Research Article
Treatment of Accidentally Diagnosed Gallbladder Cancer after Laparoscopic Cholecystectomy
Skalický T1*, Třeška V1, Liška V1, Molacek J1, Fichtl J1, Skalický A1, Brůha J2, Ferda J2, Mirka H2, Tymkivová L2 and Velková A2
1Department of Surgery, Charles University in Plzeň, Czech Republic
2Department of Imaging Methods, Faculty of Medicine, Charles University in Plzeň, Czech Republic
*Corresponding author: Tomáš Skalický, Department of Surgery, Charles University in Plzeň, Czech Republic
Published: 01 Nov, 2018
Cite this article as: Skalický T, Třeška V, Liška V,
Molacek J, Fichtl J, Skalický A, et al.
Treatment of Accidentally Diagnosed
Gallbladder Cancer after Laparoscopic
Cholecystectomy. Clin Surg. 2018; 3:
2179.
Abstract
Introduction: The aim of the study was to retrospectively evaluate a group of 34 patients who
underwent surgery due to incidental gallbladder carcinoma after laparoscopic cholecystectomy at
the University Hospital Plzeň in 2005-2015.
Cohort: 34 patients after laparoscopic cholecystectomy with an accidental finding of gallbladder
carcinoma in the definitive histological examination were included, not only at our site, but also at
other sites in the Czech Republic. Radical cholecystectomy was performed at our site.
Results: Postoperative mortality in the group was 0%, morbidity was 24%. The most frequent
complications included collection in the post-resection bed and right-side fluidothorax. The 5 year
survival rate was 68% on average, but depended on the tumour staging.
Conclusion: Due to the early stages of incidental gallbladder cancer after LCHE, the patients have a
very good prognosis in a specialized surgical centre after radical surgery.
Introduction
Laparoscopic cholecystectomy is one of the most commonly planned surgeries in the world and
in our country. Chronic cholecystitis and its more severe stages cannot be reliably distinguished
from a tumour - gall bladder carcinoma. No available examinations, such as ultrasound, computed
tomography scan, magnetic resonance imaging, endosonographic examination with FNAB, or the
use of ultrasound with contrast medium, can clearly distinguish a tumour from chronic cholecystitis.
If preoperative examinations indicate a high risk that the gallbladder will be affected by a carcinoma,
in our opinion, we should not operate laparoscopically, with the exception of laparoscopic staging in
borderline operable findings or diagnostic laparoscopies for tumour staging.
However, "uncomplicated" cholecystolithiasis is increasingly more often managed
laparoscopically, where the result of the biopsy may surprise us by malignancy in the gallbladder
wall. If we do not find the tumour during the surgery and we do not immediately attempt a radical
solution, we create a group of patients who are mostly discharged to home care after laparoscopic
cholecystectomy, and the operating surgeon receives a biopsy result confirming gallbladder cancer
only afterwards. The incidence of gallbladder carcinoma diagnosed in such manner ranges in the
reports from 0.35% to 2% [1]. The prognosis of these accidentally found, incidental gall bladder
carcinomas is significantly better than in pre-operatively confirmed tumours. Gallbladder cancer is
two times more common in women than in men, but there are significant geographical differences.
In Norway, the ratio of women to men is 2:1 while in Chile, the ratio of women to men is 2,7:1. In
Europe, the highest incidence is in Central and Southern Europe - Germany, the Czech and Slovak
Republics and Spain; in America the highest incidence is in Central and South America (Chile, Peru,
Ecuador and Colombia), and in North America, a high incidence is stated in the indigenous Indian
population. India, Japan, China and Korea are the Asian countries with the highest incidence [2].
In the case of incidental gallbladder cancer, it is necessary to consider the staging, i.e., T1, T2
and T3, grading of the tumour and the overall condition of the patient, and decide quickly on
complete radical-extended cholecystectomy - i.e., bed resection, sometimes the entire S4 and S5
liver segments, including S1, and lymphadenectomy of the hepatoduodenal ligament, or careful
monitoring of a T1a tumour. A peroperative evaluation of the spread through the ductus cysticus
towards the bile ducts is necessary. The resection line must always be free of the tumour, so that it
is a so-called "R0 resection".
