T2N0 tumors interested in organ preservation, who otherwise would require a

permanent colostomy.

LE and other forms of local therapy, such as endocavitary radiation, brachytherapy, or

electrofulguration, have been used for palliation in patients who have more advanced tumors or are

unfit for a major surgical procedure.

Transabdominal Resection for Rectal Cancer

Patient preparation for rectal cancer surgery is similar to that for colon cancer surgery. Stoma marking

is particularly important in these patients, as many will require a temporary or permanent stoma. In

addition to discuss fertility options with all individuals of child-bearing potential, female patients

receiving neoadjuvant radiation who are interested in preserving fertility should consult their

gynecologist regarding the possibility of ovarian transposition. Mechanical bowel preparation, antibiotic

and thromboembolic prophylaxis are similar to those described for colon cancer patients. Many

surgeons recommend a rectal washout immediately before surgery to eliminate exfoliated cancer cells

that could potentially implant in the anastomosis and cause LR. In fact, a recent meta-analysis with

5,012 patients found that this practice is associated with a lower incidence of LR.200 On the operative

table, the patient should be placed in lithotomy with the legs in stirrups to provide the surgeon with

simultaneous access to the abdomen and perineum. It is important to avoid pressure on the bony

prominences, which might cause peroneal nerve compression. Patients requiring prolonged

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recurrence.128,129 Application of the same surgical principles to colon cancer, including the removal of

all the lymph node–bearing mesentery to the origin of the named blood vessels – an operation called

complete mesocolic excision or CME – is also associated with a lower rate of local tumor recurrence in

colon cancer patients.130 Differences in expertise and surgical technique probably explain surgeon and

institutional differences in outcomes among patients treated for CRC. A recent study from Denmark has

shown that CME surgery is associated with better disease-free survival than conventional cancer

resection for patients with stage I to III colon adenocarcinoma.131

TREATMENT OF LOCALIZED COLON CANCER

Malignant Colonic Polyps

The identification of a focus of invasive carcinoma in a polyp removed by snare excision during

colonoscopy represents a surgical dilemma. These types of polyps are often referred to as “malignant

polyps,” to distinguish them from lesions that are almost exclusively invasive adenocarcinoma with

exophytic or polypoid morphology. Malignant polyps are encountered more often because tumors are

diagnosed at an earlier stage, as a result of screening programs. Although there are some lymphatic

channels in the lamina propria, tumors superficial to the muscularis mucosa (also known as intramucosal

carcinoma, carcinoma in situ, or Tis) are considered to carry no risk of lymph node metastasis. When

the malignant cells penetrate beyond the muscularis mucosa they can access the lymphatic channels of

the submucosa and metastasize to the regional lymph nodes. This risk of nodal metastasis depends on

the morphology of the polyp, the depth of the invasive component, the presence of unfavorable

histologic features (grade 3 or 4, angiolymphatic invasion, perineural invasion) and the margin of

resection.132 Imaging studies are usually of no help in these patients, except to exclude distant

metastases (which are uncommon). In pedunculated polyps with focus of invasive cancer located in the

head, neck, or stalk of the polyp, with favorable histologic features, resected with negative margins, the

risk of nodal metastasis is small (Fig. 68-9). In these circumstances additional surgery is considered

unnecessary, as the risk of surgery may outweigh the risk of residual tumor in the bowel wall or nodal

metastasis. On the other hand, patients with pedunculated polyps with focus of invasive

adenocarcinoma reaching the base of the polyp, sessile polyps with focus of invasive adenocarcinoma,

the presence of adenocarcinoma at the resection margin, and malignant polyps with unfavorable

histologic features, are at risk of regional nodal metastasis, and should be offered surgical

resection.133,134 Other factors such as the location of the polyp in the colon or rectum,135 the patient’s

comorbidities and performance status, and the patient’s desires, should be taken into consideration.

Therefore, a final decision should only be made after full review of the pathology reports, and

disclosure to the patient of the risks and benefits of each approach.

Figure 68-9. Malignant polyp. Haggitt levels of invasion. Level 0, Noninvasive, severe dysplasia; Level 1, Invading through

muscularis mucosa but limited to the head of pedunculated polyp; Level 2, Invading the neck of pedunculated polyp; Level 3,

Invading the stalk of pedunculated polyp; Level 4, Invading into submucosa of the bowel wall below the stalk of a pedunculated

polyp. All sessile polyps.

Surgery for Localized Colon Cancer

Patients with biopsy-proven adenocarcinoma of the colon without evidence of distant metastasis, and

1782

without contraindications to major surgery, should be treated with surgical resection. The extent of a

colon cancer resection is dictated by the location of the primary tumor. Tumors in the cecum and

ascending colon require a right hemicolectomy that implies division of the ileocolic, right colic, and

sometimes the right branch of the middle colic vessels (Fig. 68-10). The portion of the omentum

attached to the removed segment of colon should be resected en bloc with the colon and mesentery.

