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.     

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.     

Risk prediction of common bile duct stone recurrence based on new common bile duct morphological subtypes

Stones in the common bile duct (CBD) are reported worldwide, and this condition is majorly managed through endoscopic retrograde cholangiopancreatography (ERCP). CBD stone recurrence is an important issue after endoscopic stone removal. Therefore, it is essential to identify its risk factors to determine the necessity of regular follow-up in patients who underwent endoscopic removal of CBD stones. The authors identified that the S and polyline morphological subtypes of CBD were associated with increased stone recurrence. New morphological subtypes of CBD presented by the authors can be important risk predictors of recurrence after endoscopic stone removal. Furthermore, the new morphological subtypes of CBD may predict the risk of residual CBD stones or technical difficulty in CBD stone removal. Further studies with a large sample size and longer follow-up durations are warranted to examine the usefulness of the newly identified morphological subtypes of CBD in predicting the outcomes of ERCP for CBD stone removal.     

胆道手术缝合技术与缝合材料选择中国专家共识（2018版）

正胆道缝合重建是肝胆胰外科手术的最基本操作之一,建立胆汁引流通畅、无张力、血供充足的黏膜对黏膜吻合是胆道重建的基本要求。目前,胆道重建方式繁多,但根据所须重建胆道的病理生理状况选择合适的胆道缝合方法及缝合材料是保障胆道重建成功的关键因素。随着手术技术的进步及各种缝合材料的发展,胆道缝合技术越来越精细,高质量的胆道缝合重建是病人顺利康复及减少多次手术的关键。基于此,中华医学会外科学分会组织国内部分专家结合最新文献及胆道外科的最新进     

Cocrystal and Salt Forms of an Imidazopyridazine Antimalarial Drug Lead

Cocrystallization and salt formation were used to produce new multicomponent forms of a novel antimalarial imidazopyridazine drug lead (MMV652103) that displayed improved physicochemical properties. The drug lead had earlier shown good in vitro potency against multidrug resistant (K1) and sensitive (NF54) strains of the human malaria parasite Plasmodium falciparum, and high in vivo efficacy in both Plasmodium berghei and Plasmodium falciparum mouse models. A major drawback of MMV652103 is its limited aqueous solubility. Various new supramolecular products, including several multicomponent solid forms, are reported here, namely 3 cocrystal forms with the dicarboxylic acid coformers adipic acid, glutaric acid, and fumaric acid, and a salt form with malonic acid. These were characterized by thermal methods and their structures elucidated by single-crystal X-ray diffraction. A customized solubility experiment was performed in fasted-state simulated intestinal fluid for comparison of the solubility behavior of each new form of the drug lead with that of the untreated starting material. All of the multicomponent forms showed an improvement in the maximum concentrations (C_max) attained by the drug lead and the rate at which it dissolved. The recorded C_max values exceeded the concentration of the untreated compound by factors in the range 4.6-5.6.     

腹腔镜肝切除术中副损伤预防及处理

随着腹腔镜肝切除术在国内开展，腹腔镜肝切除术的手术适应证和手术范围在逐渐扩大，外科医生在手术操作过程中的意外和手术风险也逐渐提高。腹腔镜肝切除术中副损伤主要包括胆管损伤、术中出血、膈肌损伤、气体栓塞等。当在术中发生意外损伤时，应立即正确辨别出损伤类型，并迅速采取对应的处理策略，及时处理损伤，避免造成更严重的后果。同时，在术中合理使用吲哚菁绿（ICG）荧光染色及实时超声等辅助技术，可减少术中副损伤的发生。     

类似胆总管囊肿的胆总管横纹肌肉瘤：阻塞性黄疸的罕见原因

肝外胆道肿瘤罕见，其中以横纹肌肉瘤最常见。横纹肌肉瘤是一种软组织恶性肌肉骨骼肿瘤，是儿童非常罕见的一种胆总管恶性肿瘤。它通常表现为阻塞性黄疸和/或瘙痒。如果肿瘤没有局部浸润邻近组织，其影像学表现则类似胆总管囊肿。因此，确诊通常是在手术时或术前通过活检。早期诊断、与胆总管囊肿鉴别、尽早开始治疗对延长患者生存时间有重要意义。该文报道1例10岁男童，反复阻塞性黄疸和发热，术前诊断为胆总管囊肿，术后确诊为胆总管胚胎性横纹肌肉瘤。经手术切除、术后化疗，该患儿预后良好。故必须了解这种罕见的肿瘤可以类似先天性胆总管囊肿，并且在儿童阻塞性黄疸的鉴别诊断时应加以考虑。