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Presacral Tumors
JohnMigaly andChristopherR.Mantyh
22
Key Concepts
• Unless contraindicated, presacral tumors
should be surgically excised because of the
risk of malignancy.
• MRI should be performed to characterize the
lesions and to plan surgery.
• Lesions that are below sacral level S4 can be
excised through a posterior/perineal approach.
• Complete, non-piecemeal excision is critical
to avoiding recurrence or infection.
General Considerations
• Presacral tumors are a heterogeneous group of
rare tumors.
• Unless contraindicated, these tumors should
be removed surgically as a third of them may
be malignant and benign lesions can undergo
subsequent malignant transformation.
• The diagnosis of these tumors is often delayed
because of vague symptomatology, and often
these lesions are advanced when found.
• MRI is essential for characterization of the
tumor and surgical planning.
J. Migaly (*)
Division of Advanced GI & Oncologic Surgery,
Duke University Medical Center, Durham, NC, USA
e-mail: john.migaly@duke.edu
C. R. Mantyh
Department of Surgery, Duke University Medical
Center, Durham, NC, USA
• Although the role of preoperative biopsy has
been a source of debate, because of the fear of
recurrence at or seeding of biopsy tracts, there
is good single institutional data to support its
selective use.
• Complete resection is critical as it drives the
outcomes and prognosis for these patients.
• Lesions that are below sacral level S4 may be
amenable to excision via a posterior/perineal
approach.
Anatomic Considerations
• The presacral or retrorectal space is a potential
space posterior to the rectum, whose superior
extent is the pelvic peritoneal reection, the
lateral limits are ureters and the iliac vessels;
posteriorly it is dened by the sacrum, and
anteriorly it is dened as the posterior wall of
the rectum. The inferior border is the levator
complex and the coccygeal muscles
(Fig.22.1).
• It is a unique area in that it represents a developmentally critical location where several
types of embryological distinct cell lines converge for the nal steps prior to completion of
ontogeny. It is these changes that produce the
variety of benign and malignant, solid, and
cystic growths that can occur in this space.
• The retrorectal space presents a multitude of
challenges to the surgeon, and this subset of
© ASCRS (American Society of Colon and Rectal Surgeons) 2019
S. R. Steele et al. (eds.), The ASCRS Manual of Colon and Rectal Surgery,
https://doi.org/10.1007/978-3-030-01165-9_22
295
Sacrum
Presacral space
296
Rectum
Fig. 22.1 Location of the presacral space. (Reprinted
with permission from. Ghosh J, Eglinton T, Frizelle FA,
Watson AJ. Presacral tumours in adults. Surgeon. 2007
Feb;5(1):31–8 © 2007, Elsevier Ltd.)
procedures is not recommended for those
uninitiated in pelvic surgery. The sacral nerve
rootlets are located in this retrorectal space,
and thus injury to and sacrice of these structures can have substantial implications on rectoanal and sexual function. In cases requiring
the unilateral sacrice of all of the sacral nerve
rootlets, the patient will likely retain normal
anorectal and sexual function. Bilateral sacrice of the third sacral nerve rootlet will usually result in fecal incontinence.
Classication
• Congenital lesions
– Represent two-thirds of all retrorectal
lesions, which are thought to arise from
various combinations of the three embryonic cell layers. These congenital lesions
can be cystic or solid. In general, these
lesions are more common in females than
males. Can be benign or malignant.
– Dermoid and Epidermoid Cysts: Line with
squamous epithelial cells and may contain
various skin appendages such as hair or nails
(Fig.22.2). Patients can have a post-anal dimple or sinus that can be mistaken for an abscess
and errantly drained, which may account for
high rate of infection of these cysts.
J. Migaly and C. R. Mantyh
Fig. 22.2 CT image of an epidermoid cyst
Fig. 22.3 CT image of rectal duplication cyst
– Enterogenous: Unlike dermoid and epi-
dermoid cysts, enterogenous cysts are
multilocular. They arise from the endoderm of the primitive hindgut. These
lesions can also undergo malignant
degeneration.
– Tailgut Cysts (retrorectal cystic hamarto-
mas, rectal duplication cysts): Arise from
persistence of the hindgut (Fig. 22.3).
