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improved outcomes in colon and rectal surgery
differentiate fibrosis from tumor. If there is suspicion clinically
of involvement, we will treat with IORT. Sacrectomy is preserved
for those who are fit for surgery with clear cortical destruction or
marrow involvement by CT/MRI below S1-2. Our initial experience with this approach is encouraging.(27) Postoperative chemotherapy is usually recommended in our institution, but has
been variably administered in the literature.
OPERATIVE APPROACH
The patient is placed in modified lithotomy position. Initial exploration is undertaken to carefully assess for extrapelvic metastatic
disease. Careful attention is paid to the liver and the abdomen is
assessed for carcinomatous implants. All adhesions are lysed and
the ureters are identified. Ureteric catheters are typically used.
The left colon is mobilized as is the splenic flexure and attention
is focused on the IMA root. If it has not been taken it is mobilized.
An assessment for resectablity is made and if the tumor is deemed
resectable, the IMA, if not previously ligated, is taken high. The neorectum is mobilized posteriorly initially, laterally, then anteriorly.
The areas free from tumor involvement are most easily mobilized
and are approached first. As much easy dissection should be done,
as can be done, to identify landmarks initially. If anterior structures
are clinically involved they are taken en bloc with the neorectum.
It is much easier to take the bladder, seminal vesicles and prostate
en bloc with the neorectum than to try to separate them. If there is
firm adherence to the posterior aspect of the bladder, seminal vesicles or prostate, they should be taken en bloc. If the lesion is quite
low in the rectum and adherent to the prostate or vesicles alone, the
posterior portion of the prostate and/or the seminal vesicles may
be taken without the bladder, but this is much more challenging
technically than proceeding with en bloc cystoprostatectomy. In a
female en bloc posterior vaginectomy and hysterectomy should be
performed with any adherence. Pelvic sidewall involvement is technically difficult to resect secondary to the associated desmoplastic
reaction and loss of planes. The nervi erigentes and internal iliac
arterial and venous branches can be taken. However, back bleeding from distal venous branches can be torrential and difficult to
control despite proximal ligation.
The dissection is completed to the pelvic floor circumferentially
and a decision is made as to whether sphincter preservation is possible. It is sometimes feasible to preserve the sphincters even if cystoprostatectomy is performed and a coloanal anastomosis may be
possible. A double stapled technique, transabdominal-transanal
hand sewn technique, low Hartmann, or APR may be necessary.
Any suspicious areas for microscopic involvement are treated with
IORT after specimen removal. IORT for posteriorly based or pelvic
sidewall based areas is relatively easily technically performed with
appropriate positioning of a shielding cone. However, it is technically challenging to dose anteriorly unless APR is performed and
the patient is moved to the prone position. This allows dose delivery via a cone placed through the perineal wound.
If there is gross tumor left behind, we typically will not perform an anastomosis. However, if there is a suspicion of potential
microscopic disease only, and this is treated with IORT, we will
consider reanastomosis, assuming adequate sphincters and an
appropriate margin. All coloanal anastomoses are covered with a
proximal diverting loop ileosotomy.
As noted above in the case of adherence only posteriorly, IORT
is usually performed after the specimen is withdrawn. If the
sacrum is clearly involved with tumor, sacrectomy is considered.
The dissection for sacrectomy begins posteriorly, typically with
internal iliac artery and vein ligation abdominally. The remainder of the dissection is completed, laterally then anteriorly. An
osteotomy may be started, typically with the help of an orthopedic consultant. The ostomy is created, the abdomen closed and
the stoma matured. A plastic surgeon may be involved prior to
ostomy creation if a rectus abdominus myocutaneous flap for
perineal defect reconstruction is considered. The remainder of
the sacrectomy is performed after turning the patient to the prone
position. Reconstruction is completed frequently with the aid of
the plastics consultant. Other flaps such as a gluteus myocutaneous flap may be considered.(10)
Expected Outcomes
Local recurrence after proctectomy occurs in 2.6 to 32% of
patients.(2, 28, 29) Chemotherapy and radiation offer palliation
only with median survivals reported between 10 and 17 months.
(2, 28, 30) It is estimated that ~50% of patients will present with
local recurrence only, without distant metastasis.(2, 31–33) The
concept of radical excision for potential cure of recurrent rectal
cancer is not new and was reported by Dunphy in 1947.(2, 34)
The literature has expanded in recent years with multiple larger
series reported with 5 year survivals ranging from 14 to 44%
(see table).(2, 5, 10, 11, 13, 35–44) In fact in a subset of patients
with R0 resections reported by Valentini a 67% 5 year survival
was noted.(15) Long-term outcome is directly related to ability
to clear local tumor in the pelvis and the absence of metastatic
disease. Surgical intervention alone typically does not suffice. It is
clear that a multidisciplinary approach is essential in these complex patients. Case controlled data suggests IORT can decrease
local recurrence and play a role in a potentially curative treatment algorithm even in the presence of a microscopically positive margin.(45–48) In the presence of gross persistent disease it
does not appear as effective, but may be useful in a multidisciplinary approach with pre and/or postop chemo-radiotherapy.
(27) Preop chemo-radiotherapy and postop chemotherapy are
typically employed as outlined previously.
