My purpose
of study was
Ø To find
out different risk factors involved in causation of carcinoma gallbladder.
Outcome
measures of interest
Ø
Gender.
Ø
Built.
Ø
Gallstones.
Ø
Family history of carcinoma gallbladder.
Ø
Cholecystoenteric fistula.
Ø
Porcelain gallbladder.
Ø
Anomalous junction of cystic duct with pancreatic duct .
Ø
Parity.
Ø Estrogen
therapy.
a) Study
design
Descriptive
study including 50 patients was conducted at Nishtar hospital Multan.
b) Sampling
technique
Convenient type of sampling
technique was used.
.
Fifty patients were included in
the study.
d) Data type
Ordinal type of data was
maintained.
e) Inclusion
criteria
All
patients having suspicion of carcinoma gallbladder and any risk factors
involved were included in this study.
f) Exclusion criteria
All patients
having diseases other than carcinoma of gallbladder was excluded from the
study.
g) Statistical
data analysis
All the
results were analyzed through SPSS system and percentage, proportions and ratio
were calculated.
h) Data collection procedure
A separate
file was compiled for each patient consisting of patient’s complete biodata.
Complete history, full clinical examination and detail investigations were
carried out. Each patient was further evaluated for possible risk factor
involved.
1. History
History of each patient was taken under the following
headings.
A)
Patient’s biodata
Name, age, sex, marital status, weight, smoking hobbits.
It
comprised of patient’s biodata comprising of age, sex, occupation, weight;
presenting complaints, mode of onset and duration of symptoms like pain,
vomiting, anorexia, weight loss, fever etc.
C)
Past history
This
included previous history of biliary colic or upper abdominal pain, any
previous history of jaundice, hospitalization or any operation any history of
typhoid fever.
D)
Family history
Family
history comprised of history of gallstones, jaundice, obesity or malignancy in
the family or any carrier of typhoid infection.
. Personal history included smoking,
addiction, dietary habits, marital status, socio-economic status, history of
intake of any drugs and allergies.
2. Physical
Examination
It included
a) General Physical Examination
General physical examination included pulse, blood pressure, temperature, respiratory rate, anemia, nutritional status, jaundice, lymph adenopathy etc.
B)
EXAMINATION
OF ABDOMIN
This includes
a) Inspection
Which
comprise of shape, position of umbilicus, visible lump or veins, scar mark any
pigmentation etc.
b) Palpation
It
was done to check tenderness, rigidity, guarding, Murphy’s sign, any palpable
viscera or lymph node enlargement. In the case of a palpable mass, its site,
size, shape, surface, consistency, mobility and fixity compressibility or
reducibility was noted.
c) Percussion
It
was done to see the percussion note, shifting dullness and fluid thrill etc.
d) Auscultation
Auscultation
of abdomen was done to note the number and intensity of bowel sounds, to hear any
bruit etc.
In
addition to abdominal examination complete systemic examination was done in all
the patients to rule out any concomitant illness.
3) Investigations:
All the patients who were included in the study were thoroughly investigated and various related investigations were done either to confirm the diagnosis or to rule out other concomitant illnesses. These included
a. Complete Blood
Examination:
To see hemoglobin level, TLC, DLC, ESR
to see any evidence of infection and platelet count.
b. COMPLETE URINE EXAMINATION
For sugar,proteins,bilirubin and urobilinogen.
c. Liver Function
Tests:
Which included serum bilirubin,
alkaline phosphatase, SGOT, SGPT and HbsAg.
d. Clotting profile:
PT, APTT, Platelet
count, BT, CT.
e. X-ray Chest:
To Asses cardiopulmonary status,
pleural effusion and level of diaphragm and for any secondaries in chest.
f. Plain X-ray Abdomen:
To see associated radio opaque stones, which are found in
10-15% of patients and also to detect other abnormalities like soft tissue
shadow in right upper abdomen
g. Abdominal Ultrasonography
To have information about size,
shape and thickness of the wall of gall bladder, presence of stones or any mass
in the gall bladder, to asses the size of liver and spleen. In addition, to
rule out any other intra-abdominal pathology like enlargement of lymph nodes,
dilatation of extra or intrahepatic biliary passages, presence or absence of
Ascites etc.
In addition to the above-mentioned investigations certain
specific investigations were carried out in patients in whom the diagnosis and
final decision with regard to the approach towards treatment could not be
reached with the help of above-mentioned investigations. These were CT scan
abdomin, ERCP, Colonoscopy, HIDA scan and USG guided FNAC.