Tumors located at the hepatic flexure and in the right side of the transverse colon require an extended

right colectomy that, in addition to the ileocolic and right colic vessels, requires division of the middle

colic vessels at their origin (Fig. 68-10). Tumors in the mid portion of the transverse colon can be

treated with an extended right colectomy, or a transverse colectomy. A transverse colectomy involves

division of the middle colic vessels only, but often requires mobilization of both the hepatic and splenic

flexure to ensure a tension-free anastomosis (Fig. 68-10). Tumors located in the distal transverse colon,

splenic flexure, and proximal descending colon can be treated with a left hemicolectomy, which requires

division of the left branch of the middle colic and left colic artery at its branch point from the inferior

mesenteric artery (Fig. 68-10). Locally advanced tumors located in the transverse colon can metastasize

to the regional lymph nodes located along the greater omentum and gastroepiploic arcades, leading

some surgeons to recommend removal of the omentum with the gastroepiploic arcade. In these patients,

an omentectomy with division of the gastroepiploic vessels at their origin may be necessary for

complete nodal control.136 However, the benefit of such an extended lymphadenectomy is debated.

Sigmoid tumors require sigmoid colectomy, which includes the superior rectal artery and its takeoff

from the inferior mesenteric artery (Fig. 68-10).

Patients with synchronous tumors, which occur in up to 5.3% of patients with CRC, should be

investigated for hereditary CRC syndromes or other predisposing conditions. Patients with sporadic

synchronous cancers can be treated with separate resections, or an extended resection incorporating

both lesions, depending on the location of the primaries.137 When performing a segmental resection, it

is important to preserve the blood supply to the intermediate segment of colon in order to avoid

ischemia, which can lead to perioperative complications. Synchronous tumors in patients with HNPCC,

or other risk factors such as inflammatory bowel disease, are indications for a subtotal or total

colectomy.

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Figure 68-10. Segmental colonic resections. A: Right colectomy. B: Extended right colectomy to transverse colon. C:

Transversectomy. D: Right colectomy extended to splenic flexure. E: Left colectomy. F: Sigmoidectomy.

A number of well-conducted prospective trials have proved that laparoscopic colectomy for cancer is

associated with short-term benefits and equivalent long-term oncologic outcomes, compared with the

traditional open surgical approach (Table 68-8). Patients treated laparoscopically have less

postoperative pain, earlier return of bowel function, shorter hospital stay, and a decreased rate of

complications. However, laparoscopic surgery is technically challenging and has a long learning curve.

Laparoscopy may be particularly difficult in patients with multiple adhesions from previous surgery, in

obese patients, and in patients with locally advanced disease. Late conversion from laparoscopic to open

surgery (also known as reactive conversion) is associated with higher complication rates compared to

open surgery, while early or preemptive conversion is associated with complication rates similar to

open surgery.138

Laparoscopic colectomy is typically performed using a number of ports, usually 3 to 5, and a

specimen extraction site. Additional expertise allows minimally invasive surgery to use fewer ports,

smaller instruments, and shorter incisions. This trend has resulted in the single port laparoscopic surgery

(SPLS) for the treatment of colon and rectal cancers. The operation is performed through a small port

located at the specimen extraction site. The camera and the operating ports are all positioned through

the SPLS device. A recent systematic review of 38 case series, including 565 patients operated by SPLS,

suggested that the procedure is feasible but technically challenging. Evidence regarding its safety was

limited.139

Table 68-8 Open versus Laparoscopic Colon Resections, Results of the Most

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Representative Series

The authors compared results of patients included in this review with those of a group of 3,526

patients treated with conventional laparoscopic colectomy and included in a Cochrane Review. They

found that, in spite of lower BMI and smaller tumors, SPLS did not result in less postoperative pain or

shorter hospital stay, compared to conventional laparoscopic surgery.139

The introduction of robotic platforms, which enhance the visualization and dexterity of the surgeon,

has added a new dimension to minimally invasive colon cancer surgery. The evidence accumulated so

far indicates that robotic colon resection is associated with lower conversion rates, similar short-term

outcomes, and higher costs, compared to conventional laparoscopic colon resection.140

Postoperative Adjuvant Therapy for Localized Colon Cancer

Many patients with what appears to be localized colon cancer at the time of diagnosis develop

recurrence after a curative-intent surgery. These recurrences are attributed to micrometastases that are

already present, but clinically undetectable, at the time of diagnosis. Postoperative adjuvant

chemotherapy aims to improve survival by eradicating micrometastatic disease. Numerous

chemotherapeutic agents are now considered for adjuvant therapy, mostly based on their efficacy as

observed in the setting of metastatic colon cancer. However, the mainstays of adjuvant therapy

following resection of localized colon cancer remain fluoropyrimidines (5-fluorouracil [5-FU] and

capecitabine) and oxaliplatin.

5-FU, a member of the family of antimetabolites, is a pyrimidine analog that works by irreversible

inhibition of thymidylate synthase (TS), the rate-limiting enzyme in pyrimidine nucleotide synthesis,

and by incorporation of its metabolites into RNA and DNA. 5-FU can only be delivered intravenously

and is commonly administered with leucovorin, a reduced folate that is thought to stabilize

fluorouracil’s interaction with the enzyme TS. Capecitabine is an oral prodrug of fluorouracil that is

absorbed intact through the gastrointestinal mucosa and undergoes enzymatic conversion to

fluorouracil. Response rates to fluoropyrimidine, as first-line therapy alone for metastatic CRC, are only

around 10% to 20%. Neutropenia, stomatitis and diarrhea are the most common side effects of 5-FU.

