Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

The role of extra-hepatic bile duct resection in the surgical management of gallbladder carcinoma. A first meta-analysis

ObjectiveTo systematically evaluate the clinicopathological and prognostic value of extra-hepatic bile duct resection (EHBDR) in the surgical management of patients with gallbladder carcinoma (GBC), especially in non-jaundiced patients.MethodsPubMed, EMBASE and the Cochrane Library were searched up to March 1^st 2021 for comparative studies between bile duct resected and non-resected groups. RevMan5.3 and Stata 13.0 software were used for the statistical analyses.ResultsEHBDR did not correlate with a better overall survival (OS) (P = 0.17) or disease-free survival (P = 0.27). No survival benefit was also observed in patients with T2N1 (P = 0.4), T3N0 (P = 0.14) disease and node-positive patients (P = 0.75), rather, EHBDR was even harmful for patients with T2N0 (P = 0.01) and node-negative disease (P = 0.02). Significantly higher incidences of recurrent disease (P = 0.0007), postoperative complications (P < 0.00001) and positive margins (P = 0.02) were detected in the bile duct-resected group. The duration of postoperative hospital stay between the two groups was comparable (P = 0.58). Selection bias was also detected in our analysis that a significantly higher proportion of advanced lesions with T3-4 or III-IV disease was observed in the bile duct-resected group (P < 0.00001). EHBDR only contributed to a greater lymph yield (P = 0.01).ConclusionEHBDR has no survival advantage for patients with GBC, especially for those with non-jaundiced disease. Considering the unfairness of comparing OS between jaundiced patients receiving EHBDR with non-jaundiced patients without EHBDR, we could only conclude that routine EHBDR in non-jaundiced patients is not recommended and future well-designed studies with more specific subgroup analyses are required for further validation.     

The usefulness of abscess tonsillectomy followed by intraoral drainage for parapharyngeal abscess concomitant with peritonsillar abscess in the elderly

Parapharyngeal abscess (PPA) may cause life-threatening complications and peritonsillar abscess (PTA) and tonsillitis frequently precede PPA. The optimal management of PPA caused by PTA has been the subject of debate with respect to the surgical approach. We present three cases of PPA concomitant with PTA in elderly patients. In two cases, the abscesses in parapharyngeal space were drained by abscess tonsillectomy followed by intraoral incision of the tonsillar bed. On the other hand, the third case did not undergo abscess tonsillectomy because of his refusal of surgery and needed extraoral drainage after the aggravation of PPA. Based on the experience of those three cases, it was suggested that abscess tonsillectomy followed by intraoral incision of the tonsillar bed might be a useful surgical approach for the drainage of PPA concomitant with PTA, especially in elderly patients.     

Cardiac-type total anomalous pulmonary venous return is not benign

ObjectiveThe objective of this study was to investigate the association between morphological variation and postsurgical pulmonary vein (PV) stenosis (PPVS) in patients with cardiac total anomalous pulmonary venous connection (TAPVC).MethodsThis single-center, retrospective study included 168 pediatric patients who underwent surgical repair of cardiac TAPVC from 2013 to 2019 (connection to the coronary sinus [CS], n = 136; connection directly to the right atrium [RA], n = 32). Three-dimensional computed tomography modeling and geometric analysis were performed to investigate the morphological features; their relevance to the PPVS was examined.ResultsThe connection type had no association with PPVS (CS type: 18% vs right atrial type: 19%; P = .89) but there was a higher incidence of PPVS in patients with a single PV orifice than > 1 orifice (P < .001). Confluence-to-total PV area ratio (hazard ratio, 4.78, 95% CI, 1.86-12.32; P = .001) and length of drainage route (hazard ratio, 1.22; 95% CI, 1.14-1.31; P < .001) had a 4- and 1-fold increase in the risk for PPVS in the CS type after adjustment for age and preoperative pulmonary venous obstruction. In the right atrial type, those with anomalous PV return to the RA roof were more likely to develop PPVS than to the posterior wall of the RA (P < .001).ConclusionsThe number of inter-junction PV orifice correlated with PPVS development in cardiac TAPVC. The confluence-to-total PV ratio, length of drainage route, and anomalous PV return to the RA roof are important predictors for PPVS. Morphological subcategorization in this clinical setting can potentially assist in surgical decision-making.     

Computed tomography imaging features for amyloid dacryolith in the nasolacrimal excretory system: A case report

BACKGROUNDNasolacrimal duct obstruction leading to epiphora is a common ophthalmologic complaint, and it may derive from amyloidosis in rare cases. There are a few reports about localized amyloidosis, and amyloidosis with involvement and obstruction of the nasolacrimal duct is exceedingly rare. CASE SUMMARYA 54-year-old male presented with a 2-year history of a lump overlying the left lacrimal sac that had grown rapidly for nearly half a year. Physical examination touched a firm lump in the left lacrimal sac. Nasal endoscopy discovered lesions in appearance of sediments with easy bleeding at the entry of the nasolacrimal duct of the left inferior nasal meatus. Computerized tomography scan revealed speckle high density in the left lacrimal sac and the dilated nasolacrimal duct. During an endoscopic exploration and excision, a large number of dacryoliths were exposed. Pathology indicated amorphous pink material and multinucleated giant cell reaction in the fibrous tissue.CONCLUSIONThis case showed amyloidosis in localized form mimicking dacryolith with nasolacrimal duct obstruction. In clinical practice, we should be aware of the possibility of localized amyloidosis in the nasolacrimal excretory system.     

Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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