Hepato pancreatic biliary surgery

Question 1

Jaundice

1. What level is the billirubin for jaundice to be seen?
2. What is Crigler–Najjar syndrome
3. Coca cola urine means?
4. If AST:ALT ratio >2, likely ?; if AST:ALT around 1, likely ?
5. What may be seen on a FBC in jaundice
6. Ceruloplasmin is the

Answer 1

1. >50 µmol/L
2. High levels of unconjugated billuribinaemia

autosomal recessive

brain damage in infants

This syndrome is divided into types I and II, with the latter sometimes called Arias syndrome. These two types, along with Gilbert’s syndrome, Dubin–Johnson syndrome, and Rotor syndrome, make up the five known hereditarydefects in bilirubin metabolism. Unlike Gilbert’s syndrome, only a few causes of CNS are known.

3. conjugated billirubin in urine
4. alcoholic liver disease,

viral hepatitis

5. FBC (anaemia, raised MCV, and thrombocytopenia all seen in liver disease)
6. major copper-carrying protein in the blood, and in addition plays a role in iron metabolism

Question 2

Management of jaundice?

Answer 2

Obstructive causes -> removal of a gallstone through ERCP or open surgery, cholecystectomy, or stenting of the common bile duct.

itching-> cholestyramine (obstructive cause)

anti-histamines

Monitor for coagulopathy

treat hypoglycaemia orally if possible (otherwise 5% dextrose is needed)

hepatic encephalopathy: laxatives (lactulose or senna) +- neomycin or rifaximin may be used, reducing the number of ammonia-producing bacteria in the bowel.

Question 3

BILIARY COLIC AND CHOLECYSTITIS

1. types of gallstones
2. RF
3. CF
4. DD
5. Ix
6. Rx
7. Complications

Answer 3

1. Cholesterol, Pigment (haemolytic anaemia), Mixed
2. Fat, Female, Fertile, Forty, and Family history.

Others: pregnancy and oral contraceptives*, haemolytic anaemia, and malabsorption (e.g. ileal resection or Crohn’s disease).

*Oestrogen causes more cholesterol to be secreted into bile

3.

Biliary colic

cystic duct becomes impacted by a gallstone

no inflammatory response, yet the contraction of the gallbladder against the occluded neck will result in pain.

The pain is typically sudden, dull, and colicky (comes and goes) in nature.

right upper quadrant although it may radiate to the epigastrium and/or back.

precipitated by the consumption of fatty foods* and the patient often complains of nausea and vomiting. In general, once pain relief has been started, symptoms often settle quickly.

*Fatty acids stimulate the duodenum endocrine cells to release cholecystokinin (CCK), which in turn stimulates contraction of the gallbladder.

Acute cholecystitis are often similar to that of someone with biliary colic, although the pain may be constant, persistent despite pain relief, and is often associated with signs of inflammation (e.g fever, raised WCC). The patient may also demonstrate some derangement of their liver function tests.

o/e: check for signs of inflammation (e.g. tachycardia, pyrexia), signs of peritonitis or perforation, and signs of jaundice or hepatomegaly. Patients with acute cholecystitis will be tender in the RUQ and will likely demonstrate a positive Murphy’s sign.

4. GORD, PUD, acute pancreatitis, or inflammatory bowel disease.
5. Urinalysis (including a pregnancy test if female) should be performed to exclude any renal and tubo-ovarian pathology.

FBC and CRP – assess inflammatory response, which will be raised in biliary pathology such as cholecystitis, cholangitis, and pancreatitis

U&Es – assess for any dehydration, secondary to reduced oral fluid intake (as certain foods can worsen the pain)

LFTs – biliary colic and acute cholecystitis are likely to show a raised ALP (indicating ductal occlusion)

Amylase – to check for pancreatitis

Trans-abdominal ultrasound is one of the most sensitive modalities for visualising gallstone disease and is typically used first line to investigate suspected gallstone pathology (yet a sensitivity around 50%). Three specific areas are often visualised on US:

• The presence of gallstones or sludge (the start of gallstone formation)
• Gallbladder wall thickness (if thick walled, inflammation is likely)
• Bile duct dilatation (indicate a possible stone or stricture in the distal bile ducts)

Magnetic Resonance Cholangiopancreatography (MRCP), largely replacing ERCP for diagnostic purposes.

