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ANORECTAL 339
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Antibiotic therapy typically consists of metronidazole 500 mg
orally three times daily until PI clinically and radiographically
resolves or for up to 3 months. It is theorized that antibiotics can
alleviate symptoms by reducing the amount of gas produced by bacteria. Alternatives to metronidazole include ampicillin, tetracycline,
or rifaximin.
An elemental diet has been proposed for symptomatic PI. It is
theorized that an elemental diet can decrease production of gas by
colonic flora as it is totally absorbed in the small intestine. Other
mechanisms of action include alteration of intestinal flora.
Inhalational oxygen and hyperbaric oxygen therapy are effective
for patients with moderate symptoms. Although the mechanism of
action has not been fully elucidated, it is theorized that high concen-
FIG. 2 CT scan demonstrating portal venous gas.
trations of O
venous system and promote diffusion of these gases out of the bowel
wall. In addition, oxygen may act as a toxin to anaerobic bacteria in
the gut.
Endoscopic puncture, sclerotherapy, or surgical resection can be
considered in patients who remain symptomatic with bleeding or
obstruction from large blebs of intramural air.
Serial imaging should be conducted every 1 to 3 months until PI
resolution is documented. Recurrence of PI is not uncommon and
likely results from persistence of predisposing factors (see Table 10).
reduce the partial pressure of non-oxygen gases in the
2
catastrophe, the prognosis is extremely poor without immediate
surgical intervention. Therefore, the most important step in the
evaluation is determining whether there is asurgical emergency. As
discussed earlier in the chapter, signs and symptoms suggestive of a
surgical emergency include fever, pain out of proportion to physical
examination, peritoneal signs, and hemodynamic changes such as
tachycardia, hypotension, and orthostasis. Laboratory values that
are red flags include leukocytosis, hemoconcentration, metabolic
acidosis, and lactic acidosis. Most surgical emergencies will be readily evident on CT imaging of the abdomen. If PI is associated with
portal venous gas, strong consideration should be given to surgical
exploration.
A retrospective study by DuBose et al. on 500 patients with PI
showed that a lactate level ≥2.0 mmol/L, hypotension, and/or vasopressor use were highly predictive of PI from mesenteric ischemia.
In addition, a prospective study by Ferrada et al. on 127 patients
with PI indicated that a lactate level ≥2.0 mmol/L, elevated INR,
decreased hemoglobin, and peritonitis were predictive of PI from
transmural ischemia. In Ferrada’s study, the presence of small bowel
involvement, ascites, or adynamic ileus was also associated with PI
from transmural ischemia. Recently, a five-factor score ranging from
0 to 11 (low-risk 0–4, intermediate-risk 5–6, high-risk 7–8, and very
high-risk 9+) has been proposed for predicting PI from transmural
ischemia. The score is based on the presence of small bowel PI, age
≥70 years, heart rate ≥110 beats per minute, lactate ≥2 mmol/L, and
neutrophil-lymphocyte ratio ≥10. In a validation cohort, low-risk
patients for surgical causes of PI had an observed rate of 0.0% for
transmural ischemia, and very-high-risk patients had an observed
rate of 82.4%.
Medical Management of Benign Pneumatosis
Intestinalis
intraabdominal emergencies do not require exploratory laparotomy
and can be managed medically. However, there is no consensus
regarding the best treatment. Expectant management with serial
radiographs, abdominal examinations, empiric antibiotics, elemental
diet, and oxygen therapy are commonly employed.
The underlying etiologic association of PI should be treated in all
patients. This includes removal of offending medications, treatment
of inflammatory bowel disease, eradication of intestinal infections,
and treatment of pulmonary disease.
SURGICAL MANAGEMENT OF
PATHOLOGIC PNEUMATOSIS
INTESTINALIS
Patients deemed to have PI from transmural ischemiarequire emergent exploratory laparotomy. Surgical exploration is strongly recommended for these patients presenting with a lactate ≥2 mmol/L,
peritonitis, or with hemodynamic changes. Careful clinical correlation with a low threshold for emergent exploratory laparotomy
should be considered in those PI patients with small bowel involvement, adynamic ileus, or portal venous gas. Several key considerations are paramount to optimal outcome once the decision has
been taken for surgical exploration, as discussed in the following
sections.
Constant Communication with the Anesthesiologist
If the patient is in shock, anesthesia can result in a further insult.
Ensuring that further vasodilation is kept at a minimum can help
maintain adequate perfusion.
Resuscitation to Euvolemia
Hypovolemia increases the chances of further bowel necrosis and
renal failure. On the other hand, hypervolemia results in further
bowel swelling. Therefore, goal-directed resuscitation using methods such as arterial-line waveform analysis or echocardiography are
advisable to maintain strict euvolemia.
How Much to Resect
Patients with transmural ischemia are usually in a state of shock.
Minimizing blood loss and operative time is imperative. Consideration should be given to resecting only the areas of necrosis,
leaving the patient in discontinuity, if necessary, to allow for better
resuscitation.
Avoiding or Delaying an Anastomosis
Unless the cause of ischemia is clearly mechanical and can be
relieved in the operating room, consideration should be given that
the bowel might be in continued ischemia, which is disastrous for
an anastomosis. In this case, the anastomosis would likely fail and
place the patient at risk for a second source of intraabdominal sepsis.
340 MANAGEMENT OF RECTAL CANCER
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S u g g e S t e d R e a d i n g S
Brighi M, Vaccari S, Lauro A, etal. Cystamatic” review: is surgery mandatory
for pneumatosis cystoides intestinalis? Dig Dis Sci. 2019;64(10):2769–
2775.
DuBose JJ, Lissauer M, Maung AA, etal. EAST Pneumatosis Study Group.
Pneumatosis Intestinalis Predictive Evaluation Study (PIPES): a multicenter epidemiologic study of the Eastern Association for the Surgery of
Trauma. J Trauma Acute Care Surg. 2013;75(1):15–23.
