Genetic landscape of pancreatic cancer: a narrative review.

BACKGROUND AND OBJECTIVE: Pancreatic cancer is an aggressive disease with an impaired survival despite improvements in clinical management. Thus, understanding disease biology is of vital importance in order to overcome therapeutic challenges and achieve better prognosis. The purpose of this review is to outline the genetic landscape of pancreatic cancer along with its clinical implications. METHODS: We reviewed existing literature using electronic databases to outline the genetic landscape in pancreatic cancer. KEY CONTENT AND FINDINGS: This review mainly contains information on the genetic background of pancreatic cancer, mainly KRAS, CDKN2A, TP53 and SMAD4, with emphasis on the importance of understanding disease biology. CONCLUSIONS: The genetic aspects of pancreatic cancer have been well described especially with the introduction of next generation sequencing techniques. Future studies focusing on translation of these alterations in clinical application might pave the way for personalized surveillance and therapy.

A diagnostic delay of 5 hours increases the risk of death after blunt hollow viscus injury.

BACKGROUND: Hollow viscus injuries (HVI) are uncommon after blunt trauma, and accomplishing a timely diagnosis can be difficult. Time to operative intervention has been implicated as a risk factor for mortality, but reports are conflicting. METHODS: All blunt trauma admissions to an academic level 1 trauma center from January 1992 to September 2005 were retrospectively reviewed. Patients with a diagnosis of blunt HVI were included. Patients who died within 24 hours were excluded. Data regarding patient demographics, injuries, time from admission until laparotomy, length of stay, and mortality were recorded, and a multivariate analysis to determine independent risk factors for mortality was carried out. A p < 0.05 was considered significant. RESULTS: Of 35,033 blunt trauma admissions, there were 195 (0.6%) HVI patients with the following characteristics (data expressed as mean +/- 1 SD): mean age of 35 years +/- 16 years, Injury Severity Score of 17 +/- 11, time from admission to laparotomy of 5.9 hours +/- 5.8 hours, operative blood loss of 1500 mL +/- 1800 mL, and length of stay of 19 days +/- 23 days. Twelve percent presented with a systolic pressure <90 mm Hg and 9% died. Independent risk factors for mortality were age (odds ratio [OR] = 1.04, p = 0.005), Abdominal Abbreviated Injury Score (OR = 2.5, p = 0.011), the presence of a significant extra-abdominal injury (OR = 3.4, p = 0.043), and a delay of more than 5 hours between admission and laparotomy (OR = 3.2, p = 0.0499). Eighty-six percent of the deaths in patients who had a delay of >5 hours were because of abdominal-related sepsis. CONCLUSION: HVI occurred in less than 1% of all blunt trauma admissions. Delays in operative intervention are associated with an increased mortality. A high index of suspicion is needed to make a timely diagnosis and minimize risk.