Isolated lung metastases from pancreatic ductal adenocarcinoma (PDAC): Diagnostic and therapeutic challenges of a different disease.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, mostly due to the high rate of distant dissemination. However, growing evidence shows that isolated lung recurrence or metastases (ILM) from PDAC are not only less common, but also correlated with a better prognosis. Lung-only recurrence after surgery occurs later in time and is associated with more favorable prognostic characteristics of the primary tumor. Moreover, recent findings suggest that this specific site of metastases is characterized by an immunologically "hot" microenvironment and a more favorable molecular profile that could possibly justify its clinical behavior. Thus, ILM from PDAC emerge as a distinct entity, that might also benefit from a different therapeutic approach, possibly with the integration of surgery and de-intensified chemotherapy regimens, especially in selected patients. In this review we delve into the current scientific evidence on the clinical and biological characteristics of isolated LM from PDAC, also focusing on concerns with their diagnostic process and the therapeutic options for the management of this subset of patients.

Giulia O ，Alessandro B ，Angelo C ，Paolo M ，Rosa C ，Marina M ，Umberto P ，Catia C ，Giulia V ，Massimo F ，Michele R ... -  《-》

The indolent nature of pulmonary metastases from ductal adenocarcinoma of the pancreas.

The natural history of pulmonary metastases from pancreatic ductal adenocarcinoma (PDAC) is not well studied. Limited evidence suggests patients with isolated pulmonary metastases from PDAC follow a more benign clinical course than those with other sites of metastases. We performed a retrospective review of all patients with pulmonary metastases from PDAC from 2000 to 2010 and analyzed survival utilizing the Kaplan-Meier method based upon location of first metastasis (lung first, intra-abdominal first, or synchronous intra-abdominal and lung metastases). Median survival among subjects with lung as the only site of metastases was significantly longer than those with other metastatic patterns. In subjects that had undergone resection of their PDAC, survival in those with lung as a first site of recurrence remained significantly longer than those with abdominal first or synchronous intra-abdominal and lung recurrence. Among resected patients that developed lung only recurrence, survival was significantly prolonged (67.5 months) in those who underwent surgical resection/stereotactic radiosurgery compared to chemotherapy (33.8 months) or observation (29.9 months) for treatment of lung recurrence. Patients with isolated pulmonary recurrence from PDAC may realize a survival benefit from surgical intervention or stereotactic radiosurgery compared to chemotherapy or observation for treatment of lung recurrence.

Downs-Canner S ，Zenati M ，Boone BA ，Varley PR ，Steve J ，Hogg ME ，Zureikat A ，Zeh HJ ，Lee KK ... -  《-》

Different clinical presentations of metachronous pulmonary metastases after resection of pancreatic ductal adenocarcinoma: Retrospective study and review of the literature.

Lovecek M ，Skalicky P ，Chudacek J ，Szkorupa M ，Svebisova H ，Lemstrova R ，Ehrmann J ，Melichar B ，Yogeswara T ，Klos D ，Vrba R ，Havlik R ，Mohelnikova-Duchonova B ... -  《-》

Association between primary origin (head, body and tail) of metastasised pancreatic ductal adenocarcinoma and oncologic outcome: A population-based analysis.

The relation between the primary origin of metastasised pancreatic ductal adenocarcinoma (PDAC)-head, body or tail-metastatic patterns and outcomes has not yet been investigated in large population-based studies. Patients with metastasised PDAC at diagnosis from the Netherlands Cancer Registry were included (2005-2015). We compared number of metastatic organ sites (1, 2, ≥3) and specific metastatic organ sites (peritoneum, liver, lung and extra-regional lymph nodes) for the different primary tumour locations. Cox regression analyses were used to determine the association of tumour location and metastatic organ site(s) with overall survival. Overall, we included 9952 patients with metastasised PDAC. The primary origin was head in 5644 (57%), body in 1671 (17%) and tail in 2637 (26%) patients. Differences between primary origins were the number of metastatic organ sites (proportions ≥3 sites for head: 4%, for body: 8% and for tail: 13%, p < 0.0001) and peritoneal metastases (present in 13% for head, 24% for body and 30% for tail; p < 0.0001). Median overall survival was 2.6 months for head PDAC (reference), 2.4 months for body PDAC (HR 1.02 [0.97-1.08]) and 1.9 months for tail PDAC (HR 1.20 [1.15-1.26]). Of patients with one metastatic organ site, the worst survival compared with other sites was seen with liver only metastases (2.5 months vs. 2.7-5.1 months), and the best survival for patients, with extra-regional lymph node only metastases (5.1 months). Metastatic patterns differ among the primary origins for PDAC with metastasised tail tumours having more metastatic sites, more often peritoneal metastases and worse survival.

Mackay TM ，van Erning FN ，van der Geest LGM ，de Groot JWB ，Haj Mohammad N ，Lemmens VE ，van Laarhoven HW ，Besselink MG ，Wilmink JW ，Dutch Pancreatic Cancer Group ... -  《-》

New Diagnostic and Therapeutic Aspects of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is devastating. Because of its silent nature, the disease is often only diagnosed once it has reached an advanced, frequently inoperable stage. To date, we have no biomarkers that facilitate earlier diagnosis, leaving sufficient time for curative therapy that effectively lowers the very high mortality rate of this cancer entity. Because of this, the life expectancy of patients with PDAC is low (i.e. ≤ 6% five-year survival rates). New data, including particular genetic signatures and features of the stromal architecture of PDAC tumors, may better explain their aggressiveness, their relatively long-lasting painless expansion, and why chemotherapy so frequently fails. The typical tumor-induced stromal desmoplasia is characterized by cancer-associated fibroblasts (CAFs), decreased immune surveillance, cancer-associated neural remodeling, and a very low vascular density. This stromal microenvironment generates hypoxia, nutrient deficiency, immune suppression, and chemoresistance. The combination of factors results in a vicious disease that begins with the long-lasting, asymptomatic development of a large tumor mass, followed by a delayed diagnosis with a high percentage of inoperable states, exhibiting a poor response to all conservative therapeutic options, including radiation, and which ends with metastasis resulting in a rapid fatal outcome. In this article, we review coherences on genetic, cellular, immunological, Nano medical and stromal characteristics of PDAC tissue, and discuss metabolic abnormalities associated with and/or preceding the tumor progression rate. A more comprehensive understanding of the underlying mechanisms can improve the diagnostic and therapeutic management of patients suffering from this devastating type of cancer.

Mangge H ，Niedrist T ，Renner W ，Lyer S ，Alexiou C ，Haybaeck J ... -  《-》