Perfusion kinetics from clinical DCE mris increase the accuracy of predictions of tumor response to chemotherapy.

e12651 Background: Nutrient and drug penetration into any solid tumor are critical determinants of the tumor's response to treatment. They depend on both the density of microvasculature within the tumor microenvironment, as well as the exchange rates of nutrients between the microvasculature and the extracellular space. But these parameters are heterogenous, varying considerably from location to location within the tumor and surrounding tissues. The Toft's model and its analogues date back to the early 1990s, and have been used to estimate vascular density, exchange rates, and extracellular-extravascular volume in a spatially-resolved manner using dynamic contrast enhaced (DCE) MRI's. Unfortunately, accurately extracting kinetic parameters from a DCE time-series requires the images to have a time-resolution of just a few seconds, which is rarely done in clinical practice. Methods: We employ a custom designed parallel algorithm to fit DCE MRI data to an exactly-solved ODE model of tissue perfusion kinetics. Results: Here we describe a simplified model of tissue perfusion that can be fit to DCE time traces with temporal resolutions of 90 seconds or more. We show that for many breast tumors, the vascular density and tissue-vascular exchange rate are such that they give rise to a halo of fast-perfusing tissue on the tumor periphery, and slower-perfusing tissue inside. We then use this model as part of a more comprehensive tumor simulation methodology to predict how different patients will respond to neoadjuvant chemotherapy (NACT). We find that the incorporation of our microvascular model gives rise to significantly more accurate predictions of post-treatment tumor volume. Conclusions: Performing perfusion kinetics analyses on clinical MRIs is both challenging, but critical for accurately predicting how a patient will respond to treatment. Our model, which relaxes the requirement for fine DCE temporal resolution, allows for these analyses to be performed on a larger swath of patients without the need for small volumes of interest, or ultra-fast MRI techniques. Moreover, when used within a broader tumor-modeling framework, our model increases the accuracy of predictions of tumor response to NACT.

A rare cause of pericardial effusion and ascites: POEMS syndrome

POEMS syndrome is an important paraneoplastic syndrome associated with multisystem involvement. Extravascular volume overload like pericardial effusion and ascites has a broad differential diagnosis. In addition, it may be initial presentation of disease. For that reason, this case report is highlight to warn of different forms of presentation of poems syndrome.

Pathophysiology of oliguria and acute kidney injury

Oliguria and acute kidney injury (AKI) are common in critically-ill patients with studies reporting AKI affecting more than 50% of critically-ill patients. AKI is independently associated with increased mortality and is a potentially modifiable aspect of critical illness. The pathogenesis of AKI is complex and varies according to aetiology. The most common trigger in ICU patients is sepsis—the pathophysiology of septic AKI is poorly understood and probably involves intrarenal haemodynamic and inflammatory processes. In the setting of septic AKI, the classic acute tubular necrosis described in experimental models does not occur and histological changes are only minor. Activation of neurohormonal mechanisms is also important, particularly in the hepatorenal syndrome, where activation of the remain-angiotensin system appears to play a major role. The treatment of oliguria and AKI in ICU patients has traditionally relied on the administration of intravenous fluids. While such therapy is warranted in patients with a clear history, and physical examination suggestive of intravascular and extravascular volume depletion, its usefulness in other patients (e.g. septic patients) remains controversial. Removal of nephrotoxins, rapid treatment of the triggering factors, and attention to cardiac output and mean arterial pressure remain the cornerstones of the prevention and treatment of AKI in ICU.

Lenalidomide and Dexamethasone for a Patient of POEMS Syndrome Presenting with Massive Ascites

POEMS syndrome is a multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. POEMS syndrome is a rare cause of refractory ascites. We report the case of a patient with POEMS syndrome presenting with massive ascites who was treated with very-low-dose lenalidomide and dexamethasone. A 57-year-old Japanese man was admitted to our hospital with pleural effusion, massive ascites, and leg edema. The diagnosis of POEMS syndrome was made based on the combination of the following findings: peripheral neuropathy, organomegaly, endocrinopathy, serum monoclonal protein elevation, skin changes, plasma VEGF elevation, and evidence of extravascular volume overload. Renal dysfunction induced by biopsy-proven renal involvement of POEMS syndrome was observed. Massive ascites of the patient dramatically diminished with long-time treatment of very-low-dose lenalidomide and dexamethasone. Lenalidomide seems to be a very promising therapy for POEMS syndrome presenting with extravascular volume overload such as edema, pleural effusion, and ascites. Very-low-dose lenalidomide might be effective especially for the patients with POEMS-related nephropathy.