Ferrada P, Callcut R, Bauza G, et al. Pneumatosis intestinalis predictive
evaluation study: a multicenter epidemiologic study of the American
Management of Rectal
Cancer
Gregory K. Low, MD, and Matthew Mutch, MD
BACKGROUND
The rectum is the distalmost aspect of the large intestine and measures 12 to 15 cm in length. From a surgical standpoint, it extends
from the anus at the anorectal ring to the confluence of the taeniae
coli at the rectosigmoid junction. Within the pelvis, it is bordered
laterally by the pelvic sidewall, posteriorly by the sacrum, and anteriorly by the prostate gland in men and the vagina in women. From an
oncologic standpoint, rectal cancer typically refers to tumors within
the rectum located at or below the peritoneal reflection.
Current data show that there are approximately 150,000 cases
of colorectal cancer per year in the United States. Of these,
approximately 45,000 are newly diagnosed rectal cancers. There
are approximately 50,000 colorectal cancer related deaths per year,
making it the third most common cause of cancer-related death
in women and the second most common cause of cancer-related
death in men. Overall, the incidence of colon and rectal cancer
has been decreasing since the adoption of routine screening. For
patients under than age of 50, however, the incidence of both colon
and rectal cancer is on the rise, with a rate of 2% to 4% per year.
Young-onset colon and rectal cancers are more likely to be leftsided and higher-stage cancers at the time of diagnosis. Therefore
special attention should be given to this patient group when they
present with symptoms.
Rectal cancer poses a unique challenge to surgeons because of the
bony confines of the pelvis and its proximity to other vital structures,
which influences the margins of resection. Additionally, there have
been many recent changes and evolving practices within the realm of
radiation oncology and medical oncology. Overall, the management
of rectal cancer is a complex topic that should be approached in a
multidisciplinary fashion to give patients the best opportunity for
favorable outcomes.
CLINICAL EVALUATION AND CLINICAL
STAGING
The most common clinical presentation of rectal cancer is a change
in bowel habits. Other presentations include bleeding, iron deficiency anemia, change in stool caliber, presence of a palpable mass,
tenesmus, and rectal pain. Tenesmus and rectal pain are late findings
and are often indicative of locally invasive lesions. Left untreated,
rectal tumors may cause obstruction or perforation, which may significantly complicate management.
Association for the Surgery Of Trauma. J Trauma Acute Care Surg.
2017;82(3):451–460.
Gemma V, Mistrot D, Row D, etal. Pneumatosis intestinalis in solid organ
transplant recipients. J Thorac Dis. 2018;10(3):1984–1997.
Khail PN, Huber-Wagner S, Ladurner R, etal. Natural history, clinical pat-
tern, and surgical consideration of pneumatosis intestinalis. Eur J Med
Res. 2009;14(6):231–239.
Tahiri M, Levy J, Alzaid S, Anderson D. An approach to pneumatosis
intestinalis: Factors affecting your management. Int J Surg Case Rep.
2015;6:133–137.
The diagnosis of rectal adenocarcinoma is typically secured by
biopsy during endoscopy. A complete colonoscopy is preferred if
the lesion can be traversed given the 3% to 5% risk of synchronous
tumors. In-office evaluation should include a thorough personal history, family history, and a complete physical examination. Anorectal
examination should specifically note the tumor’s location relative to
the anal verge, the sphincter complex, and orientation within the
rectum. Rigid proctoscopy (as opposed to flexible endoscopy) is the
preferred method for assessment of distance from the anal verge
when tumors are not palpable on examination. On rigid proctoscopy, tumors within 12 to 15 cm of the anal verge are considered
rectal cancers; on flexible endoscopy, tumors located at or below the
third fold are considered rectal cancers. Although not diagnostic,
carcinoembryonic antigen (CEA) levels are useful for the purpose
of prognosis and posttreatment surveillance, so they should be
obtained following a rectal cancer diagnosis.
Rectal cancer staging utilizes the Tumor, Node, Metastasis
(TNM) staging system from the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC), which
is currently in its eighth edition. Locoregional staging was historically completed using endorectal ultrasound (EUS), however its use
is limited in the setting of bulky disease and posterior tumors. Additionally, EUS is highly operator dependent and does not allow complete evaluation of lymph nodes. More recently, magnetic resonance
imaging (MRI) has become the preferred method for locoregional
staging. High-resolution, T2-weighted, thin-cut images allow for
accurate evaluation of depth of invasion, locoregional lymph nodes,
and involvement of the circumferential resection margin.
Regional nodes for rectal cancer include those within the mesorectum and internal iliac drainage pathways. Nodal involvement of the
inguinal, external iliac, common iliac, or aortocaval chains is considered metastatic disease. On MRI, both the size and morphology of
the nodes are evaluated to aid in identification of clinically positive
nodes (Fig. 1). Factors associated with an increased risk of nodal
involvement include short axis greater than 9 mm, round shape,
irregular borders, and heterogeneous signal intensity.
A key component of locoregional staging is accurate assessment
of the circumferential resection margin (CRM), which is the radial
margin of the mesorectum removed during total mesorectal excision.
On imaging, the presence of a threatened CRM (tumor within 1 mm)
is highly predictive of positive radial margins at the time of surgical
resection, which translates into poor disease-free survival and overall
survival.
Up to 20% of those with colorectal cancer will present with metastatic disease at the time of diagnosis. The most common sites of
metastatic disease include the lymph nodes, liver, and lung. Distant
metastatic disease should be evaluated with computed tomography
(CT) of the chest and abdomen. If there is concern for potential liver
metastasis, MRI of the abdomen may be obtained. Similarly, positron
emission tomography (PET) is not considered part of the standard
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A B
FIG. 1 (A) T3 tumor involving the superior margin of the internal anal sphincter on axial view. (B) T4 upper rectal tumor involving the bladder on sagittal
view.
staging workup, but it may be considered in the setting of nondiagnostic CT or to confirm the presence of solitary metastasis before an
attempt at surgical resection.
