HISTORY

Presentation

This 63 year old gentleman complains of yellow discoloration of eyes for 3 months (The presenting
complaint).

He was in good health 3 months ago when his wife noticed that his eyes were yellow; this yellowish
discoloration of his eyes has been deepening since then. He has also noticed that his urine is dark
yellow (like mustard oil). On direct questioning, he says that his stool is pale or white (like clay).
There is no history of passage of dark black tarry (like coal tar, Used for road making) stool (melena).

He also has pruritus but it is mild (does not interfere with his work and sleep). One month ago, he
had an attack of fever (maximum 39°C) with chills and rigors which subsided in a few days' time with
some oral medicines (probably antibiotics).

He has no pain (painless jaundice). There is no history of vomiting, nausea or post-prandial fullness
(gastric outlet obstruction).

He has lost his appetite (anorexia) and has lost 12 kg weight (he weighed 80 kg last year when he
had a medical check up for renewal of his health insurance and his current weight is 68 kg).

There is no past history of repeated attacks of pain in the right upper abdomen suggestive of biliary
colics.

He is not a known diabetic or hypertensive but he underwent coronary artery stenting a few years
ago.

(May give a history of an endoscopy after which the jaundice decreased-most probably endoscopic
biliary stenting).

Information

Indications for biliary drainage (stenting)

 Uncontrolled cholangitis
 Intractable pruritus
 Coagulopathy or renal dysfunction due to SOJ
 Very high (15-20 mg) bilirubin
 To buy time to improve nutrition, arrange for operation, social reasons
Discussion

What does melena indicate?

Melena indicates upper GI bleeding

how (Why) the stool becomes dark black?

Blood is acted upon by the digestive enzymes in the small intestine and the iron in the hemoglobin is
oxidized to give the stool a black colour

Why did you ask about melena?

Carcinoma of duodenum, peri-ampullary carcinoma involving duodenal papilla and carcinoma of

head of pancreas infiltrating duodenum may ulcerate and bleed resulting in melena.

Information

SOJ with melena (SOJ= Surgical Obstructive Jaundice )

1. Short duration painless progressive SOJ is the predominant presentation with occasional mild
melena lasting for a few days-peri-ampullary carcinoma with necrotic sloughing of tumor resulting in
transient partial relief of jaundice

2. Significant melena (with hematemesis) is the predominant presentation with mild SOJ-portal
hypertension and portal biliopathy

3. Long-standing SOJ with melena-benign biliary obstruction with secondary biliary cirrhosis and
portal hypertension causing variceal bleeding

What causes pruritus?

Exact etio-pathology of pruritus is not known but most probably pruritus is caused by deposition of
bile salts in the cutaneous nerve endings resulting in release of endogenous opioids.

Why vomiting?

Presence of vomiting (gastric outlet obstruction) in a patient with surgical obstructive jaundice (SOJ)
indicates carcinoma of the head of the pancreas (vs. peri-ampullary carcinoma where there is no
vomiting) or gall bladder cancer.

How (Why)?

Because of duodenal infiltration and obstruction.

Can you have vomiting without (duodenal) obstruction?

Yes, because of malignant gastro-paresis.

Why did you ask about past history of attacks of pain in right upper abdomen?

To rule out gall stone disease, as the commonest cause of surgical obstructive jaundice is CBD
stones, secondary to gall stone disease.

OK, can you summarise the history?

Elderly gentleman with short-duration painless progressive obstructive jaundice with anorexia and
significant weight loss and history of cholangitis

What do you make out of this history?

I think this is malignant surgical obstructive jaundice (NOT just 'jaundice'-which even the patient can
tell!).

Why obstructive?

Urine is dark yellow and stool is pale white; presence of pruritus; history of cholangitis.

Why malignant?

Elderly patient with short duration of painless progressive (cf. painful intermittent in stone disease)
jaundice; anorexia and weight loss

Which malignancy?

It is difficult to say that based on history alone.

Possibilities?

Gall bladder, pancreas, peri-ampullary and cholangio-carcinoma (north India)

Pancreas, peri-ampullary, cholangio-carcinoma and gall bladder (south India)

Note

The diagnoses are same but note the order of mention. Gall bladder cancer is the 4th most common
cancer (following breast, cervix and ovary) and the commonest GI/HPB cancer in women in north
India; it is uncommon in south. Gall bladder cancer 'divides' India into north and south

Is it possible to have fluctuation of jaundice in malignancy?

Malignant surgical obstructive jaundice is Usually progressive (non-relenting) but a peri-ampullary

carcinoma at the duodenal papilla may ulcerate and slough; this may cause transient relief of biliary
obstruction and a decrease in otherwise progressive jaundice which once again starts progressively
increasing.

How (Why) do you say cholangitis?

High grade fever with chills and rigors

But cholangitis has a triad?

Yes, Charcot's triad of swinging fever, intermittent pain and fluctuating jaundice is classical of
cholangitis due to stone disease but cholangitis associated with malignant obstruction can have
progressive jaundice and may not have pain
Is there a pentad also?

Yes, Raynaud's pentad includes Charcots' triad (vide supra) plus shock and altered sensorium in
severe acute obstructive cholangitis.

Cholangitis Usually occurs with CBD stones. Why do you think that this patient is not suffering
from choledocho-lithiasis?

Cholangitis can occur in cancer also.