Heriot et al. hypothesize that a significant number of patients
that could be candidates for resection likely are not operated
secondary to perceived excessive morbidity and mortality associated with these difficult cases.(2) They argue, however, that in
carefully selected patients, resection is not only safe and reasonable, but indeed offers the only chance of cure. They advocate an
extended radical en bloc resection of all involved or potentially
involved structures in the pelvis. The extent of resection involves
all involved areas of tumor/desmoplastic reaction. This radical en
bloc extended resection is to include involved common or external iliac vessels with reconstruction, wide resection of the pelvic
sidewall, sacrectomy, and or partial resection of the bony pelvis if
clinically involved.(2) In their series IORT was utilized selectively
and chemo-radiotherapy was typically employed. In this exceptional series of 160 patients, only 7 were found to be unresectable.
Overall 5 year survival was 36.6% and cancer specific survival was
41.5% with a mean follow-up of 32 months. Unfavorable factors
indications and outcomes for treatment of recurrent rectal cancer
Anastomotic or perineal wound R0 90%
Anastomotic or perineal and anterior R0 72%
Lateral and/or posterior component R0 43%
Iliac vessels R0 17%
N=119 patients with pelvic recurrence of colorectal cancer.
Source: Moore et al. (9).
associated with impaired survival included a lymph node positive
primary tumor, margin involvement, use of IORT (likely secondary to use only in more difficult tumors), and lateral recurrence
(sidewall involvement). Perioperative mortality was 0.6% (1/160)
secondary to hemorrhage, morbidity was 27%.(2) They note
the need for extensive multidisciplinary involvement and planning, and comment that this surgery is not for the “occasional
participant”.(2) These data and others confirm that the overriding principle of this challenging surgery is to attempt to obtain
clear surgical margins.(2, 11, 49, 50) Others have pointed out
that the pattern of pelvic invasion and the numbers of points of
fixation have adverse prognostic implications.(9, 51, 52) Heriot
et al’s data points to the difficulty in obtaining a clear margin
when the pelvic sidewall is involved which was noted by Moore
et al. in the Memorial Sloan Kettering experience.(2, 9) They
noted that axial (anastomotic or perineal recurrences) or anterior based recurrences were more easily resected and had better
prognosis than lateral recurrences. This was felt secondary to the
difficulty in obtaining a clear margin with lateral recurrences secondary to the confines of the bony pelvis and the difficult vascular problems encountered with the iliac branches along the pelvic
sidewall. See (Table 28.1).(9) Other factors associated with low
likelihood of R0 resection include presentation with pelvic pain,
radicular pain, or hydronephrosis.(5, 9)
The use of additional preop radiation therapy in those already
radiated has been questioned for fear of introducing excessive
morbidity. Vermaas et al. note that the addition of a 50 Gy preop
dose was associated with a statistically significant improvement
in local control without increased morbidity in those eventually undergoing resection compared to a historical group which
did not receive additional preop radiation.(53) Those that had
a complete response (10%) had an improvement in survival as
well. No chemotherapy was used with the preop radiation.(53)
Dresen’s data also suggests that reirradiation is safe if the interval
to reirradiation is >6 months and the small bowel can be excluded
from the field.(11) They recommend a 30–40 Gy preop boost in
combination with chemotherapy and introperative radiation if
necessary.
They noted an increased ability to perform an R0 resection in
those reirradiated versus those who were not (64.9% vs. 29.2%,
years (58.7 vs. 17.8%, p < 0.001). As noted previously, others have
confirmed similar results.(13) It has been our practice to offer most
patients a preop radiation boost combined with 5 FU based chemotherapy in those presenting with recurrent tumors as well, although
our numbers do not allow meaningful outcome comparisons.(27)
Table 28.2 compares outcomes reported in several larger
series. The interpretation of the data from these series is difficult
Author N 5 year Survival Morbidity Mortality
Dresen (11) 147 31.5 59 4.8
Heriot (2) 160 36.6 27 0.1
Maetani (35) 36 28 – –
Wiig (36) 47 18 38 4
Yamada (37) 64 23 50 2
Jiménez (38) 55 28 78 5
Kecmanovic (38) 28 17 43 10
Ike (40) 45 14 77 13
Lopez (41) 19 44 67 0
Kakuda (42) 22 12 68 5
Moriya (43) 57 36 58 4
Vermaas (44) 35 16 70 3
Mohiuddin (12) 34 22 – 0
Wanebo (10) 61 31 38 8
Valentín (11) 59 39 – –
Source: Adopted from de Wilt et al.(5)
as they represent a diverse mix of presentations and treatment
algorithms. Some included combinations of patients with locally
advanced primary tumors as well as recurrent tumors. Some used
extended exenterative resections with en bloc resection of adjacent bony and vascular structures and some did not. Some had
preoperative radiation boosts, some did not. Some utilized IORT
and some did not. The five year survivals in the series outlined
ranged from 12 to 44%. The small numbers and mix of patients
makes comparisons of different approaches to the close surgical
margin impossible. It is not clear from the data whether extended
en bloc resection of bony or vascular structures should be performed or IORT should be preferred in these cases. However,
although morbidity (27 to 78%) and mortality (0–13%) is significant regardless of approach, the overriding theme in these series
remains that a multimodality approach including surgery offers
the only opportunity for cure, and that those patients having
the longest survival undergo R0 resection. There is a suggestion
that similar long term survivals and rates of local control can be
obtained when IORT is utilized in patients with a microscopically
involved or close margin.(5, 27)
TREATMENT OF COLORECTAL LIVER METASTASIS
Liver resection for the treatment of metastatic colon cancer was
first described by Lortat- Jacob in 1952 (54–56) and in the US
by Woodington in 1963.(57) Fifteen years later, Attiyeh (58)
described a series of 25 patients who had undergone liver resection for metastatic colon cancer with a 40% five year and a 28%
ten year survival. Although these early series were highly selected
patients, no other therapy to date provides a better therapeutic
benefit than complete resection of isolated metastatic colon cancer to the liver.