NEOADJUVANT THERAPY
Historically, proctectomy alone in the setting of rectal cancer was
associated with 5-year local recurrence rates as high as 30%. Several
sentinel clinical trials have transformed the management of locally
advanced rectal cancer. The Swedish rectal cancer trial was one of the
first studies to demonstrate the benefit of neoadjuvant short-course
radiotherapy. However, this trial was criticized because of the lack
of standardization of the surgical technique. The Dutch Colorectal
Cancer Group addressed this issue by focusing on the concept of the
total mesorectal excision. With the standardization of surgical resection, they demonstrated a significant decrease in the local recurrence
rate associated with neoadjuvant short-course radiotherapy. Finally,
the German Rectal Cancer Group demonstrated that chemoradiotherapy was best in the neoadjuvant setting given issues with
significant toxicity and patient tolerance when given after surgery.
Until recently, short-course radiotherapy was not widely accepted
in the United States. The Polish trial and Trans-Tasman Radiation
Oncology Group trial evaluated short-course radiation therapy
versus conventional chemoradiotherapy and found no significant
differences in local recurrence, disease-free survival, overall survival,
or late grade 3 or 4 toxicity.
Current indications for neoadjuvant therapy include clinical T3,
T4, or node-positive disease. Although it is occasionally discussed
that neoadjuvant treatment can be considered in the setting of distal
T2 disease in hopes of converting a planned abdominoperineal resection (APR) to a low anterior resection (LAR), this concept is not well
supported and not currently recommended by clinical guidelines.
Traditionally, neoadjuvant therapy is given as long-course chemoradiotherapy consisting of 1.8 to 2 Gy/day for 25 fractions and a fluoropyrimidine for radiosensitization. Following long-course radiotherapy,
proctectomy is typically delayed for 6 to 10 weeks (8 weeks preferred)
to allow for ongoing tumor response. Longer wait times have been
associated with increased pathologic complete response rates.
Short-course radiotherapy is typically given as 5 Gy/day over 5
consecutive days. Short-course radiotherapy is not a new concept
and is commonly utilized in Europe. In recent years, it has garnered
more attention and use in the United States given its reduced toxicity,
shorter treatment time, and lower cost with no difference in pelvic
control, overall survival, or disease-free survival. As opposed to longcourse radiotherapy, surgery can be performed within 7 to 10 days
after completion of short-course radiotherapy. Although immediate
surgery does have certain benefits, recent trials have demonstrated
a lower risk of complications for those undergoing delayed proctectomy (5–12 weeks) versus immediate proctectomy (less than 10
days).
Neoadjuvant therapy has greatly improved our ability to provide
local control of rectal cancers, but it has not improved survival.
Current local recurrent rates for stage II and III rectal cancer treated
with neoadjuvant therapy followed by surgery can be as low as 4%,
but the risk of distant recurrence remains 25% or greater. In attempts
to improve survival and decrease the risk of distant failure, the
concept of total neoadjuvant therapy (TNT) was developed. TNT
involves administration of radiotherapy and all scheduled systemic
chemotherapy in the preoperative period, with the goal of treating
micrometastatic disease as soon as possible rather than up to 4
months after initiation of therapy. Radiotherapy may be given in
short- or long-course format, and chemotherapy (typically the oxaliplatin-based FOLFOX regimen) can be given as induction (before
radiation) or consolidation (after radiation). Current National Comprehensive Cancer Network guidelines recommend TNT for T4
lesions, T3 lesions with threatened margins, and those patients that
are medically inoperable. Additionally, TNT may also be considered
in T3 lesions, even in the absence of threatened margins and for
T1–T2 lesions with positive nodes. TNT has been shown to result in
higher pathologic complete response rates compared with chemoradiotherapy alone, and patients are more likely to complete planned
treatment without dose reductions compared with postoperative
chemotherapy. Whether these benefits translate into improved survival is a topic of ongoing investigation, but there are early data
to suggest that TNT followed by surgery may result in improved
survival compared with conventional chemoradiotherapy followed
by surgery and adjuvant chemotherapy. In addition, a pathologic
complete response after completion of TNT opens the door for an
organ preservation/watch-and-wait strategy.
MANAGEMENT OF TUMOR-RELATED
COMPLICATIONS
Some patients, especially those with locally advanced tumors, may
present with complications related to tumor growth before or during
neoadjuvant treatment. Tumor-related complications may include
large bowel obstruction, bleeding, and perforation, all of which have
serious consequences for patients’ overall outcomes.
For patients presenting with large bowel obstruction, preoperative fecal diversion should be performed followed by neoadjuvant
therapy. Diverting colostomy creation is often preferred as opposed
to ileostomy as it avoids problems with dehydration and the risk of a
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closed-loop obstruction in the setting of a competent ileocecal valve.
Ideally, the stoma should be created distal to the eventual proximal
resection margin to minimize complications to the proximal colon,
which will be used to make an eventual colorectal anastomosis.
Endoscopic stent placement is generally not recommended within
the rectum as it results in pain and tenesmus. Partial or near obstructions may resolve with rapid initiation of radiotherapy, but patients
should be closely observed for an initial worsening in their symptoms, which would require operative intervention.
Perforation of rectal tumors may result in abscess and/or fistula
formation within the pelvis, perineum, or perianal regions. For
contained perforations, fecal diversion and drainage of any abscess
is necessary before initiating neoadjuvant therapy. Patients with free
perforations or who are unstable present significant challenges. Ideally, the patient can be managed with drainage, either abdominally
or transperineally, and fecal diversion. Rarely is resection required
or recommended as obtaining an R0 resection will be difficult. At
the time of radical resection, the perforation cavity and fistula track
should be excised given the high likelihood of tumor spillage. Often
this will require an abdominal perineal resection, and there may be
need for tissue transfer to reconstruct the pelvic floor.
