Background and Aims
The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3–5‐cm HCC over time.
Approach and Results
From ...2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008–2019 (n = 335 in each group) and 2014–2019 (n = 257 in each group) cohorts, respectively. For cohort 2008–2019, during a median follow‐up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65–1.19, p = 0.420), and MWA was inferior to LLR regarding disease‐free survival (DFS) (HR 1.36, 95% CI 1.05–1.75, p = 0.017). For cohort 2014–2019, there was comparable OS (HR 0.85, 95% CI 0.56–1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98–1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1–4.0‐cm HCCs (HR 0.88, 95% CI 0.53–1.47, p = 0.630) and 4.1–5.0‐cm HCCs (HR 0.77, 95% CI 0.37–1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001).
Conclusions
MWA might be a first‐line alternative to LLR for solitary 3–5‐cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.
The cytomorphology of MPNST in effusion specimens is rarely described. In this paper, the detailed cytopathological and immunohistochemical characteristics of metastatic MPNST has been described in ...pleural effusion. Patients' medical history and the judicious utilization of ancillary studies contribute to ensure precise cytological diagnoses.
The cytomorphology of malignant peripheral nerve sheath tumour (MPNST) in effusion specimens can be diagnostically challenging. The author presents detailed cytopathological and immunohistochemical characteristics of a case of metastatic MPNST in pleural effusion.
Long noncoding RNAs (lncRNAs) are known to be the important regulators in cancer progression. However, the role of lncRNA FAM66C (FAM66C) is yet to be investigated in intrahepatic cholangiocarcinoma ...(ICC). This study aimed to investigate the effects and related mechanisms of FAM66C in ICC. Human ICC tissues and cell lines were collected. The expression levels of FAM66C, hsa‐miR‐23b‐3p (miR‐23b‐3p), and KCND2 were detected by qRT‐RCR. The transfection experiments were employed to measure the effect of FAM66C on cell viabilities, migration, and invasion in ICC cells by CCK‐8, transwell assays. Glycolysis was investigated by glucose consumption, lactate production and ATP levels. The dual‐luciferase reporter and RNA pull down assays were conducted as a means of confirming the interactions between FAM66C, miR‐23b‐3p, and KCND2. Furthermore, the levels of the EMT‐associated proteins (KCND2, GLUT1, PKM2, and LDHA) in ICC cells were detected by western blot. FAM66C was increased in ICC tissues and cells, increased cell viability, glycolysis, migration and invasion, and decreased apoptosis were shown in FAM66C overexpressing cells. Mechanistic analyses revealed that FAM66C regulated the downstream target gene KCND2 by sponging miR‐23b‐3p. FAM66C effect on ICC was further validated in murine xenograft assays. FAM66C knockdown cells gave rise to tumors that were smaller in size, consistent with the role of FAM66C as a promoter of in vivo tumor growth. These data revealed that FAM66C was able to drive ICC tumor progression and glycolytic activity via the miR‐23b‐3p/KCND2 axis, indicating FAM66C may be a viable target for treating ICC.
Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid compound in herbal plants, can suppress growth in hepatocellular carcinoma (HCC). However, the microRNA (miRNA) expression profiles that ...are influenced by wogonin have not been thoroughly described. To explore the novel miRNAs and the biological mechanism underlying the effect of wogonin on HCC cells. The effect of wogonin on Huh7 cell growth was assessed both in vitro and in vivo. The expression profiles of miRNAs were obtained by small RNA sequencing. Luciferase reporter experiment and bioinformatics analysis were conducted to determine whether tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) can bind to miR-27b-5p. Effects of the ectopic expression of YWHAZ and miR-27b-5p on Huh7 cells proliferation and apoptosis were evaluated. Furthermore, the cell cycle, apoptosis and multiple signaling pathway-related molecules were detected by Western blot analysis. Wogonin substantially inhibited the growth of Huh7 cells both in vitro and in vivo. Seventy miRNAs exhibited greater than twofold changes in wogonin-treated cells. Upregulation of miR-27b-5p inhibited Huh7 cell proliferation, and the anticancer effect of wogonin was reversed after miR-27b-5p knockdown. miR-27b-5p directly targeted YWHAZ in HCC cells. The proliferation-inhibiting effect of miR-27b-5p was revoked by YWHAZ overexpression. Meanwhile, inhibition of HCC growth was achieved by downregulating YWHAZ. Wogonin exerted antitumor activity through multiple signaling molecules, such as focal adhesion kinase, protein kinase B, mammalian target of rapamycin and molecules related to apoptosis and cell cycle by upregulating miR-27b-5p and downregulating YWHAZ. Our findings suggest that miR-27b-5p/YWHAZ axis contributes to the inhibitory effect of wogonin in HCC by targeting related genes and multiple signaling pathways.
