Predictors of response and survival in patients with unresectable hepatocellular carcinoma treated with nivolumab: real-world experience

Real-world predictors of the treatment efficacy of immune checkpoint inhibitors for hepatocellular carcinoma (HCC) are unknown. This retrospective study enrolled 87 consecutive patients with unresectable HCC from May 2017 to December 2019 at two hospitals. Of the 87 patients, 7, 9, 60, and 11 patients had Barcelona Clinic Liver Cancer stages A, B, C, and D, respectively, and 45, 30, and 10 patients were Child-Pugh class A, B, and C, respectively. The median injection numbers of nivolumab and treatment duration were 6 (3-8) and 2.53 (1.47-4.23) months, respectively, and 64.4% of patients received combination therapy. Radiological imaging was not assessed for 25 patients. Objective response (OR) and disease control rates were 19.5% and 39.1%, respectively. A single tumor (odds ratio: 9.542, P = .015) and ≥20% decline in serum α-fetoprotein protein (AFP) levels within the first 3 months of treatment (defined as AFP response, odds ratio: 5.997, P = .042) were predictors of OR. Lack of macrovascular invasion, combination therapy, and AFP response were predictors of progression-free survival. A Cancer of the Liver Italian Program (CLIP) score of 0-2 (hazard ratio [HR]: 3.717, P = .004) and grade 1-2 immune-related adverse events (irAEs, HR: 2.217, P = .049) were predictors of overall survival (OS) in the entire cohort, and a CLIP score of 0-2 (HR: 3.257, P = .009) was a predictor of OS in evaluable patients. IrAEs ≥ grade 3 were noted in 14 patients, and three died as a result. Having a single tumor and AFP response were predictors of OR, and CLIP score was a predictor of OS.     

肿瘤标记物检测在消化系统肿瘤诊断中的价值

目的联合检测甲胎蛋白（AFP）、癌胚抗原（cEA）、糖类抗原19（CAl99）、糖类抗原125（CAl25）、糖类抗原153（CAl53）的水平，分析其在消化系统恶性肿瘤诊断中的价值。方法确诊的消化系统恶性肿瘤65例，其中肝癌15例，胃癌20例，胰腺癌6例，食管癌12例，结肠癌12例。选消化系统良性病变30例作对照，其中肝硬化8例，消化性溃疡15例，胰腺炎7例。用放射免疫分析法测定研究对象血中AFP、CEA、CAl9-9、CAl25、CAl5-3含量并分析其敏感性及准确性。结果胃癌、结肠癌患者血清CEA、CAl9-9、CAl25水平较消化系统良性病变明显升高（P〈O．01），而AFP、CA15-3差异无统计学意义（P〉0．05）；肝癌患者血清AFP、CEA和CA19-9水平显著升高（P〈0．01），而CA125、CA15-3差异无统计学意义（P〉0．05）；胰腺癌、食管癌患者血清CA15-3、CA19-9水平显著升高（P〈0．01），而AFP、CAl25差异无统计学意义（P〉0．05）。AFP、CEA、CA199、CA125和CA15-3联合检测其敏感性在肝癌为87％、胰腺癌为83％、胃癌为75％、食管癌为67％、结肠癌为58％，总敏感性达74％；准确性分别是93．6％、68．9％、78．0％、65．2％和71．3％，总准确性为73．5％。结论消化系统恶性肿瘤中用AFP、CEA、CA19-9、CAl25和CA15-3联合检测可明显提高临床诊断的敏感性和准确性。     

