Surgery 402

Logbook

Research

Topic: Treatment of Complicated and

Uncomplicated Gallstone Disease

Name: Razeen Riyasat Ali

ID: 20180014
Table of Contents
AIM/ OBJECTIVE.................................................................................................................3
METHOD:...........................................................................................................................4
INTRODUCTION..................................................................................................................5
Discussion..........................................................................................................................6
Anatomy and Physiology of the Gallbladder...........................................................................................................6

Pathophysiology of Gall Stone Formation..........................................................................8

Results.............................................................................................................................10
Uncomplicated Gallstone Disease.........................................................................................................................10
a) Biliary Colic:...........................................................................................................................................10
b) Asymptomatic gallstones:........................................................................................................................12
c) Hemolytic Disorders causing pigmented gall stones:..............................................................................13
Complicated Gallstone Disease..............................................................................................................................14
a) Acute Calculous cholecystitis:.................................................................................................................14
b) Choledocholithiasis:................................................................................................................................15
c) Gall Stone Pancreatitis:............................................................................................................................16
d) Gall Stone Ileus:.......................................................................................................................................17
e) Mirizzi Syndrome:....................................................................................................................................19
f) Gallbladder Cancer..................................................................................................................................21

Reference.........................................................................................................................22
AIM/ OBJECTIVE
The aim and objective of this research project is to understand the
anatomy of Gallbladder and the biliary tree as well as understand the
physiology behind bile secretion. Various Gallstone diseases were
also identified and how to treat them was noted. The purpose of this is
to prepare one for hospital periphery when faced with a patient with
gallstone disease.
METHOD:

This research project was compiled after reading and summarizing

various research projects that was taken from Medscape, ACP
Journals, UpToDate, NCBI and PubMed.
Information regarding the subject was also taken from the course
coordinator that is Dr Robert Bancod’s presentations.
INTRODUCTION

The presence of gallstones in the gallbladder (Cholelithiasis) is

common, especially in Western populations. In the United States,
gallstones are seen in roughly 6% of males and 9 percent of females.
Most people with gallstones are asymptomatic for the duration of
their life and gallstones are found unexpectedly. The way to deal with
the administration of patients with gallstones relies on the patient's
manifestations, imaging test findings, and keeping in mind of what
complications are present.

Proper decision making for gallstone disease requires that clinicians

and patients recognize three categories of disease. The first category
includes that of asymptomatic disease in which the gall stones cause
no symptoms, in other words it is called silent gallstones. The next
category is that of uncomplicated biliary pain in which there is a
symptomatic disease. The third category involves complications of
gallstone disease (complicated gallstone disease) such is acute
cholecystitis, cholangitis, gallstone pancreatitis, gallstone ileus and
Mirizzi syndrome.

This project will look at the management approaches to patients with

uncomplicated and complicated gallstone disease.
Discussion

Anatomy and Physiology of the Gallbladder

A) Anatomy
- The gallbladder is a small pear-shaped organ that is located
inferior to the right lobe of the liver
- It is divided into 4 parts which are the neck, infundibulum,
body, and the fundus.
- The cystic duct joins the common bile duct along its course
from the liver to the duodenum
- The Gallbladder is supplied via the cystic artery that is the
branch of the right hepatic artery.
- The triangle of calot aka, cystohepatic triangle is of high
surgical importance because of its content which are the cystic
artery and cystic duct. These 2 structures need to be identified in
the triangle before ligation or during cholecystectomy to avoid
intra-operative injury
- The venous drainage of the gallbladder is via the cystic vein
which drains into the middle hepatic vein.
- The sympathetic nerves that supply the gallbladder are derived
from the 9th thoracic and from the celiac plexus. The right
phrenic nerve also contributes.

