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SPECTRUM AND MANAGEMENT OF GALLBLADDER CARCINOMA

Article  in  International Journal of Scientific Research · December 2020

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 ORIGINAL RESEARCH PAPER Volume - 9 | Issue - 12 | December - 2020 | PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr

INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH

SPECTRUM AND MANAGEMENT OF GALLBLADDER CARCINOMA

Medical Science
Dr.Abdul Kaiyum MO, Habra State General Hospital,West Bengal.
Khan
Dr.Rishin Dutta MO, M R Bangur Hospital, West Bengal.
Diptendra Kumar Prof., IPGMER and SSKM Hospital,Kolkata, West Bengal.
Sarkar
Young Scientist (DST),IPGMER and SSKM Hospital,Kolkata, West Bengal.
Dr. Debarshi Jana* *Corresponding Author
ABSTRACT
Aim of this study is to evaluate the gallbladder cancer in terms of its distribution among different age group, sex, location, its clinical presentation,
food habit, histopathological nding, its treatment both in terms of surgery or adjuvant therapy and its outcome after 6 months of follow up. This
study was help to formulate better screening and management guideline and thus better prognosis.
Both Male and Female 50 Patients with suspicios gall bladder cancer or HPE diagnosed gallbladder cancer attending the General Surgery OPD,
IPGME&R and SSKM Hospital, Kolkata from January 2018 to August 2019.
Gallbladder cancer is a lethal disease as it present late in advance stages and it has very vague presentation that make difculties to suspect
gallbladder cancer early. Pain abdomen, abdominal lump, anorexia, jaundice are the common presenting symptoms of gallbladder cancer.
USG is the primary tool to detect and suspect gallbladder carcinoma whereas CT scan being done in suspected and conrmed case to conrm and
staging the cases respectively. MRI is done in selective cases where portal and biliary invasion is suspected. PET CT though has high sensitivity not
routinely advised.
Obstructive jaundice with Gallbladder cancer remains a dilemma as far as management. These are usually late presented patient and many a time
palliative stenting to relieve the jaundice remains the only intervention to do.
KEYWORDS
Gallbladder Cancer, Distribution, Screening And Management

INTRODUCTION Aim of this study is to evaluate the gallbladder cancer in terms of its
Although overall incidence of carcinoma of Gallbladder (CAGB) is distribution among different age group, sex, location, its clinical
less, it is the sixth most common cancer of the gastrointestinal tract. It presentation, food habit, histopathological nding, its treatment both
is a lethal tumor with poor prognosis due to delayed presentation and in terms of surgery or adjuvant therapy and its outcome after 6 months
early spread 1 .It's age standardized incidence rates of around 2 to 3 per of follow up. This study was help to formulate better screening and
100,000 populations in both gender separately worldwide 2,3.Though management guideline and thus better prognosis.
its distribution varies among different gender ,age ,ethnic group,
geographical area, socioeconomic status, food habit. CAGB increases MATERIALS AND METHODS
with age and is 2 to 3 times higher in women than men. a. Study setting: General Surgery OPD, Curzon Ward, Victoria Ward
and Main OT complex, SSKM&H
CAGB has wide geographical variation worldwide. The highest b. Place of study: Dept. of General Surgery, IPGMER and SSKM
incidence rates (up to 8.0 per 100,000 in men and 22 per 100,000 in hospital, Kolkata.
women) occur among population in the Indian subcontinent, in the c. Study population: Both Male and Female Patients with suspicios
western part of South America which include Colombia and Ecuador gall bladder cancer or HPE diagnosed gallbladder cancer attending the
and to a lesser extent in East Asia and Eastern Europe. In the United General Surgery OPD, IPGME&R and SSKM Hospital, Kolkata from
States, the incidence is more among American Indians and in January 2018 to August 2019.
Hispanics. d. Sample size: 50 patients, attending the General Surgery OPD of
SSKM&H, Kolkata will be chosen after informed consent.
Multiple risk factors are there for developing CAGB including e. Inclusion criteria:
cholelithiasis, porcelain gallbladder, adenomatous polyp of the Patients with diagnosed case of GBC by
gallbladder, chronic salmonella typhi infection, exposure to a. Imaging Modality
carcinogen like radon and anatomical variation like Abnormal i. Ultrasonography
pancreaticobiliary duct junction (APBDJ). ii. CT scan
iii. MRI (optional) and with b. Histological or Cytological diagnosis by
Chronic inammation of the gallbladder mucosa due to gallstone is Biopsy
hypothesized to be the major factor that leads to gallbladder cancer.
Some molecular changes are emerging as a cause of gallbladder cancer f. Exclusion criteria:
like p53, Kras, P16INK4A and ERBB2/HER24. a) Patient not willing to be part in this study
b) Patient having inadequate reports and left the study
Gallbladder cancers are mostly adenocarcinomas but other
histological type like small cell cancer, squamous cell cancer, Statistical analysis:
lymphoma and sarcoma may also be seen. Gallbladder cancer may be Data were entered in MS Excel and codied. Statistical analysis was
classied according to morphology as inltrative, nodular, papillary, done using SPSS 20.0 for Windows. Frequency distribution tables
or a combination of these type. Among them papillary carcinoma has were made to express proportions of different variables. Chi-Square
the best prognosis. The clinical feature of gallbladder cancer, test was used to show association between categorical variables.
especially in early cancer, is non specic. Hence most of the Unpaired t test was used to show mean of normally distributed
gallbladder cancer is diagnosed at a late stage. This is the main cause of continuous variables.
having poor outcome of gallbladder cancer. Besides its anatomical
location of gallbladder makes the situation further difcult as at the RESULT AND ANALYSIS
time of diagnosis most of the gallbladder cancer already involve its In our study the age range was found to be between 36 years and 78
vicinity important structure like liver, portal vein. years with a mean age of 56. The maximum incidence occurred in
International Journal of Scientific Research 1
Volume - 9 | Issue - 12 | December - 2020 PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr

above 61 years of age group then the age group between 51 years to 60 Helicobacter pylori (H. PYLORI ) are feco- orally transmitted
years. Inference: Increasing age was signicantly associated with high organisms which have been known to be associated with pathogenesis
mortality at 6 months. Distribution of patients according to sex(N=50) of GBC and are likely to be increased as the river ows downstream
10,9,11
inference: Female gender was signicantly associated with high . In North, North east and eastern India, mustard oil is the staple
mortality at 6 months. Inference: A non signicant numerical mortality cooking oil in contrast to coconut oil, sesame or groundnut oil in south
preponderance was observed among residents of Extra Gangetic area. and west India. Mustard oil has irritant property on the gut and is often
adulterated with butter yellow which is known carcinogen
It was found that 1= Cholelithisasis, 2= CaGB, 3= GB Lump, 4=
Intestinal obstruction 1= Cholelithiasis+ GB Lump 2- Cholelithiasis+ Socio-economic Status
GB wall Thickening 3= GB SOL 4- NA 5= GB Mass+ Liver SOL 6= In my study 70% patient of gallbladder cancer have literacy rate of
Cholelithiasis+ GB mass+ Liver sol 7= Cholelithiasis 1= below class X and 62% patients have monthly family income lower
Heterogenous GB Mass 2= GB Mass with hepatic decreased than 10,000.
attenuation+LN 4= Not Available 5= GB+livermets+LN CT
Diagnosis Inference: Presence of metastasis at diagnosis was Lower socio-economic status is indirectly a result of illiteracy and poor
signicantly associated with high mortality at 6 months. education standards. This leads to unemployment and decreased
livelihood capacity inuencing preventive aspects of Gall bladder
We found that 1= Stage A 2= Stage 2A 3=Stage 2B 4= Stage 3A 5= cancer 12
Stage 3B 6= Stage 4A 7= Stage 4B 8= Stage 0 1= Mucinous adenoCa
2= WellDiff AdenoCa 3= Moderately diff Adeno 4= Poorly diff 5= Sq Gallstones and lower socio economic status are independent
Cell Ca Inference: Radiological inoperability was signicantly determinants for early onset of gall bladder carcinoma.9
associated with high 6 months mortality. 1= Extended
Cholecystectomy 2=open cholecystectomy 3= No surgery done 1= Sign and Symptoms
Alive & Asymptomatic 2= Alive & Progressive 3= Died The clinical presentation of GBC is often vague or delayed relative to
pathologic progression, contributing to advanced staging and dismal
DISCUSSION prognosis at the time of diagnosis. The clinical presentation is
Age nonspecic, may include abdominal pain, weight loss, fever, and
Gallbladder cancer is a highly lethal cancer which arises from jaundice, and any of these can be seen in cholecystitis and other benign
gallbladder mucosa. In 2018, about 219,000 people were estimated to gallbladder conditions as well as in other abdominal malignancies8,13
have been diagnosed with gallbladder cancer. This constitutes 1.2% of
all cancer diagnoses 2The incidence greatly varies in different age In our study we found pain abdomen was found as major presenting
group and even .In our study 50 patients have been evaluated. We got complaint(50%).Besides it 20% patient presented with abdominal
the patients having age starting from 36 upto 78 years of age. This lump,14% presented with jaundice and 16% presented with anorexia.
study is showing maximum GBC occurs in 6th decade of life (50%) Shukla14 reviewed 315 patients and reported pain to be the commonest
and then age group between 51-60 years of age group. A single centre symptom (85 %) followed by icterus (60.3 %), lump and loss of
study regarding epidemiological factors of Gallbladder cancer in appetite (40 % each).
Eastern India showed that the peak incidence was in 41–50 years age
group. Thirty-one patients (49.20 %) were in this age group. Gall So all the previous study showing pain abdomen was major presenting
feature of gallbladder carcinoma as our study also suggest. But other
bladder carcinoma is signicantly higher for the patients older than 40
features are exactly not corresponding with our study that might be due
year 5.Here in our study it is corresponding that gall bladder cancer
to different etiology behind developing gallbladder cancer.
increases with age. Increased age group also showed higher mortality