Historically, treatment with 5 fluorouracil and leucovorin for
metastatic colon cancer resulted in 5 year survival rates of less than
5%.(59, 60) The addition of Oxaliplatin and Irinotecan based regimens have improved the median survival for patients with stage IV
disease to over two years (61), however 5 year survival rates have
improved outcomes in colon and rectal surgery
remained below 10% (62). Interestingly in stage 3 disease, analysis of patient survival reveals three groups with markedly different
survival rates. The difference in survival rates for the groups was
found to be dependent on extent of nodal involvement with survival ranging from 44% for stage IIIc patients, that is four or more
positive lymph nodes to 83% for stage IIIa, 1–3 positive lymph
nodes.(63, 64) The ability to identify a subpopulation within a
cancer stage which has a potential for improved survival also holds
true for patients with stage IV colon cancer patients.
Patients with isolated liver metastasis from their colon cancer
treated with multimodality therapy including surgery have a significantly improved 5 year survival when compared to patients
with isolated liver metastasis treated with chemotherapy alone
(65–67) or patients with nonresectable stage IV disease.(68)
Approximately, 150,000 new cases of colon cancer were diagnosed
in 2007.(69, 70) It has been estimated that almost 20% will have
isolated liver metastasis at time of presentation and for patients
presenting with local disease, 25% will eventually develop isolated
liver metastasis and be eligible for resection.(69, 71) Because of
the marked improvement in survival for patients with metastatic
colon cancer to the liver treated with resection, identification of
patients who are candidates for surgical therapy and appropriate
management is of paramount importance.
Assessing Resectability
Evaluation to determine whether a patient with colon cancer metastatic to the liver is a candidate for hepatic resection depends on
1) medical comorbidities of the patient, 2) anatomic extent of
disease in the liver and 3) the presence or extent of extrahepatic
disease. Before deciding whether a patient is a nonoperative candidate, thought should be given to downstaging with systemic or
hepatic artery infusional chemotherapy (72–74), combined resection and radiofrequency ablation (75, 76), staged resection (77)
and in the case of extended resections, portal vein embolization
(78, 79). While prior dogma limited candidates for resection based
on tumor margins, tumor number or extent of extrahepatic disease (80), the current National Comprehensive Cancer Network
(NCCN) guidelines describe outcome objectives to determine if a
patient may benefit from resection. The goals currently included in
the current NCCN guidelines focus on these ten points:
1) resection must be feasible based on adequate liver reserve
after resection and anatomic extent of disease 2) debulking is not
recommended, 3) there should be no unresectable extrahepatic
sites, 4) if tumors are downstaged, than all original sites must
be resectable, 5) resection should be the treatment of choice, 6)
ablations can be considered if all disease is treatable, 7) solitary
lesions have a better prognosis than multiple lesions, 8) arterial
embolizations should be performed only on a clinical trial, 9) the
primary tumor must have been resected for cure, and 10) reresections are possible in selected candidates (81).
Before surgical resection of liver metastasis, the patient
requires a full staging evaluation and risk stratification to determine operative risk. Staging evaluations include a CT scan of the
chest, abdomen, and pelvis obtained with oral and intravenous
contrast if possible. If poor renal function precludes IV contrast
administration for CT scanning then staging can be performed
with a noncontrasted CT scan of the chest and other imaging of
the abdomen. If the patient has mild, chronic kidney disease stage
1–3 (glomerular filtration rate > 30) than MRI scanning can be
helpful to fully evaluate the extent of disease in the liver.(82, 83)
Patients with advanced renal dysfunction, in which gadolinium
poses a significant risk, may require hepatic evaluation with
either transabdominal or laparoscopic ultrasound.
While prior studies have suggested precluding patients with
greater then three liver metastasis from consideration, outcomes
data would suggest that overall tumor burden, vascular involvement and extrahepatic spread may be more important in the
decision algorithm.(84) The addition of (18F) fluoro-2-deoxyD-glucose (FDG) PET scanning to CT or MRI staging has assisted
in identifying patients with occult extrahepatic metastasis who
may not benefit from surgery.(85–87) In these studies, the addition of FDG-PET was useful in identifying 12% of patients who
were not surgical candidates, and altered surgical therapy in an
additional 23% who underwent operation. Interestingly, the ability to detect lesions less than one centimeter in the liver was only
25% in the data by Fong et al. and the recurrence within the first
year was 40% indicating even with PET scanning that a significant
number of liver lesions were missed on imaging. Other investigators have demonstrated that addition of FDG-PET has increased
both overall and disease free survival at 5 years with overall actuarial five year survival of 58% for patients which demonstrated
no extrahepatic PET positive lesions on preoperative imaging.