Hemorrhage from a rectal tumor is ideally managed with rapid
initiation of radiotherapy as this is effective in over 90% of cases.
When this is not feasible, endoscopic management, angiography,
and topical treatments should be considered in an attempt to avoid
emergency resection.
RADICAL RESECTION
Despite many recent advances in the realm of rectal cancer, radical
resection remains the cornerstone of treatment. Radical resection
includes resection of the rectum and the associated mesorectum,
which contains the blood supply and lymphatics supplying the
rectum. The goal of radical resection is to achieve negative distal
and radial margins and restore gastrointestinal continuity with
preservation of sphincter complex when possible. The gold standard
technique for proctectomy was defined by Bill Heald in 1982 and is
known as total mesorectal excision (TME). TME involves sharp dissection within the avascular plane between the visceral and parietal
layers of the endopelvic fascia, resulting in a complete excision of
the involved mesorectum and lessening the likelihood of autonomic
nerve injury. As part of standard pathologic assessment, the quality of the mesorectal excision should be graded and reported. The
quality of TME is graded as complete (intact mesorectal fascia), near
complete (small, <5-mm defects in mesorectal fascia), and incomplete defects (>1 cm or exposure of muscularis propria).
Preoperatively, patients should receive mechanical bowel preparation in additional to oral antibiotics. This combination eliminates
the stool burden from the colon and has been shown to reduce the
risk of surgical wound infection compared with mechanical bowel
preparation alone. If a stoma is planned, preoperative site marking
should be performed to ensure a satisfactory location away from
large skin folds, scars, or hernias. On the day of surgery, all patients
should receive deep vein prophylaxis and intravenous antibiotics for
surgical site prophylaxis.
The choice among an open, laparoscopic, or robotic approach is
largely up to surgeon and patient preference as there have been no
definitive studies that demonstrate significant differences in oncologic outcomes. Compared with open proctectomy, the laparoscopic
technique is associated with improved short-term outcomes including less pain, lower rates of ileus, shorter length of stay, and less blood
loss. Robotic proctectomy has rapidly increased in utilization in
recent years, caused in part by the benefits of three-dimensional visualization and instrument articulation within the pelvis compared with
a straight laparoscopic approach. Robotic proctectomy is associated
with a lower conversion rate compared with laparoscopic proctectomy, but it is associated with longer operative times and higher costs.
The extent of resection during proctectomy for rectal cancer
depends on its location within the rectum, relation to the sphincter
complex, and involvement of additional pelvic structures (Fig. 2).
For upper rectal cancers undergoing LAR, a distal margin of 5 cm
is preferred. For low rectal tumors in which sphincter preservation
is being attempted, a margin of 1 cm is acceptable provided that the
entire mesorectum has been resected (Figs. 3 to 6).
Mesorectum
Tumor-specific
bowel and
mesorectum
transection
To tal
mesorectal
excision
Tumor
5-cm margin
Rectum
FIG. 2 For upper rectal tumors, tumor-specif-
ic mesorectal excision is appropriate. For mid to
low rectal cancers, complete mesorectal excision
is required. (From Fleshman, etal. Atlas of Surgical
Techniques for Colon, Rectum and Anus. Philadelphia:
Saunders; 2013)
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Rectosigmoid
Mesorectum
Sacral
promontory
Sacrum
FIG. 3 Total mesorectal excision is initiated at the sacral promontory. The
plane between the presacral fascia and fascia propria is identified with gentle traction. (Courtesy Corinne Sandone. From Cameron J, Sandone C. Atlas of
Gastrointestinal Surgery, vol 2. 2nd ed. Shelton, CT: People’s Medical Publishing;
2014.)
Mesorectum
L. ureter
FIG. 4 Dissect posteriorly along the areolar tissue to identify the correct
total mesorectal plane. (Courtesy Corinne Sandone. From Cameron J, Sandone
C. Atlas of Gastrointestinal Surgery, vol 2. 2nd ed. Shelton, CT: People’s Medical
Publishing; 2014.)
R. ureter
FIG. 5 Extend the dissection laterally along the pelvic sidewall. Avoid inju-
ry to side wall structures and inferior hypogastric plexus. (Courtesy Corinne
Sandone. From Cameron J, Sandone C. Atlas of Gastrointestinal Surgery, vol 2.
2nd ed. Shelton, CT: People’s Medical Publishing; 2014.)
FIG. 6 Use traction and countertraction to facilitate division of the anteri-
or peritoneal reflection. (Courtesy Corinne Sandone. From Cameron J, Sandone
C. Atlas of Gastrointestinal Surgery, vol 2. 2nd ed. Shelton, CT: People’s Medical
Publishing; 2014.)
344 MANAGEMENT OF RECTAL CANCER
Ischial tuberosity
sphincter muscle
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those with a locally advanced low rectal tumor that is prohibitive of
achieving an adequate distal margin (Fig. 7). For patients with poor
preoperative bowel function, fecal incontinence, or chronic diarrhea, an end colostomy/Hartmann resection should be considered.
Multivisceral resection refers to removal of the rectum in addition
to other pelvic organs including the bladder, prostate, vagina, pelvic
floor, and/or sacrum. Soft tissue coverage in the form of rotational or
free flaps are often necessary following APR and pelvic exenteration
given the large tissue defects in a radiated field.
be divided either near its origin (high ligation) or just distal to the
left colic artery at the origin of the superior rectal artery (low tie).
