All patients with cholangiocarcinoma require individualized
management, the following general treatment recommendations can be
made, depending on whether disease is localized and potentially
resectable, or advanced and unresectable.Surgery provides the only
possibility for a cure. Distal cholangiocarcinomas have the highest
resectability rates while proximal (particularly perihilar) tumors
have the lowest. Treatment of the cholangiocarcinoma has been briefly
discussed:
Monday, July 21, 2008
Treatment of Cholangiocarcinoma
Preoperative preparation
Jaundiced patients require vitamin K.
Resective procedures for cholangiocarcinomas are major procedures and,
therefore, patients should have good functional status especially if they are
elderly.
Preoperative biliary decompression
In general, it is preferable to avoid stents, if possible. Many surgeons find
the presence of any biliary stent a hindrance to determining the proximal tumor
extent intraoperatively. On the other hand, cholestasis, liver dysfunction, and
biliary cirrhosis develop rapidly with unrelieved obstruction. The extent of
liver dysfunction is one of the main factors that increase postoperative
morbidity and mortality following surgical resection.
* The chance of postoperative liver failure may be lessened by preoperative
decompression, especially decompression of the side to be retained.
* Decompression has the dual purpose of allowing that side to recover
function and actually to hypertrophy.
* On the other hand, stents may introduce bacteria and cause cholangitis.
* Selective percutaneous decompression is an accepted strategy in Japan and
multiple stents are often inserted.
A reasonable strategy is to proceed to surgery in younger patients (age less
than 70 years) without serious comorbidities who have been jaundiced for less
than 4 weeks, whose serum bilirubin is less than 10 mg/dL and whose future
remnant liver will be > 40% of total liver mass.
* Also, such patients should not have had biliary instrumentation, which
always contaminates the obstructed biliary tract.
* For the remainder, we routinely decompress the side of the liver to be
retained and wait until the serum bilirubin falls to 3 mg/dL.
Preoperative portal vein embolization
* Because the achievement of histologically negative resection margins is
so critical to outcome, preoperative portal vein embolization (PVE) has been
used in an attempt to increase the limits of safe resection.
* The intent of PVE is to induce lobar hypertrophy in patients who have a
predicted postoperative liver remnant volume of <25>
* By allowing a larger resection volume to be carried out safely, PVE may
permit a margin-negative resection in patients who otherwise would be
considered unresectable because of concerns about insufficient postoperative
residual liver volume.
Treatment
Hilar cholangiocarcinoma
Criteria for resectability The traditional guidelines for resectability of
cholangiocarcinoma in the United States include :
* Absence of retropancreatic and paraceliac nodal metastases or distant
liver metastases
* Absence of invasion of the portal vein or main hepatic artery (although
some centers support en bloc resection with vascular reconstruction)
* Absence of extrahepatic adjacent organ invasion
* Absence of disseminated disease
The goals of surgical resection are to remove the tumour with negative
resection margins and to perform a portal and coeliac node dissection.
* In order to achieve this, hemihepatectomy with resection of the caudate
lobe as well as the suprapancreatic extrahepatic bile duct and the portal and
coeliac lymph nodes is required.
* Resection of the caudate lobe is needed because, when the tumour is
Bismuth 2 or greater, the orifices of the caudate ducts may be involved with
tumour.
* Hemihepatectomy is required when the tumour involves the sectional ducts
(Bismuth 3) on one side of the liver or the artery or portal vein to one side
of the liver.
* Theoretically, resection of a Bismuth 2 tumour could be accomplished by
resection of bile ducts with the caudate lobe but, in practice, negative
margins are much more likely to be accomplished by a hemihepatectomy with
resection of the caudate lobe.
* Therefore, surgical practice has evolved in the past 20 years to the
point at which there is a consensus that virtually all hilar
cholangiocarcinomas should be resected by hemihepatectomy and caudate resection.
* Low-lying Bismuth 1 tumours, in which a negative upper margin can be
obtained on the common hepatic duct, i.e. below the level of the orifices of
the caudate ducts, may be resected without removing liver tissue, but these
instances are uncommon.
Unfortunately, cholangiocarcinomas have a well-known propensity to spread
microscopically for long distances along the bile duct.
* A positive resection margin occurs in 2040% of cases even when liver
resection has been done.
* The resection margin may be extended by dividing through the termination
of the sectional ducts, but there is a limit to how far this can be carried.
* Mobilizing the portal vein in the umbilical fissure aids this manoeuvre
on the left as the bile ducts to the left lateral section pass behind this vein.
* The operation can also be extended by taking the left medial section with
the right liver (right trisectionectomy) or the right anterior section with the
left liver (left trisectionectomy).
* The operation may also be extended by vascular resections.
o Involvement of the portal vein may require replacement of the
anterior wall of this structure or circumferential resection with anastomosis
of the main portal vein to the left portal vein or, less commonly, the right
portal vein with or without an interposition graft.