The toxicity profile for capecitabine is similar to 5-FU, with hand-foot syndrome being more frequent.

Oxaliplatin produces cytotoxic effects by forming both inter- and intra-strand cross links leading to

disruption of DNA replication and apoptosis. As a single agent, oxaliplatin has limited effect in CRC; but

in combination it enhances the cytotoxic effect of fluoropyrimidines, possibly through downregulation

1785

of TS. The most relevant side effect of oxaliplatin is a progressive and often irreversible peripheral

neuropathy. Other chemotherapy agents commonly used in patients with metastatic CRC have not

shown proven benefit in the adjuvant setting.

The use of adjuvant therapy for stage III colon cancer was first shown to provide measurable benefit

in the National Cancer Institute (NCI) Cooperative Intergroup trial INT-0035. Patients who received 5-

FU and levamisole for 1 year after surgical resection had a 33% risk-reduction in death or recurrence,

compared to those who underwent surgery alone.141,142 Since then, we have come to recognize that

levamisole is overall an inactive agent; therapeutic combinations have evolved and have been tested

rigorously.143 A number of multi-institutional prospective, randomized trials have demonstrated a

survival advantage with postoperative chemotherapy in selected patients after curative-intent surgery,

compared to surgery alone. Pooled analyses of these trials have reported an approximately 30%

reduction in recurrence, and 26% improvement in survival, in patients with stage III colon cancers

treated with 6 months of postoperative fluoropyrimidine-based chemotherapy.144,145 More recently, the

landmark MOSAIC (Multicenter International Study of oxaliplatin, fluorouracil, and leucovorin in the

Adjuvant Treatment of Colon Cancer) trial, which randomized 2,246 stage II/III colon cancer patients to

5-FU/leucovorin with or without oxaliplatin, reported an additional 20% reduction in recurrence and

5% improvement in 5-year disease-free survival (73.3% vs. 67.4%; p = 0.003) in patients treated with

5-FU/leucovorin plus oxaliplatin, compared to 5-FU/leucovorin alone.146,147 Based on these results, the

current recommendation for patients with stage III colon cancer following curative-intent surgery

consists of 6 months of 5-FU/leucovorin and oxaliplatin (FOLFOX), or capecitabine and oxaliplatin

(CAPEOX).

Several studies have proven that the addition of irinotecan – a topoisomerase I inhibitor that is

effective in metastatic CRC – to standard fluoropyrimidines is not superior to fluorouracil/leucovorin

combinations alone in stage III colon cancers.148 Similarly, bevacizumab (anti–VEGF-A) and cetuximab

(anti-EGFR), two biologic agents that have shown efficacy in metastatic disease, do not improve

survival, compared to FOLFOX alone.149–151 Therefore, at the present time there is no role for

irinotecan, bevacizumab, or cetuximab in the adjuvant treatment of CRC.

The use of adjuvant chemotherapy after curative resection for stage II CRC has been controversial for

more than a decade. Three prospective, randomized trials have addressed the subject using 5-FU–based

regimens,142,152,153 all of them failing to show a clear benefit of adjuvant treatment over observation

alone. The addition of oxaliplatin to the adjuvant regimen does not seem to improve the results of

pyrimidine-based regimens for stage II. Most of the evidence for adjuvant treatment in stage II CRC

comes from pooled analyses, in which stage II and III CRC patients, undergoing different chemotherapy

regimens and controls, are analyzed. The most influential one, including 37 trials and 11 meta-analyses,

found a significant improvement in DFS for 5% to 10%, favoring adjuvant chemotherapy; nevertheless,

no difference in OS was observed.154 Therefore, postoperative adjuvant chemotherapy is still not

routinely recommended after curative resection for stage II CRC. However, there is evidence that some

node-negative patients at high risk for recurrence may benefit from postoperative adjuvant

chemotherapy. Determining which patients are at high risk has most commonly included consideration

of features such as tumor perforation, T4 category tumors, poorly differentiated histology,

lymphovascular or perineural invasion, and patients with fewer than 12 nodes in the surgical specimen

(who are considered inadequately staged).155 At the present time, the use of adjuvant therapy for stage

II disease ought to be weighed carefully by a multidisciplinary team, with adequate counseling of the

patient. As mentioned earlier, some predictive nomograms may help stratify risk in patients with stage

II disease, enabling us to more effectively select those more likely to benefit from adjuvant therapy;

however, these tools have not been widely incorporated into clinical practice.

The search for molecular prognosticators aimed at stratifying stage II patients according to the risk of

relapse, is an active area of research. MMR deficiency has been associated with an improved prognosis,

but a decreased benefit from fluoropyrimidine-based adjuvant therapies, in patients with stage II

disease.156 Because of this, MMR testing is recommended for patients with stage II disease. Current

guidelines recommend no use of single-agent fluoropyrimidine treatment for patients with stage II

tumors exhibiting MSI or MMR deficiency. The multi-gene molecular signatures discussed previously

were developed, in large part, to stratify risk in patients with stage II CRC, and to identify those most

likely to benefit from adjuvant chemotherapy. While initial results are promising, there is insufficient

evidence to recommend their use in selecting adjuvant therapy for patients with stage II CRC.