High ligation is necessary in the setting of bulky adenopathy in the
IMA chain and to help improve reach for a low anastomosis. The
inferior mesenteric vein should be ligated at the ligament of Treitz
to allow complete splenic flexure mobilization and improve reach
into the pelvis.
accomplished using an end-to-end, stapled anastomosis. In appropriately selected patients with an ultra-low rectal cancer, a handsewn
coloanal anastomosis may be performed to achieve sphincter preservation. Other options for anastomotic construction include the
colonic J-pouch or an end-to-side colorectal anastomosis. In theory,
these configurations improve the capacity of the residual rectum
and improve function, however most studies demonstrated early
improvement in function, but after 2 years there appeared to be no
significant differences in long-term outcomes.
resection. In general, it should be performed in patients with a low
anastomosis (less than 5 cm), those who received neoadjuvant radiotherapy, those who are immunosuppressed, and in the presence of
a positive intraoperative leak test. Diverting stoma creation reduces
the rate of clinical anastomotic leak, reduces the rate of reoperation,
and increases the rate of salvage of the colorectal anastomosis if a
leak does occur. Loop ileostomy is the most common type of diverting stoma created following radical resection given the simplicity
of the subsequent reversal operation compared with reversal of an
end colostomy. Diverting stoma reversal is typically performed 8
Anococcygeal
ligament
Ischiorectal
fossa
External anal
Levator ani muscle
External anal
sphincter muscle
Ischiorectal fossa
APR is required when tumors involve the sphincter complex or in
Regardless of approach, the inferior mesenteric artery (IMA) may
Restoration of gastrointestinal continuity is most commonly
Temporary fecal diversion is frequently required during radical
Coccyx
Lines of dissection
Anus
Levator ani muscle
Perineal body
Vagina
FIG. 7 Pelvic floor anatomy
AB
CD
encountered during abdominoperineal resection. The anus, sphincter
complex, and portion of the levator
ani muscle are divided. The tip of
the coccyx can be used as a guide
to access the posterior pelvic space
and guide the dissection. (From
Fleshman, etal. Atlas of Surgical
Techniques for Colon, Rectum, and
Anus. Philadelphia: Saunders; 2013).
to 12 weeks following radical resection, but this timeline should be
modified for patient-specific factors such as the need for adjuvant
treatment. Before reversal, patients should undergo a water-soluble
contrast enema to evaluate the integrity of the anastomosis.
Complications of proctectomy may range from minor to major,
and they potentially have devastating consequences. Anastomotic
leak is one of the most feared complications and, after low anterior
resection, occurs in 5% to 25% of cases. For stable patients with a
contained leak, simple percutaneous drainage may be feasible, but
for unstable patients or those with an uncontained leak, reoperation
is typically required. Suture repair, drainage, and fecal diversion may
be adequate for small anterior defects in stable patients. For larger
defects, those with poor tissue quality, or in the face of hemodynamic
instability, takedown of the anastomosis and creation of an end
stoma may be required.
During TME, pelvic bleeding can arise from the presacral plexus
or the pelvic side wall. Presacral bleeding occurs as a result of injury
to the presacral venous plexus, while pelvic side wall bleeding often
originates from branches of the internal iliac vessels. Depending on
the severity, presacral bleeding may by managed with electrocautery
or direct pressure, but in the face of massive bleeding, pelvic packing
is the most appropriate next step. Muscle fragment welding with
a 2-cm area of rectus abdominus muscle or metallic thumbtacks
may also be utilized. There are also several commercially available
hemostatic agents that can be used such as Floseal or a Denver
patch. Ureteral injury can also occur, especially in the setting of
locally advanced tumors, and this typically requires reconstruction
or reimplantation into the bladder depending on the character and
location of the injury. Inadvertent injury to the superior hypogastric
plexus during inferior mesenteric artery ligation may result in retrograde ejaculation, while injury to the hypogastric nerves or inferior
hypogastric plexus during TME may result in erectile dysfunction
and urinary dysfunction.
LOCAL EXCISION
Local excision for rectal cancer avoids the morbidity of proctectomy
and may be considered in favorable lesions (Box 1). To be considered for local excision, lesions should be T0 or T1, be less than 3 cm
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BOX 1 Criteria for Local Excision of Rectal
Neoplasia
Tumor Characteristics
• T0orT1
• <3cmindiameter
• <30%lumencircumference
• Mobileonexamination
• cN0onstagingimaging
Histopathologic Criteria
• Welltomoderatelydifferentiated
• Nolymphovascularinvasion
• Noperineuralinvasion
• Negativemarginsafterexcision
FIG. 8 Full-thickness local excision of rectal neoplasia. (Courtesy Andrew
Russ, MD, and Mark Casillas, MD.)
in diameter, involve less than 30% of the lumen circumference, be
mobile, be amenable to resection with negative margins (3 mm),
have no evidence of lymph node disease on cross-sectional imaging,
and have favorable histologic features (well-differentiated, no perineural or lymphovascular invasion).
There are various techniques available for local excision depending on the tumor characteristics, location, and surgeon experience.
Transanal excision is the simplest of these techniques and may
be considered for easily accessible distal lesions. Transanal endoscopic microsurgery (TEM) and transanal minimal invasive surgery
(TAMIS) are newer techniques that offer improved visualization
and the ability to reach more proximal lesions (Fig. 8). Data show
that TEM and TAMIS result in less specimen fragmentation, a lower
risk of positive margins, and lower local recurrence compared with
transanal excision.
Following local excision, the specimen should be thoroughly
reviewed by an experienced pathologist to confirm the margin status
and depth of invasion. If there is evidence of deep T1 or T2 disease,
high-risk features, or positive margins after local excision, patients
should be offered radical resection given the risk of nodal disease.
involves intensive surveillance with MRI, endoscopy, and digital
rectal examination. At 2 years, up to 30% of patients will experience
local regrowth, and they should be offered radical resection. To date,
data demonstrate that regrowth tends to occur luminally as opposed
to within regional nodes or as distant metastatic disease. Although
national guidelines have slowly started to include watch and wait as an
acceptable management strategy in select patients, additional randomized studies are ongoing, and generally it should only be performed in
select centers where adequate support and experience are available.