MRCP can show potential defects in the biliary tree caused by gallstone disease, with a sensitivity approaching 100%. Any patient with symptoms suggestive of gallstones with inconclusive US (or CT scans) should undergo a MRCP.

6. Biliary Colic

Initial management

• Analgesia: NSAIDs and PRN opioids
• Antiemetic

If there is no improvement in symptoms with analgesia, consider a potential cholecystitis picture.

• Lifestyle factors: e.g. a low fat diet, weight loss, increasing exercise, and provided with suitable analgesia at discharge

Definitive Management

• elective cholecystectomy is warranted and should ideally be offered within 6 weeks of first presentation. The laparoscopic route is preferred for cholecystectomy but is not always possible.

Acute Cholecystitis

Initial Management

• intravenous antibiotics (such as co-amoxiclav +/- metronidazole)
• fluid resuscitation
• NG tube should be placed if the patient is vomiting and the patient made nil by mouth (NBM), as an ultrasound is more sensitive in the absence (or reduction) of bowel gas.
• analgesia, typically simple analgesics with PRN opioids, and antiemetics

Definitive Management

• laparoscopic cholecystectomy is indicated within 1 wk, however this ideally should be done within 72hr of presentation*
• For those not fit for surgery and not responding to antibiotics, a percutaneous cholecystostomy can be performed to drain the infection, with the patient advised regarding further lifestyle changes thereafter (although as the gallstones remain in-situ, the risk of recurring disease remains).

*A laparoscopic cholecystectomy after a couple of days of inflammation tends to be a more difficult procedure.

In a patient readmitted with RUQ pain post-cholecystectomy, it is important to exclude aretained CBD stone post-operatively. US abdomen scan may be useful, yet if this is unremarkable, then further investigation via MRCP imaging is warranted.

7.

• Gallbladder Empyema (laparoscopic cholecystectomy* (may require intra-operative drainage if tense gallbladder) or percutaneous cholecystostomy (if unsuitable for surgery).
• Chronic Cholecystitis
• Bouveret’s Syndrome and Gallstone Ileus

Inflammation of the gallbladder (typically if recurrent or silent) can cause a fistula to form between the gallbladder wall and the duodenum, allowing gallstones to pass into the small bowel. As a consequence, bowel obstruction can occur:

Bouveret’s Syndrome – stone impacts to cause duodenal obstruction

Gallstone Ileus*– stone impacts to cause an obstruction at the terminal ileum (the narrowest part of the adult bowel)

Other complications include obstructive jaundice, ascending cholangitis, and acute pancreatitis.

*The term ileus is misleading, as it is actually a bowel obstruction

Question 4

CHOLANGITIS (obstruction, stasis, infection)

1. A
2. CF
3. Two common eponymous syndromes associated with cholangitis are:
4. Ix
5. Rx
6. Prognosis

Answer 4

1.

• gallstones
• ERCP (iatrogenic)
• cholangiocarcinoma
• Rarer: pancreatitis, primary sclerosing cholangitis, ischaemic cholangiopathy, and parasitic infections

The most common infective organisms: Escherichia Coli (27%), Klebsiella species (16%), and Enterococcus (15%)

2.

• RUQ pain, fever, jaundice (when bilirubin >50 μmol/L)
• pruritus (itching)
• pale stool with dark urine

PMHx: gallstones, recent biliary tract instrumentation (i.e. ERCP/cholecystectomy), or previous cholangitis. Medication including oral contraceptive pill and fibrates can increase the risk, and a lipid-rich diet may be indicative of gallstones (as a potential underlying cause)

o/e: pyrexia (in 90% of cases), rigors, jaundice, right upper quadrant tenderness, confusion, hypotension, and tachycardia may be present.

3.

Charcots Triad: Jaundice, Fever, and RUQ Pain

Reynold’s Pentad: Jaundice, Fever, and RUQ Pain, Hypotension, and Confusion

4. Routine bloods: FBC (leucocytosis) and LFTs (showing a raised ALP ± GGT with a raised bilirubin).

Blood cultures should always be taken in suspected cases, despite only being positive in 20% of cases. The best opportunity to obtain a positive blood culture is early, before the start of broad spectrum antibiotics.