1786

TREATMENT OF LOCALIZED RECTAL CANCER

The treatment of rectal cancer presents different challenges, but also different opportunities, compared

to colon cancer. Given the location of the rectum within the narrow bony pelvis surrounded by the

urogenital organs, large blood vessels, and autonomic nerves, and its proximity to the anal sphincters,

rectal cancer surgery is technically challenging, potentially associated with perioperative complications,

and often followed by loss of urinary, sexual, and bowel function that permanently impairs quality of

life. In addition, rectal cancer has been associated with a higher rate of local recurrence after curativeintent surgery, compared to colon cancer. But the extraperitoneal location of most of the rectum and its

proximity to the anal orifice make it accessible to explorations (DRE, endorectal ultrasound [ERUS]) and

interventions (external beam radiation therapy, brachytherapy, and local excision [LE]) not currently

available for colon cancer.

The selection of the best treatment option for each rectal cancer patient is a complex process and

requires consideration of the clinical tumor stage, location of the tumor within the rectum, the impact

of treatment upon anorectal and genitourinary function, and the consequences for the patient in terms

of prognosis and quality of life. Some rectal cancers can be treated with LE. Others require a

transabdominal resection (TAR) of the rectum, with or without sphincter preservation. Finally, many

rectal cancer patients require chemotherapy and radiation to reduce the risk of local recurrence and

distant metastasis.

Anatomy of the Rectum

The rectum represents the distal portion of the large bowel, extending from the rectosigmoid junction –

the area where the tenia coli (characteristic of the sigmoid colon) splay and become the longitudinal

muscular layer of the rectum – to the anorectal ring, a palpable anatomical landmark that corresponds

to the imprint of the puborectalis muscle on the bowel wall. The anal canal extends from the anorectal

ring to the anal verge, the palpable groove between the distal edge of the internal sphincter and the

subcutaneous portion of the external sphincter (Fig. 68-11). For practical purposes and standardization,

the rectum is defined in terms of distance in centimeters from the anal verge. The distance of a tumor

from the anal verge is best measured using a rigid proctoscope, which allows the simultaneous

visualization of the anal verge and the centimeter marks on the outside of the scope. In European

countries, tumors with the distal edge located within the last 15 cm of the large bowel are considered

rectal cancers; in the United States, the limit is 12 cm. The location of tumor in relation to the

peritoneal reflection and the promontory, and its distance from the anal verge, can also be determined

by MRI, in particular sagittal views.

The mesorectum is the visceral mesentery of the rectum containing the terminal branches of the

superior rectal vessels and the rectum’s lymphatic drainage. The upper portion of the rectum is located

above the anterior peritoneal reflection; it is covered with peritoneum in the front and on both sides,

and has a posterior mesorectum attached to the concavity of the sacrum, which is a continuation of the

mesentery of the sigmoid colon. Below the peritoneal reflection the rectum is completely

extraperitoneal and fully surrounded by the mesorectum. The mesorectum is covered by a thin,

glistening membrane called the mesorectal fascia (MRF). Posteriorly, the mesorectum is separated from

the presacral fascia by an avascular plane of loose areolar tissue that is the natural plane of dissection

during a radical proctectomy. Anteriorly, the mesorectum is separated from the urogenital organs by a

remnant of the fusion of two layers of the embryologic peritoneal cul-de-sac known as Denonvilliers

fascia – an important anatomical landmark in rectal cancer surgery. Below the peritoneal reflection, the

lateral ligaments connect the mesorectum to the pelvic sidewall. The mesorectum tapers off distally as

the rectum funnels toward the anorectal ring, where the longitudinal layer of the muscularis propria

becomes the internal anal sphincter.

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occurring in 4% to 26% of cases.101,102 In addition to causing patient suffering, SSIs lengthen hospital

stay and increase costs.103 The institutional rate of SSI after colorectal surgery is now an important

quality metric for several benchmarking programs. A number of federal and state-wide initiatives aimed

at improving surgical care recommend implementing measures to reduce the rate of SSI and other

complications in patients undergoing elective colorectal surgery.104,105

Figure 68-7. Staging modalities for colorectal cancer. A: Obstructing colon cancer at colonoscopy. B: Polypoid colonic tumor at

colonoscopy. C: Cecal circumferential tumor with regional lymphadenopathies. D: Liver metastases of colorectal origin.

The colon has the largest concentration of bacteria in the human body. A gram of feces contains 1011

polymicrobial bacteria, mostly gram negatives and anaerobes.106 Oral mechanical bowel preparation

using polyethylene glycol to reduce the bacterial load and risk of intraoperative fecal spillage has been

considered an axiom in colon and rectal surgery. However a number of prospective trials have failed to

demonstrate benefit from mechanical bowel cleansing in preventing SSIs.107,108 These results were

confirmed by a Cochrane systematic review of 5,805 patients; the authors concluded that there is no

statistically significant evidence that patients benefit from mechanical bowel preparation or the use of

rectal enemas.109 Another recent systematic review by the Agency for Health Care Research and Quality

reached similar conclusions. Oral mechanical bowel preparation appeared to be protective, compared to

no preparation, for peritonitis or intra-abdominal abscess, but the evidence was weak. The study could

not draw any conclusion on potential harms, such as dehydration and electrolyte imbalances, related to

use of oral mechanical bowel preparation.110 Despite the lack of solid data, many surgeons still

recommend oral mechanical bowel preparation because manipulation and suturing is easier with a clean

colon.

