GANGGUAN PANKREATOBILIER

Dr Willy B Uwan, MARS, SpPD, K-GEH, FINASIM

SMF Penyakit Dalam

Klinik Penyakit Hati dan Saluran Cerna
Unit Endoskopi Diagnostik dan Terapeutik
RSU St Antonius Pontianak
 Pankreatitis Akut
Definisi
• Peradangan akut, non-bakterial pada organ pankreas.

Patofisiologis
Terjadinya pankreatitis akut diawali karena adanya jejas di sel asini
pankreas akibat:
• Obstruksi duktus pankreatikus (terutama oleh migrasi batu
empedu)
• Stimulasi hormon cholecystokinin (CCK) sehingga akan mengaktifasi
enzim pankreas (misalnya karena pengaruh hipertrigliseridemia dan
alkohol)
• Iskemia (misalnya pada pankreatitis akut paska prosedur
endoscopic retrograde cholangiopancreatography / ERCP atau
atherosklerosis)
 Etiologi
Beberapa penyebab pankreatitis akut adalah:
• Obstruksi batu di duktus koledokus (38%)
• Alkohol (36%)
• Pankreas divisium (7%)
• Komplikasi paska tindakan ERCP (5,4%)
• Hipertrigliseridemia (1-4 %)
• Obat-obatan (1-4 %)
• Hiperkalsemia
• Pankreatitis akut idiopatik (10-15 %)
ETIOLOGY
 Gallstones, microlithiasis, biliary sludge
 Ethanol (5 years, > 50g/day), ERCP
 Toxins, tumors, trauma
 Steroids and ulcers
 Mumps and other infections
 Autoimmune
 Stenosis (sphincter of Oddi dysfunction, papillary stenosis)
 Hypertriglyceridemia, hypercalcemia, hypothermia
 Genetic (<30 years old, family history)
 Drugs (Azathioprine, estrogen, HIV drugs, tetracycline,
sulfa
 Fase Pankreatitis Akut
Pada umumnya perjalanan klinis pankreatitis akut
dapat dibagi:
1. Fase awal
Fase awal terjadi pada minggu pertama, ditandai dengan
adanya systemic inflammatory response syndrome / SIRS
2. Fase lambat
Fase lambat berlangsung beberapa minggu sampai bulan
dan ditandai dengan adanya SIRS yang persisten atau
oleh karena komplikasi lokal dari pankreatitis akut.
 Diagnosis
Diagnosis pankreatitis akut ditegakkan berdasarkan:
• Anamnesis
• Pemeriksaan fisik
• Laboratorium
• Pemeriksaan imaging

Menurut klasifikasi Atlanta (2012), diagnosa pankreatitis akut

tegak bila memenuhi 2 dari 3 kriteria berikut:
• Nyeri perut bagian atas
• Peningkatan amilase atau lipase > 3x nilai batas atas normal
• Pemeriksaan imaging (USG / CT scan atau MRI)
 Sistem skor Marshall untuk menilai
gagal disfungsi organ

Sistem organ Skor

0 1 2 3 4
Respirasi >400 301 – 400 201 – 300 101 – 200 ≤101
(Pa02/Fi02)
Ginjal <1,4 1,4 – 1,8 1,9 – 3,6 3,6 – 4,9 >4,9
(serum kreatinin; mg/dl)
Kardiovaskular >90 <90, <90, <90, <90,
(mm Hg) respon(+) respon(-) pH<7,3 pH<7,2
dengan dengan
cairan cairan
 Definisi pankreatitis akut berat: perbandingan
kriteria Atlanta 1992 dan 2012

Kriteria Atlanta (1992) Kriteria Atlanta (2012)