Correct, but a so so answer! A better answer will be

Yes, cholangitis is more common with intermittent biliary obstruction as seen in CBD stones, but
progressive complete biliary obstruction of malignancy can also cause cholangitis. Also, this patient
has painless progressive jaundice; jaundice in choledocho-lithiasis is painful and intermittent.

But could it still be choledocho-lithiasis?

Unlikely, as there is no pain and the jaundice is progressive; CBD stones cause painful (biliary colic)
and fluctuating jaundice.

Could it still be benign, say an impacted stone?

Very unlikely, as there is no pain. An impacted CBD stone will cause pain.

Tip

Some (bad) examiners try to lay a trap for the candidates; if you are pretty sure, there is no harm in
being firm and confident but do NOT be rigid and adamant when you yourself are in doubt (a good
examiner may be dropping a hint!).

Why is this not sclerosing cholangitis?

Primary sclerosing cholangitis (PSC) Usually has recurrent attacks-this patient has had only one
attack of cholangitis. Sclerosing cholangitis does not cause progressive jaundice which this patient s.
Also, sclerosing cholangitis is a rare disease; I would not like to make a clinical diagnosis of a rare
disease
Discussion (contd.)

What is the likely site/cause of malignancy here?

I think it is peri-ampullary because there is no pain. Cholangio-carcinoma also causes painless

jaundice but is less common. Cancers of the pancreas and gall bladder usually cause surgical
obstructive jaundice with pain.

But you said he has no history to suggest gall stones. Does this not rule out gall bladder cancer?

No, not all gall bladder cancers have gall stones; about one-third of patients with gall bladder cancer
(in north India) do not have stones. Also not all gall stones are symptomatic so even a patient with
no history of biliary colic may still have gall stones.

Any other point in history to help you (NOT a good question-very open ended and non-specific) to
know the site of cancer (better!)?

Yes, absence of history of vomiting;

if vomiting is present, it indicates gastric outlet (duodenal) obstruction which suggests pancreatic or
gall bladder cancer in presence of jaundice or duodenal cancer in the absence of jaundice.

Note

You can use the term cancer if the discussion is being held away from the patient; if the discussion
is happening at the patient's bedside, the Author suggests (to both examiners and the candidates)
to avoid using the term cancer and instead use technical terms such as carcinoma or malignancy
Can pancreatic & gall bladder cancer also present as painless progressive jaundice?

Yes, only two-thirds (70-80%) of patients with pancreatic and a little more than half of patients with
gall bladder cancer have pain

The remaining may have painless progressive jaundice (like peri-ampullary cancers and cholangio-
carcinoma).

EXAMINATION

Presentation

He is a cooperative elderly gentleman who is short-built and well-nourished. He is deeply

jaundiced with yellow eyes; his skin and mucous membranes are also yellow. There are no scratch
marks. He is afebrile. There is no pedal edema and no peripheral lymph-adenopathy, including left
supra- clavicular (emphasise left supra-clavicular-to 'show that you know') lymph nodes.

Abdomen is scaphoid, umbilicus is normal. A globular lump is seen in the right hypochondrium just
below the costal margin in the mid-clavicular line-it moves freely with respiration.

On palpation, the lump is non-tender, pyriform (oval) in shape, about 8x6 cm, soft and cystic
(REMEMBER a very tense GB may feel firm); surface is smooth; margins are well-defined except
superior which merges under the costal margin; it has a side-to-side mobility also, in addition to its
free movement with respiration.

Liver is not palpable; no other lump is palpable.

On percussion, there is no flank dullness.

Bowel sounds are normal.

I requested the patient to allow me to do a per-rectal examination but he said it was done
yesterday only so I did not do it. I wanted to do it to palpate for any pelvic deposits in the recto-
vesical pouch anteriorly.

Discussion

Why did you specifically mention left supra-clavicular?

Left supra-clavicular is a common site of distant lymph node spread in intra-abdominal cancers
including pancreas.

What is it called?

Virchow's node

Sign?

Troisier's sign

Do you know of any other finding on general examination in intra- abdominal malignancy?

No sir, I do not know.0

Information

Say so, if you do not know something-not everyone knows everything anyway you are not expected
to know everything in order to pass an exam.

Something to do with veins?

Silence!

The examiner has recurrent migratory thrombophlebitis of superficial veins (Trousseau sign) in his
mind (just because he had seen one last month only)-anyway a clinical rarity (an example of the
examiner trying 'to show that he knows'); you will (should) not fail because you did not know this.

What is this lump?

It is distended gall bladder most probably due to a lower end CBD block- Courvoisier's law.

What is Courvoisiers' law?

In obstructive jaundice due to CBD obstruction at lower end, if the gall bladder is distended it is
unlikely to be due to stone disease and is likely to be due to pancreatic/peri-ampullary cancer.

Why GB is not distended in CBD stones?

CBD stones are Usually associated with gall stones which cause chronic cholecystitis and result in the
inflamed gall bladder to be thickened and contracted not allowing it to distend in presence of lower
CBD obstruction due to stones.

What are the exceptions to Courvoisier's law?

1. Double impaction of stones-CBD stone causing obstructive jaundice and GB (cystic duct)
stone causing mucocele (distended GB)
2. Gallbladder cancer at the neck causing obstructive jaundice due to CBD infiltration and
mucocele due to cystic duct block
3. Oriental cholangitis with primary CBD stones and no gall stones where GB is normal and can
get distended even when jaundice is due to CBD stones.

Is it a mucocele?
No, this is distended gall bladder, full of bile and not mucus. Mucocele is when the gall
bladder distends because of an obstruction of the cystic duct, Usually due to an impacted
gall stone.