High-quality evidence indicates that antibiotics covering aerobic and anaerobic bacteria, delivered

orally or intravenously (or both) prior to elective colorectal surgery, reduce the risk of postoperative

surgical wound infection by as much as 66%.111 Oral antibiotics, neomycin- and erythromycin-based, are

delivered the day before surgery, in combination with the oral mechanical bowel preparation. For

patients without penicillin allergy, a second-generation cephalosporin (cefotetan or cefoxitin) is

administered intravenously within 30 minutes of the surgical incision, with re-dosing during the

procedure as required according to the half-life of the drug and the duration of surgery. For penicillinallergic patients, metronidazole or clindamycin combined with either ciprofloxacin or gentamicin is

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acceptable, as are aztreonam and fluoroquinolones.112 Ertapenem, a long-acting carbapenem active

against gram negatives and anaerobes, is an accepted alternative to second-generation cephalosporins

for prophylaxis in CRC. Ertapenem has a long life and does not require re-dosing in prolonged

procedures, but has been associated with increasing risk of Clostridium difficile infection.113 Other

measures that prevent SSI include tight glucose control in diabetic patients, smoking cessation, clipping

rather than shaving the skin of the abdominal wall, and maintaining normothermia and adequate

oxygenation during anesthesia.114

Patients undergoing surgery for CRC are also at risk of deep venous thrombosis and pulmonary

embolism, and should have thromboembolic prophylaxis with unfractionated heparin or low-molecularweight heparin during the peri- and postoperative periods.115

As the incidence of CRC increases with age, many patients have cardiovascular or respiratory

conditions requiring medical clearance before surgery. While technical advances have made CRC

operations safer, optimal outcomes require special effort to ensure that the patient’s overall health is

optimal at the time of surgery. Many CRC patients have other comorbid conditions such as diabetes,

hypertension, and coronary artery disease requiring medical evaluation before undergoing surgery.

Comorbidities can impact decision-making and affect short- and long-term outcomes. Patient clinical and

performance status should be optimized to reduce the risk of perioperative complications. Fertility

options should be discussed with all individuals of child-bearing potential.

Patients who may require a stoma should be seen before surgery by an enterostomal therapist.

Adequate marking of the site improves outcomes for patients requiring a stoma. Preoperative teaching

shortens the time patients require to become proficient managing the stoma, and reduces hospital

stay.116

The Enhanced Recovery After Surgery (ERAS) protocols were introduced in open colorectal surgery in

the 1990s, with the aim of speeding patient recovery, improving patient outcomes and satisfaction,

shortening hospitalization, and reducing healthcare costs.117 ERAS protocols span the entire

perioperative period, and attempt to minimize surgical stress and postoperative ileus through patient

education, preoperative hydration and carbohydrate loading, goal-directed intraoperative fluid

management, narcotic sparing for intraoperative and postoperative pain control, and early mobilization

and oral feeding in the postoperative period. A number of prospective trials have indicated that the

implementation of ERAS protocols reduces length of hospital stay, compared to conventional recovery

in patients undergoing open or minimally invasive surgery for CRC.118,119 A recent systematic review

and a meta-analysis confirmed that ERAS protocols resulted in a shorter length of stay and a reduction

in overall complications, with no difference in mortality and surgical complications.120,121 Similar

results have recently been reported from an international registry.122

Principles of Surgical Treatment

The goal for any curative-intent surgery is to remove the tumor-bearing segment of the bowel with

adequate margins, along with en bloc excision of the mesentery containing the feeding vessels and

regional lymph nodes. The location of the primary tumor determines lymphatic drainage and dictates

the extent of the resection. Lymphatic capillaries are primarily located in the submucosal and subserosal

layers of the bowel wall. The lymphatic flow in the colon is primarily circumferential, with longitudinal

spread along the bowel wall thought to be less than 1 cm in each direction. Therefore, a 5-cm margin of

normal bowel on either side of the primary tumor is considered sufficient to avoid anastomotic

recurrence. The length of the terminal ileum resected in patients with rectal cancer does not influence

the risk of anastomotic recurrence. In the rectum, where the longitudinal lymphatic flow is primarily

upward, cancer cells rarely spread distally along the bowel wall farther than 1 cm from the macroscopic

distal end of the tumor. Consequently, a 2-cm margin of normal bowel distal to the tumor, or even less

in patients treated with neoadjuvant therapy, is considered appropriate to an oncologically safe

resection.123

The lymphatic channels in the bowel wall drain to the regional nodes, which are classified in different

groups according to their proximity to the bowel and its blood supply (Fig. 68-8). The “epicolic” nodes

are located in the bowel wall under the peritoneum, usually close to the epiploic appendices. The

“paracolic” lymph nodes are located along the marginal vessels. Next, the “intermediate” nodes are

positioned in the middle of the mesentery. Finally, the “central” or “apical” lymph nodes are located

close to the root of the mesentery, near the origin of the named vessels. While CRC generally spreads

sequentially from the paracolic to the central or apical lymph nodes, nodal metastases skipping one of

the groups are common.124

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The extent of the mesenteric resection is determined by the need to remove all the lymph nodes

draining the corresponding segment of bowel, including the central lymph nodes located at the origin of

the named feeding blood vessels. As most tumors are located between two named vascular pedicles,

both of these should be resected at their origin. When suspected of being involved by tumor, the central

nodes should be marked on the specimen, as they have negative prognostic information. Other lymph

nodes located away from the feeding vessels and suspected of tumor involvement during surgery,

should be removed and analyzed, because in some patients the lymphatic drainage does not follow an

orderly pattern.125,126 If residual metastatic lymph nodes remain after sampling, the resection should be

considered incomplete.