B) Physiology
- The primary function of the gallbladder is the storage of bile
- Bile is a fluid that is produced by the liver which aids in the
digestion of fat.
- Bile is released into the duodenum in response to
cholecystokinin (CCK), which is a major hormone responsible
for gallbladder contraction and pancreatic enzyme secretion.
CCK is produced in discrete endocrine cells that line the mucosa
of the small intestine.
- Cholecystokinin (CCK)-containing cells (known as I cells) are
concentrated in the proximal small intestine and decrease in
number toward the distal jejunum and ileum.
- Cholecystokinin (CCK) is secreted in response to ingestion of a
meal, after which plasma concentrations increase approximately
five- to ten-fold
Pathophysiology of Gall Stone Formation

Gallstones are hard, pebble-like structures that obstruct the cystic

duct. The formation of gallstones is often preceded by the presence
of biliary sludge, a viscous mixture of glycoproteins, calcium deposits,
and cholesterol crystals in the gallbladder or biliary ducts

In the U.S., most gallstones consist largely of bile supersaturated with

cholesterol.

This hypersaturation, which results from the cholesterol concentration

being greater than its solubility percentage, is caused primarily by
hypersecretion of cholesterol due to altered hepatic cholesterol
metabolism

A distorted balance between pronucleating (crystallization-promoting)

and antinucleating (crystallization-inhibiting) proteins in the bile also
can accelerate crystallization of cholesterol in the bile.

Loss of gallbladder muscular-wall motility and excessive sphincteric

contraction also are involved in gallstone formation. This hypomotility
leads to prolonged bile stasis (delayed gallbladder emptying).

The lack of bile flow causes an accumulation of bile and an increased

predisposition for stone formation.

Occasionally, gallstones are composed of bilirubin.  Bilirubin stones,

often referred to as pigment stones, are seen primarily in patients with
infections of the biliary tract or chronic hemolytic diseases

The pathogenesis of cholecystitis most commonly involves the

impaction of gallstones in the bladder neck, Hartmann’s pouch, or the
cystic duct.
Pressure on the gallbladder increases, the organ becomes enlarged,
the walls thicken, the blood supply decreases, and an exudate may
form. Cholecystitis can be either acute or chronic, with repeated
episodes of acute inflammation potentially leading to chronic
cholecystitis.

The gallbladder can become infected by various microorganisms,

including those that are gas forming. An inflamed gallbladder can
undergo necrosis and gangrene and, if left untreated, may progress to
symptomatic sepsis

Failure to properly treat cholecystitis may result in perforation of the

gallbladder, a rare but life-threatening phenomenon. Cholecystitis also
can lead to gallstone pancreatitis if stones dislodge down to the
sphincter of Oddi and are not cleared, thus blocking the pancreatic
duct.
Results
Uncomplicated Gallstone Disease

a) Biliary Colic:

i) Acute Pain Management:

a. During an acute attack of biliary colic,

management is focused on pain control. In terms
of Pain the treatment of choice is NSAIDs.
Opioids such as morphine, hydromorphone,
meperidine is reserved for patients who are
contraindicated to NSAIDS or to those who do not
achieve adequate pain relief with NSAIDs.

b. The job of NSAIDs in the treatment of biliary

colic was shown in a meta-examination of 11
randomized trials with 1076 patients that
contrasted NSAIDs with placebo treatment. The
NSAIDs used included ketorolac, diclofenac,
tenoxicam, flurbiprofen, and ketoprofen. NSAIDs
was found to control pain better than placebo
(relative risk [RR] 3.8; 95% confidence interval
[CI] 1.7-8.6) or antispasmodics (RR 1.5; 95% CI
1.0-2.1). There was no distinction in pain control
among NSAIDs and opioids (RR 1.1; 95% CI 0.8-
1.3). NSAIDs may also alter the natural history of
biliary colic, reasonably because of the job of
prostaglandins in the development of acute
cholecystitis.
 c. It was generally felt that Meperidine is the opiate
of choice in patients with Biliary Colic or
Gallstone Pancreatitis since it has less of an
impact on Sphincter of Oddi motility than
Morphine. Nonetheless, all narcotics bring about
increased Sphincter of Oddi pressure. there is
inadequate information proposed that Morphine
should be avoided. Morphine has a benefit and
that is it requires less successive dosing than
Meperidine, which has a more limited half-life

ii) Subsequent Management:

a) Cholecystectomy is indicated for patients who

have had complications related to gallstones in the
past, is at increased risk of gallbladder cancer, has
recurrent attacks of biliary colic.
 (F Zakko, 2021)

b) Asymptomatic gallstones:
i) The majority of patients with asymptomatic
(incidental) gallstones do not require
treatment. Patients can usually be managed
expectantly and referred for
cholecystectomy if symptoms subsequently
develop.

