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Page 2 of 8 Lo Re et al. J Cancer Metastasis Treat 2019;5:81 I http://dx.doi.org/10.20517/2394-4722.2019.30

INTRODUCTION
The severity of pancreatic ductal adenocarcinoma (PDAC) is often linked to a late diagnosis with evidence
of a locally advanced or metastatic disease, and the prognosis is poor. PDAC is one of the most chemo-
resistant tumors, which seems related to derived tumor-associated macrophages (TAMs) cells in the
[1]
tumor’s desmoplastic reaction . They are distinguished in M1 macrophages, which express inducible
nitric oxide synthase, major histocompatibility complex class II (MHC-II) proteins, and CD80, CD86, and
tumor necrosis factor α proteins, and they have immunostimulatory activity. In contrast, M2 macrophages
expressing Th2 cytokines, arginase 1, CD206, and low amounts of MHC-II have immunosuppressive
[2]
functions that allow tumor progression . Furthermore, the tumor microenvironment (TME), through
[4]
[3]
Treg and myeloid-derived suppressor cells (MDSC) cells, has negative immunosuppressive effects.
Current treatments for advanced PDAC that improve prognosis and survival are Nab-Paclitaxel-
Gemcitabine (Nab-PCT-GEM) and FOLFIRINOX . Furthermore, Nab-PCT-GEM regimen, in addition
[5]
[6]
to its direct antitumor activity, seems to have immunoregulatory function. In fact, nab-PCT polarizes M1
[8]
[2,7]
macrophages by toll-like receptor 4 signaling , whereas GEM has a dual action on MDSC and Treg .
However, a cancer patient’s immune system is affected by other factors, such as depression and impairment
of physical activity. Depression due to a cancer diagnosis, as well as chronic stress and social isolation,
[9]
suppresses immune function by the adrenergic and glucocorticoid pathways . The effects are especially
[10]
strong on the lymphocytic stromal TME , and are determinants in response to therapy.
Regarding physical activity, which could modify the depressive state, there are no conclusive data on the
real impact on the immune system. Finally, although there is experience that correlates the amplitude of
[11]
physical activity with the reduction of the risk of cancer-related and cardiovascular mortality , this has
not been reported on PDAC .
[12]
The aim of this report is to analyze the characteristics of this long-term PDAC patient and the possible
positive influence of long and constant physical activity on the global control of the disease.

CASE REPORT
A male 40-year-old patient has been recognized to have a locally advanced neoplasm of the pancreas
head. After the appearance of obstructive jaundice, he was subjected to endoscopic retrograde cholangio-
pancreatography and positioning of biliary stenting with resolution of jaundice. Subsequently, he was
subjected to exploratory laparotomy, which showed a locally advanced head pancreatic tumor that was judged
inoperable. The intraoperative biopsy provided the diagnosis of PDAC. From December 2013 to July 2014, the
patient underwent chemotherapy with Nab-PCT-GEM combination [Figure 1A and B] for seven cycles with
radiological stability (not shown). Taking into consideration the persistence of non-operability, he performed
RT 50 Gy/15 fractions combined to biweekly GEM with stabilization of the disease [Figure 1C and D].

After subsequent local progression, he was treated from April to October 2015 with FOLFIRINOX for
six months with stabilization of the disease (not shown). This treatment resulted in bone marrow and
peripheral neurological toxicity with negative repercussions on general conditions. After a slow and
progressive clinical improvement, from February 2017, the patient undertook a constant course of physical
exercise until he reached 15,000 km of walking. The reported daily route, carried out exclusively on foot,
was on average 20 km and the total distance traveled was performed in 750 days.

During the five-year follow-up period, the stability status of the disease was confirmed [Figure 1E and
F]. Furthermore, blood samples were taken the morning following a walk, periodically about every three
months. The blood data are reported corresponding to the km traveled.