Purpose: To explore the possibility of a combination of dabrafenib and SHP2 inhibitor in the treatment of anaplastic thyroid carcinoma and to provide a new therapeutic strategy for the treatment of anaplastic thyroid cancer. Patients and Methods: Firstly, a drug resistance model was established, and the expression levels of related RTK were detected by qPCR. Western blot was used to detect the protein expression levels of Akt and MAPK signaling pathways in the control group, single-drug group and two-drug combination group. The gene silencing of SHP2 was achieved by transfection of siRNA and verified by Western blot. CCK8 kit and clone formation assay were used to detect cell proliferation activity. In vivo model of mutant thyroid cancer cells was established by subcutaneous injection of mice and then divided into four groups. Tumor diameter was measured every two days. Immunohistochemistry was used to evaluate the expression of p-ERK, p-AKT and Ki67 in mouse tumors. Results: In this study, dabrafenib-resistant ATC cells were first constructed, and the response of RTKs in drug-resistant cells was upregulated to activate Akt and MER/ERK pathways. The activation of Akt and MEK/ERK pathways in the combination group was significantly inhibited, and the proliferation ability of tumor cells was significantly reduced compared with Dabrafenib, SHP099 group and DMSO group. To verify that SHP099 was not off-target, we also silenced SHP2 expression by transfection with siRNA and obtained the same results. Finally, by building a mouse drug resistance model, we confirmed that dabrafenib and SHP099 can also play a powerful anti-cancer effect in vivo. Conclusion: The SHP2 inhibitor SHP099 can effectively reverse the drug resistance of dabrafenib through inhibiting the reactivated RAS signaling pathway in anaplastic thyroid cancer.The combination of dabrafenib with SHP2 inhibitor has shown significant tumor suppressive effects for dabrafenib-resistant cells and it may be a new therapeutic strategy with longer lasting therapeutic benefits.
Objective:To explore the predictive value of tumor burden score (TBS) combined with lymph node staging (TBS-N staging) for postoperative survival of patients with intrahepatic cholangiocarcinoma (ICC).Methods:Clinical data of 335 ICC patients who underwent hepatectomy in Zhongda Hospital of Southeast University School of Medicine, Eastern Hepatobiliary Surgery Hospital and Affiliated Hospital of North Sichuan Medical College from January, 2013 to December, 2019 were retrospectively analyzed. Among them, 169 patients were male and 166 female, aged from 23 to 87 years, with a median age of 62 years. The informed consents of all patients were obtained and the local ethical committee approval was received. The TBS of all patients was calculated. All the patients were divided into stageⅠ, Ⅱ and Ⅲ according to TBS score and lymph node metastasis. The predictive ability of TBS-N staging for clinical prognosis of ICC patients after hepatectomy was analyzed by the receiver operating characteristic (ROC) curve. The risk factors of clinical prognosis of ICC patients after hepatectomy were identified by Cox proportional hazard regression model.Results:The optimal cut-off value of TBS was 4.22, including84 cases of TBS-N stageⅠ, 202 cases of stageⅡand 49 cases of stage Ⅲ. TBS-N staging was correlated with tumor diameter (F=77.639, P<0.05), intraoperative blood loss (Z=11.385, P<0.05), HBV infection rate (χ2=6.590, P<0.05), surgical resection range (χ2=9.796, P<0.05), vascular invasion (χ2=12.332, P<0.05), TNM staging (P<0.05) and postoperative complications (χ2=7.210, P<0.05) of ICC patients. Cox multivariate analysis showed that TBS>4.22, N1 stage and poor tumor differentiation were the independent risk factors for clinical prognosis of ICC patients after hepatectomy (HR=1.529, 2.100, 1.724; P<0.05). The median overall survival of patients with TBS-N stage Ⅰ, Ⅱ and Ⅲ was 51.4, 22.7 and 12.0 months, respectively, where significant differences were observed (χ2=25.797, P<0.05). The area under ROC curve (AUC) of TBS, N staging and TBS-N model for predicting clinical prognosis of ICC patients after hepatectomy was 0.596, 0.602 and 0.660, respectively.Conclusions:TBS and N staging are the independent risk factors for clinical prognosis of ICC patients after hepatectomy. Compared with TBS or N staging alone, TBS-N staging can better evaluate the clinical prognosis of ICC patients after hepatectomy.