The surgeon should indicate re-operation in the shortest possible
time after the primary surgery - laparoscopic cholecystectomy. The
optimal time is within 1week to 2 weeks after the primary surgery.
Often, we experience a delayed response from the operating
surgeon and the site where the patient is referred to oncology after
receiving the biopsy result, but the oncologist does not have any
type of successful treatment and refers the patient for a complete
radical procedure. This way, we are unnecessarily losing time before
the radical surgery, sometimes up to 3 weeks to 4 weeks. The delay
is undesirable especially in such an aggressive tumour as gallbladder
cancer. Only 4% to 16% of the findings are suitable for radical surgery.
The median 5-year survival rate of all stages of gallbladder cancer is
only 5%.
Patient Group, Method
Patients who had undergone surgery at the department of
surgery due to gallbladder cancer detected during laparoscopic
cholecystectomy between 2005 and 2015 were not retrospectively
included in the study if the primary surgery indication was not
a carcinoma or a large gallbladder polyp (more than 1 cm), but
cholecystolithiasis or chronic cholecystitis. Altogether, 34 patients
after LCHE with gallbladder cancer confirmed in a definitive biopsy
examination were referred to our department during this period. In
4 cases, the patient had already undergone primary cholecystectomy
with the conversion to an open procedure, as it was not possible
to complete cholecystectomy laparoscopically due to technical
constraints. The completion of radical R0 resection with bed resection
and lymphadenectomy was indicated in all stage T1b and T2 patients,
part of T3 patients and T1a patients were indicated if the integrity
of the gall bladder was not preserved or the biopsy finding was
unambiguous.
We attempted to perform the procedure as soon as possible
after the primary LCHE - optimally within 1 week, in our conditions
within 14 days. The longest period after the primary surgery was 3
months due to the lack of discipline of the patient.
In the pre-operative examination, we usually require at least an
ultrasound examination of the liver and computed tomography CT
scan of the liver, the lungs in more phases to identify tumour residues,
metastases in the liver, lymph nodes outside the hepatoduodal
ligaments, on the peritoneum or in the lungs. MRI, and PET-CT or
PET-MR are preferable due to their greater ability to demonstrate
extrahepatic affection. MRCP or ERCP can be used for visualisation
of the biliary tract branches in case of a suspicion of biliary tract
affection.
The procedure was performed from a subcostal incision in
the right side. At that time, we started peroperative ultrasound
examination. Further, bed resection and lymphadenectomy of
the hepatoduodenal ligament were performed. The bed resection
corresponded to the size of the infiltration mostly in the range of the
S4 and S5 segments. Lymphadenectomy was radical, leaving only
the structures of the arteries, portal vein and bile duct. The area of
the nodes in the para-aortic area was not removed. On the contrary,
the spread of the tumour to this area precluded radical management
due to a very poor prognosis. Perioperative biopsy was used in
suspicious objects or deposits outside of the resection area to exclude
generalization. The intraoperative examination always focused also
on the stub of the biliary duct or biliary tract to preserve a clean
resection line. If the gallbladder had not been removed during LCHE,
we also excised margins of the wound used to remove the gall bladder
from the abdomen. Table 1 describes number of patients according
the tumor staging (Table1, 2).
