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CHOLECYSTITIS & CARCINOMA OF GALLBLADDER

SITI NUR BAITI BINTI

SHAIK KHAMARUDIN 012013100196

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OUTLINE

•Objectives•Definition of cholecystitis•Classification of cholecystitis•Carcinoma of gallbladder•Summary•References

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OBJECTIVES To study and understand:•What is cholecystitis?•Classification of cholecystitis•Pathogenesis, morphology, clinical

features of different groups of cholecystitis.

•Carcinoma of gallbladder

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DEFINITIONWhat 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.

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CLASSES OF CHOLECYSTITIS

CHOLECYSTITIS

ACUTE

CALCULOUS

ACALCULOUS

CHRONIC

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ACUTE CALCULOUS CHOLECYSTITIS

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DEFINITIONAcute 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

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PATHOGENESIS

•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.

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• 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

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MORPHOLOGYIn 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

coagulated exudate – severe

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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.

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•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.

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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

recovery.

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ACUTE ACALCULOUS CHOLECYSTITIS

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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

Preoperative condition with inflamed gallbladder

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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

Subserosal perforation in diabetic patient with acute emphysematous cholecystitis.

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PATHOGENESISResults 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

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MORPHOLOGY

•There are no specific morphologic differences between acute acalculous and calculous cholecystitis, except for the absence of macroscopic stones in acalculous form.

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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.

Gangrenous gallbladder with empyema

Perforation (hole/piercing) at the apex of gallbladder

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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.

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CHRONIC CHOLECYSTITIS

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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.

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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.

Notice thickness of galldladder wall, abundant polyhedric stones and small papillary tumor in the cystic duct.

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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 – Rokitansky-Aschoff sinuses

Enlarged mucosal folds of the gallbladder and infiltrate of foamy histiocytes, very little inflammation, found in the muscular wall and serosal fat.

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The gallbladder mucosa is infiltrated by inflammatory cells

Outpouching of the mucosa through the wall formsRokitansky-Aschoff sinus (contains bile).

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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.

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CARCINOMA OF GALLBLADDER

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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

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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.

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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.

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• 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.

The opened gallbladder contains a large, exophytic tumor that virtually fills the lumen

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• 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.

Papillary pattern

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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.

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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.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.

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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.

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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_biliary_disorders/gallbladder_and_bile_duct_disorders/acute_cholecystitis.html

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THANK YOU FOR YOUR ATTENTION