MANAGEMENT OF METASTATIC DISEASE
For the 10% to 20% of patients who present with metastatic disease,
multidisciplinary input is essential. Systemic chemotherapy is the
mainstay of treatment and should be initiated without delay. For
those with isolated liver or lung metastases, resection with curative
intent is feasible and is associated with a 5-year disease-specific
survival up to 20%. The order of resection or decision to perform
a simultaneous resection should be individualized based on the
patient’s symptoms, overall health, and complexity of planned
operations. Outside of an attempt at surgery with curative intent,
radical resection should not be performed on asymptomatic primary
tumors. However, in the setting of highly symptomatic lesions, radical resection may be required.
POSTOPERATIVE MANAGEMENT/
SURVEILLANCE
For stage II and III patients who received neoadjuvant chemoradiotherapy but not systemic chemotherapy, an oxaliplatin-based regimen should be initiated within 8 weeks of radical resection. In the
event a patient underwent upfront surgery for what was thought to
be a stage I tumor, postoperative radiation may be administered for
high-risk stage II or III disease. Following total neoadjuvant therapy;
additional systemic chemotherapy is not generally required.
Following successful surgical management of rectal cancer and
completion of all adjuvant treatment, patients undergo surveillance,
which is based on the final pathologic stage. Rectal cancer may reoccur luminally at an anastomosis, within the pelvis, in lymph nodes,
or as metastatic disease, typically to the liver or lungs. Overall, recurrence rates are higher for rectal cancer than for colon cancer, with
local recurrence occurring in 4% to 22% of cases. Early detection is
key as it allows for potential salvage or curative surgical procedures.
Most surveillance guidelines focus on the first 5 years after surgical resection as 80% of all recurrences will occur within 3 years of
surgery, and 95% will occur within 5 years. Those with stage I disease
should receive a colonoscopy at 1 year postoperatively, with no need
NONOPERATIVE MANAGEMENT
Following administration of neoadjuvant therapy, some patients will
have a complete pathologic response. Following neoadjuvant longcourse chemoradiotherapy, this occurs in 10% to 20% of patients.
With the increasing usage of TNT has come the realization that up
to 50% of patients will have an initial complete clinical response.
These patients are candidates for an organ preservation strategy that
FIG. 9 T2-weighted MRI demonstrating local recurrence after low anteri-
or resection with tumor involvement of the vagina and bladder, which was
managed with pelvic exenteration.
346 MANAGEMENT OF TUMORS OF THE ANAL REGION
Anal verge
External sphincter
Anoderm
https://t.me/medicina_free
for CEA or additional surveillance imaging. For stage II, III, and IV,
patients should have a history and physical examination and CEA
level every 3 to 6 months for 2 years, then every 6 months for a total
of 5 years. CT of the chest, abdomen, and pelvis should be obtained
yearly for 5 years, except in the setting of stage IV disease, which warrants imaging every 6 months for the first 2 years and then yearly, for a
total of 5 years. All stages should have a surveillance colonoscopy performed at 1 year. For the select patients who undergo local excision,
proctoscopy and MRI of the pelvis should be performed every 3 to 6
months for 2 years, followed by every 6 months for a total of 5 years.
Should local recurrence be identified, management is a complex
topic that necessitates a multidisciplinary approach (Fig. 9). Treatment
options may include additional chemotherapy, radiotherapy, and/or
surgical resection depending on the site, extent of disease, and prior
treatments. It is imperative to exclude additional distant metastatic
disease, so repeat staging with PET/CT should be considered. Upfront
treatment with additional chemotherapy is common, especially in the
setting of extensive disease. If no prior radiotherapy was given, it should
be administered preoperatively, and re-irradiation may be considered
in select circumstances. Metastatic disease to the lung or liver may be
resected with curative intent when feasible. Surgical resection of local
recurrence often requires multivisceral resection, so careful assessment
of the patient’s expected postoperative function is imperative.
S u g g e S t e d R e a d i n g S
Bonjer HJ, Deijen CL, Abis GA, etal. COLOR II Study Group. A randomized
trial of laparoscopic versus open surgery for rectal cancer. N Engl J Med.
2015;372(14):1324–1332.
Jayne D, Pigazzi A, Marshall H, etal. Effect of robotic-assisted vs conventional
laparoscopic surgery on risk of conversion to open laparotomy among
patients undergoing resection for rectal cancer: The ROLARR randomized clinical trial. JAMA. 2017;318(16):1569.
Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Dutch Colorectal Cancer
Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638.
MERCURY Study Group. Diagnostic accuracy of preoperative magnetic
resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ. 2006;333(7572):779.
Petrelli F, Trevisan F, Cabiddu M, etal. Total neoadjuvant therapy in rectal can-
cer: a systematic review and meta-analysis of treatment outcomes. Ann Surg.
2020;271(3):440.
Sauer R, Becker H, Hohenberger W, et al. German Rectal Cancer Study
Group. Preoperative versus postoperative chemoradiotherapy for rectal
cancer. N Engl J Med. 2004;351(17):1731–1740 21.
van der Valk MJM, Hilling DE, Bastiaannet E, etal. IWWD Consortium. Long-
term outcomes of clinical complete responders after neoadjuvant treatment
for rectal cancer in the International Watch & Wait Database (IWWD): an
international muticentre registry study. Lancet. 2018;291:2537–2545.
Management of Tumors
of the Anal Region
Emilie C. Barnes, MD, and Jose G. Guillem, MD
OVERVIEW AND ANATOMY
The surgical anal canal extends from the anal verge proximally to
the upper part of the anorectal ring and typically measures about 4
cm in length (Fig. 1). Histologically, the canal can be divided into
three different zones. The zone proximal to the dentate line is composed of columnar and cuboidal cells that are similar to those in the
nearby rectal mucosa. The area around the level of the dentate line
and valves of Morgagni is known as the anal transition zone (ATZ)
and is composed of transitional epithelium. The most distal zone is
Squamocolumnar
Surgical anal
junction
canal
Anatomical
anal canal
Sweat glands and
hairs in perianal skin
made up of squamous epithelium. The anal margin, located at the
intersphincteric groove, is a mucocutaneous junction with non-keratinized squamous epithelium proximally and keratinized squamous
epithelium distally that contains hair follicles, apocrine glands, and
sweat glands.