(64%).p value is 0.018.
Cholelithiasis
In our study 74%(n=37) patient had gallstone. It is signicantly higher
Sex
number than patient not having gallstone. Prashanta Kumar
Out of 50, 31 patients were female and 19 patients were male.so higher
Bhattacharya et al 15 has shown that About 74.1% (n = 40) of our patient
no of gallbladder cancer has been seen in our study. In a study by Duffy cohort had gallstones. Test of proportion showed that the proportion of
et al in 2008 women are two to six times more commonly affected than patients with cholelithiasis was signicantly higher than those without
men 6. The female hormone estrogen is known to increase the stones (Z = 10.39; P < 0.0001). Corrected Chi-square test showed that
saturation of cholesterol in bile, thus increasing the risk of gallstone there was no signicant association between the age of patient and risk
formation. This pathogenesis is believed to be the primary culprit of cholelithiasis (P = 0.54).
behind the greater risk of gallbladder cancer among females 7.So other
study also corresponds with our study. The risk of a patient with GBCA having gallstones was 8.48 times
more among females as compared to males (OR = 8.48; 95% CI
Residence 2.16–33.19; P = 0.0009). Chi-square test showed a signicant
In our study (58%+24%=) 82% patient of gall bladder cancer patient association between gender and cholelithiasis (P = 0.0009).
resides in either gangetic and extended gangetic belt (According to
National geography of India , 6th edition-Both 24 Parganas, Howrah, Nearly 45% (n = 18) of our patient cohort had a single stone, whereas
Hooghly, Nadia and Kolkata districts are considered as pure gangetic 55% (n =22) had multiple stones. This difference was not found to be
belt and after adding Malda, Murshidabad, Burdwan it becomes statistically signicant (Z = 1.41; P = 0.1585). Test of proportion
extended Gangetic belt. And rest of the West Bengal is considered as showed that signicantly higher number of patients had stone size <3
Non gangetic belt). The quality of evidence for these factors is limited cm (70%, n = 28) as compared to those with stone(s) ≥3 cm (Z = 5.65; P
as they come from small case-controlled studies and requires further < 0.0001). Incidentally, multiple stones were mostly <3 cm in diameter
larger multi centric studies. The high-risk regions extend from the while single stones were ≥3 cm in size, the association was statistically
states of Jammu and Kashmir, Punjab, Haryana, Himachal Pradesh, signicant (P < 0.0001)
Uttarakhand, UP, Bihar, Bengal, Assam and Manipur. A large part of
these states is based along the major rivers of the country namely We have not studied on number of gallstone and it's diameter as
Sutlej, Ganges, Yamuna and Brahmaputra. These rivers arise from the parameter but only gallstone as a whole a parameter which as per other
glaciers and ow from the northern Himalayas towards west and east previous study showing major GBC is associated with gallstone.
and have become polluted due to human waste and industrial
pollutants. As the Ganges ows towards east, the pollutants DIAGNOSIS
concentration as well as bacterial contamination have been found to In the diagnosis of GBC, differential diagnosis and determination of
steadily rise which may account partially for high incidence in this the local extension of tumor are important. For these purposes,
gangetic region of the country. It is also an agricultural driven imaging modalities such as endoscopic ultrasonography (EUS), CT,
community. The Ganges supports a very densely populated human MRI, and magnetic resonance cholangiopancreatography(MRCP) are
civilization on its banks, especially the poorer sections, which subsist useful. EUS has good sensitivity in differentiating benign gallbladder
on the river for its daily water needs. Untreated sewage, industrial diseases from GBC
waste and agricultural efuents unfortunately get added to the water
along its course 8. The fecal coliform count steadily rises as the river
ULTRASOUND
ows towards the east 9 . Salmonella typhi (S. TYPHI) and
Ultrasound can depict a focal intraluminal, wall involvement, or large
2 International Journal of Scientific Research
Volume - 9 | Issue - 12 | December - 2020 PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr

