Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy

AIM： To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy. METHODS： Hepatocyte growth factor （HGF）, its receptor, c-Met, vascular endothelial growth factor （VEGF） and transforming growth factor-β1 （TGF-β1） mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction （BO） by quantitative reverse-transcription polymerase chain reaction （RT-PCR） using a LightCycler. Immunohistochemical staining for desmin and e-smooth muscle actin （α-SNA） was also studied. Regenerating liver weight and proliferating cell nuclear antigen （PCNA） labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal bUiary drainage in BO rats or sham-operated rats. RESULTS： Hepatic TGF-β1 mRNA levels increased significantly 14 days after BO, and further increased with duration of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-β1 mRNA was found mainly in the hepatic stellate cell （HSC） fraction. Immunohistochemical studies revealed an increased number of HSCs （desmin-positive cells） and activated HSCs （α-SMA-positive cells） in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-β1 mRNA was significantly up-regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats. CONCLUSION： BO induces HSCs proliferation and activation, leading to up-regulation of TGF-β1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice.

Vascular endothelial growth factor and angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats

AIM： To study the regulatory mechanisms of sinusoida regeneration after partial hepatectomy. METHODS： We invesldgated the expression of angiopoietin （Ang）-1, Ang-2, Tie-2, and vascular endothelial growth factor （VEGF） in regenerating liver tissue by quantitative reverse-transcription polymerase chain reaction （RT- PCR） using a LightCycler （Roche Diagnostics） and also immunohistochemical staining after 70% hepatectomy in rats. In the next step, we isolated liver cells （hepatocytes, sinusoidal endothelial cell （SEC）, Kupffer cell, and hepatic stellate cells （HSC）） from regenerating liver tissue by in situ collagenase perfusion and counterflow elutriation, to determine potential cellular sources of these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs were also evaluated by proliferating cell nuclear antigen （PCNA） staining and the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling （TUNEL） assay, respectively. RESULTS： VEGF mRNA expression increased with a peak at 72 h after hepatectomy, decreasing thereafter. The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction. Meanwhile, mRNA for Ang-1 and Ang-2 was found in the SEC and HSC fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly, reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h. CONCLUSION： Ang-Tie system, together with VEGF, plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy. However, the VEGF system plays a more important role in the early phase of sinusoidal regeneration than angiopoietin/Tie system.

Peripheral portal vein-oriented non-dilated bile duct puncture for percutaneous transhepatic biliary drainage

AIM: To evaluate the efficacy of peripheral portal vein(PV)-oriented non-dilated bile duct(BD) puncture for percutaneous transhepatic biliary drainage(PTBD).METHODS: Thirty-five patients with non-dilated BDs underwent PTBD for the management of various biliary disorders, including benign bilioenteric anastomotic stricture(n = 24), BD stricture(n = 5) associated with iatrogenic BD injury, and postoperative biliary leakage(n = 6). Under ultrasonographic guidance, percutaneous transhepatic puncture using a 21-G needle was performed along the running course of the peripheral targeted non-dilated BD(preferably B6 for right-sided approach, and B3 for left-sided approach) or along the accompanying PV when the BD was not well visualized. This technique could provide an appropriate insertion angle of less than 30° between the puncture needle and BD running course. The puncture needle was then advanced slightly beyond the accompanying PV. The needle tip was moved slightly backward while injecting a small amount of contrast agent to obtain the BD image, followed by insertion of a 0.018-inch guide wire(GW). A drainage catheter was then placed usinga two-step GW method. RESULTS: PTBD was successful in 33(94.3%) of the 35 patients with non-dilated intrahepatic BDs. A rightsided approach was performed in 25 cases, while a left-sided approach was performed in 10 cases. In 31 patients, the first PTBD attempt proved successful. Four cases required a second attempt a few days later to place a drainage catheter. PTBD was successful in two cases, but the second attempt also failed in the other two cases, probably due to poor breath-holding ability. Although most patients(n = 26) had been experiencing cholangitis with fever(including septic condition in 8 cases) before PTBD, only 5(14.3%) patients encountered PTBD procedure-related complications, such as transient hemobilia and cholangitis. No major complications such as bilioarterial fistula or portal thrombosis were observed. There was no mortality in our series.CONCLUSION: Peripheral PV-oriented BD puncture for PTBD in patients with non-dilated BDs is a safe and effective procedure for BD stricture and postoperative bile leakage.

