A comprehensive review on Brigatinib – A wonder drug for targeted cancer therapy in non-small cell lung cancer

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.     

腹腔镜大范围肝切除术和开腹大范围肝切除术治疗肝癌的对比研究

目的 探讨腹腔镜大范围肝切除术（LMH）与开腹大范围肝切除术的治疗效果。方法 选取2018 年12 月至2020 年12 月入院治疗的97 例肝癌患者为研究对象,依据随机数字表法予以分组,A 组49 例采取LMH 治疗,B 组48 例采取开腹大范围肝切除术治疗。比较两组围术期治疗指标、肝功能指标和并发症发生率。结果 A 组患者的切口长度为（9.08±0.65）cm、术中出血量为（342.15±21.26）mL、输血量为（102.03±8.54）mL,均低于B 组,差异有统计学意义（P＜0.05）。A 组患者的手术时间略长于B 组,差异无统计学意义（P＞0.05）。A 组的术后拔管时间为（4.88±0.26）d、饮食恢复时间为（2.32±0.58）d、住院时间为（6.97±0.97）d,均短于B 组,差异有统计学意义（P＜0.05）。术前,两组患者的各项肝功能指标比较,差异无统计学意义（P＞0.05）。术后1 d,A 组患者的ALT、AST 水平低于B 组,差异有统计学意义（P＜0.05）。术后3 d,A 组患者的ALT 水平低于B 组,差异有统计学意义（P＜0.05）。A 组患者的并发症发生率为6.12%,B 组为22.92%,差异有统计学意义（P＜0.05）。结论 肝癌患者采取LMH 治疗的效果优于开腹大范围肝切除术,可优化治疗指标,缩短术后康复时间,且能改善肝功能,减少并发症。     

同期三镜、鼻胆管引流术在左肝合并胆总管结石的应用研究

目的:探讨鼻胆管引流术(endoscopic nasobiliary drainage,ENBD)在同期三镜(腹腔镜、胆管镜、十二指肠镜)下治疗左肝内胆管结石合并胆总管结石的临床应用价值.方法:回顾性分析四川省成都市第二人民医院肝胆胰外科2014年1月至2018年7月收治的左肝内胆管结石合并胆总管结石其中伴或不伴有胆囊结石的患者,共49例.均行腹腔镜下规则性肝叶切除+胆道镜下胆总管探查取石,其中观察组22例,采用十二指肠镜下安置鼻胆管引流;对照组27例,采用T管引流,对比分析鼻胆管引流组与T管引流组的临床疗效.观察指标:围手术期及随访情况.采用电话方式随访.本文采用SPSS 20.0统计学软件进行数据分析.结果:术后排气时间鼻胆管引流组早于T管引流组,分别为(57.4± 13.4)h、(67.9±12.7)h,差异有统计学意义(t=-2.818,t=0.007,均P＜0.05).术后带管时间鼻胆管引流组为4～12 d,明显短于T管引流组的75～95 d,差异有统计学意义(Z=-6.022,Z=0.000,均P＜0.05).结论:针对本院有限的病例研究,左肝内肝管结石合并胆总管结石患者行鼻胆管引流术在未明显提高并发症的前提下,具有加速胃肠功能恢复时间、带管时间短等优势,是一种安全有效的手术方式.     

手术对广泛期小细胞肺癌患者生存的影响:基于SEER数据库的倾向得分匹配分析

目的:探讨手术治疗与非手术治疗对广泛期小细胞肺癌（ES-SCLC）患者的影响。方法:收集SEER数据库2004—2015年共24 677例ES-SCLC患者并将其分为手术组和非手术组,通过倾向得分匹配分析消除两组间的偏差,用Kaplan-Meier生存分析比较两组的生存情况,利用Log-rank单因素分析和多因素Cox回归对ES-SCLC患者进行校正并进行亚组分层分析。结果:倾向得分匹配后各有249例患者纳入手术组和非手术组,两组Kaplan-Meier生存曲线显示手术组预后较好且有统计学意义（χ2=13.367,P<0.001）。手术组中,接受肺叶切除术者比接受肺段、全肺切除术者预后生存率更佳（χ2=16.447,P<0.001）。单因素和多因素分析结果显示,手术治疗是影响ES-SCLC患者预后的因素（χ2=13.367,P<0.001）。亚组分析显示,≥60岁、N0和N1的手术组患者预后优于非手术组（χ2=8.974、7.732、4.077,P=0.003、0.005、0.043）,同时,无论是否化疗,手术组预后均优于非手术组（χ2=8.072、4.104,P=0.004、0.043）。结论:手术总体上可以延长ES-SCLC患者的生存时间。     

Living donor liver transplantation in children: Should the adult donor be operated on by an adult or pediatric surgeon? Experience of a single pediatric center

Background/Purpose

Living donor liver transplantation has become a cornerstone for the treatment of children with end-stage hepatic dysfunction, especially within populations or countries with low rates of organ utilization from deceased donors. The objective is to report our experience with 185 living donors operated on by a team pediatric surgeons in a tertiary center for pediatric liver transplantation.

Methods

Retrospective analysis of medical records of donors of hepatic grafts for transplant undergoing surgery between June 1998 and March 2013.