Table 1
Table 2
Results
No 30-day postoperative mortality was observed and morbidity
was 24% in this group of 34 patients after radical cholecystectomy
due to incidental carcinoma (24 women, 10 men). The most
common complication was bile collection in the resection line (8
cases), which was addressed by the supplementation of drainage
under CT navigation. The second most common complication was
bronchopneumonia, in 2 cases. The median age of the patients in the
group was 65.1 years. Recurrence was most commonly reported 6
months to 13 months after the radical surgery. In the monitoring of
the group of patients after the radical surgery at our liver centre, we
alternated between ultrasound and CT examinations. No patients after
the radical surgery had adjuvant oncological treatment. Oncological
treatment was only palliative after the discovery of an inoperable
tumour recurrence. Careful follow-up was chosen in patients with
an accidental finding of gallbladder carcinoma after uncomplicated
LCHE in the Tis and T1a stage. Two patients were not included in
the published cohort. The risk of metastatic disease in the T1a stage is
very low - 0.0% to 2.5%, but node metastases have been described in
this stage in the de-differentiated form of carcinoma [3].
We always attempted R0 resection, i.e., complete removal of the
tumour. However, we did not perform more extensive multi-visceral
resections due to poor prognosis and high morbidity. Fortunately,
these approaches were not necessary in this cohort.
In the case of peroperative detection of gallbladder carcinoma
during the primary surgery, i.e., laparoscopic cholecystectomy
in the intra-operative biopsy, it was necessary to investigate the
entire abdominal cavity, remove suspicious formations, have them
immediately examined and perform intra-operative ultrasound. In
the case of localized disease, we converted to an open procedure and
performed radical surgery from a subcostal incision.
Recurrence was found in a total of 12 patients: 1 in 18 of the
T1b patients after the surgery, 6 in 10 of T2 patients, and 5 in 6 of
T3 patients after the surgery. The average 5-year survival rate in all
stages of incidental gall bladder carcinoma after radical surgery was
excellent in our team, higher than 50%.
A positive biopsy finding in the resection material during the
radical surgery was reported in 74% of cases in the gallbladder area
and in 53% of cases in lymph nodes. No positive finding was reported
from the incision of the port after laparoscopy.
Patient follow-up after radical surgery is provided by our
department at the liver centre. For the first 2 years, patients are
examined every 3 months, alternating between ultrasound and
computed tomography or magnetic resonance imaging. It is advisable
to carry out a PET MR Examination in case of a suspicion of tumour
spread into the abdominal cavity after the radical surgery. This
examination will completely describe and differentiate the condition
of the tumour and determine the extent of the tumour.
After 2 years without gallbladder cancer recurrence, the time
between visits to the liver office was extended to 6 months, and after
5 years, the follow-up of these patients was discontinued. We did not
routinely use CIA or Ca19-9 oncomarkers in gallbladder monitoring.
Discussion
Gallbladder cancer is the most common biliary tract cancer. It
is asymptomatic for a long time and late stages are preoperatively
diagnosed in up to 60% of cases. Gallbladder cancer accidentally
detected after LCHE is often of a lower, i.e., earlier stage. For this
reason, the prognosis for incidental carcinoma is good compared to
a group of patients with preoperatively diagnosed gallbladder cancer.
Polyps with a size over 1 cm in diameter, chronic long-lasting
inflammation, and possibly hormonal dependence (oestrogen and
progesterone) affect the aetiology of gallbladder carcinoma. Thus,
such tumour is 2 times more common in women than in men,
and the number of pregnancies in women is also of interest, as
gallbladder tissue is sensitive to these hormones and their high levels
during pregnancy. Additionally, diabetes mellitus, smoking and
alcohol consumption are suspected of affecting the development of
gallbladder carcinoma. Chronic cholecystitis with gallbladder calcium
salt incrustation - porcelain gallbladder - is considered to be a quite
pronounced precancerosis where the risk of carcinoma development
is 10% to 20%. Other risk groups include patients with pancreatic
area maljunction, and patients with choledochus cysts, where chronic
inflammation also likely contributes to the development of the
carcinoma.
Symptoms in the group of patients with accidentally diagnosed
carcinoma after LCCHE do not differ from the lithiasis group.
Significant weight loss was found in only 2 cases in our study (T2
stages and T3 stages). Icterus did not occur in the group of accidentally
diagnosed gallbladder carcinomas.
