demonstrating that each 4-week delay in treatment correlated with a 14% decrease in OS.262 The low

compliance with postoperative adjuvant chemotherapy has been attributed to postoperative

complications, slow recovery after surgery, delays due to closure of the temporary ileostomy, or simply

patient refusal. Delivering systemic chemotherapy before surgery has the potential advantage of

increasing treatment compliance, potentially enhancing the efficacy of CT in preventing DM, and

ultimately improving survival. In addition, it increases response of the primary tumor, and shortens the

time to temporary ileostomy reversal. A number of studies have shown that compliance with systemic

chemotherapy is higher when it is delivered before CRT and TME, compared with conventional

postoperative adjuvant chemotherapy in patients LARC patients who are candidates for curative

surgery.263–265 Although solid data from large prospective studies are still lacking, in the most recent

edition of the NCCN guidelines neoadjuvant chemotherapy before CRT and TME is contemplated as an

option in the treatment of LARC patients.

Outcomes of Multimodality Treatment in Patients with Locally Advanced Rectal Cancer

Perioperative mortality in patients undergoing multimodality therapy, including total mesorectal

excision for LARC, ranges from 1% to 3.5%, and between 23% and 48% of patients develop

perioperative complications.250,266,267 Sepsis is the most common complication after rectal cancer

surgery. A recent systematic review of the literature, including 53 prospective cohort studies and 45

randomized trials, found a 2% postoperative death rate, 7% rate of surgical wound infection, 11% rate

of anastomotic leakage, and a 12% rate of pelvic sepsis.267 In addition to pelvic sepsis, perineal wound

dehiscence is the most common complication after APE. In a large systematic review of 32 studies, the

rate of perineal wound complication was 15.3% for patients treated with surgery alone, and 32% in

those treated with surgery and RT.227 Many of these patients also had pelvic sepsis. The proportion of

patients with perineal complication was similar for those who had ELAP: 14.8% for surgery alone and

37.6% for surgery and radiation. The rate of perineal hernia was also similar for patients treated with

SAPE and ELAPE: 1.8% versus 2%. Other common postoperative complications include urinary

retention, pneumonia, and thromboembolic disease.

Surgery for rectal cancer, particularly when combined with CRT or SCRT, has iatrogenic long-term

consequences including urinary, sexual, and bowel dysfunction. Up to 39% of patients develop urinary

complications, 45% sexual dysfunction, and even a larger proportion, bowel dysfunction.268,269 A recent

population-based study found a 26% rate of moderate bowel problems, 17% urinary dysfunction, and

25% severe problems with sexual function among patients treated for rectal cancer. Patients with a

stoma were more likely to have difficulty with body image and sexual activity compared to patients

with no stoma. Less than 30% of rectal cancer patients reported perfect health; rectal cancer patients

were more likely to report problems, compared to patients with colon cancer. A follow-up study of the

Dutch TME trial recently reported that these treatment-related symptoms persist 14 years after

treatment; they reported increased sexual dysfunction, and a small decrease in overall functioning, as

measured by a variety of quality of life questionnaires distributed to the general population.270

Algorithm 68-1. Approach to rectal cancer according to clinical staging.

Contemporary cohorts of stage II/III rectal cancer treated with neoadjuvant CRT, TME, and

postoperative chemotherapy have mostly reported 5-year LR rates between 5% and 10%, 5-year DFS of

around 60%, and 5-year OS around 70%.

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Treatment Selection in Patients with Localized Rectal Cancer

Unlike patients with localized colon cancer, who all require oncologic resection as the initial form of

therapy, patients with rectal cancer have multiple treatment options. The selection among different

options depends primarily on the clinical stage of the tumor, as determined by DRE, proctoscopy, and

imaging studies, on the distance of tumor from the anal verge, and on patient performance status and

expectations.

The standard treatment for patients with stage I rectal cancer (T1N0 or T2N0) is TME, but LE has

increasingly been chosen as a reasonable and acceptable alternative for patients with distal T1N0

tumors. CRT and LE may also be considered as an alternative to TME in patients with T2N0 tumors

interested in sphincter preservation, in whom a TME would require a permanent colostomy.

More advanced tumors – those penetrating beyond the muscularis propria (T3–4, any N) and/or

involving the regional lymph nodes (any T, N+), and without evidence of distance metastasis – have

several treatment options. In the United States and many other countries, where decisions regarding the

treatment of rectal cancer are based on clinical TNM staging, patients with locally advanced disease are

treated with 5-FU or capecitabine-based CRT, followed by TME, with consideration given to FOLFOX

prior to CRT as an acceptable option (Algorithm 68-1).

In Europe and Scandinavia, where rectal cancer patients are stratified into different risk categories

based on MRI features, patients are recommended for different treatment approaches according to their

individual risk category (Algorithm 68-2). The MRI-based risk stratification system uses a number of

features, such as the proximity of the primary tumor to the MRF, the depth of tumor penetration into

the mesorectum, the presence of large venous invasion, and the presence of metastatic lymph nodes.168

Based on these features, they have developed a three-tier classification scheme that includes low risk

(the good), intermediate risk (the bad), and high risk (the ugly); each group with a different risk of

relapse, and therefore requiring different treatment strategies.169,271 The low-risk group is

recommended TME alone. The intermediate group is recommended SCRT followed by TME, while the

high-risk group is recommended neoadjuvant CRT followed by TME. This treatment approach, guided

by MRI risk categorization, is based mainly on results of prospective observational studies conducted in

institutions with significant expertise in rectal cancer, but has not yet been tested in prospective,

randomized trials.