* It has been proposed to remove the anterior wall of the portal vein as a
routine in order to obtain a higher rate of negative margins.
* This recommendation lacks supporting randomized data and is not routinely
followed.
* Arterial reconstruction of the proper hepatic artery is less commonly
performed.
* Pancreatoduodenectomy is performed in up to 15% of cases in some series
in order to obtain negative lower margins or to remove potentially malignant
nodes.
* Reconstruction of the biliary tract is by a Roux-en-Y hepaticojejunostomy.
* The Roux limb is made at least 60 cm in length to avoid reflux of
intestinal contents into the biliary tree.
Results
The important trends are as follows.
* Portal vein embolization is becoming more common as a preoperative
preparation.
* Some 1550% of patients are found to be unresectable at surgery but, in
recent years, the figure has been decreasing towards the lower limit of this
range.
* More procedures include a major hepatic resection because the chance of
achieving an R0 resection is substantially higher when a major resection is
performed.
* Mortality rates are falling.
Morbidity rates are still high, reflecting the magnitude of the procedure.
R0 resection is necessary for cure; almost no patients who have had R1
resection survive 5 years without recurrence.
Even with R0 resection, the overall 5-year survival is only 2035%.
Factors affecting survival include
* R0 resection,
* en bloc hepatectomy,
* absence of tumour in lymph nodes,
* tumour grade and tumour type with IG type (papillary) having better
survival than other types.
The need to perform a vascular resection is associated with a poorer outcome in
some series. The value of pancreatoduodenectomy is unclear at this time. Most
patients requiring this addition to the procedure have had a relatively short
survival.
Lower duct tumours
The rationale and extent of the procedure is the same as that used for
pancreatic carcinoma.
Distal lesions are usually treated with pancreaticoduodenectomy (Whipple
procedure).
* Often, the tissue of origin of the tumour, i.e. whether pancreatic,
ampullary or bile duct in origin, is uncertain until after the specimen is
examined pathologically and, even then, doubt can remain.
* The main complication of this procedure is a fistula from the
pancreaticjejunal anastomosis, which occurs in 510% of patients.
* Biliary fistulas occur in about 2% of patients.
* Patients rarely die from these complications today because of
improvements in diagnostic and interventional radiology, intensive care and
treatment of infection.
Resection of part of the stomach is no longer required for lower duct
cholangiocarcinoma, although there is little or no difference in short-term
outcome or quality of life between the pyloruspreserving and standard types of
pancreaticoduodenectomy.
* Many patients require pancreatic enzyme replacement after this procedure,
but few become diabetic.
Five-year overall survival in recent case series varies from 16% to 37%, and
results have not improved in the last decade. Overall, the results of
pancreatoduodenectomy for lower bile duct cancer are much the same as those for
adenocarcinoma of the pancreas and unlike those for ampullary and duodenal
cancers, which have a much better prognosis.
Intrahepatic cholangiocarcinomas
The principles of treatment are as for other malignant intrahepatic hepatic
lesions.
* The tumour must be resected with a margin of normal tissue to obtain
microscopically free resection margins (a 1-cm tumour-free resection margin is
the goal), yet leave enough normally functioning liver tissue behind for the
patient to have adequate liver function in the postoperative period.
* The size of the resection may vary from a single segment or less to
resection of three of the four hepatic sections.
* The role of resection of extrahepatic lymph nodes is unclear, but it is
being done with increasing frequency. Lymph node positivity is common in
tumours over 4.5 cm in size, but rare in patients with smaller tumours, and
lymphadenectomy might reasonably be limited to large tumours.
Four recent series of patients with MF intrahepatic cholangiocarcinoma treated
by surgical resection in 60, 35, 52 and 104 patients reported 5-year survival
rates of 29%, 33%, 34%
and 10% respectively.
Multivariate analyses of prognostic risk factors identified -
* symptomatic patient,
* positive surgical margin,
* multiple tumours,
* vascular invasion,
* lymph node metastases
* high microvessel counts indicative of angiogenesis as predictors of poor
outcome.
* Mucin (MUC)4 expression in carcinoma tissues is also associated with poor
outcome in MF intrahepatic cholangiocarcinoma.
Fewer data are available for the less common IG and PI types of intrahepatic
cholangiocarcinoma.
* The IG type has the best prognosis.
Liver transplantation
Liver transplantation has been performed for intrahepatic and upper duct
cholangiocarcinoma, but the results have been disappointing until recently.
* In one series published in 1993,only 3 of 14 patients (21%) lived more
than 28 months after the procedure.
* Even in a more recent series, in which transplantation was performed in
patients with cholangiocarcinoma in the setting of PSC, the 5-year survival was
only 35%.