Results

Over the last 14 years, 185 liver transplants were performed in pediatric recipients of grafts from living donors. Among the donors, 166 left lateral segments (89.7%), 18 left lobes without the caudate lobe (9.7%) and 1 right lobe (0.5%) were harvested. The donor age ranged from 16 to 53 years, and the weight ranged from 47 to 106 kg. In 10 donors, an additional graft of the donor inferior mesenteric vein was harvested to substitute for a hypoplastic recipient portal vein. The transfusion of blood products was required in 15 donors (8.1%). The mean hospital stay was 5 days. No deaths occurred, but complications were identified in 23 patients (12.4%): 9 patients experienced abdominal pain and severe gastrointestinal symptoms and 3 patients required reoperations. Eight donors presented with minor bile leaks that were treated conservatively, and 3 patients developed extra-peritoneal infections (1 wound collection, 1 phlebitis and 1 pneumonia). Eight grafts (4.3%) showed primary dysfunction resulting in recipient death (3 cases of fulminant hepatitis, 1 patient with metabolic disease, 1 patient with Alagille syndrome and 3 cases of biliary atresia in infants under 1 year old). There was no relation between donor complications and primary graft dysfunction (P = 0.6).

Conclusions

Living donor transplantation is safe for the donor and presents a low morbidity. The donor surgery may be performed by a team of trained pediatric surgeons.     

Intrahepatic Glissonian approach and outflow vascular occlusion during partial hepatectomy

Under ultrasound guidance, a blunt suture needle was inserted around the Glissonian pedicle and then sutured. This technique significantly reduced the blood loss and facilitated the procedure of partial hepatectomy. We applied this technique in 182 patients who needed partial hepatectomy. We concluded that this method is simple and easy to occlude the vascular inflow and outflow, and allows an accurate delineation of the anatomic zone and therefore, simplifies the procedure of partial hepatectomy.     

肝癌肝切除术后感染并发症相关危险因素分析

目的 探讨肝癌肝切除术后感染并发症相关危险因素.方法 对本院近6年来行肝切除术的217例肝癌患者的临床资料进行回顾性分析,对可能引起感染并发症的因素进行统计学分析.结果 217例肝癌肝切除病例根据术后是否发生感染并发症分为感染组（n=33）与非感染组（n=184）.33例中,手术部位感染15例（占45.45％）、肝脏周围感染4例（占12.12％）、远处部位感染14例（占42.42％）;术后死亡3例（占1.38％）.多因素Logistic逐步回归分析显示年龄（P=0.006,0R=2.564）、糖尿病史（P=0.02,OR=1.996）、手术时间（F=0.005,0R=2.237）及胆漏发生率（P＜0.001,0R=7.325）是肝切除术后感染并发症的独立危险因素.结论 年龄、糖尿病史、手术时间及胆漏发生率是影响肝癌患者肝切除术后感染并发症发生的独立危险因素.     

经胸腹部联合切口的巨大肝血管瘤切除术

北京协和医院肝脏外科于2012年4月10日成功完成1例巨大肝血管瘤切除手术,手术历时11h,肿瘤最长径为48cm。该患者22年前曾因肝脏肿瘤行经胸、腹联合切口探查,但因术中出血较多未能切除肿瘤。该手术的成功受益于精准肝切除,包括CT血管重建技术、三维立体肝脏储备功能评估、术中控制性低中心静脉压以及精细肝切除操作技术的综合应用。     

Applying chemical bile duct embolization to achieve chemical hepatectomy in hepatolithiasis: a further experimental study

Background

Hepatolithiasis is the presence of calculi within the bile ducts of the liver. It represents a significant problem for hepatobiliary surgery because of its high recurrence rate and the associated risk for partial hepatectomy. This study was designed to explore the long-term efficacy of chemical biliary duct embolization (CBDE) to treat recurrent hepatolithiasis.

Materials and methods

A rabbit model of hepatolithiasis was established, and CBDE was achieved using oxybenzene and N-butyl-cyanoacrylate. The short-term (6 wk) and long-term (12 wk) efficacy of CBDE treatment was compared by observing the degree of atrophy, fibrosis, proliferation of collagen fibers, and apoptosis of hepatocytes and hepatic stellate cells in the embolized hepatic lobe. Biochemical measurement of β-glucuronidase was also evaluated to determine the effect of CBDE on stone formation.

Results

Six weeks after CBDE, there was liver cell destruction, collagen accumulation, and bile duct proliferation only in the peripheral part of the target lobe. Twelve weeks after CBDE, “self-cut” chemical hepatectomy was achieved, as manifested by the destruction of almost all the hepatocytes in the target lobe, bile duct proliferation, and collagen fiber accumulation. The β-glucuronidase activity was markedly lower in the embolized lobe than in the nonembolized lobe. In contrast, bax, caspase-3, caspase-9, and α-smooth muscle actin expression was substantially higher in the embolized lobe than in the sham-operation group at 6 wk, but was lower at 12 wk.

Conclusions

CBDE is a potentially effective therapeutic approach for treating and preventing the recurrence of hepatolithiasis.