All the resected specimens after
cholecystectomy were subjected to histopathology for the confirmation of
diagnosis and to rule out presence of any malignant change.
When possible all the preoperative work
was completed before the hospitalization to reduce patient’s stay in the
hospital.
In this
study total number of 50 patients of symptomatic gall stone disease or mass
palpable in right upper quadrant or who presented with obstructive jaundice
were treated in Nishtar Hospital Multan. Table 6 shows the mode of admission of
these patients. Out of 50 patients, 40 patients (80%) were admitted through out
door as elective cases. 5 patients (10%) were admitted through emergency ward
with the complaint of severe biliary colic. Rests of 5 patients (10%) were
shifted from the medical units where they were admitted with the complaint of
pain epigastrium and on investigation were found to be suffering from gall
stones or gallbladder growth.
AGE&SEX:
Among
the 50 patients, 15 patients (30%) were below the age of 40 years but above
/equal to the age of 30 years, 10 patients (20%) were between 40-50 years and
rest of the 25 patients (50%) were above the age of 50 years. The decade-wise
age distribution is as follows:
The
maximum incidence was seen in the fifth decade of life. None of the patients
was seen in the first or second decade of life.
Among the 50 patients, 5 (10%) were male and 45 (90%) were
female. Among the male patients, the youngest was 42 years of age while the
oldest was 60 years of age. In female patients, the youngest was 30 years of
age and oldest was 70 years of age.
All
the 45 female patients were married. 43 patients (95.55%) out of 45 were having
children while in 2 patients (4.44%) there was history of infertility. 40
patients (88.88%) were obese and multiparous having more then 5 children.
20
patients (44.44%) were using oral contraceptive pills from last 4-5 years.
4 male patients (80%) out of 5 were married and 1 (20%) was
unmarried. 3 (60%) out of 5 male patients were having office job while 2 (40%)
out of 5 were laborers.
SOCIOECONOMIC
STATUS:
Out
of 50 patients, 40 (80%) belonged to low socio-economic class while 10 (20%)
belonged to rich and middle class families. 15 patients (30%) out of 50 were
resident of urban areas while the rest of 35 patients (70%) were from rural
areas.
The
prevalence of various clinical features observed in study is shown in Table 7.
The common clinical features were pain, dyspepsia, nausea and vomiting, fever
and mass in right hypochondrium. Similarly the common clinical findings
observed were tenderness in right hypochondrium, Murphy’s sign and presence of
palpable mass in the right hypochondrium. The incidence of these features is as
follows:
In 46 patients (92%) out of 50 the presenting complaint was
pain right hypochondrium or mass in right hypochondrium while in the rest of 4
patients (8%) the major complaint was severe dyspepsia. Mild dyspepsia was
observed in 32 (64%) out of 50 patients. 44 patients (88%) were having
complaint of nausea especially after taking fatty diet. The complaint of
vomiting was found in 39 (78%) patients. High grade fever with chills was
observed in 4 (8%) patients in addition to other complaints. 2 patients (4%)
out of 50 were having a lump in the right hypochondrium.
The duration of symptoms was variable. Its detail is as
follows:
In
20 patients (40%) the duration of symptoms was found to be more than 5 years.
In 20 patients (40%) the duration of symptoms was between 3-5 years. In 10
patients (20%) the duration of symptoms was below 3 years.
4
patients (8%) out of 50 were having Diabetes Mellitus. 3 patients (6%) had
family history of carcinoma gallbladder. 2 patients (4%) were also having
colonic malignancy. One patient (2%) was having ulcerative colitis
In
all the 50 patients, the routine blood and urine examination, liver function
tests and abdominal USG was performed.
20
female patients (44.44%) out of 45 were found to be Anemic while in the rest of
25 patients (55.55%) the hemoglobin was above 10 mg/dl. 2 male patients (40%)
out of 5 were Anemic. Raised ESR was found in 35 (70%) out of 50 patients.
The
reports of complete urine examination showed positive urine sugar in 4 patients
(8%) out of 50. Among these 4 patients, 3 were known diabetic while 1 was
diagnosed for the first time.
3
patients (6%) out of 50 were having slightly increased level of alkaline
phosphatase despite of normal bilirubin.
