A Patient With Stage III Locally Advanced Pancreatic Adenocarcinoma Treated With Intra-Arterial Infusion FOLFIRINOX: Impressive Tumoral Response and Death due to Legionella pneumophila Infection: A Unique Case Report

Abstract

Patients affected by pancreatic ductal adenocarcinoma (PDAC) have very poor prognosis, whereby at a follow-up of 5 years, the mortality rate is very similar to the incidence rate. Globally, around 10% of patients are amenable to radical surgery at the time of diagnosis, which represents the only chance of cure or long-term survival for these patients. Almost 40% of patients with PDAC show locally advanced pancreatic cancer (LAPC). LAPC is not a metastatic disease, although it is not amenable to radical surgery. For these patients, systemic induction chemotherapy with intravenous FOLFIRINOX (5-fluorouracil, folic acid, irinotecan, oxaliplatin) regimen is administered, with the aim of conversion to surgery, although the conversion rate remains low, at approximately 10% to 15%. Pancreatic arterial chemotherapy has been explored to overcome the intrinsic tumor pancreatic resistance to systemic chemotherapy, where an intra-arterial port-a-cath is placed by means of interventional oncology techniques under angiographic guidance in the operating theater. Here, we treated a patient with an intra-arterially modified FOLFIRINOX regimen. Three courses were administered, and the patient experienced no adverse events. At the end of the third course, the patient rapidly developed lung failure due to nosocomial Legionella pneumophila infection, despite the impressive pathological tumor response shown in the autopsy report. This is a first and unique report that demonstrates that pancreatic intra-arterial FOLFIRINOX can be safe and efficacious. We believe that this preliminary result will be confirmed in the next patients to be enrolled and that it provides a glimmer of hope for patients with this lethal disease.

Keywords: FOLFIRINOX; arterial port-a-cath; loco-regional treatment; pancreatic arterial infusion; pancreatic cancer.

Figure 1

Abdomen CT scan. Single thin arrow, the head pancreatic tumor; short broad arrow, tumor involvement of the superior duodenal-pancreatic artery; twin open arrows, tumor involvement of the portal vein near to the spleno-portal axis.

Figure 2

Tumor pancreatic tissue section from ecoendoscopy and needle biopsy cyto included. Tumor cells are organized in differentiated adenomorphic structures or in more poorly differentiated cords, embedded in abundant stroma that are rich in inflammatory cells. Necrotic areas are also evident. Single thin arrows, clusters of tumor cells; short broad arrow, a large nucleus; twin open arrows, inflammatory cells; twin filled arrows, cord of mucous cells with large vacuole and hyperchromic nucleus. The same microscopy field is shown at magnifications of ×200 (A) and ×400 (B).

Figure 3

Angiographic scan following injection of contrast medium through the splenic artery after the completion of the technical procedure. The following arteries were embolized, as indicated (arrows): gastric-duodenal a.; superior duodenal-pancreatic a.; gastric-epiploic a.; inferior duodenal-pancreatic a.; and splenica.

Figure 4

Macroscopic examination of the pancreas, sectioned longitudinally. Single arrows, head of the pancreas, with no visible tumor lesion; twin open arrows, duodenum.

Figure 5

Hematoxylin and eosin staining of pancreatic tissue sections. (A) Twin open arrows, necrotic tumor area; single thin arrows, fibrous and adipose replacement; short broad arrow, extensive fibrotic area (magnification, ×100). (B) Twin open arrows, residual neoplastic glands with regressive phenomena; single thin arrows, major pancreatic ducts; short broad arrows, single pycnotic nuclei (magnification, ×200). (C) The important regressive phenomena. Twin open arrows, hemosiderin deposits; single thin arrows, necrotic tumor area (magnification, ×100). (D) Twin open arrows, hemosiderin deposit; single thin arrows, necrotic tumor area; short broad arrows indicate hemosiderin extravasation (magnification, ×200).

Figure 6

(A) Macroscopic examination of the lung. Single thin arrows, surface of the right upper lobe with a yellow-white color. (B) Hematoxylin and eosin staining. The completely subverted parenchyma structure with hypoarated or hepatized-like tissue. The alveoli were filled with inflammatory cells, including lymphomonocytes and granulocytes. Red blood cell infiltration is also evident. Features of emphysema can be seen at the periphery of the section, with breaking of the alveolar walls and fusion of the contained spaces.