Pankreatitis akut ringan
• Tidak adanya gagal organ
• Tidak adanya komplikasi lokal
Pankreatitis akut berat
1. Komplikasi lokal dan atau
2. Gagal organ
• Perdarahan gastrointestinal >500 cc
/24 jam
• Syok – tekanan darah sistolik ≤90
mmHg
• Pa02 ≤ 60%
• Kreatinin ≥ 2 mg/dl
Pankreatitis akut ringan
• Tidak adanya gagal organ
• Tidak adanya komplikasi lokal
Pankreatitis akut sedang – berat
1. Komplikasi lokal atau sistemik tanpa
gagal organ persisten
2. Gagal organ sementara (<48 jam)
Pankreatitis akut berat
Gagal organ persisten (>48 jam) (memakai
kriteria skor Marshall)
• Gagal organ tunggal
• Gagal organ multiple
 Klasifikasi Pankreatitis Akut
Berdasarkan Klasifikasi Atlanta 2012, tingkat
keparahan pankreatitis akut dibagi:
1. Pankreatitis akut ringan
2. Pankreatitis akut sedang
3. Pankreatitis akut berat
 Tatalaksana
• Terapi supportif: resusitasi cairan, koreksi
gangguan elektrolit dan koagulasi, pemberian
oksigen
• Antibiotik: diberikan pada infeksi ekstra
pankreas seperti kolangitis
• Analgetik: pilihan narkotik injeksi
• Terapi nutrisi
• Terapi pembedahan
ACUTE
PANCREATITIS
EPIDEMIOLOGY

 AP was responsible for approximately 300,000

hospital admissions in the United States in 2012.

 Recent studies show the incidence of AP varies

between 4.9 and 73.4 cases per 100,000
worldwide.

 Although the case fatality rate for AP has

decreased over time, the overall population
mortality rate for AP has remained unchanged.
PATHOPHYSIOLOGY

DUCT OBSTRUCTION ACINAR CELL INJURY

DIAGNOSIS (REVISED ATLANTA
CONSENSUS 2012)
2 of the 3 criteria:
1. Abdominal pain consistent with the disease
2. Serum amylase and or lipase greater than three times the
upper limit of normal, and or
3. Characteristic findings from abdominal imaging

Contrast-enhanced computed tomography (CECT)

and or magnetic resonance imaging (MRI) should
be reserved for patients in whom:
 the diagnosis is unclear or
 who fail to improve clinically within the first 48 – 72h
after hospital admission or to evaluate complications
CLINICAL PRESENTATION

 Sudden-onset abdominal pain and persists for

hours to days
 Nausea and vomiting
 Delirium, hemodynamic instability, extreme
respiratory distress
PHYSICAL EXAMINATION

 Abdominal tenderness with guarding especially

in the epigastric region
 Bowel sounds are diminished
LABORATORY STUDIES

 Elevated serum amylase and or lipase ≥ 3xULN

 > 5xULN and lipase is more specific
IMAGING STUDIES

 Ultrasound:
 Most sensitive noninvasive for detecting gallstone and
biliary tract dilation

 CT scanning:
 Superior to ultrasound for detecting the changes
associated with pancreatitis and its complications
IMAGING STUDIES

 ERCP:
 Primarily a therapeutic tool in acute biliary
pancreatitis (no role in diagnosing)

 EUS:
 A sensitive test for detecting persistent biliary stones
for further ERCP procedure
SYSTEMIC COMPLICATIONS

 Pulmonary processes (hypoxemia, pleural

effusions, ARDS)
 Renal failure
 Coagulopathy
 Delirium
 Shock
LOCAL COMPLICATION

INTERSTITIAL PANCREATITIS WITH ACUTE RESOLVING INTERSTITIAL

PERIPANCREATIC FLUID COLLECTION PANCREATITIS WITH PSEUDOCYST
LOCAL COMPLICATION

PANCREATIC AND WALLED-OFF PANCREATIC NECROSIS

PERIPANCREATIC NECROSIS (ENCAPSULATED IN 4-6 WEEKS)
INITIAL ASSESSMENT AND RISK
STRATIFICATION
 Hemodynamic status
and resuscitative
measures
 Stratify patients into
higher and lower risk
categories (admission
setting)
 Evaluate organs failure

Tenner et al, American College of Gastroenterology Guideline: Management of Acute

