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CHOLECYSTITIS & CARCINOMA OF
GALLBLADDER
SITI NUR BAITI
BINTI
SHAIK KHAMARUDIN
012013100196
1
OUTLINE
• Objectives
• Definition of cholecystitis
• Classification of cholecystitis
• Carcinoma of gallbladder
• Summary
• References
2
OBJECTIVES
To study and understand:
• What is cholecystitis?
• Classification of cholecystitis
• Pathogenesis, morphology, clinical features of
different groups of cholecystitis.
• Carcinoma of gallbladder
3
DEFINITION
What is cholecystitis?
Inflammation of the gallbladder is called
cholecystitis.
• In Malaysia, the diseases of gastrointestinal
system are getting chronic by days, making
them as one of the top 10 most prevalent
causes of death.
4
CLASSES OF CHOLECYSTITIS
CHOLECYSTITIS
ACUTE
CALCULOUS
ACALCULOUS
CHRONIC
5
ACUTE CALCULOUS
CHOLECYSTITIS
6
DEFINITION
Acute inflammation of gallbladder that contains
stones and is precipitated by obstruction of the
gallbladder neck or cystic duct.
• The most common major complication of
gallstones.
• The most common reason for emergency
cholecystectomy.
Neck
7
PATHOGENESIS
8
• Acute CALCULOUS cholecystitis results from
chemical irritation and inflammation of the
obstructed gallbladder.
• The action of mucosal phospholipases
hydrolyzes luminal lecithins (phospholipids) to
toxic LYSOLECITHINS.
• The normally protective glycoprotein mucus
layer is disrupted, exposing the mucosal
epithelium to the direct DETERGENT action of
bile salts.
9
• Prostaglandins released within the wall of the
distended gallbladder contribute to mucosal
and mural inflammation.
• Gallbladder dysmotility develops
distention and increased intraluminal
pressure
compromise blood flow to the mucosa.
ischemia
MORPHOLOGY
In acute cholecystitis
basically,
• Gallbladder is usually
enlarged and tense
• Characterized as a bright
red or blotchy, violaceous to
green-black discolouration.
• Imparted by subserosal
haemorrhages.
• Serosal covering is layered
by:
▫ Fibrin
▫ Definite suppurative
10
In acute calculous cholecystitis,
• Obstructing stones are usually present in the
neck of the gallbladder or cystic duct.
• The gallbladder lumen may contain one or more
stones, filled with cloudy or turbid bile which
may contain large amounts of fibrin, pus and
haemorrhage.
11
• Empyema of gallbladder – the contained
exudate is virtually pure pus.
• In mild cases, the wall is thickened, edematous
and hyperemic.
• Gangrenous cholecystitis – severe,
gallbladder turns into green-black necrotic
organ, with small-to-large perforations.
• Acute emphysematous cholecystitis –
invasion of gas-forming organisms i.e., clostridia
and coliforms.
12
CLINICAL FEATURES
 Patients usually, not always,
experienced previous episodes of
pain.
 May appear with remarkable
suddenness & constitute an
acute surgical emergency.
 Or may present with mild
symptoms without medical
intervention.
 Attacks usually subside in 7-10
days.
 25% of patients progressively
develop more severe symptoms
– immediate surgical
intervention.
 Recurrence is common after
13
ACUTE ACALCULOUS
CHOLECYSTITIS
14
Acute inflammation of
gallbladder that has no
relation with gallstones.
• 5%-12% of gallbladders
removal contain no
gallstones.
• Mostly happen in seriously
ill patients.
DEFINITION
15
Preoperative condition with
inflamed gallbladder
RISK FACTORS
(1) Sepsis with hypotension and multisystem organ
failure;
(2) Immunosuppression
(3) Major trauma and burns
(4) Diabetes mellitus
(5) Infections
(Salmanellosis & Cholera), Parasitic infestation
16
Subserosal perforation in diabetic
patient with acute
emphysematous cholecystitis.
PATHOGENESIS
Results from ischemia of cystic artery
Contributing factors:
- Inflammation & edema of the wall that compromise blood flow
- Gallbladder stasis
-Accumulation of microcrystals of cholesterol (biliary sludge)
-Viscous bile
-Gallbladder mucus
Cystic duct obstruction in the absence of frank stone formation
17
MORPHOLOGY
• There are no specific morphologic differences
between acute acalculous and calculous
cholecystitis, except for the absence of
macroscopic stones in acalculous form.
18
CLINICAL FEATURES
• The symptoms are more
insidious – underlying
conditions.
• Higher proportion of patients –
no symptoms referable to
gallbladder.
