Thanks to everyone who contributed to the discussions about Kenny Cheung a 48 year old man who had jaundice.
This week’s question setter and expert was Dr Bharat Paranandi, Gastroenterology ST7, UCLH
Information available at the start of the week:
Letter from Kenny’s GP:
Kenny is an otherwise fit and well 48 year old nightclub manager who i’m very concerned about. He came to see me today as his diabetic control has been a bit worse over the last two months but when he came in I was quite shocked to see he was visibly jaundice. His wife said he’d been a ‘bit yellow’ for the last month and had been complaining of itching for longr than that. On further questioning he told me he has not been eating much and has lost nearly 4KG in the last few months, he thought this was because he was not eating much as he has been stressed at work. He does not report any pain.
Kenny was diagnosed with diabetes in his late teens but has always had excellent blood sugar control, he has no other past medical history. He tells me his mother died of ‘yellow jaundice’ when he was only six but we don’t have any more information as that was back in China. He has lived in the UK since he was eleven.
Kenny has cut down his alcohol to zero over the last three months, before that he did drink a number of shots of rum at the weekend when he was working. He does still smoke 30 cigarettes a day and has done since he was 28.
I’ve taken some blood tests and hepatitis serology today, the results should be attached to this letter. His BM was 9.2 in the surgery. Please can you see him as soon as possible.
Question 1: What’s the most likely diagnosis?
HB 9.6 g/dl (11.5-15.5)
MCV 105 fl (80-99)
WCC 12.5 x109/L (3.0-10.0)
Neutrophil 8 x109/L (2.0-7.5)
PLT 468 x109/L (150-400)
Na 134 mmol/l (135-145)
K 4.2 mmol/l (3.5-5.1)
Ur 1.2 mmol/l (1.7-8.3)
CR 45 mmol/l (49-92)
Bili 210 (total) 195 (conjugated) umol/L (0-20)
ALP 656 iu/l (35-104)
ALT 444 iu/l (10-35)
ALB 30 g/l (34-50)
PT 9 secs (<12)
CRP 125 mg/L (0-5)
HAV IgG (positive), IgM (negative).
HBV sAg (negative), sAb (positive), core Ab (positive).
HCV Ab (negative).
CA 19-9: 5400 kiu/l (0-27)
AFP: 6 kiu/l (0-6).
Further information released during the week:
Kenny is seen by the StR in Gastroenterology clinic.
Examination in clinic reveals scleral icterus. Scratch marks on upper limbs. Palpable 1cm circular swelling in left supraclavicular fossa. Normal abdominal examination.
He organises further imaging:
Normal liver size, shape and echotexture. Dilated CBD 15mm to the level of the head of pancreas. GB is thick-walled (no filling defects seen). Pancreas not well visualised due to overlying bowel gas but no obvious HPB masses. Normal spleen. Absence of Doppler signal in right and left portal vein.
Question 2. What investigations should be arranged next?
CT Chest, Abdomen & Pelvis:
5cm mass in head of pancreas with associated biliary obstruction. Dilated CBD 15mm. Portal vein thrombosis (bilateral) with involvement of SMV and SMA.
A provisional diagnosis of Pancreatic cancer is made.
Question 3: What is the next best interventional procedure?
- Interpretation of deranged liver function tests and viral hepatitis serology.
- Differential diagnosis and investigation of obstructive jaundice.
- Management of pancreatic cancer.
Dr Bharat Paranandi, Gastroenterology ST7 says:
This case involves a patient who has presented with obstructive jaundice and conjugated hyperbilirubinaemia. It is important to have a structured approach to assessing a patient who is jaundiced
We will now discuss:
- Classification of jaundice – conjugated vs unconjugated hyperbilirubinaemia.
- Approach to diagnosis and investigation of a jaundiced patient.- History.
- Physical examination.
- Interpretation of deranged LFTs.
- Case review and answers to Qs.
Classification of jaundice
There are numerous causes of jaundice (or hyperbilirubinaemia) which can be subdivided into:
Predominantly unconjugated (indirect) bilirubin:
Predominantly conjugated (direct) bilirubin:
Approach to diagnosis and investigation of a jaundiced patient
The diagnostic approach to the jaundiced patient begins with a careful history, physical examination and blood tests. A differential diagnosis should be made on those results and additional investigations should be requested to narrow the diagnostic possibilities.
Country of origin/birth.
Time course of symptoms, presence or absence of pain.
Prior history of abnormal LFTs or underlying liver disease.