Pancreatitis, Am J Gastroenterol
 DEFINITIONS OF SEVERITY

• Early discharge
• No need imaging
• Very rare mortality

• SIRS
• Mortality 36-50%
• Infected necrosis

 The onset of acute pancreatitis is defined as the time of onset of

abdominal pain
DEFINITIONS OF SEVERITY

 A score of ≥ 2 in any system define the presence

of organ failure
PROGNOSTIC SCORING SYSTEM
(SEVERITY OF AP)
 Ranson’s criteria; Glasgow prognostic criteria;
APACHE II; Balthazar CT severity index;
 BISAP:
 is applicable within the first 24h presentation
 ≥ 3 had a mortality rate of approx. 15%
CRITERIA POINTS
BUN > 25mg/dL 1
Impaired mental status 1
Presence of SIRS (≥ 2 criteria) 1
Age > 60yo 1
Presence of pleural effusion 1
TREATMENT

 Supportive (first 24h is golden hours):

 Massive volume repletion
 Parenteral/enteral feeding
 NGT?
 No rule for the use prophylactic antibiotics
 No evidence to support routine use of somatostatin
 ERCP
INITIAL MANAGEMENT

 Obtain vital signs at frequent intervals (such as

every 4-6 h)

 Supplemental oxygen be administered during

the first 24–48 h, especially if narcotic agents are
used to control pain.

 BGA should be performed when oxygen

saturation is ≤95%, hypoxemia or hypotension
refractory to a bolus of IV fluids.
INITIAL MANAGEMENT

 Aggressive hydration using isotonic crystalloid

solution should be provided to all patients,
unless cardiovascular, renal or other related
comorbid factors exist (most beneficial during
the first 12 – 24 h).

 Lactate Ringer solution may be the preferred.

 Large volume normo-saline may lead to a non-

anion gap, hyperchloremic metabolic acidosis.
AGGRESSIVE HYDRATION

Bolus 1 to 2 L of crystalloids (approx. 20 mL/kg)

Continuous infusion of 150 to 300 cc/hour (approx. 3 mL/kg/h), first 24

hours

Fluid requirements assessment (intervals 6 h of admission and for 24-48 h)

 Decrease hematocrit and BUN

 Maintain a normal creatinine
ICU?

Need aggressive fluid resuscitation

(elderly and cardiovascular disease)

Deteriorating respirat
Severe (no hypoxemia)
NUTRITION IN AP

 Mild acute pancreatitis:

 Oral feedings can be started immediately if there is no
nausea and vomiting and the abdominal pain has
resolved.
 Initiation of feeding with a low-fat solid diet appears as
safe as a clear liquid diet.

 Severe acute pancreatitis:

 Enteral nutrition is recommended (nasogastric and
nasojejunal).
 Parenteral nutrition should be avoided, unless the
enteral route is not available/not tolerated/not meeting
caloric requirements.
NUTRITION IN AP

 Oral intake of limited amounts of calories is

usually initiated when:
 Abdominal pain has subsided
 Parenteral narcotics are no longer required
 Nausea and vomiting have ceased
 Abdominal tenderness has markedly decreased
 Bowel sounds are present
 Overall assessment of the patient has improved
ANTIBIOTICS IN AP

Should be given for:

 Infection included extra-pancreatic
 Necrosis who deteriorate or fail to improve after
7-10 days of hospitalization → infected

Is not recommended:
 Prophylactic antibiotics
 No source of infection is identified
 ERCP IN AP

 Concurrent acute cholangitis should undergo

ERCP within 24 h
 Progressive bilirubin increasing (CBD
obstruction/biliary pancreatitis)
 In the absence of cholangitis and or jaundice,
MRCP or EUS rather than diagnostic ERCP
should be used to screen for choledocholithiasis
if highly suspected.
 Autoimmune Pancreatitis
(Ig G4– Associated Cholangitis)
 Stricturing of the pancreatic duct, focal or generalized
pancreatic enlargement,

 IgG4 > 140 mg/dL

 Lymphoplasmacytic infiltrate on biopsy
 Response to corticosteroid therapy
Primary
Sclerosing
Cholangitis
 Epidemiology
 Prevalence: 6-16 cases/100.000
 Incidence: 1 case/100.000
 Geographical variation
 Men > Women
 Median age: 40 years
 Concomitant (60-80%) with UC
 Pathophysiology
 Immune-mediated process
 Genes: HLA-DRB1*1501-DQB1*602, HLA-
DRB1*1301-DQB1*0603, HLA-A1-B8-DRB1*0301-
DQB1*0201

