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Fontes-Sousa et al. J Cancer Metastasis Treat 2018;4:5 I http://dx.doi.org/10.20517/2394-4722.2017.70 Page 5 of 6

uresectable setting, no matter what treatment strategy is decided upon, the average survival for these patients
[4]
remains disappointingly low - less than one year . Individual factors may have prognostic implications,
[4]
such as non-functioning Lewis enzyme, since almost 10% of patients have normal CA 19.9 levels , which
[1]
is actually associated with longer survival , as in this case; nonetheless, this is infrequently seen in clinical
practice. The patient described here is an example of a long-term survivor patient with a progressively
smaller pancreatic adenocarcinoma mass (probably due to ongoing RT lethal effects) with an apparent
aggressive disease at diagnosis, with a mostly clinically silent cephalopancreatic lesion with vascular invasion.

Considering the second point, in spite of pancreatic adenocarcinoma being the obvious diagnosis for hepatic
metastization, some aspects should prompt a biopsy decision (vs. assuming origin from the previously
diagnosed primary tumor): The time interval between the primary cancer diagnosis and metastasis diagnosis
(a gap of more than three years), the current partial response status of primary disease (making less probable
the presence of progressive disease elsewhere), and other confounding and competing possible causes
such as other malignancies - a risk that in general increases with age-prostate cancer, unknown primary or
even non-malignant causes, such as hepatic abscesses, in light of previous episodes of organized pyogenic
cholangitis with need of percutaneous drainage. At this point, we cannot exclude that the possibility that
the initial pancreatic tumor could have had neuroendocrine foci that later developed. We can speculate
that it is possible that the initial biopsy did not include those components or a second primary tumor
arose independently - either way, the histological characterization of the lesion was considered useful,
since it could have different diagnostic, prognostic and therapeutic implications, especially since it can be
a mostly safe and ambulatory procedure. For example, in much-discussed breast cancer cases, even though
performing a biopsy of suspected metastases is recommended in guidelines, it is not always performed in
[9]
routine oncology practice - most often due to costs and/or invasiveness of the procedure .
Lastly, the third point: focus on pancreatic neuroendocrine tumor is generally considered to have a better
prognosis than pancreatic adenocarcinoma, but this naturally varies according to tumor location, staging,
and metastization pattern among other individual factors. Such rare tumors should ideally be managed in
[8]
reference centers dedicated to diagnosing and treating them .

Of note, the simultaneous diagnosis of pancreatic adenocarcinoma and neuroendocrine tumor is indeed
[10]
very rare . In this particular case report, unexpectedly, the patient actually died due to hepatic failure that
developed relatively quickly, and which impeded any possibility of systemic treatment.

Therefore, we conclude that patients should not be denied a treatment opportunity, if clinically compatible,
solely based on their advanced disease status, especially if based on theoretically low expectations of tumor
response or predicted prognosis. On the other hand, tumors perceived as less aggressive may prove fatal if
not timely and effectively dealt with. We urge clinicians to consider hepatic biopsy in similar situations -
generally when it may change prognosis and treatment strategies - even if the answer may seem obvious at
first.

DECLARATIONS
Acknowledgments
The authors would like to thank Gabriel Gonçalves Fagundes for proofreading the manuscript; and would
like also to thank Mariana Afonso, MD, and Ana Luísa Cunha, MD, at the Pathology Department of the
Portuguese Oncology Institute, for the help at handling pathology images.

Authors’contributions
Literature search: Fontes-Sousa M
Drafting and writing the manuscript: Fontes-Sousa M