Discussion on DIAGNOSIS
So what is your diagnosis?
My clinical diagnosis is a peri-ampullary cancer.

What do you mean by peri-ampullary?

Peri-ampullary cancers include a group of cancers viz. lower end CBD cholangio-carcinoma,
true ampullary cancer, small pancreatic cancer, papillary cancer and peri-papillary duodenal-
cancer-all within 1-2 cm of the ampulla.

Can it be anything else?

Yes, it can still be cholangio-carcinoma or pancreatic cancer.

How can GB be distended in cholangiocarcinoma ?

A mid-CBD cholangio-carcinoma can cause cystic duct obstruction resulting in mucocele.

Why not gall bladder cancer?

A distended gall bladder virtually rules out gall bladder cancer.

Can you have a mucocele in gall bladder cancer?

Gall bladder cancer in its neck can cause cystic duct obstruction and present as mucocele
(exception to Courvoisier's law).

INVESTIGATIONS

OK, what will you do (to this patient)?

I will advise investigations to arrive at a diagnosis, to evaluate liver functions and some
general investigations

What (investigations)?
First of all, 1 would like to do an abdominal ultrasound (USG).
Why

USG will confirm that it is obstructive jaundice, it will show the level of block in the biliary
tree and may also suggest the cause. It will also rule out stone disease.

Beware
Presence of GB stones on USG in a patient with SOJ may suggest the diagnosis of CBD stones
but does not rule out a diagnosis of malignant SOJ-gall stone disease is so common that it
may be incidentally present (not every problem in a patient with past history of tuberculosis
(TB) is tubercular!

What else will USG show In malignancy?

Oh yes, it also looks at the liver for metastases and detects ascites; it can also detect
cholangiolytic abscesses in the presence of associated cholangitis.

Suppose USG shows ascites?

It could be either nutritional or malignant. In this case, the patient is well. nourished and
there is no pedal edema (to suggest hypo-proteinemia hypo-albuminemia) so it is less likely
to be nutritional. I would then like to do an USG-guided needle aspiration of the ascitic fluid
and subject it to fluid cytology to look for malignant cells.

What findings on USG indicate that it is obstructive jaundice?

Intra-hepatic biliary radicles dilatation (IHBRD).

And what suggests a lower block?

Dilated CBD along its entire length

What is the diameter of normal CBD on USG?

4-7 mm; anything above 8 mm is dilated

OK, USG shows IHBRD, distended GB and dilated CBD. What next?

These findings indicate that it is surgical obstructive jaundice due to lower end CBD block. I
would like to know if the USG shows a mass in the gall bladder or pancreas and whether
the pancreatic duct is dilated

No, the US does not show any mass.

I think this further confirms my clinical diagnosis of a peri-ampullary cancer.

What next?
I would like to do a contrast-enhanced helical (spiral) CT scan of the abdomen with
pancreatic protocol (does this answer not look better than just 'CT'). However, before that I
will obtain a routine chest X-ray to look for any lung metastases.

Why CT?
To assess the stage of the disease and to evaluate the resectabilty of the lesion.

What is pancreatic protocol CT?

Pancreatic protocol includes pre-contrast imaging of the pancreas to look for any
calcification or hemorrhage, followed by dynamic contrast-enhanced images (arterial, portal
venous and delayed venous phases) with thin sections.

What findings on CT will indicate unresectability?

Liver metastases, ascites (which will have to be proven to be malignant by fluid cytology),
infiltration of superior mesenteric and portal veins superior mesenteric artery and inferior
vena cava, distant lymph nodes
Note

In some cases e.g. in presence of distant lymph nodes and metastases, technically speaking
the lesion is still resectable (can be resected) but prognosis is poor (should not be resected)..

So you want to look for liver mets on CT but US did not show any liver lesion?

Yes, but CT is better ('more sensitive' is a better term!) than US to pick up liver metastases.

Tip

A general rule, when replying to a question-first agree with the other person, then
contradict and make your point. This hurts the ego of the other person less than when you
start by straightaway contradicting him/her e.g. 'no, US is a poor investigation to show liver
mets.

What about duodenal infiltration?

Duodenal infiltration does not matter for resectability of peri-ampullary or pancreatic cancer
as duodenum is removed along with the head of pancreas in pancreatico-duodenectomy.

What are the CT findings in peri-ampullary cancer?

IHBRD, dilated CBD till lower end, dilated pancreatic duct (but may not be dilated in all
cases) and absence of an obvious mass lesion (which, if present, would then suggest
pancreatic cancer)

But would CT confirm your diagnosis?

No, CT will not confirm the diagnosis; the diagnosis of a peri-ampullary cancer is confirmed
by a side-viewing endoscopy (ERCP) which may show an ulcerated friable bleeding lesion at
the papilla on the medial wall of the second part of the duodenum and by biopsy (histology).

What is ERCP?

Side-viewing endoscopy (ERCP) is upper GI endoscopy using flexible endoscope with a side
view (as opposed to end/front view of a conventional upper GI endoscope) to visualize and
take a biopsy. It is also used for ERCP, endoscopic papillotomy (EPT) and endoscopic stenting
(ES).

Are all peri-ampullary cancers seen on ERCP?

No, only a papillary cancer and peri-papillary duodenal cancer will be seen on ERCP; lower
end cholangio-carcinoma, true ampullary carcinoma and small pancreatic cancer may not be
seen on side-viewing endoscopy.

What does the ERCP show then?

