Transient receptor potential (TRP)A1 channel has been implicated in various physiological processes, including thermosensation and pain. A recent study of TRPA1 knockout mice demonstrated deficits in sensing mechanical stimuli, suggesting a role for TRPA1 also in somatic mechanosensation. However, direct evidence of TRPA1 activation by mechanical forces has thus far been lacking. Here we show, using an intracellular calcium assay, that hypertonic solution (HTS) activates TRPA1 channels in human embryonic kidney 293 cells transiently expressing rat TRPA1. In contrast, hypotonic solution has no effect. Single-channel recordings reveal that HTS opens an ion channel that displays similar single-channel conductance to that evoked by the TRPA1 agonist allyl isothiocyanate (AITC) in both recombinant rat TRPA1 cell lines and rat dorsal root ganglia neurons. Ruthenium red reduces the open probability of the single-channel currents and blocks the whole-cell currents evoked by HTS. Camphor also blocks the whole-cell currents evoked by HTS. HTS-activated channel openings are only observed in patches that are also sensitive to AITC. Finally, like AITC, HTS depolarizes the membrane potential of dorsal root ganglia neurons leading to the generation of action potentials. Taken together, these findings indicate that TRPA1 mediates an osmotically-activated ion channel and support a role for TRPA1 in mechanosensation.

Background: The current study sought to define the impact of lymph node metastasis (LNM) relative to tumor size on tumor recurrence after curative resection for nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) ≤2 cm.Methods: Patients who underwent curative resection for ≤2-cm NF-pNETs were identified from a multi-institutional database. Risk factors associated with tumor recurrence as well as LNM were identified. Recurrence-free survival (RFS) was compared among patients with or without LNM.Results: A total of 392 ≤2-cm NF-pNETs patients were identified. Among the 328 patients who had lymph node dissection and evaluation, 42 (12.8%) patients had LNM. LNM was associated with tumor recurrence (hazard ratio, 3.06; P = .026) after surgery. RFS was worse among LNM vs no LNM patients (5-year RFS, 81.7% vs 94.1%; P = .019). Patients with tumors measuring 1.5-2 cm had a two-fold increase in the incidence of LNM vs patients with tumors <1.5 cm (17.9% vs 8.7%, odds ratio, 2.59; P = .022), as well as a higher risk of advanced tumor grade and higher Ki-67 levels (both P < .01). After curative resection, a total of 14 (8.0%) patients with a tumor of 1.5-2 cm and 10 (4.5%) patients with tumor <1.5 cm developed tumor recurrence.Conclusion: Surgical resection with lymphadenectomy should be considered for patients with NF-pNETs ≥1.5-2.0 cm. K E Y W O R D S lymph node metastasis, neuroendocrine tumor, pancreas, surgery, tumor size Ding-Hui Dong and Xu-Feng Zhang contributed equally to this work.

Background To determine short‐ and long‐term oncologic outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for the treatment of pancreatic neuroendocrine tumor (pNET). Methods The data of the patients who underwent curative MIDP or ODP for pNET between 2000 and 2016 were collected from a multi‐institutional database. Propensity score matching (PSM) was used to generate 1:1 matched patients with MIDP and ODP. Results A total of 576 patients undergoing curative DP for pNET were included. Two hundred and fourteen (37.2%) patients underwent MIDP, whereas 362 (62.8%) underwent ODP. MIDP was increasingly performed over time (2000‐2004: 9.3% vs 2013‐2016: 54.8%; P < 0.01). In the matched cohort (n = 141 in each group), patients who underwent MIDP had less blood loss (median, 100 vs 200 mL, P < 0.001), lower incidence of Clavien‐Dindo ≥ III complications (12.1% vs 24.8%, P = 0.026), and a shorter hospital stay versus ODP (median, 4 versus 7 days, P = 0.026). Patients who underwent MIDP had a lower incidence of recurrence (5‐year cumulative recurrence, 10.1% vs 31.1%, P < 0.001), yet equivalent overall survival (OS) rate (5‐year OS, 92.1% vs 90.9%, P = 0.550) compared with patients who underwent OPD. Conclusion Patients undergoing MIDP over ODP in the treatment of pNET had comparable oncologic surgical metrics, as well as similar long‐term OS.