 ‘Second Hit’ – environmental trigger, toxin or infectious

exposure

 Innate and adaptive immune system

 Lymphocyte migration, cholangiocyte damage, fibrosis
 Clinical Presentations
 Asymptomatic
 Non-specific: fatigue, pruritus, jaundice, weight loss
 Less common: fever, chill, night sweat, abdominal pain
 Jaundice, Hepato-splenomegaly, Excoriations
 Cirrhosis
 Clinical Presentations
 Elevated alkaline phosphatase and bilirubin
 Aminotransferase normal or mildly elevated
 Synthetic function altered in advanced disease
 Clinical Presentations
 US: ductal wall thickening and focal bile duct dilations,
gallbladder wall thickening, distention, gallstones and
mass

 CT: thickened and inflamed bile ducts, saccular dilation

intra-hepatic ducts and mass in gallbladder

 MRCP: “beaded” appearance – multifocal short annular

strictures alternate between normal and dilated
 Diagnosis
 Gold standard: MRCP with sensitivity and specificity of
86% and 94%, and ERCP

 Multifocal annular strictures alternating with segments

of normal or dilated bile ducts of intrahepatic and/or
extrahepaticbile ducts – ‘bead on a string apperance’

 Rule out IgG-4

 Liver biopsy rarely helpful – “onion skin” (25%), small
duct PSC, PSC-AIH overlap syndrome
Onion Skin Apperance

NEJM 1995
 Diagnosis
 Classic PSC: biliary strictures with normal intervening
segments or diffusely involved long segments.

 Radio-occult: strictures not present, shallow ulcerations

bile duct

 Small duct PSC more difficult to diagnosis

 Antibodies are non-specific
Serum Autoantibodies in PSC
Differential Diagnosis

Clinical Liver Disease, Vol 3, No 3, March 2014

 Treatments
 No proven medical therapy
 Ursodeoxycholic acid (UDCA): 15 mg/kg/day – improve
biochemical markers and inflammation

 Endoscopic treatment - dominant bile-duct stenosis

 Liver transplantation (LTx) – end stage liver disease,
portal hypertension refractory therapy, intractable
pruritus, reccurent cholangitis

 LTx: 5 and 10 year survival rates of 87.4% and 83.2 %

 Major RCT of UDCA in the
Treatment of PSC

PSC Management and Surveillance

Clinical Liver Disease, Vol 3, No 3, March 2014

 Complications
 Obstructive
 Colorectal Cancer, Cholangiocarcinoma, HCC,
Gallbladder Cancer

 Cirrhosis
 Cholelithiasis, Fat-soluble vitamin deficiencies,
Osteoporosis
 The risk of developing
PSC-associated cancers

Dtsch Arztebl Int 2013

Clinical surveillance of PSC

Dtsch Arztebl Int 2013

Cholangiocarcinoma
surveillance in PSC

Clinical Liver Disease, Vol 3, No 3, March 2014

 Prognosis
 Median time to death or transplantation:
12-18 years for asymptomatic and no IBD

9 years for symptomatic

 Mayo Risk Score: R = 0.03 (age [years]) + 0.54 loge

(bilirubin [mg/ dL]) + 0.54 loge (AST [UIL]) + 1.24
(variceal bleeding [0/1]) − 0.84 (albumin [g/dL])
Gallbladder cancer surveillance
in PSC

Clinical Liver Disease, Vol 3, No 3, March 2014

Subclassification of PSC
Relationships between
subphenotypes of PSC
Diagnostic Algorithm for the
Overlap Syndromes
Diagnostic Features of the
Overlap Syndromes
Treatment Options for the
Overlap Syndromes
Simplified Criteria for the
Diagnosis of AIH
 Kolangiokarsinoma
• Tumor primer dari epitel duktus biliaris
• Kanker hepatobilier terbanyak kedua setelah
karsinoma hepatoseluler
• 95% adalah adenokasinoma
• Lokasi 20% intra hepatik /perifer, 80% ekstra
hepatik (70-80% perihilar dan 20-30% distal
duktus biliaris)
• Faktor risiko: kolangitis sklerosing primer, kista
duktus biliaris, sirosis hepatis, hepatitis B dan C,
infeksi clonorchis sinensis