TRATAMIENTO

Surgery

The surgical management of primary rectal cancer presents unique problems for the surgeon based in large

part on the anatomic constraints of the pelvis. Small early stage lesions of the rectum that are diagnosed on

physical examination or by colonoscopy/proctoscopy can often be managed with local resection. Local

resection can be performed colonoscopically (as was described in Chapter 39.12 on colon cancer), or lesions

can be removed via a transanal excision with the patient positioned in a prone or lithotomy position.

Appropriate retractors can provide visualization, and resection should encompass a surrounding margin of

normal mucosa28 and should extend into the perirectal fat.

Stage I

The treatment of early stage rectal cancer can be confusing as there are many approaches that can be used,

and patient selection is critical to outcome. In addition, the risk of removal or damage to the anal sphincter is

substantial for low-lying tumors and must be taken into consideration, along with the desire not to have a

permanent colostomy for early stage disease. Thus, the options for these patients are primarily those of local

therapies without abdominal surgery, abdominal resection of the rectum with anastomosis and retention of the

anal sphincter, and abdominal-perineal resection. The last two options are discussed in detail in the section

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Stages II and III Rectal Cancer.

For selected T1 and T2 lesions without evidence of nodal disease, transanal excision often provides an

adequate resection of the primary tumor mass and can spare the patient the morbidity of a more extensive

rectal resection. However, it does not stage the nodal drainage areas and therefore cannot provide as

complete staging and management of the tumor as a definitive resection. Tumors considered for local excision

must meet a number of criteria to minimize the risk of local regional

failure. Generally, local excision is limited to tumors within 8 to 10 cm of the anal verge, encompass less than

40% of circumference of the bowel wall, are of well or moderately well differentiated histology, and have no

pathological evidence of venous or lymphatic vessel invasion on biopsy. Although it has not been formally

proven that these criteria need to be followed, small series have suggested a substantially higher risk of failure

after local excision when these criteria have not been met, and most surgeons are reluctant to use local

excision for the more extensive T1 or T2 lesions. Even when these criteria have been met, the local recurrence

rate can be high after local excision (even when followed by postoperative radiation therapy and

chemotherapy), so this approach must be used with caution.

Performing a good transanal excision requires substantial surgical expertise as the surgeon must retain control

over the primary tumor and obtain adequate mucosal margins as well as adequate deep resection into

perirectal fat. Once removed, the tumor must be well laid out for the pathologist so that all relevant margins

can be properly evaluated. There is some experience using preoperative radiation therapy and chemotherapy

for small lesions, but care must be taken to have the site of the primary tumor well marked with a tattoo if

this approach is taken as excellent regression could make identification of the primary site difficult. The

staging of such lesions should be performed using EUS to minimize the likelihood of doing a local excision for T3

tumors,29,30 although there are inaccuracies with this approach.

A posterior proctotomy is useful for large posterior lesions and provides better access to more proximal lesions.

This approach is known as a Kraske procedure and is performed by making a posterior longitudinal incision just

above the anus to the inferior border of the gluteus maximus. The coccyx is removed and the underlying

levator muscles are divided in a longitudinal fashion in the midline. This approach allows for the mobilization

of the rectum and a full-thickness local excision. A transsphincteric excision (Bevan's or York-Mason) involves a

similar approach as the posterior proctotomy, except the entire anal sphincter is divided posteriorly in the

midline. Most investigators now feel it appropriate to use adjuvant pelvic radiation therapy with concurrent 5-

fluorouracil (5-FU)-based chemotherapy for patients who have had a local excision for T2 tumors and also for

selected patients with T1 tumors who have adverse prognostic factors (lymphovascular invasion, close margins,

poorly differentiated histology), in order to decrease the risk of local recurrence.

Another approach that has been used sporadically for patients with early stage disease is endocavitary

radiation therapy. This technique is used for a similar category of patients who are treated with local excision;

T1 or T2 tumors less than 3 cm, not poorly differentiated, with no evidence of nodal involvement. Patients are

treated with a special low energy x-ray machine (50 kVp) that is attached to a rigid endoscopic-type device

that can be placed in the rectum directly over the tumor. As the opening of the applicator is 3 cm, it is

difficult to treat tumors larger than this, although overlapping fields have been employed. Patients typically

receive four treatments of 2,500 to 3,000 cGy each with 2 to 3 weeks between treatments to allow for tumor

regression. Although the total dose is extremely high, the minimal penetration of the radiation beam protects

the underlying normal tissue. Local control results with this approach have been very good in properly selected

patients, but specialized equipment is required (which is not generally available) and less pathological

information is obtained than after a local excision. This approach is rarely used at the present time.