ii) Prophylactic cholecystectomy is

not indicated for patients with asymptomatic
gallstones since the risk of developing life
threatening, severe complications is low, and
if symptoms do occur, they are generally
mild initially. However, patients with
 asymptomatic gallstones must be educated
about the symptoms of gallstone disease so
they can seek treatment before more severe
symptoms or complications develop

iii) There are no prospective trials comparing

surgical or medical therapy for
asymptomatic gallstones. However, decision
analysis models have shown no benefit with
prophylactic cholecystectomy. In fact, one
decision analysis demonstrated that
prophylactic cholecystectomy slightly
decreased survival and was not associated
with an appreciable gain

c) Hemolytic Disorders causing pigmented gall

stones:
i) Those patients with sickle cell
disease and hereditary spherocytosis
commonly cause pigment
gallstones. Hence, because of this,
cholecystectomy is recommended
for patients if they are undergoing
abdominal surgery for some other
reason.

ii) On the other hand, those patients

with hereditary spherocytosis, the
recommendation is to perform
cholecystectomy is the patient has
gallstones, and a splenectomy is
being performed as part of the
treatment of hereditary
spherocytosis.
Complicated Gallstone Disease

The complications of gallstone disease include acute

calculous cholecystitis, choledocholithiasis, gallstone
pancreatitis, gallstone ileus, Mirizzi syndrome and
gallbladder cancer.

a) Acute Calculous cholecystitis:

i) ACC is the most common complication of
cholelithiasis, and it represents 1/3rd of all
surgical emergency admissions.

ii) Laparoscopic cholecystectomy is the

treatment recommended for ACC and the
procedure is ideally performed within 72
hours. As early surgery is associated with
better outcome that in comparison to
delayed surgery.

iii) Recent systematic reviews and analyses

from the WSES concluded that in the
setting of ACC post operative morbidity,
mortality, and hospital stay were
significantly decreased after laparoscopic
cholecystectomy as was the incidence of
pneumonia and wound infection. Severe
haemorrhage, bile leakage rates, and/or
operative times were not significantly
different between patients undergoing
open cholecystectomy and laparoscopic
cholecystectomy. The group of experts
concluded that cholecystectomy in ACC
should be preferably managed by
laparoscopy in the first instance.
 iv) Antimicrobial agents are recommended
for high-risk patients such as the presence
of gallbladder necrosis.

v) Several journals have also stated that the

use of broad-spectrum antibiotics and the
use of antifungals is related to a better
prognosis.

b) Choledocholithiasis:
i) The ideal treatment for
choledocholithiasis should have a high
rate of success and a low rate of
complications

ii) The suggested management for

choledocholithiasis is a matter of debate.

iii) Laparoscopic cholecystectomy is the gold

standard treatment for the treatment of
gall bladder stones. Conversely, the best
approach for choledocholithiasis is still a
matter of debate. In the past, the most
commonly applied procedure was open
common bile duct (CBD) exploration
combined with cholecystectomy for
treating patients with choledocholithiasis

iv) Alongside with the improvement of

endoscopic techniques, endoscopic
retrograde cholangiopancreatography
(ERCP) / Endoscopic sphincterotomy
(EST) plays a progressively important
role in the diagnosis and management of
CBD stone and is recommended by the
2016 European Association for the Study
 of the Liver (EASL) clinical practice
guidelines. The most commonly applied
procedure is preoperative ERCP/EST
followed by Laparoscopic
cholecystectomy, especially in cases
necessitating the relief of biliary
obstruction.

v) On the contrary, several evidence suggest

that sphincter of oddi possibly can get
damaged after EST which may lead to
potential biliary infection and recurrence
of stone

c) Gall Stone Pancreatitis:

i) Gallstones and alcohol are the 2 main

etiologies for acute pancreatitis.