It may show a smooth bulge on the medial wall of the duodenum caused by a hugely dilated
CBD.
How can tissue diagnosis be obtained?
Endoscopic biopsy after endoscopic papillotomy, brush cytology from within the CBD, biopsy
using a mother baby scope and bile cytology.
More invasive?
Endoscopic US guided FNAC, percutaneous transhepatic cholangio-scopy (PTCS) and biopsy
or brush cytology.

If biopsy is negative?

While every effort is made to get a tissue diagnosis, it is not possible and essential to have it
in every case before operation; resectable peri-ampullary cancer can be operated based on
strong clinical and radiological suspicion alone even with no biopsy or negative histology.

So you want both CT and ERCP. Which first?

I will do CT first. If side viewing endoscopy (ERCP) is done first and at the same time stenting
is done, it will produce artifacts in CT done later.

Would you like to do an ERCP?

Endoscopic retrograde cholangio-pancreaticography (ERCP) is not required for the diagnosis

of a peri-ampullary cancer; it may be done as a part of a therapeutic intervention e.g.
endoscopic stenting.

Why (is ERCP) not (done)?

The CBD is blocked by the tumor; if radiological contrast is injected into the dilated
obstructed CBD proximal to the tumor, it can induce cholangitis in the obstructed biliary
system.

If you do an ERCP what will it show?

Both CBD and pancreatic duct are blocked (strictured) by the tumor and have proximal
dilatation. The two dilated ducts are NOT unduly separated (which happens in pancreatic
head cancer-the classical double duct sign).

Do you know of any other special investigation to evaluate the lower end of CBD?
Yes, endoscopic ultrasonography (EUS)

And (what else)?

EUS guided FNAC

Is there any other Investigation to detect liver metastases?

MRI

No, an Invasive procedure?

Oh yes, laparoscopy

How is laparoscopy different from US, CT or MRI for detecting liver metastases?

It detects small deposits on the surface of liver, peritoneum and omentum It detects small
depicked up on cross-sectional imaging (US, CT, MRI)

What about metastases within the liver parenchyma? Any intra-operative Investigation?

Intra-operative or laparoscopic US

Any specific general investigations in this particular patient?

Silence!

His past medical history?

Oh, sorry! He has had coronary stenting in the past; I will do ECG and ECHO and ask for
cardiology opinion.

TREATMENT
Discussion

ERCP shows a tumor and biopsy is positive, What treatment would you like to offer to this
patient?

It would depend on the stage of the disease and his fitness for anesthesia and major surgery.

OK, the disease is resectable and he has been cleared by anesthesia. I will advise him to
undergo surgery-pancreatico-duodenectomy (PD).

Do you know the types of PD?

Whipple's or classical pancreatico-duodenectomy and pylorus preserving pancreatico-

duodenectomy (PPPD).

The patient says he has read about endoscopic stenting as the treatment on the internet;
why not that?

I will explain to him that endoscopic stenting is only a palliative procedure, only surgery has
a chance of cure.

How do you prepare a jaundiced patient for surgery?

1. Hydration, to ensure good urine output (IV drip started the night before operation)

2. Diuresis with mannitol (was recommended earlier, not used now a days)

3. Vitamin K 10 mg IM daily for 3-5 days to correct coagulopathy

4. Prophylactic antibiotics

How does vitamin K help?

Bile salts in bile emulsify fats (of. detergent soaps) and help in their (as also of fat-
soluble vitamins) digestion and absorption in the small gut . In obstructive jaundice, bile
(and bile salts) do not reach the small intestine and hence fats and, therefore, fat-
soluble vitamins ( A, D E and K) are not absorbed. This results in deficiency of vitamin K.
causing inadequate prothrombin production and coagulopathy which gets corrected
with vitamin K (cf. coagulopathy in chronic liver disease which does not respond to
vitamin K but needs fresh frozen plasma FFP).

If bilirubin is very high, say 28 mg?

Pre-operative biliary drainage by endoscopic stenting may be done.
PTBD (percutaneous transhepatic biliary drainage) is rarely required if endoscopic
stenting fails.

Then?
Wait till bilirubin comes down to less than 5 mg and then operate.

Why do you want the bilirubin to come down to less than five and how long does it
take?
To reduce the risk of complications of jaundice; it may take a few weeks time.

Something else that you have missed in history? (What a vague question!)

Silence! (The question merits a blank look only!)

Would you like to know the drug history of this patient?

Oh yes, he has had coronary artery stenting and I would like to know whether he is on
anti-platelet drugs such as aspirin or clopidogrel.

Why?

These drugs may have to be discontinued for few days before surgery.

What is removed in classical Whipple's?

Distal half of stomach, entire duodenum, proximal few cm of jejur

Gall bladder, CBD (below the cystic duct)

Head of pancreas (up to neck)

Why pancreatico-duodenectomy? Why not Why sacrifice the duodenum?

1. Head of pancreas and C loop of duodenum have a common blood supply

2. Pancreatic cancer usually involves duodenum also

3. From oncological point of view to achieve RO (no microscopic resid disease) resection

How many ansotomoses?

Three:
1. Pancreatico-jejunostomy
2 Gastro-jejunostomy
3. Hepatico-jejunostomy

How do you follow up a patient with a biliary-enteric anastomosis?

Clinical (jaundice, fever, pruritus), LFT (bilirubin, ALP, GGTP), IN (IHBRD), isotope
hepato-biliary scintigraphy, MRC

What is the prognosis?