Algorithm 68-2. Approach to locally advanced rectal cancer based on a three-tier risk stratification system (“the good, the bad, and

the ugly”).

For patients requiring a TME, the decision between an APE and an SSP depends on the relationship of

the tumor with the anal sphincter and the levator muscle. In general, an APE is required when the

tumor directly involves these structures, or is so close to the sphincter that resection with a negative

resection margin will result in a loss of sphincter function. In borderline cases, baseline anal sphincter

and bowel function, as well as patient wishes and desires should be taken into consideration. The

patient should be counseled about LR rates and expected long-term surgical outcomes.

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TUMOR-RELATED EMERGENCIES

Between 15% and 30% of all CRC patients present as surgical emergencies, obstruction (78%) being the

most common presentation, followed by perforation (10%) and bleeding (4%).272–274 Chronic bleeding

leading to severe anemia is common, particularly in right-sided tumors; but acute hemorrhage requiring

surgical or endovascular intervention is infrequent. Obstruction is the presenting symptom in more than

15% of patients diagnosed with CRC, and CRC is responsible for more than 50% of all cases of acute

colonic obstruction.275 Rectal cancers seldom present as an emergency (5.9%); this is much more likely

with colon cancers (21.7%),273 most of which are in the left colon where the feces are solid, the lumen

is smaller, and tumors are more likely to be annular. Large bowel obstruction may be secondary to

other conditions such as diverticular disease and volvulus, which are the differential diagnosis of CRC.

The obstructed bowel undergoes significant changes in motility, secretion, and blood flow, which are

responsible for the clinical manifestations. Proximal to the obstructed segment, particularly in left-sided

obstructions, the colon develops mass action contractions, which cause colic pain. Persistent obstruction

and progressive distension lead to colonic hypomotility. Colonic obstruction causes progressive

abdominal distension as a result of the accumulation of gas (mostly nitrogen from swallowed air),

increased fluid secretion, and hyperproliferation of anaerobic bacteria. The accumulation of fluid in the

distended colon can lead to dehydration. Progressive distension in the presence of a competent ileocecal

valve results in a closed-loop obstruction. The increase in intraluminal pressure can compromise the

mucosal blood flow and lead to irreversible ischemia. Tension in the wall of the distended bowel

increases in proportion to the fourth power of the radius; the risk of ischemia and subsequent

perforation is therefore high, particularly in the cecum, the segment of colon with the largest

diameter.276 The risk of perforation is related not only to the caliber of the colon, but also to the onset

of obstruction (higher risk when acute) and the duration of the obstruction. Mucosal ischemia has been

implicated as the cause of a nonspecific form of colitis that, in some patients, develops proximal to the

site of obstruction. The presence of ischemia, which can only be diagnosed at the time of surgery,

should influence the extent of resection.

Acute colonic obstruction manifests as abdominal discomfort or frank pain (depending on the onset of

the obstruction), reduction or complete cessation of the passage of flatus and feces, and progressive

abdominal distension. Abdominal tenderness, particularly if associated with fever and leukocytosis,

requires immediate evaluation to exclude perforation or ischemia. DRE reveals an empty rectum in most

patients with large bowel obstruction.

Colonic obstruction must be distinguished from pseudo-obstruction. While the symptoms are similar,

colonic pseudo-obstruction often presents in a specific clinical setting (patient immobilization, use of

opioids, electrolyte imbalance), is still associated with passage of small amounts of stool and flatus, and

is not associated with tenderness.277 However, definitive diagnosis often requires specific radiologic

tests, such as a water-soluble contrast enema or CT.

A plain abdominal film demonstrates colonic distension, with air-fluid levels, and a cut-off at the site

of obstruction. The absence of small bowel distension indicates a competent ileocecal valve, with an

increased risk of cecal perforation. The presence of gas in the small bowel and rectum raises the

possibility of ileus or colonic pseudo-obstruction, but radiologic findings can be misleading. The

presence of intramural gas indicates advanced ischemia. A chest radiograph should always be obtained

to exclude the presence of pneumoperitoneum.