Rectal duplication cysts that contain all of
the layers of the intestinal tract can undergo
malignant change.
– Teratomas: Contain cells from all three
germ layers, can contain both solid and
cystic components, and can contain tissues
from almost any organ system including
digestive, respiratory, or bony tissue. Up to
10% harbor malignancy cancer and thus
aggressive extirpation should be pursued.
Because of the diverse germ cell layers,
22 Presacral Tumors
these lesions can become squamous cell
carcinomas, rhabdomyosarcomas, or anaplastic tumors.
– Chordomas: The most common malignant
tumor of the presacral space arises from
what is believed to be the vestigial notochord tissue. Can occur almost anywhere
on the spinal cord but are most commonly
found in the presacral area. The 5- and
10-year survival rates are 67% and 40%,
respectively, and although surgery remains
a mainstay of treatment, it is associated
with a high recurrence rate.
– Anterior Sacral Meningocele: Arise from
protrusions of the dural sac through a
defect in the sacrum. The classic radiologic nding of the “scimitar sign” can
often be seen on plain lms. Patients often
have vague symptomology including
headaches related to postural changes and
Valsalva. Magnetic resonance imaging
usually easily characterizes these lesions,
and percutaneous biopsy should be
avoided for fear of bacterial contamination
of the cerebrospinal uid and iatrogenic
meningitis.
• Neurogenic tumors
– Represent about 10% of all retrorectal
tumors. They arise from peripheral nerves
and include neurobromas, schwannoma,
ganglioneuroma, neuroblastomas, ganglioneuroblastoma (Fig. 22.4), and ependymoma. Ependymomas are the most
common of these tumors [1, 2].
Differentiation between benign and malignant variants can be difcult, and these
tumors can produce signicant neuropathy
as a presenting symptom.
• Osseous lesions
– Osseous lesions include giant cell tumors,
osteoblastoma, aneurysmal bone cysts,
osteogenic sarcoma, Ewing’s sarcoma,
myeloma, and chondrosarcomas. These
lesions represent 10% of all retrorectal
tumors. These may be the most aggressive
of all the retrorectal tumors and can be very
locally destructive and have pronounced
metastatic potential.
297
Fig. 22.4 CT image of a ganglioneuroblastoma
Diagnosis
• History and Physical
– Symptoms are often vague. Tumors are
often noted incidentally on cross-sectional
imaging obtained for other indications.
Occasionally presacral cystic lesions are
confused with cryptoglandular abscess and
stula. Patients with advanced tumors can
have constipation, sexual dysfunction, urinary incontinence, and other leg and gluteal symptoms related to local extension
and mass effect.
– Digital rectal examination can help assess
the consistency and xation of the lesion
and relationship to the anal sphincter.
Flexible endoscopy will often reveal subtle
extrinsic mass effect on the rectosigmoid.
Neurologic exam with attention to gluteal
and lower extremity dysfunction allows for
preoperative documentation of these
defects and aids assessing the locally invasive nature of the lesion.
• Imaging Studies
– Plain lms have limited utility but can
sometimes demonstrate osseous destruction of the sacrum or calcications within
the tumor itself. In patients with anterior
sacral meningocele, the classic “scimitar
sign” can often be seen on plain lms, but
usually cross-sectional imaging is required
for conrmation.
– Magnetic resonance imaging (MRI) with
gadolinium is the imaging modality of
298
J. Migaly and C. R. Mantyh
choice for retrorectal tumors. MRI is critical in the management of these tumors
by facilitating accurate diagnosis, determining the anatomic extent of the lesion
and selection of the optimal surgical
approach.
Characterization of the lesion as solid or
cystic is easily achievable via MRI, but
subtle nodularity or septation of these
lesions allows further characterization
of these lesions into their various subtypes (Fig.22.5).
What MRI excels at in comparison to CT
scan is dening invasion of the muscular walls of the rectum, particularly in
cases of sacrococcygeal chordoma.
• Preoperative Biopsy
– In general, biopsy of cystic lesions should
only be undertaken in situations where
there is some question of the characterization of the lesion after a high-quality
MRI interpreted by an experienced
radiologist.