mass-like lesion replacing the gallbladder. The tumor usually has potential to be curative only in local or regional diseas. According to
irregular and sometimes ill-dened margins, with heterogeneous Yuman Fong et al in 2000 17 Unresected gbc is a rapidly fatal disease.
echotexture and predominantly low echogenicity. Hyperechoic foci radical resection can provide long term survival even for large tumour
with posterior acoustic shadowing may be seen within the mass, with extensive liver invasion.
possibly reecting gallstones or gallbladder wall calcications -
porcelain gallbladder Long term survival can be achieved for patients presenting after prior
noncurative surgical exploration.
In our study 32%(n=16) patient diagnosed by ultrasound as GB
SOL,14%(n=7) patient showed only cholelithiasis and after In our study Surgical inoperability was signicantly associated with
cholecystectomy they were diagnosed incidentally with high 6 months mortality. Furthermore extended cholecystectomy
GBC.12%(n=6) patient only showed asymmetrical wall thickening. patient had signicantly higher 6 months survival than those who
GB mass with liver SOL is seen 12% patient(n=6). received only open cholecystectomy.(p value 0.004).

CT SCAN MORTALITY
If GBC is conrmed, thin-slice spiral CT can contribute valuable In our study we tried to focus different parameter and its association
information on local spread.15.Although CT is inferior to ultrasound in with mortality.
depicting mucosal irregularity, mural thickening, and cholelithiasis, it
is superior for evaluating the thickness of portions of the gallbladder Clinical inoperability was signicantly associated with high 6 months
wall that are obscured by gallstones or mural calcication on mortality. Among total 24(100%) inoperable patient 16 (66.7%) died
ultrasound. CT may show focal or irregular mural thickening; the which marks as signicant association(p-value 0.001)
images should be carefully inspected for bile duct dilation, local
invasion, metastases, and adenopathy. 27 (100%) patients underwent palliative stenting from which 8(29.6%)
patient died . So non signicant mortality preponderance was found
We in our study found 42% patient(n=21), in their CT scan GB mass among those study subjects who received palliative stenting(p value
with hepatic decreased attenuation with lymphnode. In 24% (n=12) 0.055).It might be due to fact that palliative stenting usually was given
cases CT Scan nding was heterogenous GB mass. to advanced cases which might mask the benecial effect of palliative
stenting.
On MRI, GBC usually shows hypo- to isointense signal
characteristics. An all- in-one protocol supplementing MRI with Those patients who received chemotherapy had signicant high
cholangiographic (MR cholangiopancreatography) and contrast- mortality at 6 months interval.36% patient of mortality was found
enhanced arterial and portal phase 3D angiographic (MR angiography) among chemo receiving patient than 14% non chemo recipient
images may be up to 100% sensitive for bile duct and vascular patients. That may also signify that advance stage itself increase
invasion, yet sensitivity falls to 67% for hepatic invasion and 56% for mortality. Anyway in this study it has been established that
lymph node metastases.16 chemotherapy can not improve mortality dramatically.