A water-soluble contrast enema may help to determine the degree and level of obstruction. The flow

of contrast to the cecum and the absence of mucosal abnormalities suggest pseudo-obstruction. The

osmotic effect of the water-soluble contrast material may have a therapeutic effect in decompressing the

colon in these patients.278 The mucosal detail at the site of obstruction may help to define the cause of

obstruction. However, endoscopy is a better alternative to contrast enema when confirming the

presence of cancer. CT of the chest, abdomen, and pelvis often locates the transition point between the

distended bowel above the obstruction and the collapsed bowel distal to that point. It also helps define

the cause of the obstruction and, if malignant obstruction is confirmed, it is useful in staging the

tumor.279

When compared with elective surgery, patients requiring emergency surgery have more advanced

disease. Even when stratified by stage, however, survival is worse for patients undergoing emergency

surgery.273,280 Also, an R1 resection is 10 times more likely for patients receiving emergency surgery.281

Patients presenting with obstructing CRC have higher operative mortality and morbidity and a poorer

long-term prognosis than patients undergoing elective resection.274,282 Perioperative mortality is three

times higher in surgery performed for obstruction, compared with elective surgery.274 Cardiopulmonary

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complications and abdominal sepsis are the major causes of in-hospital mortality and morbidity. The

aim of surgery is therefore to minimize morbidity while obtaining functional results similar to those

obtained for patients undergoing elective resection.

Patients with colonic obstruction are often dehydrated, and require preoperative fluid resuscitation

and correction of electrolyte imbalances before surgery. A urinary catheter facilitates fluid

management. Unstable patients should be monitored appropriately in the intensive care unit. A

nasogastric tube prevents accumulation of swallowed air. Given the large fecal load proximal to the

point of obstruction, antibiotic prophylaxis with a second-generation cephalosporin or a combination of

an aminoglycoside and metronidazole should be given at the time of surgery.

The surgical management depends on the location of the obstruction. Lesions proximal to the splenic

flexure are commonly treated by an extended right hemicolectomy, with primary anastomosis between

the terminal ileum and the nonobstructed colon distal to the lesion. This is a single procedure that

removes the entire segment of distended and potentially ischemic bowel, and eliminates the risk of

leaving a synchronous tumor in the obstructed colon. Some of these patients develop mild diarrhea,

which is usually temporary.

The management of a lesion located distal to the splenic flexure is more controversial. The earlier

described three-stage procedure is rarely used today (1 – Diverting colostomy, 2 – Tumor resection and

anastomosis, 3 – Colostomy closure). A safe choice is the two-stage procedure, with initial resection of

the segment containing the tumor, closure of the rectal stump as a Hartmann pouch, and construction of

an end colostomy, followed by bowel anastomosis at a later date. However, the cumulative mortality

and morbidity of both procedures is significant, and at least 30% of patients are left with a permanent

colostomy.283 In most tertiary centers, this operation is now limited to situations in which a primary

anastomosis is contraindicated (e.g., extensive peritoneal contamination and/or severe sepsis).

The goal of surgery today is to relieve the obstruction and treat the cancer in a single operative

procedure. Options include: (1) self-expanding metallic stents (SEMS) as a bridge to elective segmental

colon resection, (2) subtotal colectomy and ileorectal anastomosis, (3) segmental colon resection,

intraoperative colonic lavage, and primary anastomosis.

The rationale for the use of SEMS is temporary relief of the obstruction, avoiding the morbidity

associated with an emergency operation, allowing medical stabilization, full staging work-up, one-stage

surgery with primary anastomosis, and a minimally invasive approach. Most of the experience with this

method comes from retrospective case-series studies; the success in relieving the obstruction ranges

from 40% to 100%.284 SEMS also has associated complications, such as re-obstruction (12%), migration

(11%), and perforation (4.5%).284

Several randomized, controlled trials comparing SEMS with emergency surgery have been published,

with conflicting results.285–289 Overall, the clinical success rate of relieving obstruction with SEMS

ranges from 40% to 97%. It is important to recognize that the overall complication rate across these

trials is variable (8.3% to 35%) and a recent prospective trial conducted in the Netherlands was stopped

prematurely, due to an increased number of colonic perforations in the SEMS arm.289 Perforation from

the use of stents may result in a shorter DFS.290

A subtotal colectomy with ileorectal anastomosis is a quick operation in which nondistended bowel is

used for the anastomosis. This procedure minimizes the risk of fecal spillage, eliminates the risk of

missing a synchronous tumor in the obstructed portion of the colon, and facilitates surveillance. The

disadvantages, however, include a higher incidence of bowel obstruction after ileorectal anastomosis

and the development of postoperative diarrhea, which may become incapacitating in elderly patients.291

A segmental resection with intraoperative colonic lavage and primary anastomosis avoids the risk of

postoperative diarrhea, but carries a risk of fecal spillage and missing synchronous tumor. In addition, it

requires using previously obstructed bowel for the construction of the anastomosis. Surgical tradition

has condemned the performance of an anastomosis in an unprepared colon. Experience accumulated

from the management of patients with civilian colon trauma has demonstrated that, under specific

circumstances, a primary anastomosis can be performed safely in an unprepared colon, provided the

bowel appears healthy and there is no extensive soiling in the peritoneal cavity. This experience has

been transferred to the treatment of malignant colonic obstruction. Therefore, a segmental resection

with colonic lavage and primary anastomosis is a viable option, as long as the colon is not ischemic and

there is in no spillage during the operation. The use of a temporary diverting ileostomy may be

necessary, but when the safety of a primary anastomosis is questionable, a staged procedure with a

segmental resection, a Hartmann pouch, and an end colostomy, may be preferable.292

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