– Biopsy of presacral lesions via the tran-
srectal or transvaginal route is strongly discouraged, as it is possible to infect a sterile
cystic lesion. In addition, biopsy via these
Fig. 22.5 MRI of presacral cyst. T2-weighted imaging of
an epidermoid cyst shows a bilobulated cystic lesion with
pools of keratin debris (arrows) inside the larger cyst.
(Reprinted Loock MT, Fornès P, Soyer P, Rousset P, Azizi
L, Hoeffel C. MR imaging features of nongynaecologic
cystic lesions of the pelvis. Clin Imaging 2013;37(2):211-8
© 2013 Elsevier Ltd, with Permission from Elsevier)
routes necessitates either partial or complete proctectomy or vaginectomy to
remove the biopsy tract in continuity with
the presacral tumor in order to prevent
recurrence. Biopsy of a meningocele via
any route should be avoided for fear of an
infection of the cerebrospinal uid and
resultant meningitis.
– There is a role for biopsy in unresectable,
sizeable, or aggressive tumors such as
Ewing’s sarcoma or osteogenic sarcoma
where preoperative radiation or chemotherapy could be of value for systemic or local
control or to improve the likelihood of
resectability.
– Many authors recommend excision of the
biopsy tract and site at the time of denitive surgery.
Management
• Role of Preoperative Neoadjuvant Therapy
– In cases of large locally advanced presacral
tumors, where resectability is at issue, neoadjuvant radiotherapy may render some
benet in decreasing tumor size and
increasing resectability.
• Surgical Treatment
– Preoperative Planning
• In patients that have direct invasion of
the muscular wall of the rectum, proctectomy must be anticipated. In cases of
bony invasion, partial sacrectomy is
planned. Pelvic sidewall involvement
may necessitate intraoperative
radiotherapy and vascular or ureteric
reconstruction. The assembly of a multispecialty team of colorectal, urologic,
neurosurgical, orthopedic, vascular, and
plastic surgeon is a prerequisite for
many of these undertakings.
– Choice of Surgical Approach
• In lesions above the S4 level of the
spine, a purely abdominal approach can
be considered, while lesions below S4
22 Presacral Tumors
can be approached posteriorly. Lesions
spanning both above and below S4 are
best approached via a combined abdominal and posterior approach.
– Posterior Approach
• Prone jackknife position; general endotracheal anesthesia.
• Proceed as outlined in Figs.22.6, 22.7,
and 22.8. After removal of the tumor,
the operative eld is submerged beneath
the irrigant, and a proctoscope is used to
insufate the rectum to check for an air
leak and assure that the rectum has not
been violated. The soft tissue and the
incision are closed in multiple layers
over a closed suction drain.
– Combined Abdominal and Perineal
Approach
Fig. 22.7 The
anococcygeal ligament
is divided, and the
coccyx is subsequently
cleared of its lateral
attachments and
removed; this facilitates
dissection along the
sacrum. (With
permission from Ludwig
KA, Kalady
MF.Transacral
approaches for prescral
cyst: rectal tumor.
Operative Techniques in
General Surgery
2005;7:3–126–136 ©
2005 Elsevier Ltd.)
299
Parasacral
incision
Fig. 22.6 Posterior approach to removal of a presacral
tumor, placement of incision. The patient is in prone jackknife, and the incision can either be horizontal on the anococcygeal ligament or curvilinear to the left of the lower
sacrum/coccyx and into the intergluteal fold. (With per-
mission from Ludwig KA, Kalady MF. Transacral
approaches for prescral cyst: rectal tumor. Operative
Techniques in General Surgery 2005;7:3–126–136 ©
2005 Elsevier Ltd.)
Line for disarticulation of coccyx
Coccyx & annocoxygeal lig.
Coccyx
Horizontal
incision
cleared of muscular
attachments
Line of transection
of annococcygeal
lig.
300
Tumor excised
with coccyx
Fig. 22.8 Now with access to the presacral space, the
surgeon can carefully dissect the cyst off of the sacrum
and “roll” it toward himself from cephalad to caudad.
(With permission from Ludwig KA, Kalady MF.Transacral
approaches for prescral cyst: rectal tumor. Operative
Techniques in General Surgery 2005;7:3–126–136 ©
2005 Elsevier Ltd.)
• Lithotomy position with access to anus
and perineum initially.
