Liver resection with two-step vascular exclusion, in situ hypothermic portal perfusion for the treatment of end-stage hepatic alveolar echinococcosis.

PURPOSE: To evaluate the safety and efficacy of two-step vascular exclusion and in situ hypothermic portal perfusion in patients with end-stage hepatic hydatidosis. METHODS: This study involved patients with advanced hepatic hydatid disease undergoing surgical treatment between 2022 and 2023, which included resection and reconstruction of the hepatic veins, inferior vena cava (IVC), and portal vein (PV). We described the technical details of liver resection and vascular reconstruction, as well as the use of two-step vascular exclusion and in situ hypothermic portal perfusion techniques during the vascular reconstruction process. RESULT: We included 7 patients with advanced hepatic hydatid disease who underwent surgical resection using two-step vascular exclusion and in situ hypothermic portal perfusion. The mean duration of surgery was 12.5 h (range, 7.5-15.0 h). The average hepatic ischemia time was 45 min (range, 25-77 min), while the occlusion time of the IVC was 87 min (range, 72-105 min). The total blood loss was 1000 milliliters (range, 500-1250 milliliters). Postoperatively, patients exhibited good recovery of liver and renal function. The mean ICU stay was 2 days (range, 1-3 days), and the mean postoperative hospital stay was 13 days (range, 9-16 days), with no Grade III or above complications observed during a mean follow-up period of 15 months (range, 9-24 months), CONCLUSION: two-step vascular exclusion and in situ hypothermic portal perfusion for surgical resection of end-stage hepatic hydatid disease is safe and effective. This significantly reduces the anhepatic time.

NMDAR in bladder smooth muscle is not a pharmacotherapy target for overactive bladder in mice.

Overactive bladder (OAB) is a common condition that affects a significant patient population. The N-methyl-D-aspartate receptor (NMDAR) has a role in developing bladder overactivity, pharmacological inhibition of which inhibits bladder overactivity. The common pathogenesis of OAB involves bladder smooth muscle (BSM) overactivity. In this study, a smooth muscle-specific NMDAR knockout (SMNRKO) mouse model was generated. The bladders from SMNRKO mice displayed normal size and weight with an intact bladder wall and well-arranged BSM bundles. Besides, SMNRKO mice had normal voiding patterns and urodynamics and BSM contractility, indicating that NMDAR in BSM was not essential for normal physiological bladder morphology and function. Unexpectedly, cyclophosphamide (CYP)-treated SMNRKO and wild-type (WT) mice had similar pathological changes in the bladder. Furthermore, SMNRKO mice displayed similar altered voiding patterns and urodynamic abnormalities and impaired BSM contractility compared with WT mice after CYP treatment. MK801 partially reversed the pathological bladder morphology and improved bladder dysfunction induced by CYP, but did not cause apparent differences between WT mice and SMNRKO mice, suggesting that NMDAR in BSM was not involved in pathological bladder morphology and function. Moreover, the direct instillation of NMDAR agonists or antagonists into the CYP-induced OAB did not affect bladder urodynamic function, indicating that NMDAR in BSM was not the pharmacotherapy target of MK801 for CYP-induced cystitis. The findings indicated that NMDAR in BSM was not essential for normal physiological or pathological bladder morphology and function, and MK801 improving pathological bladder function was not mediated by an action on NMDAR in BSM.

Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis.

Ketamine cystitis (KC) is a chronic bladder inflammation leading to urinary urgency, frequency, and pain. The pathogenesis of KC is complicated and involves multiple tissue injuries in the bladder. Recent studies indicated that urothelium disruption, lamina propria fibrosis and inflammation, microvascular injury, neuropathological alterations, and bladder smooth muscle (BSM) abnormalities all contribute to the pathogenesis of KC. Ketamine has been shown to induce these tissue injuries by regulating different signaling pathways. Ketamine can stimulate antiproliferative factor, adenosine triphosphate, and oxidative stress to disrupt urothelium. Lamina propria fibrosis and inflammation are associated with the activation of cyclooxygenase-2, nitric oxide synthase, immunoglobulin E, and transforming growth factor ß1. Ketamine contributes to microvascular injury via the N-methyl-D aspartic receptor (NMDAR), and multiple inflammatory and angiogenic factors such as tumor necrosis factor α and vascular endothelial growth factor. For BSM abnormalities, ketamine can depress the protein kinase B, extracellular signal-regulated kinase, Cav1.2, and muscarinic receptor signaling. Elevated purinergic signaling also plays a role in BSM abnormalities. In addition, ketamine affects neuropathological alterations in the bladder by regulating NMDAR- and brain-derived neurotrophic factor-dependent signaling. Inflammatory cells also contribute to neuropathological changes via the secretion of chemical mediators. Clarifying the role and function of these signaling underlying tissue injuries in the bladder with KC can contribute to a better understanding of the pathophysiology of this disease and to the design of effective treatments for KC.