Figure 68-8. Anatomy of the colon. A: Epicolic lymph nodes. B: Paracolic lymph nodes. C: Intermediate lymph nodes. D: Apicalcentral lymph nodes.

While achieving safe oncologic margins and adequate lymphadenectomy are the main considerations

when performing a surgical resection for CRC, ensuring an adequate blood supply to the bowel ends,

and maintaining tension-free anastomosis, are also important in order to avoid anastomotic

complications.

Locally advanced tumors attached to other organs should be removed en bloc with contiguously

involved structures. As it is impossible to distinguish clinically or radiographically between

inflammatory adhesions and tumor infiltration, it is preferable to perform an en bloc resection of any

organ attached to the primary tumor, rather than spilling cancer cells by separating structures infiltrated

by tumor. Intraoperative tumor perforation has negative prognostic implications. It is important to

report the completeness of the resection (R0, R1, or R2), combining clinical and pathologic information,

to determine risk of locoregional recurrence and long-term prognosis.

The concept of the no-touch technique, with initial control of the vascular supply before manipulation

of the tumor to avoid releasing cancer cells into the blood stream, has not been shown to be associated

with improved outcomes.127 However, early vascular control with medial-to-lateral dissection of the

mesentery, before mobilization of the colon, is the preferred approach during minimally invasive

colorectal surgery, because it helps identify all vascular and retroperitoneal structures.

Proper surgical technique is crucial in achieving optimal results in CRC patients. The removal of the

rectum along with its mesorectal envelope, using sharp dissection along normal anatomical planes – an

operation called total mesorectal excision, or TME – is associated with a reduced risk of local tumor

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Double-contrast barium enema can detect most of the clinically important lesions in the colon but, as

with colonoscopy, its effectiveness as a screening test for CRC is based only on indirect evidence.

Similar to colonoscopy, it requires dietary modification and mechanical bowel preparation, and is

associated with patient discomfort. In addition, a positive test mandates a colonoscopy. While doublecontrast barium enema every 5 years should provide the same degree of protection as the other

screening strategies, it is rarely used as a primary screening method today. Its clinical role as a

screening tool at this time is primarily for visualization of the colon in patients who cannot undergo a

complete colonoscopy.

Computed tomography colonography (CTC), also referred to as virtual colonoscopy, involves thinsection, multidetector, helical CT, and three-dimensional viewing for interpretation.88 CTC identifies

90% of cancers or adenomas measuring more than 10 mm in diameter in asymptomatic individuals 50

years of age or older.89 It is more sensitive than other screening methods, but can miss flat lesions and

polyps smaller than 10 mm in diameter. CTC obviates some of the drawbacks of colonoscopy, such as

the need for sedation and recovery time, but also has downstream consequences: it delivers a dose of

radiation that may become substantial with repeated examinations, and detects incidental extra-colonic

findings that may trigger expensive, and sometimes unnecessary diagnostic investigations. Furthermore,

it requires standard bowel preparation and gaseous distension of the colon. New methods of tagging and

subtracting residual stool may obviate the routine need for mechanical bowel preparation. Finally,

patients with lesions found on CTC still require full visualization of the colon by colonoscopy. CTC is

now considered an acceptable screening alternative for average-risk individuals, starting at 50 years of

age; the interval between such examinations remains uncertain, although a 5-year interval has been

suggested, based on computer simulation models.90

Risk Categories

Patients with symptoms of CRC should undergo the appropriate diagnostic studies; they are not

candidates for screening. Screening recommendations for the general population are based on individual

risk assessment. Based on the past medical history and family history of CRC or polyps, individuals are

assigned to one of three risk categories, with different screening recommendations (Table 68-7).91

Average Risk

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People at average risk for the development of CRC (asymptomatic men and women without risk factors,

over 50 years of age in the United States and 60 in the United Kingdom) could undergo yearly FOBT,

combined with flexible sigmoidoscopy every 5 years. People with a positive FOBT or a polyp identified

by flexible sigmoidoscopy should undergo entire colon and rectum examination by colonoscopy. Doublecontrast barium enema every 5 years, or colonoscopy every 10 years, is an accepted screening

alternative in the average-risk population. CTC every 5 years is also an option. Digital rectal

examination (DRE) should be performed at the time of sigmoidoscopy or colonoscopy in all individuals.

Increased Risk

Family History. Individuals with a first-degree relative (parent, sibling, or child) with CRC or

adenomatous polyps diagnosed before 60 years of age should start screening with colonoscopy at 40

years of age or 10 years younger than the earliest diagnosis in their family, whichever comes first. The

test should be repeated every 5 years. Individuals with one first-degree relative with CRC or

adenomatous polyp diagnosed at 60 years of age or older, or with two or more second-degree relatives

(grandparent, grandchild, aunt, uncle, niece, nephew, half-sibling) with CRC or adenomatous polyps at

any age, should undergo screening as average-risk individuals – but starting at 40 years of age. Patients

with one second-degree relative or one or more third-degree relatives (first cousin) affected are

considered to be at average risk.