目的 探讨对氧磷酶1(PON1)低表达对肝癌细胞增殖和细胞克隆能力的影响.方法 提取肝癌组织及癌旁正常组织标本RNA测定PON1 mRNA的相对表达水平,ELISA法检测肝癌患者和健康人血清PON1蛋白水平.培养人肝癌细胞系PLC和Huh7,对PLC和Huh7细胞系进行转染,分为对照组和转染组(转染siPON1小干扰RNA进行基因沉默实验),使用实时荧光定量PCR及ELISA法验证转染效率,CCK-8实验检测转染后肝癌癌细胞增殖能力的变化,克隆形成实验检测细胞形成克隆的能力,流式细胞术检测细胞周期,Western blot实验检测AMP活化蛋白激酶(AMPK)信号通路相关蛋白变化.结果 肝癌组织中PON1 mRNA相对表达水平低于癌旁正常组织(P<0.05),肝癌患者血清PON1蛋白水平低于健康人(P<0.05).与对照组比较,转染组PON1 mRNA相对表达水平和PON1蛋白水平降低(P<0.05),细胞增殖能力明显增强(P<0.05),细胞克隆形成率明显增多(P<0.05),S期细胞比例明显增多(P<0.05),p-AMPK表达水平明显降低,p-mTOR表达水平明显升高.结论 PON1表达调控了AMPK信号通路活化并抑制了肝癌细胞增殖.
目的 探讨淋巴结清扫对不同位置肝内胆管癌(ICC)患者疗效的影响.方法 采用回顾性队列研究方法.收集2015年1月至2022年1月川北医学院附属医院收治的123例ICC患者的临床病理资料;男78例,女45例;年龄为55(50~60)岁.所有患者行根治性切除术.观察指标:(1)ICC患者临床特征.(2)随访情况.(3)不同淋巴结清扫数目ICC患者的手术情况.正态分布的计量资料以(x)±s表示,组间比较采用独立样本t检验;偏态分布的计量资料以M(范围)表示,组间比较采用Mann-WhitneyU检验.计数资料以绝对数或百分比表示,组间比较采用x2检验.采用Kaplan-Meier法绘制生存曲线,Log-Rank检验进行生存分析.结果 (1)ICC患者临床特征.123例患者中,81例为周围型ICC,42例为中央型ICC.周围型ICC患者的白蛋白-胆红素评分分级(1级、2~3级),术前淋巴结转移风险评估(低风险、高风险),淋巴结清扫数目(<6枚、≥6枚),淋巴结转移(有、无)分别为57、24例,51、30例,49、32例,15、66例;中央型ICC患者上述指标分别为19、23例,17、25例,14、28例,16、26例,两者比较,差异均有统计学意义(x2=7.40,5.66,8.17,5.62,P<0.05).(2)随访情况.123例患者均获得随访,随访时间为28(21~38)个月.81例周围型ICC和42例中央型ICC患者3年总生存率分别为57.8%和32.3%,两者比较,差异有统计学意义(x2=5.98,P<0.05).42例中央型ICC患者中,25例术前淋巴结转移评估高风险,17例术前淋巴结转移评估低风险.25例术前淋巴结转移评估高风险中央型ICC患者中,18例淋巴结清扫数目≥6枚和7例淋巴结清扫数目<6枚患者3年总生存率分别为28.9%和14.3%,两者比较,差异有统计学意义(x2=8.90,P<0.05).(3)不同淋巴结清扫数目ICC患者的手术情况.123例患者中,63例淋巴结清扫数目<6枚,60例淋巴结清扫数目≥6枚.淋巴结清扫数目<6枚和≥6枚ICC患者的手术时间、术中输血、术后总并发症、胆漏、肝功能不全、肺部感染、胸腔积液、腹腔积液、淋巴漏比较,差异均无统计学意义(P>0.05).同一例患者可合并多种并发症.结论 周围型ICC患者的预后优于中央型ICC患者;对于术前淋巴结转移评估高风险的中央型ICC患者,充分的淋巴结清扫可以使患者获得更佳预后.