Imaging

An ultrasound scan of the biliary tract will show bile duct dilation. The common bile duct is usually less than 6mm in size (it may be greater in the elderly and those who have had previous cholecystectomy), so any diameter larger than this suggests dilatation. Ultrasound imaging may also demonstrate the presence an underlying cause (e.g. gallstones).

The gold standard investigation for cholangitis is ERCP, as it is both diagnostic and therapeutic. Many endoscopists may require an MRCP prior to intervention, however to obtain detailed imaging of the biliary system prior to scoping.

5. Immediate Management

Could present with sepsis

• fluid resuscitation, routine bloods, blood cultures taken early, with broad spectrum IV antibiotic therapy instigated (e.g. co-amoxiclav + metronidazole)

Definitive Management

• endoscopic biliary decompression, removing the cause of the blocked biliary tree. For patients who are deteriorating, this may need to be done earlier than those who are responding well to antibiotic therapy.
• ERCP, with or without a sphincterotomy and stenting, should clear any obstruction. In patients who may be too sick to tolerate ERCP, percutaneous transhepatic cholangiograpy (PTC) is the second line intervention.

In the long-term, patients may require a cholecystectomy if gallstones were the underlying cause. Any other cause for the cholangitis identified should also be managed as appropriate.

It is important to remember that there are significant complications of ERCP, including repeated cholangitis, pancreatitis (in 3-5% of patients), bleeding (more common when a sphincterotomy is performed), and perforation (a rare complication yet requires urgent surgical intervention if present)

6. The mortality of cholangitis is around 5-10% in those who are given antibiotic therapy. Early ERCP and early antibiotic therapy have both been found to improve patient outcomes.

Factors which increase the mortality rate include delayed diagnosis, liver failure, cirrhosis, CKD, hypotension, female gender, and >50yrs.

Question 5

CHOLANGIOCARCINOMA

1. What is it?
2. E
3. A and RF
4. CF
5. DD
6. Ix
7. Rx

Answer 5

1. cancer of the biliary system (predominantly arises in the extrahepatic biliary system)
2. 2/3 of pts >65 years

most common site: bifurcation of the right and left hepatic ducts (~ slow-growing tumours that invade locally and metastases to local lymph nodes, spreading to the peritoneal cavity, lung and liver)

In this article, we shall look at the risk factors, clinical features and management of a patient with cholangiocarcinoma.

3. 95% are adenocarcinomas
   remaining: squamous cell carcinomas, with other rarer types of bile duct cancers include sarcomas, lymphomas, and small cell cancers.

RF:

• Primary sclerosing cholangitis (lifetime risk of 10-20%)
• Ulcerative colitis
• Infective (Liver flukes, HIV, hepatitis virus)
• Toxins (Chemicals in rubber and aircraft industry)
• Congenital (Caroli’s disease, choledochal cyst)
• Alcohol excess
• Diabetes Mellitus

4. Cholangiocarcinoma (both intra- and extrahepatic) is generally asymptomatic until a late stage in the disease.

Symptoms include post-hepatic jaundice and pruritus, with pale stools and dark urine. Other less common features include RUQ pain, early satiety, weight loss, anorexia and malaise.

On examination, jaundice and cachexia is often evident. Courvosier’s law can be applied in clinical assessment.

5. obstructive choledocholithiasis, bile duct strictures, choledochal cysts, external compression from extra biliary tumour, benign biliary tumours, pancreatic tumours, primary biliary cirrhosis, and primary sclerosing cholangitis.

6.

• Biochemical will confirm an obstructive jaundice (elevated bilirubin, ALP and ɣGT). Tumour markers CEA and CA19-9 may also be elevated.
• Ultrasound scanning may be used initially to confirm an obstructive cause.
• MRCP is the optimal imaging for diagnosing cholangiocarcinoma;
• ERCP may be used to demonstrate the site of obstruction and also has the ability to obtain samples for cytology/histology.
• Staging -> CT imaging> MRI scanning for locating distant metastases and can further evaluate the level of biliary obstruction.
• Angiography may be used in pre-op planning to image the hepatic arteries or portal vein. If encasement is demonstrated, any surgical intervention is unlikely to be successful.

Staging is based on the TNM classification, with some variations depending on whether the tumour is intrahepatic, hilar, peri-hilar or distal

7. Surgical:

complete surgical resection* (majority of patients have inoperable disease at the time of presentation with only 10-15% suitable for surgical intervention)

Intrahepatic and Klatskin tumour resection requires a partial hepatectomy and reconstruction of the biliary tree.

distal common duct tumours require a pancreaticoduodenectomy - Whipple’s procedure.