Most (90-95%) of peri-ampullary cancers are resectable and 5 year survival is good (cf.
very few 20-25% of pancreatic cancers are resectable and 5 year survival is poor).

What about lymph nodes (in terms of resection and prognosis)?

Presence of enlarged distant lymph nodes (LNs) e.g. celiac, superior mesenteric and
para-aortic/aorto-caval, indicates advanced stage of the disease and poor prognosis
(outcome) even if the primary tumor is resectable

If this patient (with possible peri-ampullary cancer) was young say 30 years and
complains of fresh rectal bleed, what would you suspect?
Silence!
Any syndrome?
Polyposis syndrome (familial polyposis coli FPC or familial adenomatosis polyposis FAP)
with associated peri-ampullary cancer

Anecdote

25 year old female with 2 months history of progressive jaundice and pruritus but no
cholangitis; significant anorexia and weight loss
Too young for cancer but progressive jaundice and significant anorexia and weight loss
suggested malignancy
CT showed large necrotic lymph nodes around the CBD-FNAC revealed tuberculosis (TB)
Past history of pulmonary TB was missed

ALTERNATE SCENARIO

The same patient is 78 year old with known cardiomyopathy. He can not walk even to
the toilet without having dyspnea; ECHO reveals left ventricular hypokinesia and
dilatation and ejection fraction (EF) is 20%.

Once the diagnosis of a peri-ampullary cancer is suspected (on US) and proved (by ERCP
and biopsy), the patient can straightaway be taken for endoscopic palliation of jaundice
and pruritus. CT is not required because even if the lesion is found to be resectable (as it
is likely to be), the patient is not fit enough to undergo a major surgery i.e. pancreatico-
duodenectomy.

Note

It is the patient who has to undergo the operation (safely); NOT the tumor which has to
be resected (irrespective of the outcome)!

PANCREATIC (HEAD) CANCER

Presentation

Short duration (few months) history of obstructive jaundice with severe 5 continuous
relentless unremitting intractable deep boring gnawing (radiating to back) epigastric
pain, may be aggravated on lying down (supine) and relieved by sitting and leaning
forwards (pancreatic position); post-prandial fullness, nausea and vomiting (suggestive
of gastric outlet obstruction GOO due to duodenal obstruction); anorexia and significant
(>10% in 6 months) weight loss.

GB may be palpable.

Diagnosis

Pancreatic (head) cancer or gall bladder cancer (pain and GOO with malignant
obstructive jaundice).

Information

Upper abdomen pain with anorexia and weight loss-pancreatic body and tail cancer or
HCC (pain is not a predominant feature in carcinoma stomach and colon which may be
associated with pallor due to Gl bleed)

Discussion

(If your diagnosis is pancreatic head cancer) would you like to ask about any significant
past history?

Silence!
Any pre-malignant condition?

Silence again!!

Common in South India? (A good and generous examiner drops hints. (s)he wants to
know what the candidate knows!)

Yes, chronic calcific pancreatitis (CCP)

I would like to ask if he has had long history of recurrent attacks of epigastric pain
radiating to back with diabetes and steatorrhea.

How do you ask about steatorrhea?

Large volume bulky semi-solid greasy frothy foul-smelling stools which float on water
and stick to the toilet pot (difficult to flush)
Any other important recent history?

Silence!

Diabetes?

Recent onset of diabetes in a middle-aged elderly patient is suggestive of pancreatic

cancer.

Can CP (chronic pancreatitis; NOT Connaught Place!) cause jaundice?

Yes, chronic pancreatitis can cause surgical obstructive jaundice (SOJ) by obstructing the
CBD due to fibrosis, inflammatory mass or a pseudocyst in the head of pancreas.

So why is this not CP?

Short duration of history, dull continuous pain, gastric outlet obstruction (GOO) and
anorexia and weight loss suggest malignancy; chronic pancreatitis will have long
duration of history, recurrent attacks of pain, GOO is rare; weight loss may be present
(due to malabsorption) but there is no anorexia.

Are there any tumor markers for pancreatic cancer?

CA19-9; for diagnosis (to differentiate from chronic pancreatitis) and follow up only-
(NOT for resectability-some reports, however, suggest that very high (> 1000mu / m * L )
levels indicate unrescetability).

What does US show (in pancreatic cancer)?

IHBRD, dilated CBD till lower end and dilated pancreatic duct but with wide separation
of the two ducts (double duct sign), mass in head of pancreas (cf. in peri-ampullary
cancer also both ducts are dilated, but they are not separated and meet each other;
also, no mass is seen)

If US/CT shows SOL in liver?

A space occupying lesion in the liver will usually suggest metastasis and inoperable
disease.

Always?

No, not always; in presence of cholangitis, the patient can have cholangio- lytic
abscesses in liver which can mimic metastatic lesions and hence I would like to confirm
the diagnosis of metastasis by getting a tissue diagnosis.
How?

by US/CT guided fine needle aspiration cytology (FNAC) from the liver SOL.

Any precaution before FNAC?

will obtain a coagulation profile ----bleeding time, clotting time, prothrombin time (PT)
and activated partial thromboplastin time (aPTT), P time INR

What all do you look for in CT?

Irregular heterogenous but largely hypodense pancreas mass, local infiltration and
extent, liver metastases, lymph nodes, adjacent organ (duodenum, colon) infiltration,
infiltration of adjacent vessels (superior mesenteric vessels, portal vein and inferior vena
cava IVC), ascites, pelvic, peritoneal and omental deposits

How do liver mets look on CT?