A giant cervical goiter, defined as a thyroid mass larger than 8 cm in diameter, is usually a nodular or adenomatous goiter. A giant cervical goiter can also be caused by hyperthyroidism (i.e., Hashimoto’s thyroiditis). The surgical indications for patients with Hashimoto’s disease include suspected malignant tumors, persistent symptoms related to the disease, or persistent enlargement of the goiter. We herein describe a woman who developed symptoms of compression from a thyroid tumor, the volume of which was almost the largest reported in the relevant literature to date. The bilateral lobes of the giant thyroid tumor were removed by total en bloc excision. We protected the bilateral recurrent laryngeal nerve and preserved the bilateral upper and lower parathyroid glands in situ. The excised left lobe tumor was 16 × 9 × 5.5 cm, whereas the right lobe tumor was 12 × 8 × 4 cm. The pathological diagnosis was Hashimoto’s thyroiditis. Although surgical excision is difficult, it is still the main treatment modality for giant goiters in patients with Hashimoto’s thyroiditis and can help to reduce the occurrence of complications.
肝癌作为最常见引起患者死亡的恶性肿瘤之一,其中肝细胞肝癌(hepatocellular carcinoma,HCC)发病率明显较多。因其缺乏典型的临床症状,故HCC患者很难达到早期诊断。合并门静脉癌栓(portal vein tumor thrombus ,PVTT)作为HCC患者中的一种类型,因其肿瘤特性,使得这类肝癌患者预后不佳。目前HCC合并PVTT患者的治疗暂无明确治疗指南,随着医学技术的进步,越来越多的治疗方式运用到此类型患者。本文就其中靶向治疗、免疫治疗、放射治疗、HAIC、TACE、肝切除术、肝移植术、全身治疗等最新治疗方案进行综述。
目的 探讨曲美替尼(Trametinib)对维莫非尼(Vemurafenib)治疗BRAFV600E突变型甲状腺乳头状癌抵抗的逆转作用和机制.方法 应用CCK-8实验检测Vemurafenib及Trametinib在人甲状腺癌K-1、BCPAP细胞中的半数抑制浓度(IC50)及两药联合指数(CI).蛋白质印迹法检测Vemurafenib不同处理时间对丝裂原活化蛋白激酶(MAPK)通路的抑制作用,确定产生抵抗的机制;随后联合使用Trametinib分别进行CCK-8、平板克隆、流式细胞术和蛋白质印迹实验观察肿瘤细胞的增殖、凋亡及MAPK通路变化.结果 Vemurafenib在K-1和BCPAP细胞中的IC50分别为37.21、22.61μmol/L,Trametinib的IC50分别为776.50、990.40 nmol/L;Vemurafenib处理K-1和BCPAP细胞24 h后,MAPK通路被再次激活,p-MEK、p-ERK显著升高,48 h后回升至初始水平.选用10μmol/L Vemurafenib和1μmol/L Tra-metinib进行后续实验.联合使用Trametinib可抑制Vemurafenib处理24 h后出现的p-MEK及p-ERK回升现象.Ve-murafenib及Trametinib均可有效抑制K-1(t值分别为9.113和13.150,均P<0.001)及BCPAP(t值分别为7.290和8.920,P值分别为0.002和0.009)细胞的增殖及克隆形成能力(K-1:tVemurafenib=8.898,tTrametinib=11.730,均P<0.001;BCPAP:tVemurafenib=6.015,P=0.004;tTrametinib=7.109,P=0.002),并促进细胞凋亡(K-1:tVemurafenib=3.610,P=0.023;tTrametinib=4.666,P=0.009.BCPAP:tVemurafenib=3.334,P=0.029;tTrametinib=5.603,P=0.005),差异均有统计学意义.同时,Trametinib可提高Vemurafenib抑制K-1和BCPAP细胞增殖(tK-1=10.170,tBCPAP=9.662,均P<0.001)、克隆形成(tK-1=11.660,tBCPAP=10.170,均P<0.001)及促进凋亡(tK-1=5.336,tBCPAP=5.420,均P=0.006)的能力,差异有统计学意义.在处理48 h时,与对照组相比,Vemurafenib对K-1及BCPAP细胞的增殖抑制作用(tK-1=3.893,P=0.018;tBCPAP=3.141,P=0.035)及促凋亡作用(tK-1=3.976,P=0.017;tBCPAP=4.495,P=0.011)稍降低,差异有统计学意义;对细胞克隆形成的抑制能力差异无统计学意义.Trametinib仍可有效抑制K-1及BCPAP细胞增殖(tK-1=14.190,tBCPAP=13.490,均P<0.001)及克隆形成能力(tK-1=16.470,tBCPAP=8.966,均P<0.001),并促进细胞凋亡(tK-1=6.331,P=0.003;tBCPAP=7.472,P=0.002),差异有统计学意义.同时,Trametinib仍逆转Vemurafenib处理48 h后出现的耐受现象,提高Vemurafenib抑制K-1及BCPAP细胞增殖(tK-1=23.360,tBCPAP=21.540,均P<0.001)、克隆形成(tK-1=27.320,tBCPAP=22.840,均P<0.001)及促进凋亡(tK-1=11.590,tBCPAP=13.110,均P<0.001)的能力,差异有统计学意义.结论 Vemurafenib治疗甲状腺乳头状癌所产生的耐受机制之一为MAPK通路的再度激活,联合使用MEK抑制剂Trametinib可显著提高Vemurafenib的抗肿瘤作用,逆转药物抵抗.