The blood supply and lymphatic drainage vary depending on
the location within the anal canal. The proximal anal canal is supplied by the superior rectal artery. Venous drainage occurs via the
superior and middle rectal veins, and lymphatic drainage occurs via
the mesorectal, internal iliac, and inferior mesenteric lymph nodes.
In contrast, the distal anal canal (below the dentate line) is supplied
by the inferior rectal branch of the pudendal artery, and venous
drainage occurs via the inferior hemorrhoidal vessels that drain to
the internal iliac veins. Lymphatic drainage occurs via the inguinal
lymph nodes. This distinction between the proximal and distal anal
canal is important when considering locoregional spread of anal
neoplasms.
Rectum
Anal columns
of Morgagni
Pectinate or
dentate Iine
Internal sphincter
muscle
Anal crypt
Anal gland
muscle
FIG. 1 Anatomy of the anal canal.
(From Steele SR, etal. The ASCRS Textbook
of Colon and Rectal Surgery. 3rd ed.
Springer; 2016.)
ANORECTAL 347
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Although the diagnosis of anal cancer remains rare, the incidence
is on the rise and now accounts for about 0.5% of all cancer diagnoses
in the United States and roughly 3% of all gastrointestinal malignancies. The vast majority (85%) are of squamous cell histology, followed
by adenocarcinoma (5%–10%) in addition to rare lesions such as
melanoma, mesenchymal tumors, neuroendocrine tumors (NETs),
and lymphoma. Patients often present with rectal bleeding and pain,
which can sometimes be confused for benign anal conditions, such
as hemorrhoids. Others have no symptoms, and the diagnosis is
made incidentally. HPV infection is highly associated with the development of anal cancer, and up to 90% of anal cancers are attributed
to this infection. Other major risk factors include older age, smoking,
and immunocompromised states, particularly patients with human
immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) or transplant patients.
SQUAMOUS NEOPLASMS
Human Papilloma Virus and Anal Squamous
Neoplasia
Human papilloma virus (HPV) is the most common sexually transmitted infection in the United States. Although there are over 100
subtypes, subtypes 16 and 18 have a strong relationship with the
development of anal squamous cell carcinoma (SCC). The Centers
for Disease Control and Prevention (CDC) estimates that these two
subtypes of HPV account for up to 79% of all anal cancers. The
quadrivalent HPV vaccine, which targets subtypes 6, 11, 16, and 18,
has been shown to be efficacious in reducing rates of anal intraepithelial neoplasia and the subsequent development of cancer. However, uptake of the vaccine in the United States has been suboptimal.
Currently, the CDC recommends routine vaccination for children
beginning at age 11 and for all patients up to the age of 26 who have
not been previously vaccinated.
Condyloma Acuminatum (Anal Warts)
Condyloma acuminatum, also known as anal warts, occurs second-
ary to HPV infection, most commonly subtypes 6 and 11 (Fig. 2).
Other factors that increase the risk of development, larger size, and
recurrence after treatment include smoking and immunocompromised states such as HIV. Lesions can present in a variety of ways,
including single, multiple, flat, dome-shaped, cauliflower-shaped,
skin-colored, erythematous, hypopigmented, or hyperpigmented.
Location can also be within the anal canal or on the perianal skin.
Evaluation of these lesions should include a complete anogenital
examination, including anoscopy and referral to gynecology for vaginal examination with a Papanicolaou (Pap) smear in females.
Although it is estimated that up to one-third of anogenital warts
will regress on their own within 4 months of detection, recurrence
rates are high, therefore treatment should be offered to all patients.
Options include topical therapies such as imiquimod cream, podophyllotoxin, and sinecatechins, with clearance rates ranging from
35% to 75%. Other treatment options include application of trichloroacetic acid (TCA) to cryotherapy and surgical fulguration/
excision. Recurrence rates for all of the aforementioned treatments
remain high at about 20% to 40% and are likely attributed to persistent HPV infection.
Buschke-Lowenstein Tumor (Verrucous Carcinoma)
The Buschke-Lowenstein tumor, also known as verrucous carcinoma
or giant condyloma acuminatum, is a rare, slow-growing SCC that
lacks basement membrane invasion (Fig. 3). As a result, it tends to
spread laterally and rarely metastasizes. This tumor presents as an
exophytic, fungating, cauliflower-type mass that is strongly associated with HPV (particularly subtypes 6 and 11). The standard of care
involves wide local excision and potentially abdominoperineal resection (APR) for more extensive disease. Even with aggressive surgical
management, recurrence rates are high (up to 70%), and malignant
transformation occurs in up to 50% of cases.
Anal Intraepithelial Neoplasia
Anal intraepithelial neoplasia (AIN) is a premalignant lesion for
anal SCC characterized by cellular and nuclear abnormalities of
the squamous epithelial cells without extension into the basement
membrane. In more recent years, the terminology surrounding AIN
has evolved to a two-tier system of low-grade squamous intraepithe-
lial lesions (LSILs) and high-grade squamous intraepithelial lesions
(HSILs). AIN I, which involves replacement of the lower third of the
epithelium with abnormal cells, is now considered LSIL. What was
formerly described as AIN II/III and involved replacement of greater
than one third of the epithelium now corresponds to HSIL. The use
of the term Bowen disease, which is synonymous with AIN III or SCC
in situ, is no longer encouraged. In addition to HPV infection, major
FIG. 2 Condyloma acuminatum. (From Fazio V, Church J, etal. Current
Therapy in Colon and Rectal Surgery. 3rd ed. Philadelphia: Elsevier).
FIG. 3 Buschke-Lowenstein tumor. (From Fazio V, Church J, etal. Current
Therapy in Colon and Rectal Surgery. 3rd ed. Philadelphia: Elsevier).
