Thesis synopsis profarma

1. SYNOPSIS PRESENTATION
Submitted by – Dr Angela Ankita Suna (Junior Resident)
Department of Pathology
Under the guidance of –
Dr. Reena Banerjee, Associate Professor (Guide)
Dr. Pooja Waghmare, Assistant Professor (Co-guide)
Department of Pathology

2. TITLE:
HISTOPATHOLOGICAL CHANGES IN
GALLBLADDER MUCOSA ASSOCIATED
WITH GALLSTONES: A PROSPECTIVE
STUDY

3. Introduction
Gallstone disease is an emerging health problem worldwide including
India. It is most commonly observed in northwestern India due to
the prevalence of sedentary lifestyle and cholesterol-rich diet.[2][5]
Most of the cases of Cholelithiasis are asymptomatic and only 10 –
20% will become symptomatic, warranting a therapeutic
intervention. [4]
Cholelithiasis gives rise to a range of histopathological alterations in
the mucosa of the gallbladder. These include inflammation (both
acute and chronic), hyperplasia, cholesterolosis, dysplasia and
carcinoma, showcasing the diverse nature of changes caused by his
condition.[4][6]

4. Cholelithiasis, regardless of age or sex, is often linked to carcinoma of
the gallbladder in a significant percentage ranging from 40% to
100%, making it the most prevalent contributing factor. [7]
This study is planned to investigate and find out incidence of different
histological changes (neoplastic and non-neoplastic) in the
gallbladder mucosa in cases of Cholelithiasis.

5. Review of literature
• Khannaetal.[3] in 2002, studied140 gallbladders, on microscopy
they describe epithelial hyperplasia (69%), antral metaplasia
(16.5%), intestinal metaplasia (15.5%), dysplasia (8.5%) and
carcinoma in situ (0.7%). They concluded that gallstones can
produce a series of histopathological changes in the gallbladder
mucosa which can then become a malignant precursor lesion.
• Zuhair et al.[5]in 2010 studied total 30 patients in which mucosal
hyperplasia was noted in 26.6% cases, Rokitansky- Aschoff sinuses
in 13.3%, distended columnar cells in 23.3% and mucus gland
metaplasia was found in 26.6% of cases. Hence, concluding that
major changes were seen in the gallbladder mucosa in relation to
gallstones.

6. • According to Sharma et al. [8],in their study in 2014 of 100 cases,
they demonstrated that the epithelium exhibited various
histopathological features, involving focal and diffuse ulceration,
hyperplasia, atrophy and metaplasia of pyloric and intestinal
type.These histopathological changes occurring in the gallbladder
mucosa alters the normal tissue pattern and can bring on the
process of carcinogenic progression and metastasis.
• Nasar et al.[9] in 2016, studied 104 specimens, in which most
common histological findings observed were hemorrhage and
congestion seen (74%), then antral metaplasia (73.1%), epithelial
hyperplasia (62.5%) and intestinal metaplasia (51.9%). Normal
epithelium was noted in 10.6%. Also noted were 55 cases with
antral metaplasia, 43 with epithelial ulceration, 25 with Rokitansky-
aschoff sinuses and 24 cases with Cholesterolosis.

7. • As per Singh et al. [4] in 2019, who studied total 100 patients
undergoing cholecystectomy, show that most of the cases i.e., 79%
presented with chronic inflammation, 8% with chronic cholecystitis
with metaplasia, another 2% were diagnosed with carcinoma and
1% of cases were seen with intestinal metaplasia. They concluded
that gallstones are accompanied by major changes in the
gallbladder mucosa mainly due to the irritation caused by the large
stones in the background of the toxic effects caused by the bile.
• According to Kumar et al.[2] in 2022, studied total 150 cases, in
which they found that most common change observed in
gallbladder mucosa was Chronic cholecystitis, seen in 110 cases
(73.3%), Cholesterolosis in 15 cases (10%), acute on chronic
cholecystitis and xanthogranulomatous cholecystitisin 3 cases each
(2%), with one case (0.6%) each of mucocele and follicular
cholecystitis. Adenomatous and adenomyomatous were found in 8
cases (5.3%) along with cholecystitis with metaplasia in 5 cases
(3.3%). Also noted were 4 cases (2.6%) of carcinoma, predominantly
Adenocarcinoma.

8. • In the case of Anand et al. [7], who studied 72 specimens in 2022,
out of which calculous cholecystitis was seen in 62 (86%) and
acalculous cholecystitis was found in 10 (14%). They also came to
the conclusion that malignancy of the gallbladder was a rare
occurrence in the studied population.

9. Research Question
1. What is the incidence of non-neoplastic and neoplastic lesions
occurring in cases of cholelithiasis?
2. What are the various histopathological changes in the gallbladder
mucosa due to Cholelithiasis?

10. Aims and Objective
1. To study the incidence of non-neoplastic and neoplastic
lesions occurring in cases of Cholelithiasis
2. To study the various histopathological changes in the
gallbladder mucosa due to Cholelithiasis.
3. To evaluate the age and gender distribution of changes
occurring in cases of Cholelithiasis.