BackgroundSpontaneous regression of primary liver cancer is a rare event, and currently the exact pathogenesis of spontaneous tumor regression remains unclear.Case descriptionClinical information was collected from a patient with spontaneous regression of liver cancer at our center. The patient was a 41-year-old male. He was admitted to the hospital on 3 May 2019, due to aversion to fatty or greasy food, anorexia, loss of appetite, and abdominal distension. Laboratory examination results included hepatitis B surface antigen positivity, hepatitis B e antigen positivity, and hepatitis B core antibody positivity and tumor marker levels of alpha-fetoprotein 142,938.20 µg/L, abnormal prothrombin 4,599.91 mAU/ml, and carbohydrate antigen 19–9 82.05 U/ml. Upper abdominal enhanced computed tomography indicated right hepatocellular carcinoma with portal vein tumor thrombus formation. The patient declined any treatment. The tumor in the right lobe of the liver completely regressed after 1 year, and the patient is still undergoing follow-up.ConclusionsWe encountered a hepatocellular carcinoma patient who underwent spontaneous regression, but the exact pathogenesis remains unknown. Understanding the pathogenesis of spontaneous regression of hepatocellular carcinoma has the potential to contribute to the development of an effective treatment for hepatocellular carcinoma.
A large number of studies have reported that microRNA (miR)-374c-5p plays an important role in the occurrence and development of malignant tumors, but there is no research on the role of miR-374c-5p in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the role of miR-374c-5p in HCC and the underlying molecular mechanism. The expression of miR-374c-5p in HCC tissues and HCC cell lines was analyzed via reverse transcription-quantitative PCR. The association between miR-374c-5p and clinical pathology was also analyzed in patients with HCC. Kaplan-Meier analysis and Cox multivariate analysis were used to evaluate the prognostic significance of miR-374c-5p in HCC. The biological functions of miR-374c-5p, including cell proliferation, migration and invasion and its potential molecular mechanism were analyzed in vivo and in vitro. In addition, the molecular mechanism of miR-374c-5p in HCC was further explored. The results demonstrated that miR-374c-5p expression was lower in HCC than in matched adjacent tissue samples. Patients with low expression of miR-374c-5p had poor prognosis and short survival time. Overexpression of miR-374c-5p inhibited HCC cell proliferation, migration and invasion in vitro. In vivo, it was found that overexpression of miR-374c-5p significantly inhibited the growth and proliferation of HCC cells. Dual-luciferase reporter assays verified that miR-374c-5p directly targets the 3 '-untranslated region of pituitary tumor-transforming 1 (PTTG1) and regulates PTTG1 expression. In general, it was revealed that miR-374c-5p regulates the malignant biological behavior of HCC through PTTG1, thereby affecting epithelial-mesenchymal transition. Thus, miR-374c-5p is a potential biological indicator to predict poor prognosis in patients with HCC.