Low attenuating space occupying lesions (SOLs)

How do involved lymph nodes look on CT?

Involved (metastatic) lymph nodes are large (>10 mm), round (cf. oval normal LNs) and
show ring like (peripheral) or heterogeneous enhancement.

What indicates unresectability?

Liver metastases, vascular infiltration

How is vascular involvement classified?

Proximity, abutment (<180°) and encasement (>180°)

Which vessels?

Superior mesenteric vessels (artery and vein), portal vein and inferior vena cava

What is borderline resectable pancreatic head cancer?

Impingement/abutment of superior mesenteric vessels, encasement of gastro-duodenal

artery, involvement of transverse colon/mesocolon

How do you manage (borderline resectable pancreatic head cancer) ?

Neo-adjuvant chemo-radiotherapy (NACT) can convert borderline resectable pancreatic
head cancer to resectable.

What about lymph nodes?

 Involvement of distant lymph nodes e.g. aorto-caval, usually contraindicates resection

What are resectability rates?

Only 20-25% of pancreatic (head) cancers are resectable (cf. 90-95% of peri-ampullary
cancers)

What are the operative findings in pancreatic cancer?

Firm to hard mass in the pancreatic head and rest of pancreas is soft (cf chronic
pancreatitis where the entire gland is firm)

What are the methods to get a per-operative tissue diagnosis?

ERCP and biopsy...

Per-operative? (Listen to the question properly! The examiner said per. operative NOT
pre-operative!)

FNAC (you had just now used the full term so it is ok to say FNAC now) from the
pancreatic mass, core (needle) biopsy, incision biopsy (not recommended), biopsy of an
enlarged lymph node, ascitic fluid cytology

Any special technique for core (needle) biopsy?

Trans-duodenal, to avoid a pancreatic fistula (in case the lesion is not resected)

CT shows infiltration of superior mesenteric vessels, what palliation can be offered to

unresectable pancreatic cancer?

Patients with unresectable pancreatic cancer may have pain, jaundice (and associated
pruritus and cholangitis) and gastric outlet (duodenal) obstruction (GOO) and need
palliation from these symptoms.

1. Pain-analgesics, celiac plexus neurolysis (CPN), trans-thoracic splanchnectomy

2. Jaundice-endoscopic biliary stenting, percutaneous trans-hepatic biliary drainage

(PTBD), surgical biliary bypass (choledocho- or cholecysto- jejunostomy)

3. GOO-gastro-duodenal stenting, surgical gastric bypass in the form of gastro-

jejunostomy (NOT just 'GJ!)

What is triple bypass?

1. Gastro-jejunostomy to relieve gastric outlet (duodenal) obstruction (G00)

2. Choledocho-or cholecysto-jejunostomy to relieve biliary obstruction

 3. Jejuno-jejunostomy anastomosis (BEA) to divert food stream from the biliary enteric

How is cellac plexus block done?

1. Percutaneous US or CT-guided
2. Intra-operative-laparoscopic or at laparotomy

Any better guidance for pre-operative (celiac plexus) block?

Endoscopic Ultrasound (EUS)

The biliary stent is often called pig-tail stent. Why?

The ends of the stent are coiled/curled like a pig-tail-they open up (straighten) when a guide wire is
introduced into the stent for its passage through the endoscope but recoil/recurve when the guide
wire is removed after the stent has been placed in the CBD; the pig-tails at the end of the stent
prevent it from slipping out/down through the papilla inside duodenum.

What is SEMS?

Self-expanding metal stents

Any chemotherapy (for pancreatic cancer)?

Gemcitabine

Which cases?

Node-positive, margin positive.

What is the prognosis (of pancreatic cancer)?

5 year survival in pancreatic cancers is poor (cf. peri-ampullary cancers where 5 year survival is good)

What is the differential diagnosis of a (pancreatic) head mass?

Tip

This is a theoretical question; time to show your knowledge-so mention all probable and possible
causes and classify them, but since the question is being asked during a clinical examination,
mention the more common ones first in each group!

The differential diagnosis of a pancreatic head mass (the examiner, as usual, has the liberty to say
just 'head mass'; but you should use the complete term 'pancreatic head mass'!) includes the
following

1. cystic neoplasms, neuro-endocrine tumors Neoplasms-adeno-carcinoma, (NET), lymphoma

2. Inflammatory-chronic pancreatitis (CP), acute pancreatitis (AP), auto- immune pancreatitis

(AIP)*, xantho-granulomatous pancreatitis

3. Infective-tuberculosis (TB), actinomycosis

The differential diagnosis of a pancreatic head mass can be further and classified as:
i) With/without Chronic Pancreatitis i.e whether the rest of the pancreas (other than
pancreatic head ) is showing changes of chronic pancreatitis or is normal

(ii) Solid or cystic

(m) Calcified (chronic pancreatitis, neuro-endocrine tumor NET, mucinous cyst-adenoma) or

not

On imaging how do you differentiate between pancreatic cancer and

chronic pancreatitis?

In pancreatic cancer, there is a localised mass and there is abrupt change from normal to
dilated duct.
In chronic pancreatitis, the entire gland is involved and there are multiple areas of stricture
and dilatation of pancreatic duct

CHOLANGIO-CARCINOMA (CC)

Cholangio-carcinoma can be intra-hepatic (cholangio-cellular carcinoma CCC, which mimics

hepato-cellular carcinoma HCC), hilar or proximal (Klatskin's, commonest-two-thirds of all
CCs), mid (mimics gall bladder cancer) and lower or distal (peri-ampullary).