Stages II and III Rectal Cancer

The primary treatment of patients with stages II and III rectal cancer (T3-4 and/or N+) is surgical. However, in

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contrast to the treatment of patients with stage I disease, there is a strong body of information to suggest that

combined modality therapy with radiation therapy and chemotherapy should be used in conjunction with

surgical resection. This conclusion is based on both patterns of failure data, which demonstrate a substantial

incidence of local, regional as well as distant disease failure, and the fact that this incidence of tumor

recurrence at all sites is decreased with the use of trimodality therapy.

The desire when performing a resection for rectal cancer is to preserve intestinal continuity and the sphincter

mechanism whenever possible while still maximizing tumor control. Therefore, careful preoperative screening

is crucial in the determination of the location of the lesion and its depth of invasion. Large lesions may respond

to preoperative adjuvant chemoradiation in order to downstage the lesion to increase the likelihood of a

successful sphincter-preserving operation. The use of chemotherapy and radiation for this purpose will be

discussed in greater detail in later sections. As described above, it is convenient to think of the rectum as

divided into thirds for the purposes of the evaluation and preoperative determination of the surgical approach

for resection. The upper third of the rectum is often considered the region of large intestine from the sacral

prominence to the peritoneal reflection. These lesions are in almost all cases managed with a low anterior

resection in much the same way as a sigmoid colon cancer (see Chapter 39.12 on colon cancer). An adequate 1

to 2 cm distal mucosal margin can be achieved for these lesions well above the sphincter mechanism, and

intestinal continuity can be restored using either a hand-sewn technique or a circular stapling device inserted

through the rectum.29,31

Tumors in the middle and lower thirds of the rectum can be considered as lying entirely below the peritoneal

reflection. The resection of these tumors can be challenging due to the confines of the pelvic skeletal

structure, and the ability to perform a resection with an adequate distal margin is significantly influenced by

the size of the lesion. Nevertheless, tumors of the middle third of the rectum in most cases can be safely

resected with a low anterior resection, with restoration of intestinal continuity and preservation of a continent

sphincter apparatus.

Lesions in the distal third of the rectum, defined as those within 5 cm of the anal verge, can present the

greatest challenge to the surgeon with respect to sphincter preservation. This is often influenced by the extent

of lateral invasion of the lesion into the muscles of the sphincter apparatus and how close distally the tumor is

to the musculature of the anal canal. The abdominal perineal resection (APR) has historically been considered

the standard treatment for patients with rectal cancers located within 6 cm of the anal verge. This procedure

requires a transperitoneal as well as a transperineal approach with removal of the entire rectum and sphincter

complex. A permanent end colostomy is created and the perineal wound either closed primarily or left to

granulate in after closure of the musculature.

Although an APR is associated with a relatively low rate of local recurrence, it is not without the obvious

problems of the need for a permanent colostomy and loss of intestinal continuity and sphincter function.

Therefore, intense interest has been focused on developing approaches to the resection of tumors in the distal

third of the rectum that would both avoid local regional recurrence and preserve intestinal continuity and

sphincter continence.

Tumors within 1 to 2 cm of the dentate line, that is those that can be removed with at least a 1-cm distal

margin, can be resected and intestinal continuity restored with a coloanal anastomosis.32,33 When performing a

very low coloanal anastomosis, it is often prudent to protect the healing suture line with a diverting loop

ileostomy, which can be reversed in 4 to 6 weeks after the anastomosis has healed. Despite the potential

benefits of sphincter preservation, APR is still the most common procedure performed for rectal lesions in the

distal and middle thirds of the rectum.34

A recent review of the published literature demonstrates that between 10% and 67% of procedures for the

management of rectal cancers are APR procedures.32 In order to increase the number of sphincter-preserving

operations performed, several authors cite the use of preoperative chemoradiation as a means to decrease the

local recurrence rate.32,35 They cite statistics that rectal carcinoma responds to preoperative chemoradiation

therapy with a 10% to 15% pathologic complete response rate and substantial tumor down-staging. The goal of

such an approach would be to reduce the need for APR to an incidence of 10% or less.

When performing a sphincter-preserving operation, in order to preserve the lateral musculature and therefore

a functional sphincter complex, the resection by necessity does not have as wide a margin as one performed

during an APR. In order to improve on margin status, intersphincteric resections have been performed.36 This

approach includes a partial sphincteric resection designed to improve margin status without sacrificing

sphincter function. In small series, functional results have been comparable to less aggressive sphincterpreserving

operations. The impact on oncologic outcome is difficult to interpret and will require larger series.

