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Pancreatoduodenectomy, the primary surgical strategy for managing cholangiocarcinoma, is executed via two distinct methodologies, namely minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD). The selection between these surgical options is critical, as it directly influences patient outcomes, encompassing both short-term recovery metrics and long-term survival rates. Despite the clinical significance of these procedures, there exists a notable void in the literature regarding a comprehensive comparison of MIPD and OPD, particularly in assessing their respective efficacies and complications. This lack of detailed comparative analysis has left a gap in evidence-based guidance for clinicians faced with the decision of choosing the most appropriate surgical approach for their patients. The absence of robust data comparing the two techniques underscores the necessity for a meta-analysis that rigorously examines and contrasts the outcomes associated with MIPD and OPD. By drawing upon a wide array of international studies, this research aims to shed light on the advantages and potential drawbacks of each method, thereby providing a more informed basis for surgical decision-making in the treatment of cholangiocarcinoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Domene et al.)

The lateral line (LL) is a sensory system that allows fish and amphibians to detect water currents. LL responsiveness is modulated by efferent neurons that aid in distinguishing between external and self-generated stimuli, maintaining sensitivity to relevant cues. One component of the efferent system is cholinergic, the activation of which inhibits afferent activity. LL hair cells (HCs) share structural, functional, and molecular similarities with those of the cochlea, making them a popular model for studying human hearing and balance disorders. Because of these commonalities, one could propose that the receptor at the LL efferent synapse is a α9α10 nicotinic acetylcholine receptor (nAChR). However, the identities of the molecular players underlying ACh-mediated inhibition in the LL remain unknown. Surprisingly, through the analysis of single-cell expression studies and in situ hybridization, we describe that α9, but not the α10, subunits are enriched in zebrafish HCs. Moreover, the heterologous expression of zebrafish α9 subunits indicates that homomeric receptors are functional and exhibit robust ACh-gated currents blocked by α-bungarotoxin and strychnine. In addition, in vivo Ca 2+ imaging on mechanically stimulated zebrafish LL HCs show that ACh elicits a decrease in evoked Ca 2+ signals, regardless of HC polarity. This effect is blocked by both α-bungarotoxin and apamin, indicating coupling of ACh-mediated effects to small-conductance Ca 2+ -activated potassium (SKs) channels. Our results indicate that an α9-containing (α9*) nAChR operates at the zebrafish LL efferent synapse. Moreover, the activation of α9* nAChRs most likely leads to LL HC hyperpolarization served by SK channels. SIGNIFICANCE STATEMENT The fish lateral line (LL) mechanosensory system shares structural, functional, and molecular similarities with those of the mammalian cochlea. Thus, it has become an accessible model for studying human hearing and balance disorders. However, the molecular players serving efferent control of LL hair cell (HC) activity have not been identified. Here we demonstrate that, different from the hearing organ of vertebrate species, a nicotinic acetylcholine receptor composed only of α9 subunits operates at the LL efferent synapse. Activation of α9-containing receptors leads to LL HC hyperpolarization because of the opening of small-conductance Ca 2+ -activated potassium channels. These results will further aid in the interpretation of data obtained from LL HCs as a model for cochlear HCs., (Copyright © 2021 the authors.)