Pancreatic ductal adenocarcinoma (PDAC) is rich in dense fibrotic stroma that are composed of extracellular matrix (ECM) proteins. A disruption of the balance between ECM synthesis and secretion and the altered expression of matrix remodeling enzymes lead to abnormal ECM dynamics in PDAC. This pathological ECM promotes cancer growth, survival, invasion, and alters the behavior of fibroblasts and immune cells leading to metastasis formation and chemotherapy resistance, which contribute to the high lethality of PDAC. Additionally, recent evidence highlights that ECM, as a major structural component of the tumor microenvironment, is a highly dynamic structure in which ECM proteins establish a physical and biochemical niche for cancer stem cells (CSCs). CSCs are characterized by self-renewal, tumor initiation, and resistance to chemotherapeutics. In this review, we will discuss the effects of the ECM on tumor biological behavior and its molecular impact on the fundamental signaling pathways in PDAC. We will also provide an overview of how the different ECM components are able to modulate CSCs properties and finally discuss the current and ongoing therapeutic strategies targeting the ECM. Given the many challenges facing current targeted therapies for PDAC, a better understanding of molecular events involving the interplay of ECM and CSC will be key in identifying more effective therapeutic strategies to eliminate CSCs and ultimately to improve survival in patients that are suffering from this deadly disease.

Introduction: Noninvasive ventilation (NIV) is a standard procedure in selected patients with acute respiratory failure. Previous studies have used noninvasive ventilation to ensure adequate gas exchange during fiberoptic bronchoscopy in spontaneously breathing hypoxemic patients, thus avoiding endotracheal intubation. However, it is unknown whether bronchoscopy can be performed safely in patients with acute hypoxemic respiratory failure already in need of NIV prior to the decision for bronchoscopy. Methods: We prospectively investigated 40 consecutive, critically ill, adult patients with acute hypoxemic respiratory failure (14 women, 26 men, age 61 ± 15 years, partial pressure for oxygen/fraction of inspired oxygen (PaO₂/FiO₂) < 300 under noninvasive ventilation, Simplified Acute Physiology scores (SAPS II) 47 ± 9.9 points). All patients required noninvasive ventilation prior to the decision to perform bronchoscopy (median 10.5 h; range 2.2 to 114). Blood gases, heart rate, blood pressure and ventilation were monitored before, during and up to 120 minutes after bronchoscopy. Results: Bronchoscopy could be completed in all patients without subsequent complications. Oxygen saturation fell to < 90% in two patients (5%), and the lowest value during the procedure was 84%. The mean PaO₂/FiO₂ ratio improved from 176 ± 54 at baseline to 240 ± 130 (P < 0.001) at the end of bronchoscopy and 210 ± 79 after 120 minutes. The transient mean partial pressure of carbon dioxide in the arterial blood (PaCO₂) increase was 9.4 ± 8.1 mm Hg. Four patients (10%) required endotracheal intubation during the first eight hours after the procedure. Bronchoalveolar lavage yielded diagnostic information in 26 of 38 (68%) patients. Conclusions: In critically ill patients with acute hypoxemic respiratory failure requiring noninvasive ventilation, bronchoscopy can be performed with an acceptable risk. Since these patients per se have a high likelihood of subsequent endotracheal intubation due to failure of NIV, bronchoscopy should only be performed by experienced clinicians.

Minimally invasive surgery (MIS) has superior short-term outcomes than open surgery (OS) for colorectal cancer (CRC). However, a nationwide dataset has not been analysed to confirm these findings. We evaluated the distribution and outcomes of MIS for CRC from 2005 to 2015; all in-patients with CRC surgery procedure codes were identified from hospital data, which are entered into the nationwide diagnosis-related group database and forwarded anonymised to the Federal Bureau of Statistics. We determined absolute MIS, morbidity, and mortality rates for specific sub-categories, including procedure type. We identified 345,913 in-patient files. The MIS rate increased from 6.4% (n = 2366; 2005) to 28.5% (n = 8363; 2015), with the highest rates for sigmoid colon (38%) and rectal (39%) resections. The overall conversion rate was 14.4%, without noticeable improvement over time. International Classification of Disease codes related to postoperative complications were documented more frequently after OS than after MIS. OS was associated with a higher mortality rate (4.7%) than MIS (1.8%) (P < 0.001), even after stratifying patients according to the resection site. Use of MIS remains low in Germany compared with that in other European countries. Underutilization of MIS has to be addressed in the future by promoting structured training programs and standardization of laparoscopic surgery.