- Prior history of metabolic syndrome, obesity, abdominal operations, including gallbladder surgery.
- Use of medications (eg. antibiotics), herbal medications, dietary supplements, and recreational drugs.
- Use of alcohol.
- Hepatitis risk factors (eg. family history, travel, possible parenteral exposures).
- History of inherited disorders, including liver diseases and hemolytic disorders.
Associated symptoms often help narrow the differential diagnosis.
- Colicky right upper quadrant pain is more common in patients with gallstone disease.
- Pale stools indicates biliary obstruction.
- History of fever, particularly when associated with chills or right upper quadrant pain issuggestive of acute cholangitis.
- Symptoms such as anorexia, malaise, and myalgias with a prodromal illness may suggestviral hepatitis.
Physical examination may suggest the presence of chronic liver disease and it may point to the underlying cause of the liver disease.
The abdominal examination should focus on the size and consistency of the liver, the size of the spleen (a palpable spleen is an enlarged spleen), and an assessment for ascites (usually by determining whether there is shifting dullness). Patients with cirrhosis may have an enlarged left lobe of the liver (which can be felt below the xiphoid) and an enlarged spleen (which is most easily felt with the patient in the right lateral position).
A grossly enlarged nodular liver or an obvious abdominal mass suggests malignancy. An enlarged, tender liver could be due to viral or alcoholic hepatitis or, less often, an acutely congested liver secondary to right-sided heart failure or Budd-Chiari syndrome. Ascites in the presence of jaundice suggests either cirrhosis or malignancy with peritoneal spread
Peripheral stigmata of Cirrhosis (chronic liver disease):
- Digital clubbing, Dupuytren’s contractures, palmar erythema, spider naevi, muscle wasting,parotid gland enlargement, gynecomastia, caput medusa & hypogonadism.
- Temporal and proximal muscle wasting suggest longstanding disease.
- Ascites or asterixis (liver flap due to hepatic encephalopathy) may be seen in patients withdecompensated cirrhosis. Other signs:
- An enlarged left supraclavicular node (Virchow’s node) or periumbilical nodule (Sister Mary Joseph’s nodule) suggest an abdominal malignancy.
- Increased jugular venous pressure, a sign of right-sided heart failure, suggests hepatic congestion.
- An isolated right pleural effusion may be seen in advanced cirrhosis.
- Neurologic signs and symptoms may be seen in patients with Wilson disease
Interpretation of deranged LFTs:
LFT abnormalities can often be grouped into one of several patterns: hepatocellular, cholestatic, or isolated hyperbilirubinemia. In addition, the abnormalities may be acute or chronic based on whether they have been present for more (chronic) or less (acute) than six months.
o Disproportionate elevation in the serum aminotransferases compared with the alkaline phosphatase.
o Serum bilirubin may be elevated.
o Tests of synthetic function may be abnormal.
o Disproportionate elevation in the alkaline phosphatase compared with the serum aminotransferases.
o Serum bilirubin may be elevated.
o Tests of synthetic function may be abnormal.
o In severe or acute extrahepatic biliary obstruction, serum aminotransferases may be significantly elevated.
o Elevated bilirubin level with normal serum aminotransferases and alkaline phosphatase
Abnormal tests of synthetic function may be seen with both hepatocellular injury and cholestasis.
- Low albumin suggests a chronic process, such as cirrhosis or cancer, whilst a normal albumin suggests a more acute process, such as viral hepatitis or choledocholithiasis.
- Prolonged Prothrombin Time indicates either vitamin K deficiency due to prolonged jaundice and intestinal malabsorption of vitamin K or significant hepatocellular dysfunction.
This is a case of a man who has come to Gastroenterology outpatients with jaundice. The main clues, pertaining to the diagnosis, should be retrieved from the history. As a general rule, I try to establish a short list of differential diagnoses (most likely at the top of the list) before I examine the patient. Patients rarely present with multiple coincidental pathologies or textbook symptoms/signs, in my experience. Therefore, I usually try to formulate a single unifying diagnosis.
Q1: What is the most likely diagnosis and discuss why? A: Pancreatic Cancer.
Pancreatic cancer is an aggressive solid organ malignancy. Surgical resection is the only potentially curative treatment for exocrine pancreatic cancer, but because of the late presentation of the disease, only 15 to 20 percent of patients are candidates for pancreatectomy. Furthermore, the prognosis of pancreatic cancer is poor even in those with potentially resectable disease. The five-year survival following pancreaticoduodenectomy is only about 25 to 30 percent for node- negative and 10 percent for node-positive tumors.