348 MANAGEMENT OF TUMORS OF THE ANAL REGION
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risk factors for the development of LSIL/HSIL, and eventually SCC,
include HIV-positive status, men who have sex with men (MSM),
women with a history of cervical dysplasia, and cigarette smoking.
Although the prevention of cervical cancer with screening for
precancerous lesions has proven to be effective, it is less clear if the
same principles apply to anal carcinoma. There is currently no data
to support screening in the general population, however, screening
with anal Pap tests may be beneficial in high-risk patients, such as
those that are HIV positive, MSM, and females with a history of
cervical dysplasia. Unfortunately, there is no current conclusive data
to support the use of anal cytology to identify patients at risk for
dysplasia, resulting in a reduction in rates of anal cancer, therefore
the decision to perform screening anal Pap tests should be a shared
decision between patients and providers.
Diagnosis
Most patients with anal squamous intraepithelial lesions are asymptomatic, and diagnosis is made either incidentally or as part of a
surveillance program. If symptomatic, the most common symptoms
include rectal bleeding, perianal pruritis or irritation, and tenesmus.
Diagnosis typically is initially based on cytology and is obtained via
anal Pap smear. The Bethesda classification system classifies cells as
atypical squamous cells of undetermined significance (ACUS), LSIL,
HSIL or atypical squamous cells cannot exclude HSIL. Immunohistochemical stains, such a p16, can be used to help differentiate HSIL
from other mimics. Abnormal anal cytology should be followed by
direct anal examination and tissue biopsy. This can be accomplished
with either traditional anoscopy or high-resolution anoscopy (HRA).
Although in some patients LSIL or HSIL regresses without treatment, in others it progresses to malignancy. Patients with HIV are at
the highest risk of progressing from LSIL to HSIL. In fact, in patients
with HIV, the rate of progression from HSIL to SCC ranges from
8.6% to 19.6%.
Management
All patients with evidence of anal dysplasia should be followed clinically at regular intervals with a history and physical examination.
The frequency of these examinations and the addition of HRA is
debated and is also dependent on patient risk factors, most importantly HIV status, and provider training with HRA. For patients with
LSILs who are HIV negative, examinations can be performed every
6 to 12 months. However, HIV-positive patients with LSILs should
be examined more frequently, on the order of every 3 to 6 months.
Local therapy, which includes topical or ablative treatments, is
indicated for HSILs and can also be considered in patients with
LSILs, given the small but real risk of progression to invasive cancer.
Topical options include imiquimod, 5-fluorouracil (5-FU), and trichloroacetic acid (TCA). Imiquimod is an immune modulator that
can be directly applied to the anal canal by the patient or provider.
One randomized trial in HIV-positive MSM who received either
placebo or imiquimod demonstrated 43% resolution or downgrading
of their dysplasia with a 61% sustained response at 36 months. Use
of this medication is somewhat limited by side effects that include
have been difficult to estimate because of the number of patients
lost to follow-up. Finally, electrocautery ablation has been shown to
have initial clearance rates as high as 80%, but recurrence was also
extremely common (up to 61%). Surgical excision remains an option
for recalcitrant lesions but is challenging with larger lesions and
resultant large defects that may require local flaps that may lead to
stenosis and/or seepage.
In patients with HSIL who are treated with local topical or ablative therapy, surveillance involves regular follow-up with a complete
history and physical examination with the addition of HRA being
provider-dependent. Patients with persistent dysplasia or who are
HIV-positive should be examined every 3 to 6 months, and those without evidence of persistent dysplasia and who are HIV negative can be
seen annually. The ANCHOR study is a randomized controlled clinical trial comparing topical or ablative treatment with active monitoring in preventing anal cancer in HIV-positive patients with evidence of
HSIL. As of October 2021, the study was halted after researchers found
that treating HSIL lesions significantly reduced chances of progression
to anal cancer. Although official results have yet to be published, this
randomized controlled trial will hopefully provide the information
needed to establish definitive treatment and surveillance strategies for
HIV-positive patients with anal intraepithelial lesions.
Squamous Cell Carcinoma
Diagnosis
SCC accounts for the vast majority of anal neoplasms (up to 85%)
(Fig. 4). Although many patients are asymptomatic, about 45% pres-
ent with anorectal bleeding. Unfortunately, this is often attributed to
hemorrhoids, which leads to a delay in diagnosis. Other symptoms
include anorectal pain, inguinal pain, tenesmus, and change in
bowel habits, particularly narrowing of stool caliber. About one-half
of patients are found to have localized, node-negative disease at the
time of diagnosis, while another one-third of patients are found to
be node positive. The remaining 10% to 15% present with evidence
of distant metastases.
Initial evaluation should involve a thorough history including
evaluation of baseline anal sphincter continence, prior radiation, and
assessment of risk factors such as MSM, anal receptive intercourse,
and immunosuppression. If HIV status is unknown, this should be
included in addition to basic laboratory studies. Physical examination should include a thorough examination of the perianal skin,
examination of the inguinofemoral region for adenopathy, digital
rectal examination, and anoscopy. Specific attention should be paid
to the sphincter tone, size of the mass, and any evidence of fixation to
with topical 5-FU, with response rates up to 57% (39% with complete response). However, recurrence rates remain high at around
50%. Finally, although it is well tolerated by patients, TCA has been
reported to have response rates up to 72%, but with recurrence
occurring in about 20% of cases.
Options for local ablative therapy include radiofrequency ablation (RFA), infrared coagulation, and electrocautery. Studies on
RFA and infrared coagulation are limited to a small number of retrospective studies that have shown response rates up to 64% (either
complete resolution or downgrading of dysplasia) but dramatic
recurrence rates, up to 91% in HIV-positive MSM at 17 months.
Data on the outcomes regarding infrared coagulation are also limited, but one single-center retrospective study reported an up to
82% treatment response in HIV-positive patients. Recurrence rates
FIG. 4 Anal squamous cell carcinoma: fungating mass at the anal verge.
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