* While these are not poor results for a visceral cancer, they must be
evaluated with the knowledge that many patients with endstage chronic liver
disease are dying while on a waiting list for liver transplantation, and the
comparative survival rate in this group of patients would be expected to be
about 90%.
* However, two American centres have reported better results for hilar
cholangiocarcinoma.
The Mayo Clinic group reported on 56 patients who entered a trial of liver
transplantation for unresectable cholangiocarcinoma or cholangiocarcinoma in
the setting of PSC.
* The patients were staged by EUS and also by staging laparotomy.
* All patients received neoadjuvant chemoradiation.
* Approximately half the patients were transplanted, with a 5-year
actuarial survival of 82% in transplanted patients.
* The other group using a similar approach achieved a 5-year survival rate
of 50%.
Adjuvant chemotherapy or radiotherapy
One randomized controlled trial of adjuvant therapy using mitomycin C and
5-fluorouracil vs. surgery alone enrolled 139 patients with cholangiocarcinoma
at various levels. There was no survival benefit, although there was benefit in
a group of patients with gallbladder cancer treated with the same regimen.
External beam radiotherapy was associated with improved postoperative survival
in patients with hilar cholangiocarcinoma in one non-randomized trial. However,
patients in the control group were treated at an earlier time period or tended
to be in poor general condition. In an earlier study in which groups of
patients with hilar cholangiocarcinoma were more comparable, external beam
radiation did not result in
improved survival. Intraluminal brachytherapy does not extend survival and is
associated with an increased incidence of complications.
Recurrence of cholangiocarcinoma is often local, suggesting that adjuvant
chemotherapy and/or radiation would be beneficial but, currently, there is no
evidence to support its use outside clinical trials.
Palliation
The purpose of palliation is to relieve jaundice and pruritus and to extend
life.
* Jaundice and pruritus are treated by stenting, usually by endoscopic or
percutaneous means or, less commonly, by surgery.
* Several randomized trials of surgical bypass vs. endoscopic intubation
for lower duct tumours have been published.
* The three earlier trials favoured endoscopic stenting.
* Two of these trials were quite small and, in the third, the surgical
procedures were performed by registrars; surgical complication rates were
unusually high by current standards.
* The reintervention rate was high in the stent group.
* There was no difference in survival.
* In a more recent trial of patients found to be unresectable by staging
laparoscopy, surgical bypass was favoured over stenting with the surgical group
achieving a longer survival.
The current surgical consensus is that a surgical bypass should be performed by
an experienced HPB surgeon in younger patients without distant metastases or
obvious peritoneal disease.
* When unresectability is determined at laparotomy, a double bypass is
performed to decompress the biliary tree and bypass the duodenum, which may
become obstructed.
* Surgical decompression of hilar tumours may also be accomplished by
bypass to the segment 3 duct, the so-called BismuthCorlette procedure.
* This provides decompression of the left liver.
* It is usually only done when a patient is found to be unresectable at the
time of exploration.
Decompression with stents may be achieved by endoscopic or percutaneous means,
with the former favoured because it is less invasive.
* Metal stents are generally used because of improved stent patency rates.
* In the hilum, plastic stents also have the theoretical disadvantage that
their solid walls may block smaller side-branches.
* For lesions below the bifurcation, a single stent will decompress the
entire liver.
* Bilateral stents or forked stents have been used to decompress tumours
obstructing the confluence.
* However, it seems that a unilateral stent is often just as effective
provided that it is placed selectively, based upon a preprocedure MRCP, on the
side of the liver that will result in decompression of the most functional
liver.
* It is essential that the side of the liver not to be stented is not
cannulated as that often results in cholangitis on that side, and this is
associated with much poorer results.
* Should inadvertent cannulation of the side of the liver occur on the side
that was not intended to be decompressed, then it is best to employ bilateral
stents in order to avoid cholangitis.
Intraluminal brachytherapy has not improved results and, as reported in the
adjuvant setting, is associated with more complications.
Photodynamic therapy Photodynamic therapy (PDT) involves the injection of an
intravenous porphyrin photosensitizer followed by the endoscopic application of
light (of a specific wavelength) to the tumor bed. The interaction between
light and the photoagent causes tumor cell death, presumably by the generation
of oxygen free radicals.
* Initial uncontrolled series suggested that in addition to facilitating
biliary decompression in patients with locally advanced disease, that survival
might be improved in patients who underwent PDT.
* It is thought that the survival benefit is related to prolonged relief of
obstruction rather than to any reduction in tumor mass.
* PDT is now being studied preoperatively as a means of improving the
likelihood of achieving a margin-negative resection. Unfortunately, treatment
is not widely available.
Posted by jitendraagrawal2000 at 10:39 PM
http://www.surgerysearch.blogspot.com/
Dr. Jitendra Agrawal, Kanpur, India.
