Polymodal Activation and Desensitization of TRPV1 Receptor in Human Odontoblasts-Like Cells with Eugenol.

Dentinal hypersensitivity is a frequent reason for dental consultation, and its pathophysiology has not been fully clarified. Previous findings have made it possible to establish a relationship between the cellular sensory capacity and the activation of the polymodal transient receptor potential vanilloid 1 (TRPV1), which is responsible for the nociceptive response and whose desensitization could cause analgesia. Thus, the objective of this study was to determine the expression, localization, and functional activity of TRPV1 in human odontoblasts-like-cells (hOLCs) and the effect of eugenol (EUG) on its activation and desensitization. Human dental pulp stem cells (hDPSCs) were obtained from third molars and were characterized using flow cytometry, and their differentiation potential toward the osteoblastic, chondrogenic, and adipogenic lineages was investigated. Subsequently, the hDPSCs underwent odontogenic differentiation for 7, 14, and 21 days, and their phenotype (odontogenic markers dentin matrix protein-1 (DMP-1) and dentin sialoprotein (DSP)) was evaluated using immunofluorescence. The TRPV1 gene expression in hOLCs was estimated using RT-qPCR, and its localization was analyzed using immunofluorescence. Half-maximal effective concentration (EC50) from both eugenol (EUG) and capsaicin (CAP) was determined; in addition, receptor activation was evaluated against chemical, thermal, and pH stimuli. For the statistical analysis, a one-way ANOVA with a Tukey post hoc test (p < 0.05) was used. After establishing the in vitro model of hOLCs and the membrane location of TRPV1, its chemical activation with EUG and CAP was demonstrated, as well as its thermal activation at ≥ 43°C and with an acidic (<6) or basic pH (between 9 and 12). Receptor desensitization was achieved after 20 min of exposure to two concentrations of EUG (603.5 and 1000 µM). These findings represent a stepping-stone for the construction of a pulp pain study model oriented toward a therapeutic alternative for the treatment of dentinal hypersensitivity.

Is hepatectomy safe following Yttrium-90 therapy? A multi-institutional international experience.

BACKGROUND: Single institution reports demonstrate variable safety profiles when liver-directed therapy with Yttrium-90 (Y-90) is followed by hepatectomy. We hypothesized that in well-selected patients, hepatectomy after Y90 is feasible and safe. METHODS: Nine institutions contributed data for patients undergoing Y90 followed by hepatectomy (2008-2017). Clinicopathologic and perioperative data were analyzed, with 90-day morbidity and mortality as primary endpoints. RESULTS: Forty-seven patients were included. Median age was 59 (20-75) and 62% were male. Malignancies treated included hepatocellular cancer (n = 14; 30%), colorectal cancer (n = 11; 23%), cholangiocarcinoma (n = 8; 17%), neuroendocrine (n = 8; 17%) and other tumors (n = 6). The distribution of Y-90 treatment was: right (n = 30; 64%), bilobar (n = 14; 30%), and left (n = 3; 6%). Median future liver remnant (FLR) following Y90 was 44% (30-78). Resections were primarily right (n = 16; 34%) and extended right (n = 14; 30%) hepatectomies. The median time to resection from Y90 was 196 days (13-947). The 90-day complication rate was 43% and mortality was 2%. Risk factors for Clavien-Dindo Grade>3 complications included: number of Y-90-treated lobes (OR 4.5; 95% CI1.14-17.7; p = 0.03), extent of surgery (p = 0.04) and operative time (p = 0.009). CONCLUSIONS: These data demonstrate that hepatectomy following Y-90 is safe in well-selected populations. This multi-disciplinary treatment paradigm should be more widely studied, and potentially adopted, for patients with inadequate FLR.

Robotic Versus Open Minor Liver Resections of the Posterosuperior Segments: A Multinational, Propensity Score-Matched Study.

BACKGROUND: Minor liver resections of posterosuperior segments (1, 4A, 7, 8) are challenging to perform laparoscopically and are mainly performed using an open approach. We determined the feasibility of robotic resections of posterosuperior segments and compared short-term outcomes with the open approach. METHODS: Data on open and robotic minor (≤ 3 segments) liver resections including the posterosuperior segments, performed between 2009 and 2016, were collected retrospectively from four hospitals. Robotic and open liver resections were compared, before and after propensity score matching. RESULTS: In total, 51 robotic and 145 open resections were included. After matching, 31 robotic resections were compared with 31 open resections. Median hospital stay was 4 days (interquartile range [IQR] 3-7) for the robotic group, versus 8 days (IQR 6-10) for the open group (p < 0.001). Median operative time was 222 min (IQR 164-505) for robotic cases versus 231 min (IQR 190-301) for open cases (p = 0.668). Median estimated blood loss was 200 mL (IQR 100-400) versus 300 mL (IQR 125-750), respectively (p = 0.212). In the robotic group, one patient (3%) had a major complication, versus three patients (10%) in the open group (p = 0.612). Readmissions were similar-10% in the robotic group versus 6% in the open group (p > 0.99). There was no mortality in either group. CONCLUSION: Minor robotic liver resections of the posterosuperior segments are safe and feasible and display a shorter length of stay than open resections in selected patients at expert centers.