Intra-abdominal ectopic bronchogenic cyst with a mucinous neoplasm harboring a GNAS mutation: A case report

BACKGROUND Bronchogenic cysts are congenital cysts caused by abnormal sprouting from the ventral foregut during fetal life.They usually occur in the mediastinum or lung,but there are very rare cases of ectopic bronchogenic cysts that develop in the abdominal cavity.A unique intra-abdominal ectopic bronchogenic cyst with a mucinous neoplasm that was producing carcinoembryonic antigen(CEA),harboring a GNAS mutation,is reported.The present case may contribute to clarifying the mechanism of tumorigenesis and malignant transformation of ectopic bronchogenic cysts.CASE SUMMARY In 2007,a man in his 50s was incidentally found to have an intra-abdominal cystic mass,8 cm in diameter.Surgical resection was recommended,but he preferred to remain under observation.In 2020,his serum CEA level increased to 26.7 ng/mL,and abdominal computed tomography showed a 15 cm×12 cm,multifocal,cystic mass located predominantly on the lesser curvature of the stomach.Since malignancy could not be ruled out,he finally underwent surgical resection.Histologically,the cystic wall was lined by ciliated columnar epithelium,accompanied by bronchial gland-like tissue,bronchial cartilage,and smooth muscle.Part of the cyst consisted of atypical columnar epithelium with an MIB-1 index of 5%and positive for CEA.Moreover,a GNAS mutation(p.R201C)was detected in the atypical epithelium,leading to a diagnosis of an ectopic bronchogenic cyst with a low-grade mucinous neoplasm.The patient is currently undergoing outpatient follow-up without recurrence.CONCLUSION An extremely rare case of an abdominal bronchogenic cyst with a low-grade mucinous neoplasm harboring a GNAS mutation was reported.

Cisplatin Inhibits AhR Activation

The AhR binds to contain ligands, such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, 3-methylcholantrene, or β-naphthoflavone. The activation mechanism of AhR is not yet fully understood, but it is known that AhR associates with the molecular chaperone HSP90 in the cytoplasm. There are a few reports about the association or dissociation of AhR and HSP90, and which domain of HSP90 binds to AhR. We reported the association and activation mechanisms between HSP90 and AhR-PAS or AhR-bHLH. In the current study, we found that cisplatin inhibits the AhR activation. Although ATP and 17-DMAG have no effect on the dissociation of HSP90 from AhR, some contents of HSP90 were dissociated from AhR in the presence of cisplatin. We could detect the increase of CYP1A in the presence of 3-MC. On the contrary, the induction of CYP1A1 was inhibited in the presence of cisplatin. We couldn’t detect AhR in the HeLa cell soluble fraction in the presence of 50 μM cisplatin. In the presence of MG-132, we could detect AhR. These results suggested that AhR was dissociated from the HSP90 chaperone complex and processed during the protein proteasome degradation system in the presence of cisplatin.

胆道肿瘤临床实践指南(英文第三版)

日本肝胆胰外科学会(JSHBPS)于2007年出版第一版胆道肿瘤(胆管癌、胆囊癌及壶腹癌)临床实践指南,于2014年更新第二版,2021年英文第三版胆道肿瘤临床实践指南围绕6个主题提出若干临床问题,基于相关循证医学证据并组织专家讨论后,最终确定推荐意见、推荐强度以及推荐说明。根据证据推荐分级的评估、制订与评价(GRADE)系统,推荐强度被分为1级(强)或者2级(弱)。英文第三版胆道肿瘤临床实践指南中提出的31个临床问题涵盖:(1)预防性治疗;(2)诊断;(3)胆道引流;(4)外科治疗;(5)化疗;(6)放疗。31个临床问题中,14个问题给予推荐强度为强的推荐意见,14个问题给予推荐强度为弱的推荐意见,剩余的3个问题未给予推荐意见。每条推荐意见都进行推荐强度说明。最新版指南基于循证医学证据,为临床提供了重要建议。未来与癌症登记数据库协作将是评估指南和建立新证据的关键。