• Incidence of gangrene and
perforation is higher than in
calculous cholecystitis.
• Rarely, acute acalculous occurs
due to primary bacterial infection
(e.g., Salmonella typhi,
staphylococci).
• Less painful acute acalculous –
systemic vasculitis, severe
atherosclerotic ischemic disease
in elderly, AIDS patients & biliary
tract infection.
19
Gangrenous gallbladder
with empyema
Perforation
(hole/piercing)
at the apex of
gallbladder
MANAGEMENT FOR ACUTE
CHOLECYSTITIS
• Initial treatment management is conservative, consisting of nil
by mouth, IV fluids, opiate analgesia and IV antibiotics
(cephalosporins, fluoroquinolones or
piperacillin/tazobactam).
• Cholecystectomy cures acute cholecystitis and relieves
biliary pain. It is usually delayed for a few days to allow the
symptoms to settle.
• Surgery may be delayed when patients have an underlying
severe chronic disorder (eg, cardiopulmonary) that increases
the surgical risks. In such patients, cholecystectomy is
deferred until medical therapy stabilizes the comorbid
disorders or until cholecystitis resolves.
▫ If cholecystitis resolves, cholecystectomy may be done ≥ 6
wk later. Delayed surgery carries the risk of recurrent biliary
complications.
20
CHRONIC CHOLECYSTITIS
21
CHRONIC CHOLECYSTITIS
• In most cases, it develops without any history if
acute attacks, but in some cases, it happens as
a sequel to repeated bouts of acute
cholecystitis.
• Almost associated with gallstones but they do
not have direct role in development of pain or
inflammation.
▫ Symptoms and morphologic alterations similar to
those seen in calculous form.
• Since it is associated with cholelithiasis in more
than 90% of cases, the patient populations are the
same as those for gallstones.
22
MORPHOLOGY – GROSS
• The serosa - smooth and glistening but maybe dulled by subserosal
fibrosis.
• Dense fibrous adhesions.
• Wall - thickened with opaque gray-white appearance.
• In uncomplicated cases – lumen contains fairly clear, green-yellow,
mucoid bile and stones.
• Mucosa is preserved.
23
Notice thickness of galldladder wall, abundant polyhedric stones
and small papillary tumor in the cystic duct.
Morphology – histologic examination
• In the mildest cases, only
scattered lymphocytes,
plasma cells and
macrophages are found in
the mucosa & subserosal
fibrous tissue.
• In advanced cases, there is
marked subepithelial &
subserosal fibrosis, with
mononuclear cell infiltration.
• Buried crypts of epithelium
due to reactive proliferation
of mucosa & fusion of
mucosal folds.
• Outpouchings of mucosal
epithelium through the wall –
24
Enlarged mucosal folds of the
gallbladder and infiltrate of foamy
histiocytes, very little inflammation,
found in the muscular wall and
serosal fat.
25
The gallbladder mucosa is
infiltrated by inflammatory cells
Outpouching of the mucosa
through the wall forms
Rokitansky-Aschoff sinus
(contains bile).
CLINICAL FEATURES
• Has no striking manifestations of acute forms.
• Usually characterized by recurrent attacks of
steady epigastric or right upper quadrant
pain.
• Nausea, vomiting and intolerance for fatty foods.
26
CARCINOMA OF GALLBLADDER
27
EPIDEMIOLOGY
More common
in women
Occurs in 7th
decade of life
Mexico & Chile
– high
incidence of
gallstone
disease
In US, most
common in
Hispanics and
Native
Americans
Although
uncommon, it
is the most
frequent
malignant
tumor of biliary
tract
28
PATHOGENESIS
• Gallbladder cancer arises in the
setting of chronic
inflammation. In the vast
majority of patients (>75%), the
source of this chronic
inflammation is
cholesterol gallstones.
• The presence of gallstones
increases the risk of gallbladder
cancer 4- to 5-fold.
• Other unusual causes are
associated with gallbladder
cancer, including primary
sclerosing cholangitis, ulcerative
colitis, liver flukes,
chronic Salmonella typhi and
paratyphi infections, and
Helicobacter infection.
29
MORPHOLOGY
Cancer may exhibit exophytic or infiltrating
growth patterns.
• The infiltrating pattern is more common and
usually appears as a poorly defined area of
thickening and induration of the gallbladder wall.
• Deep ulceration can cause direct penetration of
gallbladder wall or fistula formation to adjacent
viscera where neoplasm grow.
• These tumors are scirrhous and very firm.
30
• The exophytic pattern grows into the lumen as an
irregular, cauliflower-like mass but also invades the
underlying wall.