11. Material and Objective
a.Study Design: This is a cross sectional hospital based observational
study.
b. Study Setting: All the open and laparoscopic cholecystectomy
specimens received for histopathological examination at Central
laboratory, Department of Pathology, Shri Shankaracharya Institute
of Medical Sciences will be included.
c. StudyDuration:2 years.

12. d. Sample size: In a study published by Hema M et al[1] in 2019, they
found that the prevalence of neoplastic lesions occurring in
gallbladder is 2.5%. Therefore, the sample size for this study is
determined to be minimum sample size 105, to be sufficient to
estimate prevalence of neoplastic lesions occurring in gallbladder,
at 95% confidence interval and 3% allowable error in estimate.
e. Sampling method: Convenience sampling.
f. Inclusion criteria: All fixed and well preserved open and laparoscopic
cholecystectomy specimens of gallbladder with gallstones received
at histopathological section in the Department of pathology after
surgeries performed at SSIMS hospital.

13. g. Exclusion criteria:
– Autolyzed specimens.
– End organ damage.

14. Study plan/ Data collection
• The proposed study will be carried out on the biopsy specimens
submitted to the Department of Pathology, SSIMS, Junwani, Bhilai
during the period of 2 years. Clinical details like sociodemographic
profile, clinical findings, provisional diagnosis and procedure
performed will be collected for these cases. Biopsy of gallbladder
specimen received will be initially fixed in 10% formalin. Gross
findings will be recorded and specimen will be processed by routine
histological techniques.
• 1. Submitted biopsies will be processed -
– Cholecystectomy specimen will be partially embedded after taking
sections from neck, body and fundus of the gallbladder.
– Presence of stones will be noted.
– Additional sections will be taken from abnormal-looking areas if
deemed necessary. 2.

15. 2. Tissue blocks will be prepared and sections will be cut into 5-micron
thickness using rotatory microtome.
3. Subsequently sections will be stained with Hematoxylin and Eosin
stain (H&E stain), Periodic acid Schiff (PAS) and Alcian blue.
4. All the slides of the cases will be retrieved and examined for
diagnostic confirmation.

16. Data entry and Analysis
• The data will store in Microsoft Excel Spreadsheet and
analysis will be done using IBM SPSS statistics version 28.0.
• The data will be represented in form of table and graphs.
Frequency, percentage and descriptive statistics will be use
to summarize data.
• To check the normality of data Shapiro-Wilk test will use.
• Further, to detect the difference between continuous
normally distributed variables t- test will be used (for non-
normally distributed variable Mann Whitney U test will be
used).
• Chi-square test /Fisher exact test will be used to detect the
association between nominal/ordinal variables.
• P-value less than 0.05 will be consider significant.

17. • Feasibility (If any other Dept. & Institute is involved name and
signature of the head)
Technical : Not Applicable
Infrastructural : Not Applicable
Financial : Not Applicable
• Ethical consideration: Approval of the institutional ethics committee
will be taken prior to initiating the study.

18. References
1. Hema M et al. Neoplastic diseases of the gallbladder- a 5-year study, Indian Journal of
Pathology and Oncology, October-December 2017;4(4):551-554
2. Kumar, Sanjeew et al. Relevance of Stones in Gall Bladder Histology in A Tertiary Care Hospital
in Sasaram, International Journal of Scientific Research. 9-10. 10.36106/ijsr/0700449.
3. Khanna R, Chansuria R, Kumar M, Shukla HS. Histological changes in gallbladder due to stone
disease. Indian J surg. 2006 Aug 1;68(4):201-4.
4. Singh A, Singh G, Kaur K, Goyal G, Saini G, Sharma D. Histopathological changes in gallbladder
mucosa associated with cholelithiasis: a prospective study. Nigerian Journal of Surgery.
2019;25(1):21-5.
5. Zuhair M. Histological changes of gall bladder mucosa: correlation with various types of
cholelithiasis. Iraqi journal of community medicine. 2011;24(3).
6. Zaki M, Al-Refeidi A. Histological changes in the human gallbladder epithelium associated with
gallstones. Oman Medical Journal. 2009 Oct 1;24(4):269-73.
7. Ikram F, Anand S, Singh P. A Study on Histopathological Changes in Spectrum of Gallbladder
Diseases. European Journal of Molecular & Clinical Medicine. 2022 Aug 5;9(4):1970-5.
8. Sharma H, Sharma M, Gupta G. Evaluation of histological changes in chronic cholecystitis and
cholelithiasis of the human gallbladder. Int J Anat Res. 2014;2(4):752- 6.
9. AreebaNasar, SadiqWadood Siddiqui, Prerna Gupta, Anas Ahmad Khan, Neel Kamal
Arora,Histological Changes of Gall Bladder Mucosa and Its Correlation with Various Types of
Cholelithiasis, J Res Med Dent Sci, 2021, 9(7): 211-218