Biliary complications of arterial chemoembolization of hepatocellular carcinoma

Rationale and backgroundTransarterial chemoembolization (TACE) is the most frequently used palliative therapy for unresectable hepatocellular carcinoma (HCC). It is a safe and effective procedure with few major and minor complications. Rarely, biliary complications are also encountered following TACE. The goal of our study was to investigate the incidence and the presentation of biliary complications following TACE in patients with HCC.Material and methodsIn this retrospective study, data of patients with HCC who underwent TACE between June 2002 to December 2014 were obtained from the records. Their detailed information about the procedure of TACE, diagnosis of biliary complications and subsequent management details were reviewed.ResultOne hundred and sixty-eight patients with HCC underwent 305 procedures of TACE. Of these, biliary complications of various severities developed in 6 (3.6%) patients leading to an incidence of 1.9% (6/305). Minimal intrahepatic biliary dilatation (IHBD) occurred in three, biliary stricture in one and intrahepatic biloma in two patients. Supportive management was undertaken for IHBD patients while percutaneous aspiration and naso-biliary drainage was performed for the infected bilomas.ConclusionBiliary complications following TACE are infrequent. Diagnosis should be suspected clinically and confirmed with imaging. Treatment depends on the severity. Enforcing specific measures can minimize its frequency.     

Clinical Utility of Protein Induced by Vitamin K Absence-II in Patients with Hepatocellular Carcinoma

Objective: Despite moderate sensitivity, alpha fetoprotein (AFP) is widely used in screening and prognostication for hepatocellular carcinoma (HCC). The objective of the current study was to assess clinical utility of Prothrombin induced by Vitamin K absence-II (PIVKAII) in addition to AFP in patients with HCC. Methods: We retrospectively reviewed 244 patients with documented AFP, PIVKA II and dynamic imaging of the liver. Using ROC curves, cutoff values for AFP and PIVKAII for HCC detection, tumor grade and microvascular invasion (MVI) were assessed. In patients who underwent liver transplantation (LT) for HCC, survival was determined using Kaplan Meier curves. Results: The median PIVKAII in healthy living donors was 28.6mAU/ml (15.9-55). In cirrhotics, the sensitivity of an AFP cutoff of 7.6 ng/ml or PIVKAII  cutoff of 250 mAU/ml for HCC detection was 91.7% (176/192) and specificity was 62.9%(68/108) (p <0.0001). In patients with HCC, PIVKAII values were significantly elevated with tumor size > 5 cm (P < 0.0001), tumor nodules > 3(P=0.01), and macrovascular invasion(p <0.0001).  The high risk group (patients with AFP ≥ 40 ng/ml + PIVKAII ≥ 350 mAU/ml), had a sensitivity of (23/33) 69.6% and specificity of (22/22)100% for MVI (P <0.001). The estimated 3 year RFS after LT in the low risk group (AFP     

Clinicopathological characteristics and prognosis of alpha-fetoprotein positive gastric cancer in Chinese patients

Purpose: This study aimed to review the clinicopathological, histochemical, and prognostic features of Alpha-Fetoprotein (AFP) positive gastric cancer. Patients and methods: Six hundred and fifty one patients with gastric cancer who underwent gastrectomy between January 2009 and December 2012 at The First Hospital of Jilin University were enrolled in the study. Among them, 45 patients were identified as AFP positive gastric cancer. The clinicopathologic characteristics and prognosis of the AFP positive gastric cancer patients were analyzed. Results: Among the 45 AFP positive patients, serum levels of AFP were < 100 µg/L in nine patients. The histological classification of 45 patients was as follows: hepatoid type, 25 (55.6%) cases; fetal gastrointestinal type, 12 (26.7%) cases; yolk sac tumor type, 2 (4.4%) cases; and mixed type, 6 (13.3%) cases. Twenty nine (64.4%) cases were AFP positive by immunohistochemical analysis; we found no significant difference in AFP positivity and histologic type. However, the differences in the number of metastasis lymph nodes, the maximum tumor diameter, pathological stage, vascular invasion and liver metastasis between the AFP positive group and the negative group were significant. At the same T stage, the liver metastasis status of the AFP positive group was higher than that of the negative group. The AFP positive group had a much poorer prognosis than the negative group. Conclusion: AFP positive gastric cancer is associated with aggressive behavior and poorer prognosis compared to that of AFP negative gastric cancer.     