Note

The term bile duct cancer (cholangio-carcinoma) is NOT the same as biliary tract cancer,
which includes gall bladder cancer also.

Classification (Bismuth's) of cholangio-carcinomas

Type I Tumor involves the common hepatic duct (CHD) below the confluence (confluence is
free)
Type II Tumor involves the confluence

*Auto-immune pancreatitis (AIP) more frequent in young females; may be associated with
other auto-immune diseases such as auto-immune thyroiditis; US and CT show pancreatic
head mass with (sausage shaped) diffuse enlargement of pancreas and narrowed pancreatic
duct; raised ESR; immune-globulin (Ig) G, anti-nuclear antibody (ANA) and anti-smooth
muscle antibody (ASMA) are present; histopathology shows lymphocytic infiltration;
responds to steroids

Type III

a Tumor involves the confluence and the right hepatic duct (RHD)
b Tumor involves the confluence and the left hepatic duct (LHD)

Type IV
Tumor involves the confluence and both right and left hepatic ducts (RHD and LHD)

Types II, III and IV are included in hilar cholangio-carcinomas.

Presentation
Short duration (weeks or months) painless progressive surgical obstructive
jaundice with pruritus and cholangitis.

Jaundice, firm hepato-megaly with rounded edges (cholestatic liver), GB may be distended if
it is a lower or mid CBD cholangio-carcinoma.

The patient may have a tube in situ exiting from right lower chest and draining bile
(percutaneous transhepatic biliary drainage PTBD placed most probably for control of
cholangitis or to bring serum bilirubin down in preparation for a major liver resection)

Tip

Painless surgical obstructive jaundice (SOJ)

Malignant Peri-ampullary cancer, cholangio-carcinoma

Benign Choledochal cyst, primary sclerosing cholangitis

Discussion

What is hilum?
Hilum of the liver is at the upper end of the hepato-duodenal ligament (HDL) where
(branches of) hepatic artery and portal vein enter the liver and (right and left) hepatic ducts
come out of it.

What are the USG findings in cholangio-carcinoma?

The commonest (two-thirds) site of cholangio-carcinoma is hilar at the Confluence of the

right and left hepatic ducts-USG will show bilateral dilatation of intra-hepatic ducts with
blocked confluence (right and left Hepatic ducts do not join and are separated) but GB is not
distended and CBD is not dilated. USG may also show liver metastases and enlarged lymph
nodes

USG shows one lobe of liver to be smaller than the other. (What does It mean?)

This suggests atrophy-hypertrophy complex.

Cause?
Infiltration of one branch of portal vein by the tumor.

Differential diagnosis (of CC)?

Carcinoma neck of the gall bladder infiltrating the common hepatic duct

How do you differentiate?

No mass is seen on imaging (US, CT, MRI) in cholangio-carcinoma; gall bladder cancer has a
mass.
Any benign (DD)?

Mirizzi's syndrome, focal primary sclerosing cholangitis (PSC)

What is the main aim of further investigation (after USG)?

Evaluation of:

1. Vertical (longitudinal) extent of ductal (intra-mural) involvement-upper ie. extension into

right and left hepatic ducts and their sectoral and segmental branches which will decide
whether hepatectomy will be required and which hemi-liver will have to be removed, and
lower ie involvement of intra-pancreatic part of CBD which will decide whether pancreatico-
duodenectomy will be required.

2. Horizontal (circumferential) extra-mural involvement of vessels (portal vein and hepatic

artery) in the hepato-duodenal ligament.

What investigation after US?

Triple phase contrast enhanced CT scan which will evaluate liver (for metastases, volume-
atrophy and hypertrophy, cholangiolytic abscess), bite ducts, vessels (hepatic artery and
portal vein), lymph nodes and ascites.

What indicates unresectability?

1. Involvement of a main vessel (hepatic artery or portal vein) in the hepato- duodenal
ligament
In case of a hilar cholangio-carcinoma.

2. Involvement of both branches of a main vessel (hepatic artery or portal vein)

. Involvement of duct on one side and vessel on other side

What is the investigation of choice to know the extent of ductal involvement?

Magnetic resonance cholangiography (MRC); (it is called MRCP (magnetic resonance
cholangio-pancreaticography) when pancreatic duct is also evaluated e.g. in pancreatic
cancer, chronic pancreatitis, etc.) MRC is non-invasive and does not involve any radiation; it
is, however, expensive.

Why not PTC?

Percutaneous trans-hepatic cholangiography (PTC) is an invasive investigation associated
with complications such as bleeding, bile leak and cholangitis. PTC is, however, preferred
over ERCp for upper CBD obstruction e.g. gall bladder cancer, hilar cholangio-cracinoma.

Why not ERCP?

Endoscopic retrograde cholangiography (ERC) is better suited for lower

CBD obstruction e.g. CBD stones, pancreatic and peri-ampullary cancers.

What is the most important factor to assess resectability of hilar cholangiocarcinoma?

Involvement of the vessels in the hepato-dudoenal ligament (HDL) viz. hepatic artery and
portal vein.
How is that assessed?

Angiography

Conventional (angiography)?

No, the investigation of choice today is non-invasive magnetic resonance angiography (MRA)
done at the same time as MRC; even CT can be combined with angiography (CT angiography
CTA).

Any non-invasive method?

Doppler US

How is tissue diagnosis obtained?

Brush cytology at ERC or PTC.