The choice of a straight coloanal versus a pouch anastomosis is a decision that is based to a large degree on

surgeon's preference and experience. Some advocate a pouch operation, citing improved anal function as

measured by decreased stool frequency and urgency and improved continence.4 Others have demonstrated

that results are equivalent with a straight coloanal anastomosis.37

Chemoradiation should be added either preoperatively or postoperatively when performing sphincterpreserving

resections for T3 or T4 rectal lesions or for node positive disease stages II or III). There is some

evidence that preoperative radiation results in less morbidity than postoperative radiation therapy when a

coloanal anastomosis is planned. In a study of 109 patients treated with a low anterior resection and a straight

coloanal anastomosis, those receiving preoperative radiation therapy had a lower incidence of adverse effects

on anal function than those receiving postoperative radiation.37 The authors attributed this to sparing of the

neorectum from these effects. Relative benefits and outcomes for preoperative chemoradiation versus

postoperative chemoradiation will be discussed in detail in following sections.

Total Mesorectal Resection

The goal of the resection of rectal tumors is the removal of the tumor with an adequate margin as well as

removal of draining lymph nodes and lymphatics in order to properly stage the tumor and to reduce the risk of

recurrence and spread. For lesions in the intraperitoneal colon, the lymphatics and vascular supply are found in

the mesentery associated with that region of bowel.

In the rectum the mesorectum is the structure that contains the blood supply and lymphatics for the upper,

middle, and lower rectum. Most involved lymph nodes for rectal cancers are found within the mesorectum,

with T1 lesions associated with positive lymph nodes in 5.7% of cases; T2 lesions having positive lymph nodes in

20% of cases, and T3 and T4 lesions having positive lymph nodes in 65% and 78% of cases, respectively.38

The anatomy and approach to mesorectal excision is depicted in Figure 39.13.3. This operation involves a sharp

dissection occurring in an avascular plane beyond the perirectal fat that is beyond the region where most of

the nodes are located. After a TME the specimen is typically shiny and bilobed in contrast to the irregular and

rough surface after a blunt dissection where much of the mesorectal fat is left behind. TME attempts not only

to clear involved lymph nodes but also to adequately manage the radial margins of the rectal tumor. These

radial margins have been shown to be more important with respect to the risk of local regional recurrence than

the distal mucosal margin.35,39 Distal mucosal margins of 1 cm or greater are adequate for local control;

however, the margin on the mesorectum should extend beyond the distal mucosal margin in order to ensure a

successful surgical outcome.33,35 A number of studies have demonstrated the benefit of TME, and it is thought

by many that this is the procedure of choice for the management of middle- and lower-third rectal

cancers.5,40,41,42 Although some studies have suggested that an adequate TME might in and of itself be

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sufficient management for T2 and T3 rectal cancers, the majority of the literature still supports the use of

adjuvant chemoradiation for stages II and III disease even when combined with TME.

Large studies of proctectomy with TME have demonstrated a reduction in the overall incidence of local

recurrence to less than 10%.4 The consequences of TME can be impairment in erectile and bladder function due

to disruption of parasympathetic nerves that are located in proximity to the mesorectum. Several authors have

stressed the importance of the experience of the surgeon performing the procedure, and some have suggested

specific techniques for monitoring modalities that can be used during this procedure to minimize morbidity.5,6

A careful understanding of the anatomy and adequate visualization during sharp dissection will help in

minimizing injury to the parasympathetic nerves and the consequent morbidity.3,4

Adequate visualization in the deep pelvis can often be a challenge. This may be a situation where the visual

magnification and ability to enter tight spaces that are unique to the laparoscopic approach may be an

advantage. Several groups have demonstrated the feasibility of laparoscopic TME for low rectal cancer as part

of a sphincter-preserving operation.43,44,45 Some of the larger series, while demonstrating that TME using

laparoscopic techniques can be performed safely, do not have adequate follow-up to demonstrate whether

there were any oncologic disadvantages to such an approach. Unfortunately, the

prospective random assignment trial conducted in the United States to evaluate the role of laparoscopic

surgery for colon cancer excluded patients with low rectal lesions. Therefore, the ultimate role of the

laparoscopic approach to TME will have to await prospective randomized trials utilizing this technique and

comparing it to the standard open approach.

a Local recurrence highly dependent on site in rectumโ€”18% overall for tumors โค7 cm from anal verge.