• Rectosigmoid mobilization.
• There is often a feeding vessel to the
tumor in the midline, and ligating the
middle sacral vessels can often help
stem potential blood loss.
• The tumor is then dissected anteriorly
off of the rectum and posteriorly off of
the sacrum and laterally off of the
sidewalls.
• In situations where tumor is densely
adherent to the posterior rectum, a proctectomy should be performed for en
bloc removal with the tumor.
• If the internal iliac artery or vein needs
to be sacriced, communication with
J. Migaly and C. R. Mantyh
the anesthesiologist in advance of ligation is ideal, as the sacrice of these vessels can sometimes be associated with
large volume bleeding misadventures
and blood products should be on hand.
If involvement of these vessels is identied preoperatively, catheter-based
venous or arterial embolization can be
considered in advance of surgery.
• In situations where the lower most portion of the tumor cannot be reached
from the abdominal approach, there are
two options: the rst is to place the
patient in high lithotomy and proceed
via a posterior approach or the second is
to close the abdomen and place the
patient in prone jackknife position. The
visualization and performance of the
posterior approach with the patient
placed in high lithotomy are challenging, and it is our preference to close the
abdomen and subsequently ip the
patient to the prone jackknife position.
• Transabdominal rectus abdominis or
gracilis myocutaneous aps can be
transposed into the pelvis to ll large
defects.
Outcomes
• The rarity of these tumors and the heterogeneous approach to them preclude rigorous
assessment of outcomes. Nevertheless,
patients can be cured of presacral malignancies. Lesions that are resected completely
without disruption have a better prognosis
than those that are not.
Molecular Basis ofColorectal
Cancer andOverview ofInherited
Colorectal Cancer Syndromes
MatthewF.Kalady andY.NancyYou
23
Key Concepts
• Colorectal cancer is a genetically heterogeneous disease that arises via at least three
main oncogenic pathways: chromosomal
instability, microsatellite instability, and the
methylator phenotype. Each pathway produces distinct but overlapping clinical phenotypes. These pathways are represented in
sporadic colorectal cancer as well as in hereditary colorectal cancer syndromes.
• Identication and diagnosis of a hereditary
colorectal cancer syndrome require a high
level of suspicion and appropriate knowledge
to evaluate the patient and at-risk family members. These syndromes have distinct genetic
and clinical traits and are broadly classied
into polyposis (adenomatous, hamartomatous,
serrated polyps) and nonpolyposis (HNPCC
and Lynch syndrome).
• Familial adenomatous polyposis is a multisystem disease that confers a near 100% colorectal cancer malignancy risk. Close endoscopic
surveillance and timely prophylactic surgery
are required to limit colorectal cancer forma-
M. F. Kalady (*)
Department of Colorectal Surgery, Digestive Disease
Institute, Cleveland Clinic, Cleveland, OH, USA
e-mail: kaladym@ccf.org
Y. NancyYou
Department of Surgical Oncology, University
of Texas MD Anderson Cancer Center,
Houston, TX, USA
tion. Desmoid disease and duodenal adenocarcinoma are other leading causes of morbidity
and mortality.
• MUTYH-associated polyposis (MAP) is a
recessively inherited syndrome that carries an
approximately 75% lifetime risk of colorectal
cancer. Annual colonoscopic surveillance is
necessary, and surgery is indicated for uncontrolled polyp burden or the development of
adenocarcinoma. Extended colectomy should
be offered in healthy patients.
• The hamartomatous syndromes (PeutzJeghers syndrome, juvenile polyposis syndrome, and PTEN hamartoma syndrome) are
rare but are associated with signicant
colorectal cancer and extracolonic multisystem malignancy. Early recognition and extensive screening and surveillance protocols are
required.
• Serrated polyposis syndrome is characterized
by numerous and/or large serrated polyps.
Although no genetic etiology has been identied, it carries an approximately 25% risk of
developing colorectal cancer. Annual colonoscopic surveillance is necessary, and surgery
is indicated for uncontrolled polyp burden or
the development of adenocarcinoma. Extended
colectomy should be offered in healthy
patients.