Medical:

• Radiotherapy may be used in some cases as adjunct or neoadjunct therapy. There is limited evidence at present for the use of post-op chemotherapy.

Palliative:

Most cases will end up only having pallative management. The palliative treatment options in cholangiocarcinoma include:

• Stenting: ERCP may be used to stent the bile duct and relieve obstructive symptoms. Self-expanding metal stents offer the best outcome but are prone to occlusion and may need replacing frequently (every 3-4 months).
• Surgery: Surgical bypass procedures may be required if the obstruction cannot be relieved by stenting
• Medical: Palliative radiotherapy may be used to prolong survival

A combination of chemotherapy agents (e.g. cisplatin and gemcitabine) can also be used to slow tumour growth, however when used without radiotherapy, it has not shown any significant survival benefit

Question 6

ACUTE PANCREATITIS (distinguished from chronic pancreatitis by its limited damage to the secretory function of the gland, with no gross structural damage developing)

1. A
2. P
3. CF
4. DD
5. Ix
6. Rx

There is no curative management for acute pancreatitis, so supportive measures are the mainstay of treatment. Treat any underlying cause as necessary (e.g. urgent ERCP and sphincterotomy if gallstones are demonstrated within the common bile duct) when deemed appropriate.

Supportive treatment includes:

7. Complications
8. Local Complications

Answer 6

1.

• Gallstones
• Ethanol (Alcohol)
• Trauma
• Steroids
• Mumps
• Autoimmune disease, such as SLE
• Scorpion venom (a rare and unlikely cause in most countries)
• Hypercalcaemia
• Endoscopic retrograde cholangio-pancreatography (ERCP)
• Drugs, such as Azathioprine, NSAIDs, or Diuretics

2. premature and exaggerated activation of the digestive enzymes within the pancreas

pancreatic inflammatory response -> inc in vascular permeability and subsequent fluid loss into the third space (transcellular space, e.g. peritoneal cavity).

Enzymes -> systemic circulation -> autodigestion of fats (‘fat necrosis’) & blood vessels (sometimes leading to haemorrhage in the retroperitoneal space).

Fat necrosis can cause the release of free fatty acids, reacting with serum calcium to form chalky deposits in fatty tissue, resulting in hypocalcaemia.

Severe end-stage pancreatitis will eventually result in partial or complete necrosis of the pancreas.

3.

sudden onset of severe epigastric pain, which can radiate through to the back

N+V

O/e: epigastric tenderness, but often a soft abdomen with normal bowel sounds. Severe acute pancreatitis can present with signs of guarding and a rigid abdomen, with potential circulatory instability (including hypovolaemic shock).

Rarer: Grey Turner’s Sign (bruising in the flanks) and Cullen’s Sign (bruising around the umbilicus), representing retroperitoneal haemorrhage.

Tetany may occur from hypocalcaemia secondary to fat necrosis and any gallstone pathology may also result in a concurrent jaundice or cholangitis clinical picture.

4. ruptured AAA, chronic pancreatitis, aortic dissection, and a duodenal ulcer

5.

• Serum amylase – diagnostic of acute pancreatitis if 3x the upper limit of normal*

raised in bowel perforation, ectopic pregnancy, mesenteric ischaemia, and DKA

• LFTs – assess for any concurrent cholestatic element to the clinical picture

Two large observational studies of patients with acute pancreatitis noted that an alanine transaminase (ALT) level >150U/L has a positive predictive value of 85% for gallstones as the underlying cause

• Serum lipase – remains elevated longer than amylase

Imaging

• abdominal USS may be requested if the underlying cause is unknown; it is typically used to identify a possible gallstone, by demonstrating dilation of the bile ducts.
• not routine AXR can show a ‘sentinal loop sign’ - a dilated proximal bowel loop adjacent to the pancreas, which occurs secondary to localised inflammation.
• A CXR should be undertaken to look for pleural effusion or signs of ARDS.
• A contrast-enhanced CT scan can be performed if the clinical assessment and blood tests prove inconclusive (or because the severity of clinical presentation raises the possibility of other intra-abdominal pathology). If performed after 48hrs from initial presentation, it will often show areas of pancreatic oedema and swelling, as well as any potential complications that may have developed*.