Radical surgery, bed resection and lymphadenectomy of the
hepatoduodenal ligament were first performed in 1954 by Glenn
[4]. Since then, it has been used in the therapy as it can be curative
and significantly affects the survival of patients with lower-stage
gallbladder carcinoma. For a long time, there have been disputes
as to whether to perform this radical intervention at the T1a stage.
The gall bladder wall has only 3 layers – the mucosa, muscular layer
and serous layer. Lamina muscularis mucosae and submucosa are
missing. For this reason, node metastases have been described even
in the T1a stage. However, the risk is very small and careful follow-up
provides the same long-term results.
Another source of discussion is whether gallbladder carcinoma
should be removed in an open or laparoscopic procedure. In our
opinion, the procedure in a diagnosed carcinoma should always be
open. Laparoscopic management has recently been described in T1b
stages, where radical procedure was performed laparoscopically [5].
The use of laparoscopy in the early stages of gallbladder cancer
is, contrary to our position, supported by negative findings in all
excised scars after ports performed in 7 patients in the T2 stage and
T3 stage. The small number of these patients will probably be of some
importance, although no cases of recurrence in the scar after radical
cholecystectomy (N=34) were found in the follow-up period.
However, due to the metastases in the port and on the
peritoneum after laparoscopy in gallbladder carcinoma reported
in the literature, laparoscopic management is not recommended.
Radical cholecystectomy in all stages of gallbladder cancer clearly
shows better long-term outcomes than simple cholecystectomy [6].
Because of the poor prognosis of gallbladder cancer, the radical
procedure should be performed as soon as possible and with utmost
care and radicality. Other therapeutic modalities - adjuvant oncology
therapy or radiotherapy, do not prolong life expectancy. Besides
lymph nodes, it is also good to remove lymphatic vessels from the
area of the ligament and hilum of the liver, so that only the portal
vein, the left and right branch of the hepatic artery and biliary duct
enter the liver. When exploring the nodes in this location, it is also
advantageous to perform Kocher's manoeuvre. If we preserve the
exposed biliary duct, we should try to preserve both small arteries
together with the delicate pericholedochus vascular plexus that
nourishes its wall. Their names are derived from their course - 3
o’clock and 9 o’clock artery.
Removal of these structures may lead to ischaemia and stenosis of
the biliary duct. In our case, such a stenosis developed in one patient
within 10 months of the radical surgery. The advantage was that this
stenosis could be resolved endoscopically - dilatation and stenting.
With regard to the findings of submucosal infiltration, some
authors (Shimitu, Japan) recommend a complete resection of
the biliary tract, in addition to lymphadenectomy, in gallbladder
carcinoma cases. On the other hand, other authors such as Makuuchi,
Japan [2,7], do not recommend this radical approach. We incline to
intra-operative biopsy of the cystic duct and, in the case of a positive
finding, resect the biliary tract up to the microscopically healthy
tissue.
In inoperable findings, which we encounter rather sporadically
after LCHE, we indicate symptomatic treatment after consulting
an oncologist - pain relief, endoscopic therapy of icterus, etc. Some
literature reports from recent years suggest better gallbladder cancer
survival when using the combination of 5-fluorouracil, doxorubicin
and mitomycin C [8,9].
In the case of a relapse, it is possible to perform a repeated
procedure with the removal of the affected area, unless the disease
is generalized. However, the success rate of repeated surgeries due
to the recurrence of gallbladder cancer is very low. In most cases, reoperations
will find inoperable generalization of the tumour.
Conclusion
If gallbladder carcinoma is revealed in the definite histological examination after LCHE, the patient should always be referred to a specialized site for consideration of radical surgery as soon as possible after the primary surgery. Only radical surgery may be curative or can significantly prolong the survival of patients with a good quality of life. However, the indication of radical extended cholecystectomy must be based on multiple factors. In addition to staging and grading the tumour, the patient's age and comorbidities must be seriously considered.
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