目的 探究胆管癌术后腹腔感染患者血清肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)、CD4+/CD8+T细胞的变化及影响因素分析.方法 选取2015年1月-2019年5月于川北医学院附属医院进行胆管癌术的患者共70例,根据其术后腹腔感染情况,分为感染组和对照组,各35例.采用全自动微生物检定仪和细菌测定系统对胆管癌术后腹腔感染的患者进行植株鉴定;采用ELISA法对血清中TNF-α、IL-1β进行检测,采用流式细胞仪对CD4+/CD8+T细胞进行检测;分析年龄、性别、合并高血压、合并高血脂、手术时间、术中出血量、白蛋白、白细胞等资料,归纳胆管癌患者术后腹腔感染的影响因素.结果 在35例腹腔感染患者的血液标本中共检测出83株病原菌,其中以革兰阴性菌为主,共52株占62.65%;感染组血清TNF-α、IL-1β水平(132.22±34.64)μg/L、(36.42±4.94)pg/L)高于对照组(P<0.05),CD4+/CD8+T细胞水平(0.60±0.12)低于对照组(P<0.05);合并糖尿病、手术时间、肠功能障碍时间是胆管癌术后腹腔感染的影响因素(P<0.05).结论 胆管癌术后腹腔感染的主要病原菌是革兰阴性菌;当胆管癌术后患者发生腹腔感染时,血清TNF-α、IL-1β水平显著升高,CD4+/CD8+T细胞水平明显降低,临床中应加强对影响因素的针对性预防.
Background: Though hepatic resection (HR) is the standard local therapy for patients with colorectal cancer liver metastases (CRLMs), currently, radiofrequency ablation (RFA) may play an alternative role for elderly and vulnerable patients with various organ dysfunctions. This study aims to compare the prognosis of RFA and HR in treatment of CRLMs. Methods: A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to October 1, 2020 was conducted for relevant studies that compared the prognosis of RFA with HR in the treatment of CRLMs. The primary outcomes were 30-day mortality, long-term recurrence, overall survival (OS) and disease-free survival (DFS). The secondary outcomes were various factors of OS, recurrence-free survival (RFS), survival, recurrence and complication. Results: A total of 22 studies including 4385 CRLM patients were identified. There was no significant difference between RFA and HR in 30-day mortality, with a pooled OR of 0.88 (95% CI 0.34?2.29; P = 0.80). CRLM patients undergoing RFA experienced significantly higher incidences of marginal and intrahepatic recurrence than HR, with pooled ORs of 7.09 (95% CI 4.56?11.2; 1251 pts) and 2.02 (95% CI 1.24?3.28; 1038 pts). In addition, RFA showed lower 1-, 3- and 5-yr OS rate than HR with pooled ORs of 0.39, 0.40 and 0.60 respectively. A lower 5-yr DFS rate was also found in RFA than HR group, with a pooled OR of 0.74 (95% CI 0.56?0.97; P = 0.03; 1231 pts). Multivariable analysis showed that tumor size, multiple tumors, age, primary node positive and metachronous metastasis were independent factors of OS, and multiple tumors was also an independent factor of RFS. Conclusions: Though the 30-day mortality of RFA was equal to HR, RFA showed a higher recurrence rate and poor long-term survival outcomes for CRLM patients. Tumor size, multiple tumors, age, primary node positive and metachronous metastasis were independent factors of survival. However, the results were limited because of the inequality baseline characteristics between the comparative groups. Randomized or propensity score matching studies should be performed to clarify the effectiveness of RFA and to determine target populations that benefit Background: Though hepatic resection (HR) is the standard local therapy for patients with colorectal cancer liver metastases (CRLMs), currently, radiofrequency ablation (RFA) may play an alternative role for elderly and vulnerable patients with various organ dysfunctions. This study aims to compare the prognosis of RFA and HR in treatment of CRLMs. Methods: A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to October 1, 2020 was conducted for relevant studies that compared the prognosis of RFA with HR in the treatment of CRLMs. The primary outcomes were 30-day mortality, long-term recurrence, overall