History of Polyps at Previous Colonoscopy. Patients undergoing endoscopic excision of a small (<1

cm) adenomatous polyp should have the entire colon examined at the time of the polypectomy.

Colonoscopy should be repeated 5 years later. If the test is negative, they should then follow the

screening recommendations for average risk.92

Patients with more than three adenomas, adenomas with villous features or high-grade dysplasia, or a

large adenomatous polyp (>1 cm) who have the entire colon examined at the time of polypectomy,

should undergo complete colonoscopy 3 years later – and, if normal, every 5 years thereafter.

A complete colonic examination should be carried out before surgery in any patient undergoing a

planned curative resection for CRC. The colonoscopy should be repeated at 1 year to exclude

metachronous lesions. If the examination at 1 year is normal, it should be repeated after 3 years, and

every 5 years thereafter if the previous one was normal.

Patients with Colorectal Cancer. Patients with colon and rectal cancer should undergo high-quality

perioperative clearing of polyps with colonoscopy 3 to 6 months after resection, if not performed before

surgery. Surveillance after curative resection is described in detail in Surveillance after Curative

Resection for Colon and Rectal Cancer section.

High Risk

This category includes individuals from families diagnosed with hereditary forms of CRC.

Familial Adenomatous Polyposis. Once the diagnosis of FAP is established, the patient should

undergo colectomy, or a yearly colonoscopy until colectomy. Upper gastrointestinal endoscopy should

be performed every 1 to 2 years. Siblings and children of a patient with FAP should start surveillance by

flexible sigmoidoscopy at puberty.

MYH-Associated Polyposis. Depending on the individual, age of presentation, and number and size of

polyps, the patient may be advised to undergo a prophylactic colectomy or yearly colonoscopy

beginning at 25 years of age. Upper gastrointestinal surveillance should be performed following the

guidelines for patients with FAP.

Lynch Syndrome. Individuals from families fitting the Amsterdam criteria for HNPCC should have a

colonoscopy at 21 years of age, then every 2 years until 40 years of age, and yearly thereafter. Genetic

counseling and testing should be considered.

At-risk members of families with hereditary cancer syndromes should be informed about the benefits

and limitations of genetic counseling and genetic testing.

Consequences of Screening

The full spectrum of clinical consequences of screening, other than the prevention of deaths from CRC,

is difficult to predict because every screening strategy initiates a cascade of events, each one with

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uncertain probability. The rate of false-positive tests, the number of colonoscopies performed, the

complications of the screening and diagnostic tests, and the number of patients who may require

surveillance as a consequence of screening, are complex factors that arise at different times over several

decades. However, cost-effectiveness analysis in the United States has demonstrated that screening for

CRC in average-risk patients, according to the strategies outlined above, compares favorably with other

healthcare interventions such as mammography or treatment of mild hypertension.93,94 It is important

to understand that screening does not completely eliminate the risk of CRC. Up to 9% of CRCs are

diagnosed within 6 to 36 months after a screening colonoscopy.95,96 These interval cancers tend to be

preferentially located in the proximal colon. This may be related to failure to reach the proximal colon,

residual stool obscuring the view in the proximal colon, or different characteristics of the proximal

lesions that makes them more difficult to detect or remove.

Implementation of Guidelines

The general population has limited awareness of the risks of CRC or its symptoms; as a result the

number of individuals participating in screening programs has been low. The dissemination of

information to patients is an essential part of the screening program. Primary care physicians have a

responsibility to inform their patients about their risk of CRC, the benefits of screening and different

screening strategies, and to set up a system for implementing these guidelines.94,97,98 Through such

efforts, the proportion of adults 50 to 75 years of age having colonoscopy has increased steadily in the

last decade: from 19.1% in 2000 to 55% in 2010.3

DIAGNOSIS

While the proportion of CRCs diagnosed through screening is increasing, most are still diagnosed after

patients become symptomatic. CRC can cause a myriad of symptoms, many of which are nonspecific and

highly prevalent among healthy individuals. Therefore, the diagnosis of colorectal carcinoma often

requires a high index of suspicion.

Symptoms and Signs

The most common symptoms in patients with CRC are abdominal pain, change in bowel habits, rectal

bleeding, anemia, anorexia, and weight loss. The clinical manifestations of CRC differ depending on the

location and stage of the tumor.

Abdominal pain is nonspecific; it may be localized to any quadrant of the abdomen, or may be diffuse.

When the pain is persistent and colicky, it is more likely to represent obstructive symptoms resulting

from a left-sided lesion. More localized tenderness with signs of localized peritonitis indicates local

invasion of the adjacent peritoneum or perforation. It can be difficult to distinguish the pain associated

with diverticular disease from that due to a carcinoma in the sigmoid or descending colon. Patients with

diverticular disease may also have an underlying carcinoma. Abdominal pain may occasionally be

related to extensive metastatic disease in the liver or retroperitoneal lymph nodes. Rectal cancer can

also cause perineal discomfort and is often associated with tenesmus, the sensation of incomplete

defecation. A locally advanced rectal cancer can also cause sacral or sciatic pain.