• Lynch syndrome is the most common of the
hereditary syndromes and is responsible for
about 3% of all colorectal cancers. Universal
© ASCRS (American Society of Colon and Rectal Surgeons) 2019
S. R. Steele et al. (eds.), The ASCRS Manual of Colon and Rectal Surgery,
https://doi.org/10.1007/978-3-030-01165-9_23
301
302
adenoma
adenoma
epithelium
M. F. Kalady and Y. NancyYou
APC
mutation
Normal
Fig. 23.1 Schematic representation of the traditional adenoma-to-carcinoma sequence resulting in chromosomal
instability
Small
screening and systematic molecular analysis
of newly diagnosed colorectal cancer for DNA
mismatch repair deciency provide an effective approach to identifying patients at risk for
Lynch syndrome.
• Patients with Lynch syndrome face signicantly elevated risks for colorectal and extracolonic cancers in multiple organs. Lynch
syndrome patients benet from colonoscopic
screening and participation in a hereditary
registry.
• After development of an initial colorectal cancer, patients with Lynch syndrome have high
risk for metachronous colorectal neoplasia.
Extended resection (total abdominal colec-
KRAS
mutation
p53
mutation
AdenocarcinomaLarge
that gene function. APC and p53 are examples of tumor suppressor genes, whose loss
via this mechanism results in chromosomal
unstable CRC.
• The traditional adenoma-to-carcinoma
sequence as described by Vogelstein and
Fearon is characterized by the accumulation
of genetic changes over time and the prototype chromosomal instability of CRC. An
overview of this pathway is given in Fig.23.1.
Clinically, CRCs arising via chromosomal
instability tend to be located in the left colon,
have male predominance, and develop later in
life. Genetically, key genes mutated in this
pathway include APC, KRAS, and p53.
tomy for colon cancer and total proctocolectomy for rectal cancer) should be considered
in weighing risks of future malignancy and
Microsatellite Instability
quality of life.
• Microsatellite instability results from faulty
DNA mismatch repair (MMR) function.
Chromosomal Instability
Routine DNA replication is associated with
high indelity, with specic sites along the
• Chromosomal instability refers to an alteration in the chromosome copy number or
structure and is the most common form of
genomic instability in CRC, accounting for
about 75% of all CRC. Physical loss of a
chromosome segment may delete entire genes
and produce loss of heterozygosity for those
genes. That is, as one allele is lost, only one
functional copy of the gene exists, and there
is no longer redundancy for that gene. Loss of
the second allele results in complete loss of
DNA strand that are prone to errors. These sites
are areas of repetitive DNA sequences, called
microsatellites. Microsatellites are noncoding
segments of DNA that contain repetitive
sequences of one to four nucleotides. There are
hundreds of thousands of microsatellites in the
genome, and microsatellite patterns provide a
unique DNA ngerprint. When these errors are
not repaired due to MMR deciency, the length
of the microsatellite regions is altered, and the
ngerprint changes; i.e., there are different
23 Molecular Basis ofColorectal Cancer andOverview ofInherited Colorectal Cancer Syndromes
303
lengths of the DNA fragments. Thus, the
pattern of fragments detected by PCR techniques produces a different pattern of microsatellites, and thus the term microsatellite unstable
or microsatellite instability-high (MSI-H).
• Functionally, loss of MMR function leads to
an accumulation of unrepaired errors. Several
key tumor suppressor genes have multiple
short repetitive sequences that make them
prone to DNA mismatch. Loss of MMR function allows accumulation of mutations in these
genes that subsequently lead to adenoma and
cancer formation. Cancers arising through this
molecular pathway are termed the mutator
phenotype as these tumors tend to be hypermutated and account for approximately 15%
of CRC. Inherited mutations in one of the
DNA mismatch repair genes result in Lynch
syndrome.
CpG Island Methylator Phenotype (CIMP)
• Epigenetic mechanisms such as hypermethylation of DNA promoter regions can affect
gene expression and protein translation without changing the inherent DNA sequence.
Methylation of cytosine is a common biological phenomenon that occurs throughout the
genome and controls multiple processes.