ii) The JPN Guidelines for managing

gallstone-induced acute pancreatitis
recommends two procedures.
iii) Firstly, an urgent endoscopic procedure
should be performed in patients in whom
biliary duct obstruction is suspected and
in patients complicated by cholangitis
(Recommendation A).
iv) Emergency endoscopic approaches to the
management of bile duct stones in
gallstone associated acute pancreatitis
include endoscopic sphincterotomy (ES),
endoscopic papillary balloon dilation
(EPBD), endoscopic nasobiliary drainage
(ENBD), and stenting. Those procedures
are performed to remove gallstones and to
drain the bile duct, which mostly results
 in relieving the obstruction of the
pancreatic duct.

v) Secondly, after the attack of gallstone

pancreatitis has subsided, a laparoscopic
cholecystectomy should be performed
during the same hospital stay
(Recommendation B).

d) Gall Stone Ileus:

i) Gall stone ileus is when gall stones
manage to form a fistula between the gall
bladder and commonly the duodenum and
the stone manages to cause intestinal
obstruction at any portion of the GIT.
ii) If the gallstone managed to enter the
duodenum, then the most common site for
obstruction will be the terminal ileum and
the ileocecal valve because of the narrow
lumen.

iii) To a lesser extent, the gallstone may be

impacted in the proximal ileum or in the
jejunum, especially if the gallstone is
large enough.

iv) Less common locations include the

stomach and the duodenum (Bouveret’s
syndrome), and the colon.
v) The duodenum is most common location
for the fistula due to its proximity to the
gall bladder however it can form with any
position of the gastrointestinal tract.
 (Nuño-Guzmán, 2016)

vi) The current surgical procedures include:

a. Simple enterolithotomy
b. Enterolithotomy, cholecystectomy and
fistula closure (one stage procedure)
c. Enterolithotomy with cholecystectomy
performed later (two stage procedure)
vii) Enterolithotomy is a common surgical
procedure. Through an exploratory
laparotomy, the site of gastrointestinal
obstruction is confined. A longitudinal
incision is made on the antimesenteric
line proximal to the site of gallstone
impaction.
viii) Whenever the situation allows, through
delicate control the gallstone is brought
proximally to a non-edematous fragment
of gut. Most of the occasions, this is hard
because of the grade of impaction of the
 gallstone. The enterotomy is performed
over the gallstone and it is removed.
ix) Cautious closure of the enterotomy is
expected to try not to cause narrowing of
the digestive lumen and a transverse
closure is advised.
x) Intestinal resection is at times vital,
especially within the sight of ischemia,
perforation or stenosis. Manual
movement of the gallstone through the
ileocecal valve is to be saved for certain
circumstances due to risk of mucosal
injury and inside perforation.
Additionally, endeavors to break the
gallstone in situ can harm the gut divider
and ought to be avoided.

e) Mirizzi Syndrome:
i) Pathophysiologically, Mirizzi syndrome is a
condition which involves extrinsic
compression of the bile duct by pressure
applied upon it indirectly from an impacted
stone in the infundibulum or Hartman’s
pouch of the gallbladder
i. Surgery is the mainstay treatment of Mirizzi
syndrome.
ii. If the diagnosis of Mirizzi syndrome is made
preoperatively, endoscopic retrograde
cholangiopancreatography can be both
diagnostic and therapeutic.
iii. If Mirizzi syndrome is diagnosed
incidentally at the time of cholecystectomy,
intraoperative cholangiogram should be
performed prior to cholecystectomy to
confirm the diagnosis and characterize the
biliary anatomy
 iv. For patients who are unsuitable surgical
candidates, endoscopic retrograde
cholangiopancreatography with stenting can
be definitive treatment for Mirizzi syndrome
v. The surgical approach to Mirizzi syndrome
is based on the presence and type of
cholecystobiliary fistula:
a. Type I: Partial or total
cholecystectomy, either
laparoscopic or open. Common
bile duct exploration is typically
not required.
b. Type II: Cholecystectomy plus
closure of the fistula, either by
suture repair with absorbable
material, T tube placement, or
choledochoplasty with the
remnant gallbladder.
c. Type III: Choledochoplasty or
bilioenteric anastomosis
(choledochoduodenostomy,
cholecystoduodenostomy, or
choledochojejunostomy)
depending on the size of the
fistula. Suture of the fistula is not
indicated.
d. Type IV: Bilioenteric
anastomosis, typically
choledochojejunostomy, is
preferred because the entire wall
of the common bile duct has been
destroyed.
vi. The surgeon should also maintain a high
index of suspicion for gall bladder cancer.