More recent reports have demonstrated the ability of recent
chemotherapy to affect the ability of FDG-PET to identify viable
tumor.(88–91) In a study by Akhurst et al. evaluating the sensitivity of FDG-PET, patients undergoing surgery for resection of
metastatic colon cancer were evaluated by PET imaging. Thirteen
of 42 patients had received chemotherapy within three months
of surgery and 29 /42 had not. In the group which had received
chemotherapy 37% of lesions were PET negative as compared to
27% of the lesions in the no chemotherapy group. Interestingly,
no tumor >1.2 cm was missed in the group without chemotherapy while some tumors as large as 3.2 cm were PET negative after
chemotherapy. In this study, 92% of all tumors smaller than 1 cm
were undetected by PET imaging. In a study by Carnaghi et al. PET
imaging sensitivity dropped to 62% after chemotherapy and was
as low as 18% for lesions under 1 cm in size. Taken together, these
data would support use of PET imaging prior to chemotherapy
to fully stage the extent of disease and nonreliance on conversion
of intrahepatic lesion to PET negative on decision making concerning hepatic resection. Extrahepatic disease remains a relative
contraindication for liver resection although published studies
would support resection in limited cases if all extrahepatic disease
can be resected (92). Several studies have demonstrated decreased
survival rates for patients resected with positive portal or hepatic
artery lymph node metastasis (93, 94). Unfortunately, these studies do not comment on the use of adjuvant therapies after surgery
or whether patients had chemotherapy sensitive disease prior to
resection. In our practice we will offer resection to patients with
extrahepatic lymph node metastasis if the disease is localized to
the porta hepatis, is completely resectable at the time of surgery,
and had a favorable response to medical therapy. In addition to
staging studies, a medical workup would obviously include cardiac
evaluations for those displaying cardiac risk factors and pulmonary
indications and outcomes for treatment of recurrent rectal cancer
function testing for those with significant lung disease or smoking
history. Cardiac stress echo testing can be performed for patients
with significant cardiac risk factors. Because there is considerable
variability between patients, decisions as to whether a patient is a
candidate for resection must take into account the patients overall
medical status and the type of procedure being planned.
Decision making regarding operative timing can be complicated by presentation of the disease. For patients who present with synchronous asymptomatic colon and liver disease,
no single treatment algorithm has been established in the field.
Acceptable treatment protocols range from complete resection of
the colon and liver disease at one operation (95–97) to neoadjuvant chemotherapy followed by synchronous or staged colon
and liver resection (98–102). Outcomes from studies evaluating
simultaneous liver and colon resections have suggested higher
incidences of recurrence and lower overall 5 year survival rates
in patients undergoing combined resection. Other authors have
recommended a waiting period of 3 months between colon resection and liver resection in order to better select patients for surgery (103, 104).
Regardless of the manner in which patients undergo resection, the efficacy of post operative chemotherapy has recently been
shown to provide a small survival advantage.(105, 106) Treatment
algorithms for resection of metachronous lesions have suggested
resection followed by either chemotherapy or hepatic artery infusional (HAI) therapy.(81) Several studies have demonstrated a
improvement in disease free and overall survival with the use of
HAI (72, 74, 107–109), however, prior studies demonstrating lack
of efficacy, introduction of newer chemotherapeutic regimens
and high rates of mechanical problems with the pumps (110),
have limited there widespread use.
Patients who are candidates for liver resection and are on chemotherapy regimens including irinotecan, oxaliplatin, or bevacizumab
should be evaluated for hepatic dysfunction prior to surgery.(111)
Recent reports have associated the use of irintotecan-based chemotherapy regimens with hepatic steatosis and oxaliplatin based
regimens with sinusoidal dilatation.(112, 113) These may occur
in 20–30% of patients on therapy. There has been concern that
Bevacizumab may potentially increase postoperative complications
and mortality due to its effect on vascular endothelial growth factor.
In a recent study evaluating 81 patients receiving chemotherapy with
Bevacizumab to 44 patients receiving chemotherapy alone, no significant increase in complications were seen after liver resection (114),
although increased morbidity and mortality has been reported with
patients having increased steatosis at time of resection (113, 115).
Preoperative preparation often is related to the extent of liver resection planned. For patients with bilobar disease treatment plans need
to be formulated to determine if the tumor can be treated all in one
operation or whether sequential procedures will be needed to treat the
full extent of the disease.(78, 99) In cases of bilobar disease preference
should be given to resection if possible. Occasionally, treatment will
involve a combination of resection with the possibility of radiofrequency ablation of remaining contralobar lesions. If the tumors are
located near or on the middle vein, and resection will involve removal
of more than 70% of the liver, then thought should be given to preoperative portal vein embolization to allow for hypertrophy of the
remaining segments prior to tumor removal. Studies have shown
decreased morbidity and mortality in patients undergoing preoperative portal embolization before major surgical resection.(79, 116–119)
In order to determine the resectability of the patient, factors
such as extent of disease, number and location of lesions, synchronous or metachronous presentation, and exposure to previous
therapy should all be taken into account. Special consideration
should be given for patients with rectal cancer with synchronous liver metastasis. Current standard of care for primary rectal
cancers remains combined chemotherapy with rectal and pelvic
radiation. The most common regimen would use 5-fluorouracil
for radiation sensitization. The poor response rates of metastatic
lesions from this chemotherapeutic regimen have led some investigators to suggest initial treatment with oxaliplatin or irinotecan
containing regimens, yet local recurrence rates for rectal primaries treated with this regimen followed by resection have not been
well defined. Currently there is no defined standard of care and
the treatment of these patients should be individualized.