survival (OS) and disease-free survival (DFS). The secondary outcomes were various factors of OS, recurrence-free survival (RFS), survival, recurrence and complication. Results: A total of 22 studies including 4385 CRLM patients were identified. There was no significant difference between RFA and HR in 30-day mortality, with a pooled OR of 0.88 (95% CI 0.34?2.29; P = 0.80). CRLM patients undergoing RFA experienced significantly higher incidences of marginal and intrahepatic recurrence than HR, with pooled ORs of 7.09 (95% CI 4.56?11.2; 1251 pts) and 2.02 (95% CI 1.24?3.28; 1038 pts). In addition, RFA showed lower 1-, 3-and 5-yr OS rate than HR with pooled ORs of 0.39, 0.40 and 0.60 respectively. A lower 5-yr DFS rate was also found in RFA than HR group, with a pooled OR of 0.74 (95% CI 0.56?0.97; P = 0.03; 1231 pts). Multivariable analysis showed that tumor size, multiple tumors, age, primary node positive and metachronous metastasis were independent factors of OS, and multiple tumors was also an independent factor of RFS. Conclusions: Though the 30-day mortality of RFA was equal to HR, RFA showed a higher recurrence rate and poor long-term survival outcomes for CRLM patients. Tumor size, multiple tumors, age, primary node positive and metachronous metastasis were independent factors of survival. However, the results were limited because of the inequality baseline characteristics between the comparative groups. Randomized or propensity score matching studies should be performed to clarify the effectiveness of RFA and to determine target populations that benefit most from RFA in the future.
Hepatocellular carcinoma (HCC) is a type of primary liver cancer, which is associated with high mortality. HCC is one of the most common malignant tumors worldwide. Cell division cycle 20 (CDC20) has been reported to be associated with the development of various malignant tumors and epithelial-mesenchymal transition (EMT) has been reported to be involved in the malignant metastasis of HCC. Therefore, the present study hypothesized that CDC20 may participate in the malignant biological behavior of HCC via EMT. The present study analyzed the expression levels of CDC20 in HCC and the association between CDC20 and poor prognosis. Furthermore, the effects of CDC20 on the proliferation, invasion and migration of HCC cells were examined using proliferation, migration and invasion assays. Finally, alterations in EMT were analyzed. The results revealed that CDC20 was highly expressed in HCC and HCC cell lines (P<0.05), and its high expression level was significantly associated with poor prognosis in patients with HCC (P<0.05). CDC20 silencing inhibited the proliferation, migration and invasion of HCC cells. Furthermore, CDC20 silencing increased the expression levels of E-cadherin, and decreased the expression levels of N-cadherin, vimentin and Ki-67. In conclusion, the present study reported that CDC20 may be a novel therapeutic target in HCC and CDC20 could promote the progression of HCC by regulating EMT.
肝门部胆管癌是起源于起源于左肝管、右肝管、肝总管以及三者汇合区的恶性肿瘤.Gerald Klatskin于1965年首先在American Journal of Medicine报道,故又称Klatskin瘤 [1].肝门部胆管癌占胆管癌的50%~70%,总体发病率较低,但预后较差.外科手术切除是目前肝门部胆管癌唯一有效的治疗手段,对肝门部胆管癌进行规范化诊治有助于提高患者生存率[2-4].
腹腔镜肝切除术因具有切口小、出血量少、住院时间短等优势,目前已成为肝胆外科的主流发展趋势[1] ,但全腹腔镜复杂肝切除术仍存在巨大挑战.近年我科从护理工作实际出发,依据腹腔镜肝切除术中配合的实践经验,对术中护理程序进行精确细化,并强调精准配合,采取精准护理的配合模式展开了一系列工作.为探讨最佳的护理配合方法,现将我院为46例复杂肝脏肿瘤患者行全腹腔镜肝切除术的临床资料及护理配合体会报道如下.