Relationship between the expression of MDR1 in hepatocellular cancer and its biological behaviors

Objective: By the detection of HBV infection, AFP and AST, the targets of biological behavior and the gene expression of multi-drug resistance gene 1 (MDR1) in hepatocellular carcinoma (HCC), we investigate characteristics of the expression of MDR1 in HCC and its relationship with HCC biological behavior. Methods: Using real-time fluorescence quantitative PCR (FQ-PCR) to detect the expressions of MDR1 in 102 samples of HCC tissue and 20 samples of non-cancerous tissue, we analyze the relationship between expressions of MDR1 and biological characteristics of HCC. Results: The expression of MDR1 in HCC is 0.55±0.27, and in normal liver tissues is 0.23±0.10, respectively. The expression in HCC is higher than it in normal liver tissue, the difference is statistically significant (P<0.05) and the difference between the expression and the HCC envelopes is statistically significant, and the expression increases along with the increase of Edmondson classification (P<0.05). HBV infection, AFP positive, the rise of AST, all these factors have positive correlations with the expression (r=0.463, 0.473, 0.299). In MDR1 expressions of HCC patients, the survival curve of the negative is higher than that of the positive, but the difference is not statistically significant. Conclusion: There are drug resistance phenomena in HCC, MDR1 expression may play an important role in primary HCC drug resistance. HBV infection can be detected as a reference indicator of HCC chemotherapy resistance, plasma levels of AFP, AST can be used as a reference index change dynamic monitoring of MDR1 expression.     

血清学指标在肝硬化合并原发性肝癌诊断中的价值

目的探讨肝硬化患者血清学指标在肝硬化并发原发性肝癌诊断中的价值。方法收集2012年1月-2013年12月入住我院消化内科的肝硬化患者89例,其中肝硬化并发原发性肝癌(PHCC)23例,单纯性肝硬化(HC)66例。根据纳入与排除标准,最终选择55例患者作为研究对象(PHCC组14例,HC组41例)。所有患者均行血常规、肝功能、电解质、凝血指标、甲胎蛋白及肝炎标志物检查。结果 2组患者流行病学资料未见明显差异,PHCC组患者血清AFP水平显著地高于HC组患者(737.89±197.21 vs 54.29±10.08,P=0.003),与HC组患者相比,PHCC组患者AST/ALT比值(1.76±1.05 vs 1.25±0.49,P=0.018)和GGT/ALT比值(6.70±10.92 vs 2.84±3.29,P=0.047)均显著增高。在肝硬化并发原发性肝癌的诊断中,AST/ALT的敏感性为64.3%,特异性73.2%(cutoff值1.43);GGT/ALT敏感性为42.9%,特异性为85.4%(cutoff值3.72)。结论肝硬化并发原发性肝癌患者血清AFP水平显著升高,联合AST/ALT比值、GGT/ALT比值检测能够提高肝硬化患者并发原发性肝癌的检出率。     

AFP、CEA检测对良恶性腹腔积液的诊断价值

目的:探讨腹腔积液患者甲胎蛋白(alpha-fetoprotein,AFP)、癌胚抗原(carcinoembryonic antigen,CEA)表达水平对良恶性腹腔积液的诊断价值。方法:回顾性分析本院97例腹腔积液患者的临床资料,按照腹腔积液性质分为良性组42例和恶性组55例,应用罗氏Cobas E601全自动电化学发光免疫分析仪检测并比较两组患者血清和腹腔积液中AFP、CEA的测定结果。结果:恶性腹腔积液组血清和腹腔积液表达均显著高于良性腹腔积液组的表达(P<0.05);恶性腹腔积液组AFP和CEA的腹腔积液/血清比值显著高于良性组(P<0.05);腹腔积液AFP和CEA的表达同血清中的表达比较具有显著性差异(P<0.05)。单项肿瘤标志物检测腹腔积液AFP检测的准确度最高,两项指标联合检测腹腔积液检测的准确度高于血清检测的准确度(P<0.05)。结论:检测腹腔积液患者AFP、CEA表达水平有助于积液性质的良恶性鉴别;腹腔积液AFP、CEA的检测对恶性腹腔积液的诊断较血清学检测更有价值;肿瘤标志物联合检测能提高恶性腹腔积液诊断的准确度。