The most important piece of information on local recurrence rates with TME are the data from the Dutch TME

study in which patients were randomized to receive either TME alone or a short course of preoperative

radiation therapy followed by TME.41 All patients with rectal cancer were eligible including those with early

stage disease. Special attempts were made to have good surgical and pathology quality control. The early

results (2 years) relating to local tumor recurrence have been reported and are summarized in Table 39.13.2.

The study demonstrates that there are subsets of patients in whom TME alone is likely sufficient for obtaining

good pelvic control, including patients with high rectal tumors (some of these may have been sigmoid cancers,

rather than rectal), and low stage tumors (T1-2, N0). On the other hand, low-lying rectal tumors that are

moderately advanced (T3-4 and/or N+), had a higher incidence of local-regional failure. Local failure after TME

alone was 15% in node positive patients at 2 years, not corrected for site of the primary, and longer-term

follow-up will undoubtedly demonstrate higher local failure rates. In addition, as these results were obtained

in a controlled setting, one would likely not obtain similarly good results when surgery is done with less careful

quality control. There was a consistent decrease in local failure rate by the addition of preoperative radiation

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therapy, but the absolute magnitude of the effect varied by the tumor characteristics discussed above.

The data are excellent that radiation therapy, especially when combined with chemotherapy, can decrease the

local failure rate. This is shown by a Swedish study of preoperative radiation therapy compared to surgery,57

the Dutch TME trial in the preoperative setting,41 and by multiple studies in the postoperative

setting.58,59,60,61,62,63 There are also excellent data to show that local-regional failure is decreased by the use

of radiation therapy and is further decreased by the use of concurrent 5-FU-based chemotherapy (Table

39.13.3).58,59,64 Most studies have demonstrated that local failure decreases by about 50% with the use of

adjuvant radiation therapy, with a greater effect when concurrent 5-FU is used with irradiation. This appears

to provide a

strong justification for the use of adjuvant radiation therapy. What is less clear is (1) whether trimodality

therapy with radiation therapy improves survival, (2) if radiochemotherapy should be given preoperatively or

postoperatively, and (3) precisely which patients should be irradiated.

T

Does Adjuvant Radiation Therapy Impact Survival?

Although there have been multiple randomized trials addressing the use of adjuvant radiation therapy or

chemoradiation therapy, and although they consistently show an improvement in local control with adjuvant

radiation therapy, the survival outcome data have been mixed. In the past few years there have been two

meta-analyses performed.65,66 Table 39.13.4 shows the results of a meta-analysis by Camma et al.66 showing a

decreased local recurrence rate, cancer mortality rate, and overall mortality rate with the use of preoperative

radiation therapy, although without a decrease in distant metastasis rate. The Colorectal Cancer Collaborative

Group (Table 39.13.5) study demonstrates no improvement in the likelihood of curative surgery with

preoperative therapy or of overall survival with all types of radiation therapy combined.65 Preoperative

radiation therapy, however, was shown to improve local control, disease-free survival, and overall survival

compared to surgery alone, although deaths within the first year after surgery were higher after radiation

therapy. Local recurrence with preoperative radiation therapy was 46% lower than surgery alone, and cancer

deaths were

decreased from 50% to 45%. Postoperative radiation therapy was shown to improve local control (although less

than preoperative therapy), but did not impact long-term survival. Lending substantial strength to the

conclusion that there was a true advantage to radiation therapy is the fact that there was a dose response

demonstrated for the radiation effect on local control (i.e., better control was obtained with higher radiation

dose). This observation strengthens the conclusion, as it demonstrates a direct correlation between the amount

of therapy and outcome. The data from this analysis are heavily influenced by the results of a single Swedish

study that showed a long-term survival advantage to the use of preoperative radiation therapy compared to

surgery alone.57 Thus, these data show that improving local control with the use of radiation therapy (and

presumably with concurrent chemoradiation therapy) is beneficial, and that trimodality therapy, especially

when chemoradiation therapy is used preoperatively, can improve survival.

Table 39.13.4 Results of Meta-Analysis, Preoperative Radiotherapy

versus Surgery Alone

Preop Radiotherapy versus Surgery

Overall 5-y mortality OR 0.84 (P = .03)

5-y cancer mortality OR 0.71 (P <.001)

5-y local recurrence OR 0.49 (P <.001)

5-y distant metastases OR 0.93 (P = .54)

OR, overall recovery.