Objective:To evaluate the strategy and efficacy of laparoscopic hepatectomy in the classified treatment of hepatolithiasis.Methods:Clinical data of 81 patients with hepatolithiasis who underwent laparoscopic hepatectomy in the Affiliated Hospital of North Sichuan Medical College from January 2016 to December 2018 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 19 patients were male and 62 female, aged from 30 to 83 years with a median age of 53 years. According to the classification of hepatolithiasis, 61 cases were classified as type Ⅰ and 20 cases type Ⅱb. The atrophic liver lobes or segments in patients with type Ⅰ hepatolithiasis were resected. For patients with type Ⅱb hepatolithiasis, the limited nonfunctional liver lobes or segments were resected. The incidence of complication during and after operation was observed.Results:All patients completed laparoscopic hepatectomy successfully. Among them, 11 patients underwent left lateral lobectomy,57 cases left hemihepatectomy, 8 cases right hemihepatectomy, 1 case right posterior lobectomy, 1 case left lateral lobectomy combined with right anterior lobectomy, and 3 cases of left lateral lobectomy combined with the upper right posterior lobectomy. The mean operation time was (220±96) min, the intraoperative blood loss was (424±120) ml, the off-bed time after operation was (2.8±1.1) d, the postoperative eating time was (1.4±0.7) d, and the length of postoperative hospital stay was (14±6) d. Residual stones occurred in 2 cases. Intraoperative gastrointestinal injury occurred in 4 cases. Postoperatively, 12 cases developed pulmonary infection, 20 cases of pleural effusion, 9 cases of hepatic cross-section effusion including 7 cases complicated with infection, 5 cases of bile leakage, 2 cases of incisional infection and 2 cases of gastrointestinal dysfunction. All complications were cured after conservative treatments.Conclusions:Individual therapeutic strategy should be adopted according to the classification and distribution of hepatolithiasis. Laparoscopic hepatectomy is a safe and efficacious treatment for type Ⅰ and type Ⅱb hepatolithiasis, which can achieve satisfactory clinical efficacy.
The aim of the present study was to compare the effects of percutaneous transhepatic biliary drainage (PTBD) and endoscopic biliary drainage (EBD) for resected malignant obstruction jaundice (MOJ) on the incidence rate of implantation metastasis. Databases including PubMed, EMbase, Web of Science and Cochrane Library were utilized. With reference to literature reported until January 2019, controlled clinical trials were designed to compare the effects of PTBD and EBD for MOJ on the incidence rate of implantation metastasis. Subsequently, odds ratio (OR) with 95% confidence interval (CI) was calculated with Review Manager 5.3.0 software. A total of 10 studies were enrolled in this meta-analysis, including 1,085 cases in the PTBD group and 1,379 cases in the EBD group. The results revealed that there was a significant difference in the incidence rate of implantation metastasis between the PTBD group and EBD group (OR=0.35, 95% CI: 0.23-0.53, P<0.00001). Subgroup analysis revealed that the incidence rates of both catheter-related implantation metastasis and peritoneal metastasis were lower in the EBD group (OR=0.23, 95% CI: 0.12-0.44, P<0.00001; OR=0.47, 95% CI: 0.31-0.74, P=0.0008, respectively), and the advantage of EBD was demonstrated in perihilar cholangiocarcinoma, distal cholangiocarcinoma and pancreatic carcinoma (OR=0.35, 95% CI: 0.17-0.74, P=0.006; OR=0.32, 95% CI: 0.17-0.60, P=0.0005; OR=0.27, 95% CI: 0.19-0.40, P<0.00001, respectively). In conclusion, this meta-analysis revealed the appropriate choice of preoperative biliary drainage for resected MOJ. The application of EBD reduced the incidence rate of implantation metastasis, however more evidence is required from future studies, to confirm the results.