Abdominal
USG showed multiple stones with thick-walled gall bladder in 45 patients (90%).
gall bladder mass was present In 20 patients (40%), the mass was limited to
gallbladder in 6 (30%) out of 20 patients. In remaining 14 patients (70%), the
disease was advanced with involvement of lymph nodes and liver. One patient
(2%) out of 50 was having porcelain gallbladder. Three patients (6%) was having dilated common bile duct, who was
further investigated by ERCP. ERCP was performed in three patients (6%) who
presented with fever and raised LFTS but there were no evidence of stones in
common bile duct and gallbladder showing anolomous junction of cystic and
pancreatic duct. One patient (2%) on ERCP and CT was diagnosed to be having
biliary –colic fistula.
CT
scan abdomen was performed in 20 patients (40%) whom USG was suggestive of gall
bladder mass. Only three patients (15%) showed early carcinoma limited to
gallbladder. 16 patients (80%) had disease involving the adjacent liver and
lymph nodes. One patient (5%) had gallbladder polyps.
Colonoscopy
was performed in 4 patients (8%) out of 50 who were having history of colonic
malignancy and ulcerative colitis.
Simple
cholecystectomy was performed in 30 patients (60%) who were diagnosed to be
having thick walled gallbladder with multiple stones in it. Rest of the twenty
patients (40%) in whom the mass was detected, six (30%) out of 20, who were
having mass limited to the gallbladder wall also undergone simple
cholecystectomy while the remaining 14 (70%) out of 20 who were having advance
disease involving the liver and lymph nodes underwent extended cholecystectomy.
All
the resected gall bladder specimens were sent for histopathology and the
results were as follows:
Out of 50 patients, in 47 patients (94%) the histopathology
report was suggestive of adenocarcinoma and cholelithiasis. squamous carcinoma
was present in the remaning 3 (6%) of patients.
DISCUSSION
Carcinoma
of the gallbladder is the most
common malignancy of
the biliary tract
and accounts for
5% of all the cancers1 and is a common surgical
problem. The incidence increases with increase in the age and ninety one
percent of the patients who
develop this malignancy
are 50 years of age or
older2. Incidence of
cancer in females
is three to
four times to
that in males3 .
Carcinoma of
the gallbladder is a very aggressive tumor having five
years survival rate
of about 4%4. Among the etiological factors,
gallstones co-exist in
about 75% of
cases3 and chronic
cholecystitis is a
frequent association; Other
conditions associated with
an increased risk
of gallbladder carcinoma
are edinomyomatosis8, polyposis coli9, gardener's syndrome10 and anomolous
connection between the common bile
duct and pancriatic
duct11. Porcelain (calcified) gallbladder is more likely to
develop cancer14. Other risk factors are multiparity17,
estrogen therapy18 and ulcerative collitis19.
The
area of this study included South East Punjab and adjacent parts of Sindh and Baluchistan. In this region
illiteracy is common. Moreover, most of the people are poor and health
facilities are deficient. Due to all these factors, in the case of any illness,
the people usually reach the hospital quite late and there is an increased
incidence of complications. It is true for patients of gallbladder cancer. In
the initial stages when the symptoms are not very severe they usually take
treatment from local Hakeems or unqualified medical practitioners and come to
hospital quite late when the disease is advanced or some complication has
occurred. This results in delay in treatment and metaplastic, dysplastic or
neoplastic changes do have occurred in diseased gall bladder.
In
present study the highest incidence of gall stone disease is in the fifth
decade of life. This shows development of gall bladder disease at a relatively
younger age as compared to Western society where average age of involvement is
much higher125. The reason for this early involvement in our set up
is attributed to young age marriages, high rate of pregnancies, low immunity,
exposure to various infective agents and environmental pollution. Similar
results have been reported in the study performed at Hyderabad129,
which showed relatively younger age involvement. Similarly another study
performed at Karachi125showed an early development of gall stone
disease in younger patients. Thus the result of our study correlates with the
other Pakistani literature. However our figures are less than the Western
literature suggesting an early age involvement in our set up.
In present study, carcinoma gall bladder is more common in females (90 %). A study was carried out in the Department of Surgery, Liaquat Medical Hospital, Jamshoro (LMCH), Jamshoro / Hyderabad between February 1993 and January 1996 on 188 patients.148 patients (78.7%) were females 148. this study has a gross difference in this regard. the reason being is that the present study comprises of only 50 patients while the above mentioned study has 188 patients. More over above-mentioned study was not particularly specific for carcinoma gall bladder. Moreover over a study conducted in Agha khan hospital showed that carcinoma gallbladder was the second most common tumor in females149.