Adjuvant Therapies
In addition to surgical resection and systemic chemotherapy, a significant number of alternative liver directed therapies exist. Treatments
including radiofrequency ablation, cryotherapy, microwave ablation,
chemoembolization, yttrium-90 and stereotatic high dose radiation
are alternate tools for site directed therapy.
Cryotherapy has been shown to be an effective treatment
for liver metastasis with or without resection.(120–124) When
initially introduced, complications including liver fracture, bleeding, systemic cytokine induced lung injury, myoglobinuria and
pleural effusion reduced its overall popularity and widespread
use. Radiofrequency ablation was initially described in the treatment of metastatic colon cancer in 1996.(125) While a much less
morbid procedure than resection or cryotherapy, limits to the size
of treatable tumors and higher incidence of recurrence as well as
lower overall survival when compared to resection have prevented
this from replacing surgery as the gold standard for therapy.(126,
127) Microwave ablation, chemoembolization and stereotatic body
radiotherapy remain investigational in the US at this time. Injection
of yttium-90 labeled beads into the hepatic artery of tumor containing segments of liver has received approval by the Federal Drug
administration for the treatment of unresectable colon cancer
metastasis to the liver. Current trials are underway to determine the
role of this therapy in downstaging liver metastasis and as primary
therapy with chemotherapy in the adjuvant setting.
Operative Approach
Patients who have single or peripherally located metastatic lesions
may be candidates for laparoscopic liver resection. Anteriorly located
lesions in either the right or left lobes can often be approached in the
supine position. A full explanation of all the techniques and equipment available for resection are beyond the scope of this chapter
but have been summarized recently in a review.(128–130) In our
practice, we find the LigaSure™ Vessel Sealing System (Valley Lab,
Boulder, CO) and the TissueLink Endo SH2.0™ Sealing Hook (SH)
(TissueLink Medical Inc., Dover, NH). to be the most useful for
laparoscopic resections. Port placement often varies significantly
improved outcomes in colon and rectal surgery
depending on the location of the lesion to be removed. Addition
of the hand port has been described to assist with right lobe liver
resection and may be useful depending on the body habitus of the
patient, the location of the tumor and the characteristics of the
liver, i.e, underlying fibrosis, steatosis, etc. In general, a 5–15 mm
port is often placed in the plane of the liver dissection to facilitate stapling of the liver. The initial step of the procedure involves
localization of the tumor and demarcation of the liver division
plane. Laparoscopic ultrasound is needed to define the location
and extent of the tumor and to map the appropriate vascular
structures. The surface of the liver is marked in the division plane
often with electrocautery. The margin status for resection has been
a topic of considerable debate in the literature. Several studies have
suggested that no significant margin is necessary as long as the capsule of the tumor has not been violated during the resection. Other
studies have suggested higher local recurrence rates when tumor
was present at the resection margin, regardless of the method of
resection.(131, 132) Resection can be performed with or without
hilar control. Vascular clamping before resection is not necessarily needed. Parenchmal dissection can be performed with various
energy sources. Venous bleeding is controlled by adjusting the pressure of the pnuemoperitoneum and the central venous pressure.
The portal vein and the hepatic vein are taken with a laparoscopic
GIA stapler using 2.5 mm staples.
The approach to posterior lesions can be more difficult.
Descriptions on resection techniques utilizing anterior and lateral approaches to these lesions have been described (133, 134).
Resection principles are similar.
The majority of resections are performed using an open technique. Open approaches may be more appropriate if there are
multiple lesions, if the lesions involve or abut the major portal
structures or if obtaining a margin on or near a hepatic vein may
be difficult. For patients with bilobar disease or larger primary
tumors, laparoscopy at the time of, but prior to open resection
may help differentiate resectable from nonresectable patients.
Laparoscopic ultrasound is an invaluable aid in determining the
number and extent of hepatic metastases. Laparoscopy before
laparotomy in patients at high risk to have unresectable disease is
helpful to limit the patient morbidity and recovery time.
The approach to open resection differs from laparoscopic in
that vascular control is often mandatory in limiting operative
blood loss. Exposure is obtained with either a Mercedes incision
or via a Chevron approach. Use of the Bookwalter, Thompson or
upper hand retractor often aids in exposure. Again, full descriptions of resection techniques are beyond the scope of this chapter (reviewed in (135–137)) but in general formal resections do
not confer survival advantage. Studies which have evaluated long
term survival would suggest that liver conservation during the
resection of metasatic disease does not increase the overall recurrence rates and may confer a better long-term outcome.(138)
Expected Outcomes
Early series looking at survival of patients undergoing liver resection have demonstrated 5 year survival rates of 25–37%.(139,
140) Further screening patients with FDG - PET imaging has
resulted in increasing the sensitivity of identifying patients with
extrahepatic disease. Better patient selection has resulted in five
year survival rates of almost 60%.
Even with better imaging most patients will develop recurrent
disease of which half will have liver only recurrence. These patients
can safely undergo repeat resections with equivalent outcomes.(141–
143) Addition of adjuvant chemotherapy after resection has been
recommended as part of the NCCN treatment recommendations
based on improvement in survival for patients treated with 5-flourouracil or oxaliplatin based regimens.(61, 105, 106) Treatment of
patients with synchronous colon and liver lesions with simultaneous liver and colon resection have demonstrated increased risk of
early recurrence and lower overall disease free survival. These data
were from studies conducted before treatment with current chemotherapy based adjuvant therapies. Treatment of patients with
adjuvant therapy prior to liver resection has been advocated by
several different authors as a way to identify favorable, chemotherapy sensitive tumors. Other authors have argued that resistance to
chemotherapy is a poor prognostic sign even in resectable disease.