• Luminal portion may be necrotic, hemorrhagic
and ulcerated.
• Most common sites: fundus & neck; 20% involve
lateral walls.
31
The opened gallbladder contains a large, exophytic tumor
that virtually fills the lumen
• Most are adenocarcinomas – may be papillary or
poorly differentiated.
• About 5% are squamous cell carcinomas.
• Neuroendocrine tumors, which is rare, also occur.
• By the time this cancer is discovered, most have invaded
the liver or spread to the bile ducts or portal hepatic
lymph nodes.
32
Papillary pattern
CLINICAL FEATURES
• Onset is insidious and indistinguishable from those
associated with cholelithiasis (e.g., abdominal pain,
jaundice, anorexia and nausea and vomiting).
• Early detection may be possible in patients with
palpable gallbladder & acute cholecystitis before
extension of tumor into adjacent structures.
• Or when carcinoma is found during
cholecystectomy.
33
PROGNOSIS
• Outlook by stage
• Sadly, for most people cancer
of the gallbladder does not
have a very good outlook.
• By the time it is diagnosed, it is
often in the later stages and
treatment is unlikely to cure
it.
• 1 out of 10 (10%) will live for
more than 5 years.
34
Although overall prognosis is improving, many patients with
gallbladder cancer continue to have advanced disease at the
time of their diagnosis, and subsequent poor survival rates.
May 2009 issue of the Archives of Surgery.
SUMMARY
• Cholecystitis is the inflammation of the
gallbladder, almost always associated with
gallstones.
• Divided into acute (calculous & acalculous) and
chronic.
• Carcinoma of gallbladder is a rare disease in
which malignant (cancer) cells form in the
tissues of the gallbladder.
• Although carcinoma of gallbladder is a rare
disease, it has a bad prognosis.
35
REFERENCE
• Robbins Basic Pathology – 9th Edition
• Robbins and Cotran Pathologic Basis of Disease – 8th Edition
• http://emedicine.medscape.com/article/278641-
overview#aw2aab6b2b2aa
• http://www.medicinenet.com/gallbladder_cancer/article.htm
• http://www.medscape.com/viewarticle/703085
• http://www.cancerresearchuk.org/about-
cancer/type/gallbladder-cancer/treatment/statistics-and-
outlook-for-gallbladder-cancer#outlook
• Kumar & Clarks’s Clinical Medicine – 7th edition
• http://www.merckmanuals.com/professional/hepatic_and_bilia
ry_disorders/gallbladder_and_bile_duct_disorders/acute_chol
ecystitis.html
36
THANK YOU FOR YOUR ATTENTION
37

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Cholecystitis & carcinoma of gallbladder

  • 1. CHOLECYSTITIS & CARCINOMA OF GALLBLADDER SITI NUR BAITI BINTI SHAIK KHAMARUDIN 012013100196 1
  • 2. OUTLINE • Objectives • Definition of cholecystitis • Classification of cholecystitis • Carcinoma of gallbladder • Summary • References 2
  • 3. OBJECTIVES To study and understand: • What is cholecystitis? • Classification of cholecystitis • Pathogenesis, morphology, clinical features of different groups of cholecystitis. • Carcinoma of gallbladder 3
  • 4. DEFINITION What is cholecystitis? Inflammation of the gallbladder is called cholecystitis. • In Malaysia, the diseases of gastrointestinal system are getting chronic by days, making them as one of the top 10 most prevalent causes of death. 4
  • 7. DEFINITION Acute inflammation of gallbladder that contains stones and is precipitated by obstruction of the gallbladder neck or cystic duct. • The most common major complication of gallstones. • The most common reason for emergency cholecystectomy. Neck 7
  • 8. PATHOGENESIS 8 • Acute CALCULOUS cholecystitis results from chemical irritation and inflammation of the obstructed gallbladder. • The action of mucosal phospholipases hydrolyzes luminal lecithins (phospholipids) to toxic LYSOLECITHINS. • The normally protective glycoprotein mucus layer is disrupted, exposing the mucosal epithelium to the direct DETERGENT action of bile salts.
