Ep 123: 65-Year-Old Male with Hepatocellular Carcinoma (HCC)

This episode presents a 65-year-old man recently who was diagnosed with hepatocellular carcinoma. We discuss environmental risk factors for the development of malignancy.

Transcript

[upbeat intro music]

[Dr. Handy] Hi everyone. Welcome
back to Harrison's Podclass.
We're your co-hosts. I'm Dr. Cathy Handy.

[Dr. Wiener] And I'm Dr. Charlie
Wiener, and we're joining
you from the Johns Hopkins
School of Medicine.

[music continues]

[Dr. Handy] Welcome to episode 123:
a 65-year-old man with
hepatocellular carcinoma.

[Dr. Wiener] Hey, Cathy.
So today's patient is a 65-year-old man
who was recently diagnosed
with hepatocellular carcinoma.
He's a recent immigrant from Bangladesh
where he lived in a rural setting
with minimal primary healthcare.
His physical examination is only notable
for him being thin with a palpable liver.
His granddaughter, who grew up in the US,
is in clinic with him
today and is wondering
if she is also at risk for cancer.
And the question's going
to ask about risk factors
for his current malignancy.

[Dr. Handy] Well, we know that hepatitis B
and hepatitis C are the
most common risk factors
for the development of cirrhosis
and hepatocellular carcinoma,
but I'm guessing that
that's not going to make it
to the answer/questions and
it'll be harder than that.

[Dr. Wiener] Yeah, I'm not
going to make it that easy.
So the question asks,
which of the following is
the most likely risk factor
for his current hepatocellular carcinoma?
And the options are A,
aluminum; B. arsenic;
C. cadmium; D. lead; or E. mercury.

[Dr. Handy] Okay. So it sounds
like today we're talking about
heavy metals, an excellent
and not often discussed topic.

[Dr. Wiener] You're stalling.

[Dr. Handy chuckles] All right.
The answer is B. arsenic.

[Dr. Wiener] You saw
"Arsenic and Old Lace,"
the famous Carrie Grant movie?
Tell me more. What do
you know about arsenic?

[Dr. Handy] Arsenic
has been clearly linked
with an increased risk for many cancers.
And this is even at
moderate levels of exposure.
So in addition to
hepatocellular carcinoma,
it's also been linked to
cancers of the skin, bladder,
the renal pelvis, ureter, and kidney.

[Dr. Wiener] Outside of the movies,
where do people get exposed
to arsenic these days?

[Dr. Handy] Exposure to arsenic
can derive from smelting
in microelectronics
industries, wood preservatives,
pesticides, herbicides, fungicides,
bulk remedies sometimes,
or incinerators that burn these products.
For this gentleman, it's
possible that he was exposed
due to well water contamination.
It's been well known
that deep water wells
are sources of arsenic
but more recently, shallow tube wells
for drinking water in
Bangladesh and Western India
have shown to have high
levels of arsenic too.
And this is problematic
because for millions,
this is their major
source of potable water.

[Dr. Wiener] Does arsenic have any
other risks besides malignancies?

[Dr. Handy] Yes. More
bad news on this front.
Recent studies in community-based
populations have generated
strong evidence that arsenic
exposure is also a risk factor
for an increased risk of hypertension,
coronary heart disease and
stroke, lung function impairment,
acute respiratory tract
infections, respiratory symptoms,
and non-malignant lung disease mortality.
The association with
cardiovascular disease may hold
at levels of exposure in drinking water
that are below the WHO
provisional guideline value
of 10 micrograms per liter.
Evidence has also continued
to build indicating
that low-level arsenic is a likely cause
of neurodevelopmental delays in children
and also likely contributes to
the development of diabetes.

[Dr. Wiener] I'm glad
we're discussing this,
but I've also heard that
seafood is a source of arsenic.

[Dr. Handy] Seafood and fish
contain organic arsenic,
which is non-toxic.
What we're talking about
today is inorganic arsenic.
The toxic metal that we worry
about in fish is mercury.

[Dr. Wiener] Okay, well, in someone
who has potential
chronic arsenic toxicity,
how do we diagnose it
and how do we treat it?

[Dr. Handy] The best
test for chronic toxicity
is to measure arsenic in
the hair or fingernails,
which represents deposition
over 6 to 12 months.
You can also measure levels in the blood
or urine for more acute exposures.
Chronic arsenic exposure
is also associated
with hyperkeratosis,
exfoliative dermatitis,
and Mees' lines on the nails.
Treatment is chronic
chelation with Dimercaprol.

[Dr. Wiener] Okay. I
do want to get back to
"Arsenic and Old Lace," the movie.
You've talked about
chronic arsenic exposure.
What are the symptoms of
acute arsenic poisoning?

[Dr. Handy] All right, acute
arsenic poisoning results in
necrosis of intestinal
mucosa with hemorrhagic
gastroenteritis, fluid
loss, hypotension, delayed
cardiomyopathy, acute tubular
necrosis, and hemolysis.

[Dr. Wiener] Got it. So we now
understand acute and chronic
arsenic but let's finish up
with the typical clinical
manifestations for our other
choices in this question.

[Dr. Handy] Okay. Aluminum
contributes to the encephalopathy
in patients with severe renal disease
who are undergoing dialysis.
Serious cadmium poisoning
from the contamination of food
and water by mining effluents
in Japan contributed
to the 1946 outbreak of itai-itai disease,
so named because of
cadmium-induced bone toxicity
that led to painful bone fractures.
Modest exposures from
environmental contamination
have been associated in some studies
with a lower bone density,
a higher incidence of fractures,
and a faster decline in
height in both men and women,
effects that may be related
to cadmium's calciuric
and other toxic effects on the kidney.

[Dr. Wiener] So, itai-itai
apparently means "ouch ouch."
And I love that we have a
disease called "ouch ouch."
What about lead and mercury?

[Dr. Handy] Lead has
gotten a lot of publicity
in the United States in recent years.
It's associated with a host of cognitive
and developmental problems
in children and young adults.
Less well-known is the strong association
between chronic lead toxicity or exposure
and increased cardiovascular
morbidity and mortality,
hearing loss, Parkinson's disease,
and amyotrophic lateral sclerosis as well.
With respect to
pregnancy-associated risks,
high maternal bone lead levels were found
to predict lower birth
weight, head circumference,
birth length, and
neurodevelopmental performance
in the offspring by age two years.

[Dr. Wiener] And mercury,
you already mentioned,
it could be found in some fish.

[Dr. Handy] Yeah, the concern
is neurobehavioral performance
in the offspring of mothers
that ingested mercury-contaminated fish.
The current recommendation
is for pregnant women
to avoid fish known to have high levels
of mercury contamination,
and that would include fish
like swordfish, king mackerel,
and some varieties of tuna.
Notably, salmon, sardines,
and shellfish have low mercury levels.

[Dr. Wiener] Okay, so
today's teaching points are
that heavy metals can cause
acute and chronic toxicity.
Chronic arsenic exposure,
often through drinking
water in parts of the world
that are at risk, can
place patients at high risk
of a variety of medical
disorders including malignancies.

[Dr. Handy] And you can find
this question and questions
like it in the Harrison's Review
Questions book and online,
and more about heavy metals in
the chapter on heavy metals.
Visit the show notes for
links to helpful resources,
including related chapters
and review questions from Harrison's.
And thank you so much for listening.
If you enjoyed this episode,
please leave us a review
so we can reach more
listeners just like you.

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