Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective.

PURPOSE: For patients with cancer of unknown primary (CUP), treatment options are limited. Precision oncology, the interplay of comprehensive genomic profiling (CGP) and targeted therapies, aims to offer additional treatment options to patients with advanced and hard-to-treat cancers. We aimed to highlight the use of a molecular tumor board (MTB) in the therapeutic management of CUP patients. METHODS: In this single-center observational study, CUP patients, presented to the MTB of the Comprehensive Cancer Center Munich LMU, a tertiary care center, were analyzed retrospectively. Descriptive statistics were applied to describe relevant findings. RESULTS: Between June 2016 and February 2022, 61 patients with unfavorable CUP were presented to the MTB, detected clinically relevant variants in 74% (45/61) of patients, of which 64% (29/45) led to therapeutic recommendation. In four out of 29 patients (14%), the treatment recommendations were implemented, unfortunately without resulting in clinical benefit. Reasons for not following the therapeutic recommendation were mainly caused by the physicians' choice of another therapy (9/25, 36%), especially in the context of worsening of general condition, lost to follow-up (7/25, 28%) and death (6/25, 24%). CONCLUSION: CGP and subsequent presentation to a molecular tumor board led to a high rate of therapeutic recommendations in patients with CUP. Recommendations were only implemented at a low rate; however, late GCP diagnostic and, respectively, MTB referral were found more frequent for the patients with implemented treatment. This contrast underscores the need for early implementation of CGP into the management of CUP patients.

Symmetric dimethylarginine concentrations in dogs with hypothyroidism before and after treatement with levothyroxine.

OBJECTIVES: To evaluate the serum symmetric dimethylarginine (SDMA) and serum creatinine concentrations in a population of hypothyroid dogs at the time of diagnosis and after treatment. MATERIALS AND METHODS: Serum SDMA and serum creatinine were measured in serum samples of 24 healthy dogs and 24 hypothyroid dogs, at the time of diagnosis (T0) and after supplementation with levothyroxine (T1). RESULTS: The mean SDMA concentrations (reference intervals [RI] <18 µg/dL and <14 µg/dL depending on the source) were 11.7 ± 3.5 µg/dL, 13.8 ± 3.1 µg/dL and 11.83 ± 2.87 µg/dL in healthy dogs, and in the hypothyroid dogs at T0 and T1, respectively. The SDMA concentrations were higher in the hypothyroid dogs at T0 in comparison with the healthy dogs. Of the hypothyroid dogs, 1 out of 24 had an SDMA concentration above 18 µg/dL and 12 out of 24 above 14 µg/dL at T0. At T1, none of the hypothyroid dogs had SDMA concentrations above 18 µg/dL and two of them had SDMA concentrations above 14 µg/dL. The serum creatinine concentration was higher in the hypothyroid dogs at T0 as compared to the healthy dogs. At T0, 8 out of 24 hypothyroid dogs had serum creatinine concentrations above the RI (>1.4 mg/dL). In all but one dog, serum creatinine normalised after treatment. CLINICAL SIGNIFICANCE: The SDMA and serum creatinine concentrations were higher in hypothyroid dogs at diagnosis as compared to healthy dogs. Serum creatinine concentrations were increased in one-third of the hypothyroid dogs and in the majority of cases normalised after levothyroxine supplementation. SDMA concentrations were rarely above the upper limit of the RI when the higest (<18 µg/dL) cut-off was employed. The diagnostic accuracy of SDMA in dogs with thyroid dysfunction requires additional evaluation.

Sensorial and fatty acid profile of ice cream manufactured with milk of crossbred cows fed palm oil and coconut fat.

This work was carried out to study the nutritional quality of milk of cows fed palm oil (PAL) or coconut fat (COC), and the use of that milk as raw material for ice cream production. Three treatments were tested with 23 healthy cows: control (CON), PAL, and COC. The milk was collected at d 21 and 36 of the experimental diet. Proximate composition (moisture, ash, fat, protein, and carbohydrates) and fatty acid composition were evaluated on milk and ice cream, and sensorial analysis, color (lightness, green/red, and blue/yellow), overrun, and texture were evaluated on the ice cream. Fatty acids present in milk and ice cream were determined by gas chromatography. Sensory analysis results showed that the ice cream acceptability index was above 70%. No difference was observed for proximate composition in milk and ice cream. Chromatographic analysis showed an increase in saturated fatty acid concentration in CON and lower levels in PAL; polyunsaturated fatty acid concentration was higher in PAL and lower in CON, in milk and ice cream; monounsaturated fatty acid concentration in milk was higher in PAL and lower in CON but no difference was found in ice cream. Comparing n-3 content in milk and ice cream, we observed that PAL had higher levels than CON and COC. The results indicate that it is feasible to add sources of fat to the animal feed for fatty acid composition modulation of milk and ice cream.

Biliary secretion of phosphatidylcholine and its molecular species in cholecystectomized T-tube patients: effects of bile acid hydrophilicity.

The aim of the present study was to establish whether the oral administration of bile acids with different hydrophilic properties affects the amount of phosphatidylcholine as well as the pattern of PC molecular species secreted in bile. We studied the biliary output of total and individual PC species in cholecystectomized T-tube patients, with a total biliary outflow, after oral administration of 750 mg of ursodeoxycholate (3 patients) or deoxycholate (3 patients). The latter experiments were repeated after 3 days of taurine supplementation (1500 mg daily) in order to increase, by means of the tauro-conjugation, the hydrophilicity of the secreted BA. A linear function was observed, during all the studies, between BA and PC biliary secretion, but the amount of PC secreted per mole of BA was higher for the less hydrophilic BA, such as deoxycholate, than for the more hydrophilic ursodeoxycholate or during deoxycholate plus taurine experiments. With regard to the pattern of PC molecular species, we observed no changes after administration of ursodeoxycholate. An increase in the secretion of the major polyenoic species (i.e., 16:0-18:2 and 16:0-20:4), with respect to the secretion of the monoenoic, was revealed during deoxycholate experiments. Conversely, during the deoxycholate plus taurine experiments, the secretion of the major monoenoic PC species (i.e., 16:0-18:1) increased more than that of the polyenoic species. We suggest that the observed modifications of the pattern of PC molecular species, secreted in bile, represent the result of a physicochemical effect of BA on liver membranes.