f) Gallbladder Cancer.
 i. Gallbladder cancer is the most
common cancer of the biliary tract
worldwide.
ii. Cholelithiasis is a major risk factor but
<1% of patients with cholelithiasis
develop this cancer.
iii. Staging of the gallbladder cancer
follows the TNM classification.
iv. The mainstay treatment is surgical,
either simple or radial cholecystectomy
(partial hepatectomy and regional
lymph node dissection) for stage I and
stage II respectively.
v. Adjuvant therapy has not been proven
to be effective.
vi. Gallbladder cancers at stages III and
IV are considered to be unresectable.
vii. For patients with ECOG 0-1,
chemotherapy with gemcit- abine and
cisplatin is the standard of practice
based on data from the subgroup
analysis including 181 patients with
gallbladder cancer in the setting of two
clinical trials. Overall, median survival
is 10–12 months in advanced cases.
Percutaneous transhepatic drainage is
indicated in case of biliary obstruction.
viii. Radiotherapy is not effective.
Reference

Gomes, C., Junior, C., Di Saveiro, S., Sartelli, M., Kelly, M., Gomes,
C., Gomes, F., Correa, L., Alves, C. and Guimarães, S., 2017. Acute
calculous cholecystitis: Review of current best practices. World
Journal of Gastrointestinal Surgery, 9(5), p.118.

F Zakko, S., 2021. Approach to the management of gallstones.

[online] Www-uptodate-com.unifiji.idm.oclc.org. Available at:
<https://www-uptodate-com.unifiji.idm.oclc.org/contents/image?
imageKey=GAST%2F104170&topicKey=GAST
%2F673&search=Mirizzi
%20Syndrome&rank=6~18&source=see_link> [Accessed 19
September 2021].

Zhu, J., Wu, S., Feng, Q., Li, F., Han, W., Xiu, D., Tan, H., Fu, J., Li,
X., Shang, D., Liu, H., Li, B., Yang, L., Kong, Y., Zhan, S., Guo, W.
and Zhang, Z., 2019. Protocol for the CREST Choles (Chinese
REgistry Study on Treatment of Cholecysto-Choledocholithiasis)
study: an ambispective, multicenter, observational, open-cohort
study. BMJ Open, 9(11), p.e030293.

Nuño-Guzmán, C., 2016. Gallstone ileus, clinical presentation,

diagnostic and treatment approach. World Journal of Gastrointestinal
Surgery, 8(1), p.65.

Wang, Y., Oh, S., Boo, J., Abraham, A. and Tan, M., 2019. Surgical
challenges in Mirizzi's syndrome from retained cystic duct - common
bile duct junction stones after subtotal cholecystectomy. HPB, 21,
p.S328.
Umashanker, R. and Smink, D., 2021. Mirizzi syndrome. [online]
Www-uptodate-com.unifiji.idm.oclc.org. Available at: <https://www-
uptodate-com.unifiji.idm.oclc.org/contents/mirizzi-syndrome?
search=Mirizzi
%20Syndrome&source=search_result&selectedTitle=1~18&usage_ty
pe=default&display_rank=1> [Accessed 21 September 2021].

Chen, H., Siwo, E., Khu, M. and Tian, Y., 2018. Current trends in the
management of Mirizzi Syndrome. Medicine, 97(4), p.e9691.

Simore Afamefuna, G., 2021. Gallbladder Disease:

Pathophysiology, Diagnosis, and Treatment. [online]
Uspharmacist.com. Available at:
<https://www.uspharmacist.com/article/gallbladder-disease-
pathophysiology-diagnosis-and-treatment> [Accessed 21
September 2021].

Carey, M., 1992. Pathogenesis of gallstones. PuBMed.gov,

[online] Available at:
<https://pubmed.ncbi.nlm.nih.gov/1529152/> [Accessed 21
September 2021].