In
present study the obesity and infertility were also main factors in carcinoma
gallbladder. A study was conducted in
Epidemiology Department, Population Health Research Center, National
Institute of Public Health, Cuernavaca, Morelos, and Mexico concluding obesity
and reproductive factors as major etiological factors in carcinoma gallbladder 150.
In
present study 90 % of patients with carcinoma gallbladder were having stones
correlating the study performed at Mexico in
1,367 cholecystectomy specimens were studied 80% had lithiasis 151.Similarly an interesting case
was reported in 2000 in Japan where following a simple cholecystectomy, a
63-year-old woman with gallstones was histologically diagnosed as having minute
squamous cell carcinoma of the gallbladder152. Present
study is comparable to the above-mentioned international literature.
Present study can be compared with the national literature
as well
A
study performed at Jamshoro139 showed incidence of chronic
inflammation and gallstones in 80% patients of carcinoma gall bladder. Another
study138 showed incidence of cholelithiasis in 94.12% patients of
carcinoma gall bladder.
In present study one patient (2%) out of 50, has gall bladder polyp. A study was published in Mexico in 1998 showing the gallbladder polyps as a major risk factor for carcinoma gallbladder present in (2%) of patients151.
In
present study APDJ was present in (2%) of the patients. The present study is
comparable to the study conducted in Department of Surgery, Chang Gung
University College of Medicine, Taipei.
In that study, it was concluded that Anomalous pancreaticobiliary ductal junction (APDJ) is a rare
congenital anomaly, which is considered to be an etiological factor in
the development of carcinoma of
the biliary tract153.
In
another study conducted by Department of Internal Medicine, National Taiwan
University Hospital, Taipei showing 8.7% patients with APDJ having carcinoma
gall bladder154, 155.
Present study can be correlating with the above-mentioned
studies.
In
present study, cholecystocolic fistula was present in 2% of the patients. An
interesting case was reported in Good Hope Hospital, Coldfield, West Midlands,
and UK. Cholecystocolic fistula was the etiological factor in carcinoma gall
bladder156.
In present
study Adeno-carcinoma is commonest type of carcinoma gall bladder (94%)
followed by squamous carcinoma present in
(6%) of patients. A study performed at Allied Hospital Faisalabad138
showed a prevalence of Adeno-carcinoma in 100% cases. Another study performed
atJamshoro139showed Adeno-carcinoma in 90% cases while squamous cell
carcinoma was seen in 10% cases.
The other studies published in National and International literature
showed a 75-85% prevalence of Adeno-carcinoma gall bladder148, 149.
Present
study can be compared to the national and international literature.
CONCLUSIONS AND SUGGESTIONS
The present study concludes and suggests:
1. Carcinoma gall bladder like cholelithiasis is more common in females. However males are not spared or immune to carcinoma.
2. In our study most of the patients were in the fourth and fifth decade of life suggesting an earlier age involvement in our set up.
3. Cholecystitis and cholelithiasis are the most important predisposing factors for carcinoma of gall bladder.
4. Early carcinoma is asymptomatic and routine investigations are not helpful in the diagnosis.
5. Ultrasonography is very helpful in the diagnosis of cholelithiasis but is not very sensitive in the diagnosis of early carcinoma of gall bladder.
6. CT scan is very sensitive for the diagnosis of carcinoma of gall bladder but being expensive cannot be used as a routine investigation in all the patients of gallstones.
7. Due to high incidence of association of gallstones with carcinoma gall bladder early cholecystectomy should be performed for the prevention of CA in patients of chronic cholecystitis and cholelithiasis.
8. All the resected specimens should be sent for histopathology.
9. Adeno-carcinoma is the commonest type of carcinoma involving the gall bladder.
10. Considering the increased incidence of disease in younger age in our country, a need for intensified research in this field cannot be overlooked.
11. A suspicion of malignancy should always be kept in mind in patients of long standing cholelithiasis.
12. In all the patients with a long standing history of gall stones it is better to perform a CT scan abdomen to rule out early carcinoma gall bladder as USG is not very sensitive for the diagnosis of early carcinoma.
13. A screening programme for patients with gall bladder disease should be started using USG as a main diagnostic screening test so that cases of gallstones and chronic cholecystitis are detected earlier and hence managed in time.
14. We should also try to improve the availability of health facilities for rural and far away areas. Moreover, health education should be given to the general public through mass media so that diseases are diagnosed at an earlier stage.