• Several key tumor suppressor genes contain
cytosine-guanine (CpG) repetitive sequences,
which are prone to hypermethylation in the
promoter region, which silences transcription
of that gene, and thus no functional protein is
made. As the areas prone to hypermethylation
contain regions rich in cytosine and guanine
dinucleotide repeats, or CpG islands, they
have been termed CpG island methylator phenotype (CIMP or CIMP-high).
• This pattern is reproducible in approximately
20% of CRCs and is associated with aberrant
methylation of the mismatch repair gene,
MLH1. Approximately 85% of MSI-H CRCs
develop via loss of the expression of the
MMR gene, hMLH1, caused by DNA
hypermethylation.
• In contrast to CRC arising via chromosomal
instability in which the precursor lesions are
adenomatous polyps, the precursor lesions in
CIMP cancers are serrated polyps.
• The most common initial mutation occurs in
the BRAF oncogene. BRAF mutations support
the transformation of normal mucosa to
aberrant crypt foci or a hyperplastic polyp or
sessile serrated polyp (SSP).
• Increasing methylation gives rise to CIMP and
eventual methylation of MLH1, which in turn
silences transcription. Loss of MLH1 results
in MMR deciency and thus the development
of an MSI-H CRC.As CIMP CRCs develop
through serrated polyp intermediates, this
pathway is called the serrated pathway. An
overview of this process is shown in Fig.23.2.
• Clinically, CIMP CRC tends to develop in the
right colon, at advanced age, and is more common in females.
General Approach
andClassication ofSuspected
Hereditary Syndromes
• Awareness and suspicion are the keys to identifying hereditary CRC syndromes. Although
only about 5–10% of all CRCs arise with a
known hereditary syndrome, recognizing
these cases and making the correct diagnosis
impact care of that particular patient and their
family including future generations.
• Clinical evaluation should include a personal and
family history, physical examination, documentation of gastrointestinal polyps or cancers, and
identication of extracolonic manifestations.
• A specic diagnosis is warranted to assign
risk for cancer development and guide surveillance and prophylactic interventions.
Information gained from the initial evaluation
can guide the specic diagnostic tests required
to make a diagnosis. Genetic counseling is a
critical component to this evaluation and is
recommended before genetic testing to discuss potential implications of the results. An
overview of the classication of hereditary
CRC syndromes is given in Table23.1.
304
Serrated pathway to CRC
M. F. Kalady and Y. NancyYou
Intermediate
lesions
Advanced lesions
SSA/SSP with
dysplasia
CIMP
Normal
colon
Early lesions
Hyperplastic
polyps
SSA/SSP
Genetic and molecular changes
BRAF Mutation
Fig. 23.2 Schematic representation of proposed serrated pathway to colorectal cancer
Table 23.1 Classication and overview of hereditary colorectal cancer syndromes
Polyposis syndromes
Main polyp
Syndrome Gene(s)
type Inheritance Predominant clinical ndings
FAP
Classical APC Adenoma AD 100–1000 adenomas; duodenal
adenomas and carcinomas; gastric
fundic gland polyps desmoid tumors,
epidermoid cysts, extra teeth, osteomas
Profuse APC Adenoma AD >1000 adenomas; duodenal adenomas
and carcinomas; gastric fundic gland
polyps desmoid tumors, epidermoid
cysts, extra teeth, osteomas
Attenuated APC Adenoma AD <100 adenomas; gastric fundic gland
polyps desmoid tumors, epidermoid
cysts, extra teeth, osteomas
MAP MYH Adenoma AR 0–1000 adenomas, CRC <50years;
gastric fundic gland polyps, duodenal
adenomas and carcinomas
≥5 juvenile polyps;
Any juvenile polyp and JPS family
JPS BMPR1A
SMAD4
Hamartoma AD
history; HHT
PJS STK11 Hamartoma AD Peutz-Jeghers polyps;
orocutaneous pigmentation;
family history of PJP; cancer of small
bowel, colon, stomach, pancreas,
breast, ovary, testis
PHTS PTEN Hamartoma AD Colorectal adenomas, lipomas,
bromas, ganglioneuromas, juvenile
hamartomas; colorectal cancer;
macrocephaly, trichilemmomas
CIMP-H
cancer
MLH-1
Approximate
CRC risk
100%
100%
80%
80%
40%
40%
10%
(Cowden)