  • 9. 9 • Prostaglandins released within the wall of the distended gallbladder contribute to mucosal and mural inflammation. • Gallbladder dysmotility develops distention and increased intraluminal pressure compromise blood flow to the mucosa. ischemia
  • 10. MORPHOLOGY In acute cholecystitis basically, • Gallbladder is usually enlarged and tense • Characterized as a bright red or blotchy, violaceous to green-black discolouration. • Imparted by subserosal haemorrhages. • Serosal covering is layered by: ▫ Fibrin ▫ Definite suppurative 10
  • 11. In acute calculous cholecystitis, • Obstructing stones are usually present in the neck of the gallbladder or cystic duct. • The gallbladder lumen may contain one or more stones, filled with cloudy or turbid bile which may contain large amounts of fibrin, pus and haemorrhage. 11
  • 12. • Empyema of gallbladder – the contained exudate is virtually pure pus. • In mild cases, the wall is thickened, edematous and hyperemic. • Gangrenous cholecystitis – severe, gallbladder turns into green-black necrotic organ, with small-to-large perforations. • Acute emphysematous cholecystitis – invasion of gas-forming organisms i.e., clostridia and coliforms. 12
  • 13. CLINICAL FEATURES  Patients usually, not always, experienced previous episodes of pain.  May appear with remarkable suddenness & constitute an acute surgical emergency.  Or may present with mild symptoms without medical intervention.  Attacks usually subside in 7-10 days.  25% of patients progressively develop more severe symptoms – immediate surgical intervention.  Recurrence is common after 13
  • 15. Acute inflammation of gallbladder that has no relation with gallstones. • 5%-12% of gallbladders removal contain no gallstones. • Mostly happen in seriously ill patients. DEFINITION 15 Preoperative condition with inflamed gallbladder
  • 16. RISK FACTORS (1) Sepsis with hypotension and multisystem organ failure; (2) Immunosuppression (3) Major trauma and burns (4) Diabetes mellitus (5) Infections (Salmanellosis & Cholera), Parasitic infestation 16 Subserosal perforation in diabetic patient with acute emphysematous cholecystitis.
  • 17. PATHOGENESIS Results from ischemia of cystic artery Contributing factors: - Inflammation & edema of the wall that compromise blood flow - Gallbladder stasis -Accumulation of microcrystals of cholesterol (biliary sludge) -Viscous bile -Gallbladder mucus Cystic duct obstruction in the absence of frank stone formation 17
  • 18. MORPHOLOGY • There are no specific morphologic differences between acute acalculous and calculous cholecystitis, except for the absence of macroscopic stones in acalculous form. 18
  • 19. CLINICAL FEATURES • The symptoms are more insidious – underlying conditions. • Higher proportion of patients – no symptoms referable to gallbladder. • Incidence of gangrene and perforation is higher than in calculous cholecystitis. • Rarely, acute acalculous occurs due to primary bacterial infection (e.g., Salmonella typhi, staphylococci). • Less painful acute acalculous – systemic vasculitis, severe atherosclerotic ischemic disease in elderly, AIDS patients & biliary tract infection. 19 Gangrenous gallbladder with empyema Perforation (hole/piercing) at the apex of gallbladder
  • 20. MANAGEMENT FOR ACUTE CHOLECYSTITIS • Initial treatment management is conservative, consisting of nil by mouth, IV fluids, opiate analgesia and IV antibiotics (cephalosporins, fluoroquinolones or piperacillin/tazobactam). • Cholecystectomy cures acute cholecystitis and relieves biliary pain. It is usually delayed for a few days to allow the symptoms to settle. • Surgery may be delayed when patients have an underlying severe chronic disorder (eg, cardiopulmonary) that increases the surgical risks. In such patients, cholecystectomy is deferred until medical therapy stabilizes the comorbid disorders or until cholecystitis resolves. ▫ If cholecystitis resolves, cholecystectomy may be done ≥ 6 wk later. Delayed surgery carries the risk of recurrent biliary complications. 20
  • 22. CHRONIC CHOLECYSTITIS • In most cases, it develops without any history if acute attacks, but in some cases, it happens as a sequel to repeated bouts of acute cholecystitis. • Almost associated with gallstones but they do not have direct role in development of pain or inflammation. ▫ Symptoms and morphologic alterations similar to those seen in calculous form. • Since it is associated with cholelithiasis in more than 90% of cases, the patient populations are the same as those for gallstones. 22
  • 23. MORPHOLOGY – GROSS • The serosa - smooth and glistening but maybe dulled by subserosal fibrosis. • Dense fibrous adhesions. • Wall - thickened with opaque gray-white appearance. • In uncomplicated cases – lumen contains fairly clear, green-yellow, mucoid bile and stones. • Mucosa is preserved. 23 Notice thickness of galldladder wall, abundant polyhedric stones and small papillary tumor in the cystic duct.