(144) Multiple studies have demonstrated the ability to downstage
metastatic tumor burden in the liver by neoadjuvant therapy either
given systemically or by hepatic artery infusion. Rates of converting
unresectable colorectal liver metastasis to resectable disease vary
from 16% to 51%.(101, 145)
One inherent problem with current studies evaluating the efficacy of various treatments for patients with stage IV disease is the
ability to control for the extent of disease in the treatment group.
Similar to the patients with stage III disease who can be divided
into three separate categories based on extent of nodal involvement, stage IV patients represent a spectrum of disease burden
requiring a more complex substaging to accurately identify and
evaluate different treatment options. Unfortunately, this currently
does not exist. Several authors have reported risk factors which correlate with patient outcome. In 1997, Fong et al. reported on scoring system which included points awarded for size of the tumor,
disease free survival<12 months, number of tumors >1, node positive disease, and a CEA greater the 200. For patients with 0–1 point,
2–3 points, and 4–5 points, five years survival was 50%, 20% and
10% (146). Studies to evaluate the use of this and other scoring systems when applied to an independent population proved unsuccessful and have led to the development of other nomograms for
predicting disease-specific survival.(147, 148) Although predicting
outcome is useful, a staging system is needed to be able to evaluate
treatment outcome in similarly controlled groups. One such system has been recently proposed.(149)
Significant progress continues to be made in the treatment of
metastatic colon cancer to the liver. An aggressive multimodal
approach between surgical, medical and radiologic specialties is
required for optimizing outcome. While treatment algorithms continue to evolve, there is one tenet that remains constant: patients
need to be constantly reevaluated for the appropriate medical or
surgical care and that aggressive intervention can significantly
improve disease free and overall survival.
COLORECTAL LUNG METASTASIS
When colorectal cancer (CRC) is confined to the bowel, the workup and management are usually fairly straight forward. When
indications and outcomes for treatment of recurrent rectal cancer
there is disease (suggested or proven) outside the bowel, the management becomes debatable. As early as the 1980s and 1990s, CRC
which had spread to the liver or lung was considered unresectable
at most hospitals, and therefore incurable. There are reports of
metastectomies going back to the 1940’s (150), but this approach
was not widely accepted. As new technologies developed, such as
chemoembolization, cryotherapy, radiofrequency ablation, and
safe techniques for metastectomies, aggressive medical centers
began resecting or ablating metastatic foci once the primary site
was controlled. These centers then began finding that in some situations metastectomy offered a chance at cure and long term cancer free survival. Those surgeons who pushed the envelope even
further began finding that repeat lung resections for second and
third recurrences can still offer chances at cure.(151–154) Cure
rates for metastectomies were not high, and most patients eventually developed further metastatic deposits and succumbed to
their disease, but a noticeable percentage maintained their disease
free state and lived normal life spans. From the patient’s perspective, this was a tremendous leap. Imagine the difference between
being told you have almost no chance of cure and will probably
die of cancer in the next few years, to being told that with some
extra surgery you may have a 25% chance of cure. Suddenly 25%
sounds like a wonderful number. In a day when cancer still is a
major cause of pain and suffering, we applaud those who work to
give us further means of saving patients, and will review some of
their work, as well as explain our approach to managing known
CRC with known or suspected lung metastases.
Assessing Resectability
The first step is finding and working up lung nodules. Suspected
lung mets can be found before or after the CRC is found. Most
commonly the bowel cancer is found first. Preoperative chest
x-rays may show an asymptomatic lung mass, or staging CT chest/
abdomen/pelvis +/- PET scan may show the suspected lung mass.
If the lung mass is seen on preoperative chest x-ray, then CT/PET
is recommended. Although biopsy and pathologic examination of
tumors is the gold standard for differentiating malignant nodules
from benign nodules, the radiographic characteristics can help.
Primary lung cancers tend to have irregular, spiculated borders, and
if >8 mm in diameter, most state-of–the-art PET scanners should
start to show PET activity. There are, of course exceptions to this.
Primary carcinoid tumors of the lung have smooth borders and
have low to no PET activity. Luckily these tend to be slow growing,
and if not biopsied right away, can be followed with serial scans
until growth is confirmed. Bronchoalveolar lung cancer (a variant
of adenocarcinoma) can present as a mass, but can also appear with
an infiltrative pattern which is often read as pneumonia, initially.
Failure to improve after a course of antibiotics, or lack of any recent
or current infectious symptoms in the patient should increase your
suspicion for cancer. Multiple smooth bordered nodules of varying
sizes, especially in a patient with a known CRC, tend to be metastases. PET activity should start to show in colorectal metastases
greater than 10 mm. Large (>10 mm) lung nodules without PET
activity in the presence of a PET avid colorectal cancer are still concerning, but could very well be non-malignant processes such as
rounded atelectasis, scar, or granulomatous disease. If old radiographs, especially CTs, are available, then these should be viewed. If
the suspected nodules are not new, and have been present for more
than 2 years without increasing in number or size, then the likelihood of metastatic disease or primary lung cancer is extremely low.
Any nodules that are new or increasing in size are suspect.