Is it usually positive?

No, it is frequently negative.

Why?

Because of dense fibrosis in the tumor.

So (what else)?
Endoscopic US guided FNAC can be done.

Any other more Invasive?

Percutaneous transhepatic cholangioscopy (PTCS) and biopsy.

If (tissue diagnosis is) not possible?

Tissue diagnosis is difficult to obtain in cholangio-carcinoma. It is, however, not necessary if

the lesion is resectable.
What is the treatment of hilar cholangio-carcinoma?

Treatment of choice is surgical resection. This is, however, possible in very few cases only
and usually includes some (right or left) liver resection and removal of lymph nodes in the
hepato-duodenal ligament.

Information

Bismuth type I cholangio-carcinoma, where confluence is free, can be treated with bile duct
resection (and biliary-enteric anastomosis) alone-frozen section of the resection margins
(especially proximal) must be obtained to ensure RO resection.

Extent of liver resection in hilar cholangio-carcinoma • Caudate lobe (segment I) is always

removed

* Right (more often performed than left)

* Sometimes extended right (removes right IV leaves left lateral II + III)

* Sometimes extended left (removes left + right anterior V +VIII leaves right posterior VI + VII
)

Problem of major liver resections in presence of SOJ(Surgical obstructive jaundice)-post-

operative liver failure

* What can predict post-operative liver failure-functional residual volume (FRV)

* How do you assess FRV?-CT, isotope scan

* How can you improve FRV-portal vein embolisation (PVE) on the side to be resected

* How is PVE(Portal vein embolization) done-Percutaneous transhepatic approach

Can a cholangio be resected without liver resection?

Bismuth type I cholangio-carcinoma (confluence not involved) and mid- CBD cholangio-
carcinoma can be treated with CBD resection alone (without liver resection).

What about lower CBD cholangio-carcinoma?

It is included in peri-ampullary cancers (surgical obstructive jaundice with distended gall
bladder) and is treated as such (pancreatico-duodenectomy)

Anything special in liver resection for cholangio?

Caudate lobe (segment I) is almost always removed (along with right or left hemi-liver)

Why?

Because ducts and veins from the hepatic ductal confluence drain into the caudate lobe.

Do you know of more major resections (for CC)?

Vascular (portal vein more often than hepatic artery) resection and reconstruction.

Any preparation (before operation)?

Most (almost all) of these patients are jaundiced and may require a major hepatic resection.
Preparation includes two important procedures.

1. Pre-operative biliary drainage (PBD)

2. Portal vein embolisation (PVE)

Why?

1. Pre-operative biliary drainage to bring serum bilirubin down

2. Portal vein embolisation to induce atrophy of the liver lobe to be resected and
compensatory hypertrophy of the liver lobe to be preserved and to avoid post-resection liver
failure

Which part of liver is drained?

Preferably the part to be retained

Bilirubin down to what level?

Preferably less than 3 mg/dL

Any other indication for PBD?

To control cholangitis

How long do you wait after PVE?

About 3-6 weeks

What is the optimal volume to be left behind?

The optimal functional residual volume (FRV) of liver is 30-40%.

What about unresctable cases?

They need palliation for jaundice.

How?

By drainage PTBD -Percutaneous trans-hepatic biliary drainage-- biliary obstruction in hilar

CC is difficult to palliate with endoscopic stenting (two stents may have to be placed as the
confluence of right and left hepatic ducts is blocked

Why not endoscopic?

Endoscopic stenting is good for lower CBD block e.g. in cholangio-carcinoma pancreatic
cancer;

What is the difference between PTC and PTBD?

PTC is percutaneous trans-hepatic cholangiogram and is a diagnostic investigation to

delineate the biliary tract, especially proximal.
A (22G) Chiba needle is used. (Chiba is not the name of the person who devised the needle:
it is the name of the University where it was developed another example of Japanese
patriotism!)

PTBD is percutaneous trans-hepatic biliary drainage and is a therapeutic procedure to

externally drain the obstructed biliary system.

Which (type of) stents?

Plastic or metal (self expanding metal stent SEMS)

Complications (of PTBD)?

Bleeding, bile leak

Any therapeutic option to control the tumor( In unresectable cases)?

Interstitial radio-therapy (brachy therapy) using an Iridium192 wire passed through the
PTBD

What about intra-hepatic cholangio-carcinoma?

Intra-hepatic cholangio-carcinoma (also called cholangio-cellular carcinoma CCC) mimics
(liver mass with no jaundice but pruritus) hepato-cellular carcinoma (HCC) and is treated on
the same principles (hepatic resection as HCC.

Anecdote

47 year old female with 4 months history of post-prandial dull ache in epigastrium with
significant anorexia and weight loss.

Possible malignancy-Pain suggests pancreas (but not head, as there is no SOJ),

incidence favours GB, it may be HCC,
post-prandial symptoms may indicate stomach;
colon is less likely as it does not have pain and anorexia and weight loss are infrequent.

USG shows SOL in liver-could be a metastasis or primary (HCC).

CT shows mass in segment IV with left IHBRD-likely to be intra-hepatic cholangio-cellualr
carcinoma (CCC).

It is not GBC as the right hepatic duct is not involved.

Do you know of any premalignant conditions (for cholangio- carcinoma)?

Choledochal cyst, Caroli's disease, primary sclerosing cholangitis (PSC), recurrent pyogenic
cholangitis (RPC).

Any infective etiological factor for CCC?

Opisthorchis (trematode-a liver fluke)