  • 24. Morphology – histologic examination • In the mildest cases, only scattered lymphocytes, plasma cells and macrophages are found in the mucosa & subserosal fibrous tissue. • In advanced cases, there is marked subepithelial & subserosal fibrosis, with mononuclear cell infiltration. • Buried crypts of epithelium due to reactive proliferation of mucosa & fusion of mucosal folds. • Outpouchings of mucosal epithelium through the wall – 24 Enlarged mucosal folds of the gallbladder and infiltrate of foamy histiocytes, very little inflammation, found in the muscular wall and serosal fat.
  • 25. 25 The gallbladder mucosa is infiltrated by inflammatory cells Outpouching of the mucosa through the wall forms Rokitansky-Aschoff sinus (contains bile).
  • 26. CLINICAL FEATURES • Has no striking manifestations of acute forms. • Usually characterized by recurrent attacks of steady epigastric or right upper quadrant pain. • Nausea, vomiting and intolerance for fatty foods. 26
  • 28. EPIDEMIOLOGY More common in women Occurs in 7th decade of life Mexico & Chile – high incidence of gallstone disease In US, most common in Hispanics and Native Americans Although uncommon, it is the most frequent malignant tumor of biliary tract 28
  • 29. PATHOGENESIS • Gallbladder cancer arises in the setting of chronic inflammation. In the vast majority of patients (>75%), the source of this chronic inflammation is cholesterol gallstones. • The presence of gallstones increases the risk of gallbladder cancer 4- to 5-fold. • Other unusual causes are associated with gallbladder cancer, including primary sclerosing cholangitis, ulcerative colitis, liver flukes, chronic Salmonella typhi and paratyphi infections, and Helicobacter infection. 29
  • 30. MORPHOLOGY Cancer may exhibit exophytic or infiltrating growth patterns. • The infiltrating pattern is more common and usually appears as a poorly defined area of thickening and induration of the gallbladder wall. • Deep ulceration can cause direct penetration of gallbladder wall or fistula formation to adjacent viscera where neoplasm grow. • These tumors are scirrhous and very firm. 30
  • 31. • The exophytic pattern grows into the lumen as an irregular, cauliflower-like mass but also invades the underlying wall. • Luminal portion may be necrotic, hemorrhagic and ulcerated. • Most common sites: fundus & neck; 20% involve lateral walls. 31 The opened gallbladder contains a large, exophytic tumor that virtually fills the lumen
  • 32. • Most are adenocarcinomas – may be papillary or poorly differentiated. • About 5% are squamous cell carcinomas. • Neuroendocrine tumors, which is rare, also occur. • By the time this cancer is discovered, most have invaded the liver or spread to the bile ducts or portal hepatic lymph nodes. 32 Papillary pattern
  • 33. CLINICAL FEATURES • Onset is insidious and indistinguishable from those associated with cholelithiasis (e.g., abdominal pain, jaundice, anorexia and nausea and vomiting). • Early detection may be possible in patients with palpable gallbladder & acute cholecystitis before extension of tumor into adjacent structures. • Or when carcinoma is found during cholecystectomy. 33
  • 34. PROGNOSIS • Outlook by stage • Sadly, for most people cancer of the gallbladder does not have a very good outlook. • By the time it is diagnosed, it is often in the later stages and treatment is unlikely to cure it. • 1 out of 10 (10%) will live for more than 5 years. 34 Although overall prognosis is improving, many patients with gallbladder cancer continue to have advanced disease at the time of their diagnosis, and subsequent poor survival rates. May 2009 issue of the Archives of Surgery.
  • 35. SUMMARY • Cholecystitis is the inflammation of the gallbladder, almost always associated with gallstones. • Divided into acute (calculous & acalculous) and chronic. • Carcinoma of gallbladder is a rare disease in which malignant (cancer) cells form in the tissues of the gallbladder. • Although carcinoma of gallbladder is a rare disease, it has a bad prognosis. 35
  • 36. REFERENCE • Robbins Basic Pathology – 9th Edition • Robbins and Cotran Pathologic Basis of Disease – 8th Edition • http://emedicine.medscape.com/article/278641- overview#aw2aab6b2b2aa • http://www.medicinenet.com/gallbladder_cancer/article.htm • http://www.medscape.com/viewarticle/703085 • http://www.cancerresearchuk.org/about- cancer/type/gallbladder-cancer/treatment/statistics-and- outlook-for-gallbladder-cancer#outlook • Kumar & Clarks’s Clinical Medicine – 7th edition • http://www.merckmanuals.com/professional/hepatic_and_bilia ry_disorders/gallbladder_and_bile_duct_disorders/acute_chol ecystitis.html 36
  • 37. THANK YOU FOR YOUR ATTENTION 37