In this study much focused was not given on MRI. For few cases where In this study we evaluated mortality according to stage and found
biliary invasion was suspected MRI was done (16% cases) advancing stage was signicantly associated with high 6 months
mortality (p value 0.004).
METASTASIS
In our study 40% patients (n=20) were diagnosed with liver metastasis. Non modern treatment, negligence in attending modern medical
It means a large number of patients presented in an advance stages. system is also hindering better mortality outcome. We evaluated the
Most of these patients were radiologically inoperable. This amounts a gap (in month) in attending modern treatment facilties and its
large no 28%(n=14).Six patients more(12%) has been found to be association with mortality. And we found more the gap more is the 6
inoperable after exploring. months mortality.

CYTOLOGY/BIOPSY CONCLUSION
Other than radiology histological diagnosis was also done in our study. On the basis of our study we can draw the following conclusion:
And in case of all incidental nding of GBC diagnosis was done by Average age of Gallbladder carcinoma in India is 56 of years though it
histopathology of resected gallbladder. In 14 cases (28%) GBC may occur even in 3rd decade and 7th decade also.
diagnosed as incidental nding in this study.
Female sex has more incidence than male.
In our study mostly adenocarcinoma was diagnosed (92%).In 8% Gangetic and extended gangetic belt has higher incidence rate.
cases (n=4) squamous cell carcinoma was found. Among Poor educational qualication and poor monthly income individuals
adenocarcinoma mo derately differentiated was the major type 42% are more affected. Low socio-economic status patients even contact
(n=21). modern medical system late and this causes poorer outcome.

MANAGEMENT The single most common associated factors with GBC is Gallstone.
As Gallbladder carcinoma present late and very less chemoradio Though simple gallstone as an etiological factor for developing
sesnsitivity surgical management is the principal effective Gallbladder cancer has not been established.
management in gallbladder carcinoma. GBC is characterized as an
aggressive and highly lethal disease, and surgery is the only option for Gallbladder cancer is a lethal disease as it present late in advance
the treatment. A more aggressive surgical approach, including stages and it has very vague presentation that make difculties to
resection of the gallbladder, liver, and regional lymph nodes, is suspect gallbladder cancer early. Pain abdomen, abdominal lump,
advisable for patients with T1b to T4 tumors. Aggressive resection is anorexia, jaundice are the common presenting symptoms of
necessary because a patient's GBC stage determines the outcome, not gallbladder cancer.
the surgery itself. Therefore, major resections should be offered to
appropriately selected patients. Patients with advanced tumors or USG is the primary tool to detect and suspect gallbladder carcinoma
metastatic disease are not candidates for radical resection and thus whereas CT scan being done in suspected and conrmed case to
should be directed to more suitable palliation. conrm and staging the cases respectively. MRI is done in selective
cases where portal and biliary invasion is suspected. PET CT though
Complete surgical resection remains the only potentially curative has high sensitivity not routinely advised.
treatment for primary adenocarcinoma of the gallbladder. Several
basic concepts of surgical management of this illness are Obstructive jaundice with Gallbladder cancer remains a dilemma as far
straightforward, whereas others remain controversial. Aggressive as management. These are usually late presented patient and many a
surgical therapy of GBC is becoming more common as large time palliative stenting to relieve the jaundice remains the only
institutional series demonstrate longer survival times from more intervention to do.
extensive resections.] Long-term survival is possible in early stage of
gallbladder carcinoma. Surgery for gallbladder carcinoma has the Radical/Extended cholecystectomy is the surgery of choice and
International Journal of Scientific Research 3
Volume - 9 | Issue - 12 | December - 2020 PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr

followed by chemotherapy completes the treatment and these are the

only treatment available till date.

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