Once the lung nodules are found, the next step is deciding what
to do with them. Most CRC patients are middle aged to elderly
and a good proportion have smoking histories. We need to be just
as concerned about a second primary lung cancer as we are about
metastatic disease. Once again, the radiographic characteristics can
help. As stated before, multiple, smooth bordered, PET avid nodules are probably metastatic CRC, but intrapulmonary metastases
from a lung cancer are still possible. A solitary PET avid lung mass
several centimeters in size, without any other suspicious metastatic
deposits either intra or extra-thoracic would be suspicious for a
primary lung cancer. While CRC can spread to the hilar, internal
mammary, and mediastinal lymph nodes, the presence of nodal
enlargement >10 mm would also make us suspect lung cancer
more than CRC. Differentiating lung cancer from CRC is important because the survival of the cancers is different, and knowing
the patient’s prognosis may affect the aggressiveness of treatment
for the other cancer. For example, let us imagine that two nodules
are found in different lobes, with no other suspected sites of metastases, in a patient with proven CRC. If both of these nodules are
resected and proven to be metastatic CRC, then aggressive management of the primary cancer is warranted, since long term survival
may be 25–40%. On the other hand, if biopsies of the lung nodules show primary lung cancer with an interlobar metastasis, then
the patient has stage IV lung cancer, and overall survival is usually
measured in months to a couple of years, and less aggressive CRC
management might be appropriate. If the PET scan shows suspected disease in other extra-thoracic and extra-abdominal sites,
such as bone lesions, then these areas need to be biopsied before
embarking on lung resections. Usually CT guided biopsies of suspected bone mets are safer and easier than lung resections.
Who to operate on, and in which order to operate (bowel or lung
first) can be tricky. Patient selection for lung surgery involves several
factors. These include 1) exclusion of other sites of metastatic disease 2) adequate lung function for resection based on pulmonary
function tests and clinical exam 3) ability to control intra abdominal disease. Excluding extra-thoracic and extra-colonic metastases
is critical. Spread of CRC to sites other than the liver and lung, such
as the bone, would preclude performing thoracic resections. If the
only sites of disease are the bowel, liver, and lung, and the abdominal surgeons feel that curative resections can be performed on these
two organs, then curative lung surgery is considered.(152, 153) In
order to resect portions of the lung, the patient must have enough
residual lung function not only to support life, but also allow for a
quality of life acceptable to the patient. Pulmonary function tests
are usually easy to obtain. We base our decision for resection on the
FEV1 (forced expired volume in 1 second), the diffusion of carbon
monoxide (DLCO), and the clinical exam. If after viewing the CT
chest and deciding on the extent of resection, the predicted postoperative (ppo) FEV1 is > 0.8 L, then surgery is considered. If the predicted postoperative DLCO is >40% of predicted, then surgery is
considered.(155) These formulas should by no means be followed
blindly. Just, if not more, important is the clinical evaluation of the
patient. As a general rule, if the patient can climb three flights of
improved outcomes in colon and rectal surgery
stairs without having to stop due to shortness of breath, then they
should be able to tolerate a pneumonectomy or equivalent resection. I also ask if they can walk around the block without stopping.
Usually the PFT numbers will support the patient’s answers on the
clinical exam. Sometimes they don’t, and I tend to trust the clinical
exam over the numbers. For example, we had a patient whose FEV1
and diffusion capacity were >100% of predicted. Based on those
numbers a pneumonectomy should have been possible. When seen
in clinic he could barely walk from the waiting room to the exam
room due to dyspnea and desaturation. Conversely, one patient
had a PFT FEV1 of 0.7 L, but biked 5 miles a day with her husband
without oxygen. I based my decisions on the clinical evaluation,
did not operate on the first patient, and successfully performed a
lobectomy on the second patient. Some patients will be borderline
resectable based on PFTs and clinical exam. A split perfusion V/Q
scan can then be performed. With this test the nuclear medicine
doctors can estimate which parts of the lungs are performing what
percentage of the work. This allows for a more exact calculation
of ppoFEV1. For example, if a tumor is obstructing a lobar bronchus, then the V/Q scan should show that that lobe is contributing
almost nothing to the overall lung function, and resection can be
performed with no decrease in PFTs.
Operative Approach
As mentioned above, part of the decision is how much lung needs
to be taken out. Obviously, if we are aiming for cure, then all sites
of pulmonary metastases need to be addressed. Metastatic disease
is different than primary lung cancer. For lung cancer, anatomic
resection is the gold standard (156), with lobectomy being preferred
(unless pneumonectomy is required) over segmentectomy, and
segmentectomy preferred over wedge resection. Metastectomies are
the converse. Lung sparing is very important, especially since the
chance for future metastases is high. Also, larger anatomic resections of metastases offer no survival advantage, so wedge resections with negative margins are adequate. Anatomic resections
are considered when the size or position of the cancer precludes a
wedge resection. Tumors on the periphery of the lung <3 cm in size
can usually be excised by a wedge. Larger masses can sometimes
be resected by a wedge, especially if in the inferior lingula. Large
tumors, those positioned several centimeters deep to the visceral
pleura, mid basilar tumors, or those near the hilum will probably
require a segmentectomy, multiple segmentectomy (ex. basilar segmentectomy, lingular sparing left upper lobectomy), or lobectomy.
Pneumonectomy will be described later. With this information a
thoracic surgeon can estimate the percentage of overall lung to be
resected, and calculate the ppoFEV1 and ppoDLCO.