An unexplained change in bowel habits lasting more than 2 weeks requires investigation for CRC.

Constipation associated with colicky abdominal pain is a common manifestation of partially obstructing

tumors. Abdominal pain, constipation, and abdominal distension suggest a complete colonic obstruction,

which is more common in tumors located in the sigmoid colon and rectum. Some patients with sigmoid

or rectal cancer may also complain of diarrhea, which may sometimes be bloody.

Bleeding from tumors in the sigmoid colon and rectum is often wrongly attributed to hemorrhoids or

other benign anal conditions. However, blood from hemorrhoids is usually bright red and is

accompanied by anal discomfort; the bleeding is intermittent and splashes the toilet pan. Anal fissure is

also a common cause of rectal bleeding; the blood is often bright, occurring after defecation, and is

typically associated with sharp anal pain triggered by defecation. Painless defecation with rectal blood

that is darker in color and mixed in with stool is more likely to be secondary to an underlying

carcinoma. Rectal bleeding, particularly when associated with tenesmus, requires a thorough diagnostic

investigation to exclude an underlying rectal tumor.

The development of nonspecific anemia of unknown origin is a common manifestation in patients

with a carcinoma in the proximal colon. Patients with unexplained microcytic anemia should be

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examined initially with colonoscopy. Anorexia and weight loss frequently accompany CRC, and are

often associated with advanced disease. The differential diagnosis in these patients is a gastric

carcinoma, but when investigations are negative it is important to exclude a large-bowel malignancy. As

the bowel lumen is larger and the stools overall looser in the proximal colon, obstructive symptoms are

uncommon; therefore, patients with tumors proximal to the splenic flexure often present with advanced

disease.

It should be remembered that the presence of colon cancer can also be identified incidentally during

investigations for other pathologies such as gallstones, gynecologic, or urinary conditions. A complete

family history, with emphasis on past history of CRC or polyps, is essential to diagnose some hereditary

cancer syndromes. A family history of endometrial, gastric, urologic, or other HNPCC-associated cancers

is also important because it may help in diagnosing Lynch II syndrome.

The evaluation of patients suspected of CRC requires a complete physical examination. Features that

should arouse suspicion of malignancy include pallor, palpable abdominal mass, and a palpable mass on

DRE. Hepatomegaly indicates advanced disease with extensive liver metastases, and consequently a

very poor prognosis. A hard mass in the pouch of Douglas felt on DRE may indicate peritoneal

carcinomatosis. Other signs of an underlying CRC include pneumaturia, ischiorectal or perineal

abscesses, or even deep venous thrombosis.

The differential diagnosis of CRC includes diverticulitis, irritable bowel syndrome, inflammatory

bowel disease, ischemic colitis, and benign anorectal conditions such as hemorrhoids or rectal mucosal

prolapse.

Diagnostic Evaluation

Patients with symptoms suggesting CRC should have a colonoscopy to evaluate the entire colon (Fig.

68-7). The examination should be complete, as up to 4% of patients with CRC have synchronous cancers

and many more have colorectal polyps.99,100 Up to one-third of these synchronous cancers are in

locations requiring a different surgical resection, further emphasizing the importance of complete

colonoscopy. As many patients undergo minimally invasive surgery today, the endoscopist should mark

the vicinity of the tumor with India ink to help locate the lesion intraoperatively. CT colonography and

DCBE are less effective in investigating patients with symptoms suggestive of CRC, but they are useful

in patients with partially obstructive tumors, in whom colonoscopy cannot be completed. In patients

with obstructive lesions, the proximal colon can be examined either by preoperative imaging studies

such as PET-CT, or intraoperatively by direct palpation of the colon. In any case, patients with a

complete colonoscopy before surgery should have a surveillance colonoscopy 6 months after surgery.

Assessment of the extent of disease at the time of diagnosis is important because clinical stage,

particularly in rectal cancer, dictates treatment decisions. A CT scan of the chest, abdomen, and pelvis

with intravenous and oral contrast is important in order to locate the tumor, detect mesenteric nodes,

and exclude liver metastasis and gross peritoneal carcinomatosis (Fig. 68-7). In addition, preoperative

imaging helps the surgeon plan the resection. In patients with iodine allergy, and in patients with

undetermined lesions on CT, a PET-CT or and abdominal or pelvic MRI may provide additional

information.

Laboratory evaluation includes complete blood cell count, coagulation parameters, and chemistry

panel. Preoperative CEA should be measured because it provides prognostic information, and can be

useful during patient surveillance.

TREATMENT

Surgery is the primary treatment for CRC, but for many patients surgery is not the initial form of

treatment and some do not require surgery at all. Treatment is different for colon than for rectal cancer,

and depends also on the clinical stage of the tumor. Treatment decisions must also take into account the

patient’s performance status, comorbidities, hereditary CRC predisposition, as well as desires and

expectations.

Preoperative Preparation

All patients undergoing surgery for colon and rectal cancer require similar preoperative preparation

aimed at optimizing the technical success of the procedure and avoiding perioperative complications.

Surgical site infection (SSI) is the most common complication after colon and rectal cancer resection,

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