Looking at our case specifically:
- The history is suggestive of biliary obstruction due to a HPB malignancy – painlessjaundice, pale stools and weight loss are all red flag symptoms. The LFTs are indeed a mixed picture but are predominantly cholestatic/obstructive (predominantly elevated ALP/GGT). The aminotransferases are elevated due to severe acute/complete biliary obstruction.
- The absence of pain makes choledocholithiasis (CBD stones causing biliary obstruction) much less likely.
- There are clues in the history (alcohol consumption to excess and that he is a “nightclub manager”) to point towards a diagnosis of decompensated alcoholic liver disease. However, the history is very short and the LFTs provide the answer. ALT is rarely elevated above 300 in patients with alcohol aetiology. An AST to ALT ratio of 2:1 or greater is predictive of an alcohol aetiology, particularly in the setting of an elevated GGT. Kenny’s AST:ALT ratio is < 1. Also, diagnosis of acute alcoholic hepatitis requires alcohol exposure within the past 6 weeks.
- There are clues in the history towards viral hepatitis (the serological markers, ethnic origin, family hx of mother dying in 30s of liver failure in China) – however, the history and bloods are more suggestive of obstructive/cholestatic jaundice. Also, his HBV serology shows simply prior exposure to HBV which has been cleared (ie. Core Ab positive, sAb positive). There is no active HBV as the sAg is negative. The HAV serology suggests prior exposure (IgG positive, IgM negative). Hepatitis A is usually a self limiting illness with approximately 85 percent of HAV-infected individuals have full clinical and biochemical recovery within three months.CA 19-9 is not a useful screening test for pancreatic cancer as it has suboptimal sensitivity and speificity. It is frequently elevated in patients with cancers other than pancreatic cancer and various benign pancreaticobiliary disorders.
Q2: What is the likely primary diagnosis and what is the cause for his jaundice? What is the next most important investigation? What are possible treatment options for the underlying disease?
- Pancreatic Cancer with associated stricture of the CBD.
- Staging CT Chest, Abdomen and Pelvis.
- Options include curative surgery (ie. Whipple’s procedure -partialpancreaticoduodenectomy) with adjuvant chemotherapy, palliative chemotherapy or conservative management (ie. palliative care with symptom control only).
The clinical examination revealed an enlarged left supraclavicular node (Virchow’s node), which suggests HPB malignancy.
In patients in their 40s, the normal common bile duct (CBD) diameter is 4mm. The normal diameter then increases by 1mm every decade and in elderly patients the normal upper limit of normal is 8.5mm. The CBD commonly measures up to 10mm in patients who have undergone a cholecystectomy. In this case, the CBD is grossly dilated (15mm) on USS (to the level of the head of pancreas) suggesting pancreatic malignancy is the cause.
The USS appearances of a normal liver and normal spleen make cirrhosis and portal hypertension unlikely. The pancreas is often incompletely visualised on USS however this modality is a good initial screening test for a patient who is jaundiced. The absence of Doppler signal in the portal vein implies a portal vein thrombosis – CT is necessary to evaluate the extent of thrombosis as this will determine resectability of a possible pancreatic cancer.
Staging CT is the next best investigation to assess for local and distant spread and to assess extent of vascular involvement in order for a decision to be made as to whether the tumour is resectable.
Q3: What are the available treatment options? What is the next best interventional procedure? Is a histological diagnosis required or helpful – discuss?
A: -Palliative chemotherapy or palliative care with symptom control only.
– ERCP and biliary stent.
– Yes, tissue diagnosis helpful to guide chemotherapy.
The presence of thrombosis in the superior mesenteric artery renders this tumour inoperable. Therefore, palliative care with either chemotherapy or only symptom control are the available options. A histological diagnosis of the tumour is vital to allow guided chemotherapy and to ensure that the correct diagnosis has been made. Benign inflammatory pathologies such as Chronic pancreatitis, IgG4 disease or AIP can mimic pancreatic cancer. Once histology is confirmed, the oncologists will not be able to proceed with chemotherapy if the patient is significantly jaundiced – so, biliary decompression will need to be pursued.
Therefore, Endoscopic retrograde cholangiopancreatography (ERCP) and insertion of a stent into the common bile duct to bypass the stricture (and allow biliary drainage) is the next best procedure.
ERCP image of a distal common bile duct stricture due to pancreatic cancer:
At that time, brush cytology can be taken from the stricture or biopsy of the pancreatic mass (via Endoscopic ultrasound) to enable a histological diagnosis to be made.