BACKGROUND:Microwave ablation (MWA) is an important method in the treatment of liver cancer. This systematic review compared MWA with liver resection (LR) for liver cancer treatment. In recent years, the MWA has been also reported to play an important role. Studies comparing MWA and LR are lacking. This study aims to compare the efficacy of MWA and LR in the treatment of hepatocellular carcinoma (HCC). METHODS:A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to April 1, 2019 was conducted for relevant studies that compared the efficacy of MWA and LR in the treatment of HCC. The primary outcomes were local tumor recurrence (LTR) and overall survival (OS) of patients. The secondary outcomes included disease free survival (DFS), extrahepatic metastasis, intrahepatic de novo lesions, length of stay, complications, intraoperative blood loss and operative time. RESULTS:A total of 16 studies including 2622 patients were identified. Incidence of LTR was significantly higher in patients with MWA than LR, with a pooled OR of 2.69 (95% CI 1.33-5.41; P = 0.006). No significant difference in 1-year OS was found. However, patients with MWA experienced higher 3- and 5-year OS, with pooled ORs of 1.40 (95% CI 1.07-1.84; P = 0.01) and 1.41 (95% CI 1.10-1.80; P = 0.007) respectively. In secondary measures, the 1- and 3-year DFS were significantly higher in patients with MWA. However, no significant difference of 5-year DFS was observed. In addition, lower incidence of complications, less intraoperative blood loss and shorter operative time and shorter length of stay were observed in MWA. CONCLUSIONS:Though MWA may lead to higher incidence of recurrence, it may be an effective and safe alternative in patients with HCC or liver metastases. MWA may have benefits in patients' survival and safety. Randomized studies should be performed to determine the target population that benefits most from MWA in the future.
Accumulating evidence indicates an unexpected role of aberrant splicing in hepatocellular carcinoma (HCC) that has been seriously neglected in previous studies. There is a need for a detailed analysis of alternative splicing (AS) and its underlying biological and clinical relevance in HCC. In this study, clinical information and corresponding RNA sequencing data of HCC patients were obtained from The Cancer Genome Atlas. Percent spliced in (PSI) values and transcriptional splicing patterns of genes were determined from the original RNA sequencing data using SpliceSeq. Then, based on the PSI values of AS events in different patients, a series of bioinformatics methods was used to identify differentially expressed AS events (DEAS), determine potential regulatory relationships, and investigate the correlation between DEAS and the patients' clinicopathological features. Finally, 25,934 AS events originating from 8,795 genes were screened with high reliability; 263 of these AS events were identified as DEAS. The parent genes of these DEAS formed an intricate network with roles in the regulation of cancer-related pathway and liver metabolism. In HCC, 36 splicing factors were involved in the dysregulation of part DEAS, 100 DEAS events were correlated with overall survival, and 71 DEAS events were correlated with disease-free survival. Stratifying HCC patients according to DEAS resulted in four clusters with different survival patterns. Significant variations in AS occurred during HCC initiation and maintenance; these are likely to be vital both for biological processes and in prognosis. The HCC-related AS events identified here and the splicing networks constructed will be valuable in deciphering the underlying role of AS in HCC.
To develop a drug carrier sensitive to reactive oxygen species (ROS), a nanocomplex (NCs) based on sulfuric hyaluronic acid (sHA)-anthocyanin (ATC) was developed. Doxorubicin (DOX) is loaded into the sHA-ATC NCs (AD@sHA) through intermolecular π-π stacking and hydrophobic interactions. AD@sHA can be prepared in aqueous phase by simple mixing method. In AD@sHA, DOX content and load efficiency are high. Compared with D@sHA (without ATC), the ROS-ATC co-mediated responsive degradation and drug release of AD@sHA was confirmed. In addition, AD@sHA also improved apoptosis of CD44+ colon cancer HT29 cells. HT29 tumor-bearing mice model was used to confirm the role of AD@SHA in targeted tumor therapy. The results showed that AD@SHA could optimize the biodistribution of DOX. These data, from tumor volume and TUNEL analysis, observed the delay of tumor growth and apoptosis of cancer cells. Even more exciting is that AD@sHA significantly reduces the myelosuppression of DOX. This study means that AD@sHA has a better effect on chemotherapy for CD44-positive tumors.