Once it has been decided that the patient could undergo lung
surgery, the order of surgery is decided upon after discussion
between the colon, hepatic, and lung surgeons. If the thoracic
metastectomies can be performed with quick wedge resections
with low morbidity, then I would operate first if my finding will
change the other surgeons’ resections. If larger, more risky thoracic resections are needed (especially pneumonectomy), then
I would prefer the abdominal surgeons to proceed and make sure
that the primary tumor and intraabdominal metastases can be
controlled first. If the resection pathology is favorable and the
patient has recovered, then definitive lung resection is done. It is
nice for the patient if combined surgery can be performed. For
video-assisted thoracoscopic surgery (VATS) wedge resections
I feel comfortable removing the thoracic disease and then letting
the abdominal surgeons proceed at the same setting. The VATS
approach allows for less pain and earlier mobility, and usually
doesn’t hinder patient recovery from the laparotomy. If the lung
surgery requires a thoracotomy, lobectomy, or pneumonectomy,
I prefer not to operate at the same setting, as postoperative recovery becomes much more difficult for the patient.
Video Assisted Thoracoscopic Surgery (VATS)
A relatively new factor that has changed our approach to metastectomies is the VATS, or video assisted thoracoscopic surgery, technique.
Traditionally lung resection required a lateral or posterolateral thoracotomy. These incisions are painful, usually involve transecting
the latissimus muscle, require several days of hospital stay to recover
and several weeks or months as an outpatient to recover, and frequently require epidural placement preoperatively for pain control.
As the size of the thoracotomy increases, the chance for chronic pain
increases as well. If the patient recurs on the ipsilateral side, then
repeat thoracotomies are needed. The amount of scar tissue in the
thorax increases after larger dissections, and any redo operation runs
the risk of having to deal with this. Sometimes the lung is so scarred
in that exposure and resection are not possible. Usually, however,
the surgery just takes longer as the scar tissue is dealt with, and may
require even further extension of the old incision to facilitate exposure. Just like surgery in other areas of the body, the longer and more
difficult the dissection, the greater the risk of complications. With
VATS, wedge resections require only three incisions 10 mm or less in
length. Pain is managed more easily and discharge is usually anticipated in 1 to 2 days postop. Changing to lobectomy only needs one
of those incisions to be lengthened to a 3–4 cm utility incision. The
latissimus and serratus muscles are spared, and no rib notching is
needed. We no longer use epidurals, and instead leave a PCA (patient
controlled analgesia) for one day as well as placing a marcaine infuser
catheter in the intercostal space and subcutaneous tissue of the utility
incision. The marcaine pump we use will last for about three days.
On post op day 1 the PCA is discontinued and oral pain meds are
started. Discharge is anticipated on postop day 4–5 to home without any chest tubes. Since the amount of intercostal muscle being
transected during VATS surgery is minimal, chest wall adhesions
with redo operations is usually minimal, especially after wedge resections. Even multiple surgeries on the same side can be managed with
only a short increase in operative time to take down adhesions, and
often the same incisions can be used.
Expected Outcomes
Now that we know how to work up a patient for lung surgery, decide
if they can tolerate lung surgery, and understand the latest approach
to lung resections, we need to review our chances for helping these
people survive metastatic CRC. We will review a select number of
studies. The Mayo Clinic, Rochester, reported in 1992 their experience with 139 consecutive lung resections for metastatic CRC.(154)
Resections were performed via wedge resection in 68, lobectomy in
53, and more extensive resections including pneumonectomy in 18.
During follow up, 19 patients recurred in the lung and needed repeat
resections. Median follow up was 7 years (range 1–20.4). Overall
indications and outcomes for treatment of recurrent rectal cancer
5- and 20- year survival was 30.5% and 16.2%, respectively. Five
year survival for solitary metastases was 36.9% compared to 19.3%
for patients with two lesions. For those who recurred and required
repeat resection, 5- year survival after the second resection was just
over 30%. Twenty patients had extrapulmonary metastases as well as
lung lesions. Survival after resection for these patients was also 30%.
Interestingly, they noted that patients with prethoracotomy CEA
levels >5 ng/ml had much poorer survival at 5 years compared to
lower CEA level patients (16% vs. 46.8%). This same poor prognostic indicator has been realized by others.(151, 157) Based on their
experience, they supported resection of intra- and extrapulmonary
metastases, even if they recur.
Irshad et al. reported on a 25 year experience, from 1975 to
1999, in which 49 patients underwent curative colorectal surgery
followed by curative thoracic metastectomies. Overall survivals at
5, 10, and 15 years were 55%, 40%, and 25%. Patients with solitary metastases did better, but multiple metastectomies still had a
survival advantage.(158)
One area of debate is how aggressive of a resection should be
performed. More precisely, should a patient undergo pneumonectomy for stage IV colorectal cancer? Pneumonectomy alone carries
a higher mortality than lesser resections, with an operative mortality
around 7%. In centers accustomed to taking care of these patients,
and surgeons who specialize in this procedure, the mortality is lower.
Hendricks et al. looked at 10 cases of pneumonectomy for metastectomy and found 5 year survival of around 45%.(159) Koong et al.
reviewed 133 patients who underwent pneumonectomy or completion pneumonectomy for metastases. Of those patients who underwent R0 resection, operative mortality was 3% and 5 year survival
was 30%.(160) It is our practice to consider pneumonectomy for
metastatic CRC if the abdomen is cleared of disease, there is no sign
of extrathoracic metastases, and the surgical risk is acceptable.
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