(From ref. 66, with permission.)

Table 39.13.5 Colorectal Cancer Collaborative Group 2001 Adjuvant

Radiation Therapy in Rectal Cancer

Preop RT versus Surgery Postop RT versus Surgery

Yearly risk of local recurrence 46% decrease with RT 37% decrease with RT

Death rate 5% less than with surgery No difference from surgery

RT, radiotherapy.

(From ref. 65, with permission.)

Preoperative Radiation Therapy

The second issue of importance is whether adjuvant therapy should be given preoperatively or postoperatively

and the exact timing of the chemotherapy. There have been relatively few studies that have compared these

approaches in a randomized controlled trial. A Swedish study reported in the early 1990s compared a short

course of radiation therapy preoperatively to a more protracted course and higher total dose delivered

postoperatively and found a decreased local failure with the use of preoperative therapy compared to

postoperative therapy (13% vs. 22%).67,68 Two trials in the United States have attempted to compare combined

chemoradiation therapy delivered preoperatively to the same chemoradiation therapy regimen given

postoperatively. However, neither study (National Surgical Adjuvant Breast and Bowel Project [NSABP] or

Gastrointestinal Intergroup) could accrue a sufficient number of patients to answer the question.69 The

inability to accrue patients to these studies makes it unlikely that such a study will be attempted in the near

future in the United States.

In addition to improving survival, another reason for using preoperative chemoradiation therapy is to increase

the chance for sphincter preservation for patients with low-lying tumors of the rectum, where an

abdominoperineal resection would be conventionally used. The NSABP trial mentioned above was able to

obtain worthwhile information regarding this issue. When the patient was first seen, the surgeon was asked (for

both preoperative and postoperative patients) what operation was needed. In the patients randomized to

postoperative radiation therapy (i.e., immediate surgery), the determination in the office corresponded

extremely well to the operation actually performed. However, in the patients who received preoperative

radiation therapy, sphincter-preserving surgery was done in 50% of patients compared to 33% of those who had

initial surgery.70 However, overall the data have been inconsistent in demonstrating an advantage to

preoperative therapy in terms of sphincter preservation. The analyses are complicated because the decision as

to whether sphincter-preserving surgery should be done is heavily dependent on the biases of the surgeon. If

the surgeon believes that the same operation should be done regardless of tumor regression, then clearly the

same surgery will be done. There are clearly some surgeons who will do sphincter-preserving operations after

preoperative irradiation, when they would not have done so if the surgery had been done first.

Perhaps the most important study addressing the issue of pre- versus postoperative adjuvant therapy is a

German trial of preoperative versus postoperative chemoradiation with radiation therapy given at 180 cGy per

fraction and using continuous infusion 5-FU chemotherapy as a 120-hour infusion, for which results have been

reported by Sauer et al.71 This study demonstrates an advantage in sphincter preservation with the use of

preoperative therapy. Of the patients thought to need an APR at initial assessment, only 19% had a sphincterpreserving

surgery when operation was done immediately versus 39% after preoperative radiation therapy,

although there was no difference in the overall sphincter preservation rate. There was a statistically significant

decrease in local failure with preoperative radiation therapy compared to postoperative treatment (6% vs. 13%;

P = .006). The relative risk of local failure in the pre- versus postoperative treatment group was 0.46. The 5-

year disease-free survival showed a small advantage to preoperative therapy (68% vs. 65%; P = .32), which was

not statistically significant. There was a decrease in late anastomotic strictures with preoperative therapy, and

acute toxicity was also decreased by the use of preoperative radiation and chemotherapy, both statistically

significant. This provides strong evidence of the superiority of preoperative adjuvant treatment in patients in

whom it is determined that adjuvant therapy is needed.

If one is using preoperative radiotherapy to try to improve the likelihood of sphincter preservation, the

radiation must be given in such a way as to maximize the likelihood of this occurring. Specifically, a โ

€ standardโ€ long course of irradiation to a dose of approximately 5,000 cGy at 180 to 200 cGy per fraction over

5 to 5.5 weeks (as given in the German trial above) has been thought by most U.S. investigators to be optimal.

The short-course therapy with immediate surgery (typically 500 cGy for five fractions given over 1 week), as

often used in Europe, followed by immediate surgery is not likely to produce enough tumor shrinkage to allow

for sphincter preservation in patients with very low-lying tumors. Bujko et al.72 have published data that

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	Criado por Saul Rodriguez quase 5 anos atrás

ca de recto tratamiento