*In cases of known pancreatitis, if the pancreas no longer enhances then this may suggest a necrosing pancreas

Current UK guidelines state that any CT scan used to assess for severity of disease should only be performed 6-10 days after admission in patients with features of persistent inflammatory response or organ failure*.

*Prior to this time frame, CT-based severity scoring systems have been shown to be equivocal to clinical scoring systems in predicting severity, whilst increasing length of hospital stay with no improvement in clinical outcome

6.

• High-flow oxygen
• IV fluid resus

250-500ml/hr of crystalloid solution to be given to all patients (unless cardiovascular or renal co-morbidities) in the initial period, with Hartmann’s solution as the preferred choice of fluid.

• Nasogastric tube if the patient is vomiting profusely
• If the patient is able to eat, oral intake can be encouraged
• Catheterisation to accurately monitor urine output and start a fluid chart (due to the potential for rapid third space losses). Aim for a urine output of at least >0.5ml/kg/hr and check U&Es regularly
• Opioid analgesia*
• severe acute pancreatitis: HDU or ITU

7. Systemic Complications:

• Disseminated Intravascular Coagulation (DIC)
• Acute Respiratory Distress Syndrome (ARDS)
• Hypocalcaemia
• Hyperglycaemia
• Secondary to destruction of islets of Langerhans and subsequent disturbances to insulin metabolism
• Hypovolemic shock and multiorgan failure

8.

• Pancreatic Necrosis

Ongoing inflammation eventually leads to ischaemic infarction of the pancreatic tissue, hence such progression should be suspected in patients with evidence of persistent systemic inflammation for more than 7-10 days after the onset of pancreatitis.

Any suspected pancreatic necrosis should be confirmed by CT imaging and treatment will often warrant pancreatic necrosectomy (open or endoscopic)*.

Pancreatic necrosis is prone to infection and should be suspected if there is a clinical deterioration in the patient associated with raised infection markers (or from positive blood culture or changes of low density within the pancreas on CT). Definitive diagnosis of infected pancreatic necrosis can be confirmed by a fine needle aspiration of the necrosis.

*General consensus for intervention in cases of confirmed pancreatic necrosis is to be delayed until walled-off necrosis has developed, typically 3-5 weeks after the onset of symptoms

• Pancreatic Pseudocyst

Collection of fluid (pancreatic enzymes, blood, necrotic tissue); they can occur anywhere within or adjacent to the pancreas, ~lesser sac obstructing the gastro-epiploic foramen by inflammatory adhesions..

They are typically formed weeks after the initial acute pancreatitis episode. They lack an epithelial lining, therefore termed pseudocyst, and instead have a vascular and fibrotic wall surrounding the collection.

Pseudocysts may be found incidentally on imaging or can present with symptoms of mass effect, such as biliary obstruction or gastric outlet obstruction. They are prone to haemorrhage or rupture, and can become infected.

About 50% will spontaneously resolve, hence conservative management is usually the initial treatment of choice. Cysts which have been present for longer than 6 weeks are unlikely to resolve spontaneously. Treatment options include surgical debridement or endoscopic drainage (often into the stomach).

Question 7

CHRONIC PANCREATITIS

1. A
2. P
3. RF

Answer 7

• Chronic alcohol abuse (60%)
• Idiopathic (30%)
• Metabolic (Hyperlipidaemia, Hypercalcaemia)
• Infection: Viral (HIV, mumps, coxsackie), Bacterial (Echinococcus)
• Hereditary (Cystic fibrosis)
• Autoimmune (Autoimmune pancreatitis (AIP), SLE)
• Obstruction (of pancreatic duct) (Stricture formation, Neoplasm)
• Congenital (Pancreas divisum, Annular pancreas)

2.

Chronic pancreatitis can occur in large duct or small duct form:

Large duct disease – dilatation and dysfunction of the large pancreatic ducts, therefore visible on most diagnostic imaging. The pancreatic fluid changes composition and facilitates the deposition of precursors to calcium carbonate stones and causes diffuse pancreatic calcification. This subtype is more commonly found in males.

Small duct disease – usually associated with normal imaging and no pancreatic calcification, making it difficult to diagnose. It is predominantly found in females.

3. excess alcohol consumption

Smoking