Background
CyberKnife stereotactic body radiation therapy (CK-SBRT) has been applied to hepatocellular carcinoma (HCC) patients for several years. The study aim was to compare the efficacy of hepatic ...resection (HR) and CK-SBRT in naive small hepatocellular carcinoma (sHCC) patients with hepatitis virus-related cirrhosis using a 5-year follow-up study.
Materials and methods
This retrospective cohort study included 317 naive sHCC patients (246 men and 71 women) with hepatitis B or C virus cirrhosis who were treated with HR (
n
= 195) or CK-SBRT (
n
= 122) from November 2011 to December 2015. Cumulative overall survival (OS) rates and progression-free survival (PFS) rates were calculated using Kaplan–Meier method.
Results
After the propensity score-matched analysis, 104 patients were selected from each group for further analysis. The 1-, 2-, 3-, and 5-year OS rates were 96.2%, 89.4%, 85.5% and 70.7% in the HR group and 93.3%, 89.4%, 83.7% and 71.0% in the CK-SBRT group, respectively. The 1-, 2-, 3-, and 5-year PFS rates were 78.8%, 64.3%, 56.4% and 47.3% in the HR group and 84.5%, 67.8%, 58.9% and 49.0% in the CK-SBRT group, respectively. No significant difference was found between the two groups in the OS and PFS rates (OS,
p
= 0.673; PFS,
p
= 0.350). No death occurred due to the toxicity or complications of HR or CK-SBRT.
Conclusion
CK-SBRT could be an effective alternative to HR for sHCC naive patients with hepatitis-related cirrhosis, especially if patients have higher CP scores and lower PLT counts. PLT counts should be factored into survival evaluation of HCC treatment.
Background & Aims To investigate diagnostic and prognostic values of sulfite oxidase (SUOX) in patients with hepatocellular carcinoma (HCC) who underwent curative resection. Methods We investigated ...immunohistochemically the expression dynamics of SUOX, aldo-ketoreductase family 1 member B10 (AKR1B10) and CD34 at different stages of HCC. The differential diagnostic performance of three markers or their combinations in high-grade dysplastic nodules (HGDNs) and well-differentiated small HCC (WD-sHCC) were investigated by logistic regression models and validated in an independent testing set. Overall survival (OS) and time to recurrence (TTR) were evaluated in 300 patients with HCC as the testing cohort, and validated in 198 patients with HCC. Results SUOX was decreased and AKR1B10 and CD34 were increased with the stepwise progression of hepatocarcinogenesis. For differential diagnosis of WD-sHCC from HGDNs, the sensitivity and specificity of the SUOX + AKR1B10 + CD34 combination for WD-sHCC detection were 93.8% and 95.2%, respectively, and overall accuracy was much higher than any of the three individual markers and two marker combinations. In addition, SUOX, but not AKR1B10 and CD34, was an independent prognostic factor for OS and TTR, and showed better correlation with OS and TTR if combined with serum α-fetoprotein (AFP) for both the testing and validation cohorts. Conclusions SUOX + AKR1B10 + CD34 combination could make a substantial contribution to hepatic immunopathological diagnosis to distinguish WD-sHCC from HGDNs. Meanwhile, SUOX combined with serum AFP may predict postoperative outcome and tumor recurrence risk.
Intraductal papillary neoplasm of bile duct (IPNB) is characterized by a spectrum of diseases ranging from low-grade intraepithelial neoplasia to invasive carcinoma. In the present study, we aimed to ...investigate immunophenotypic features and KRAS mutations in relation to pathological subtypes and grades in Chinese patients with IPNBs. A total of 46 patients with IPNBs and 11 invasive adenocarcinomas arising in IPNBs (invasive IPNBs) were enrolled and clinicopathological data were analyzed. It was found that CK7 was expressed in 42 of the 46 neoplastic lesions. HepPar1 was expressed in 11 of the 46 noninvasive IPNBs, but not in invasive IPNBs. Additionally, CK19 was frequently expressed in both noninvasive IPNBs and invasive IPNBs. The intestinal-type IPNBs had a significantly higher percentage of MUC2 expression relative to the pancreaticobiliary (P=0.015) and gastric-type IPNBs (P<0.001). High-grade IPNBs and invasive IPNBs showed increased expression of cyclin D1, Ki-67, p53, mCEA, and CA19-9. The rate of KRAS mutation was significantly higher in high-grade IPNBs (P=0.001) and invasive IPNBs (P=0.006) than that in low- to intermediate-grade IPNBs. Additionally, KRAS mutation was significantly associated with tumor size, and Ki-67 expression. In conclusion, the expression of cyclin D, Ki-67, p53, mCEA and CA19-9 and KRAS mutation status are significantly correlated with histological grades of IPNBs.
Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and ...epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression.
Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ
test or the Fisher exact test (categorical variables) and independent group t test or Mann-Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19.
The mean incubation was 8.67 (95% confidence interval, 6.78-10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86-12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8
T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4
T cells, and CD8
T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8
lymphocyte count in pneumonia patients did not recover when discharged.
Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8
cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.
AIM：To evaluate the results of hepatic resection with ex-situ hypothermic perfusion and without veno-venous bypass.METHODS：In 3 patients with liver tumor,the degree of the inferior vena cava and/or ...main hepatic vein involvement was verified when the liver was dissociated in the operation.It was impossible to resect the tumors by the routine hepatectomy,so the patients underwent ex-situ liver surgery,vein cava replacement and hepatic autotransplantation without veno-venous bypass.All surgical procedures were carried out or supervised by a senior surgeon.A retrospective analysis was performed for the prospectively collected data from patients with liver tumor undergoing ex-situ liver surgery,vein cava replacement and hepatic autotransplantation without veno-venous bypass.We also compared our data with the 9 cases of Pichlmayr＇s group.RESULTS：Three patients with liver tumor were analysed.The first case was a 60-year-old female with a huge haemangioma located in S1,S4,S5,S6,S7 and S8 of liver;the second was a 64-year-old man with cholangiocarcinoma in S1,S2,S3 and S4 and the third one was a 55-year-old man with a huge cholangiocarcinoma in S1,S5,S7 and S8.The operation time for the three patients were 6.6,6.4 and 7.3 h,respectively.The anhepatic phases were 3.8,2.8 and 4.0 h.The volume of blood loss during operation were 1200,3100,2000 mL in the three patients,respectively.The survival periods without recurrence were 22 and 17 mo in the first two cases.As for the third case complicated with postoperative hepatic vein outflow obstruction,emergency hepatic vein outflow extending operation and assistant living donor liver transplantation were performed the next day,and finally died of liver and renal failure on the third day.Operation time（6.7 ± 0.47 h vs 13.7 ± 2.6 h） and anhepatic phase（3.5 ± 0.64 h vs 5.7 ± 1.7 h） were compared between Pichlmayr＇s group and our series（P = 0.78）.CONCLUSION：Ex-situ liver resection and liver autotransplantation has shown a potential for treatment of complicated hepatic neoplasms that are unresectable by traditional procedures.
Pathological consultation on intraoperative frozen sections plays a crucial role in the management of patients undergoing surgical therapy, and is also a key indicator for quality assurance in ...anatomical pathology. This study aimed to evaluate the diagnostic accuracy and technical quality of frozen sections in detecting hepatobiliary lesions with malignant potential.
A retrospective database review was performed for 1208 cases intraoperative pathology consultation who underwent hepatobiliary lesions resection at our institution from 2016 to 2020. The intraoperative consultation cases during a 5-year period were reviewed and analyzed, including the measurement of the diagnostic accuracy and turnaround time of frozen sections, the reasons for discrepancies, and the rates of discordance and deferral.
In this study, we confirmed that the overall accuracy, sensitivity and specificity were 95.3 %, 96.3 % and 96.6 %, respectively, in distinguishing benign from malignant lesions. The rates of deferred and discordant diagnoses were 2.57 % and 2.2 %, respectively. The overall frozen section turnaround time was 22.1 min. The most common cause of deferred and discordant was poor section quality, the lesion of bile duct margin on the frozen section, misinterpretation of difficult and complicated cases, etc.
This study confirms that the intraoperative frozen sections can serve as a rapid, accurate and robust method for the pathological diagnosis of suspected hepatobiliary lesions. However, it should be noted that some poor technical problems, pathological assessment of tumor margin and difficult cases are the most frequently causes of deferred and discordant interpretations.
•Intraoperative frozen sections can serve as a rapid, accurate method for intraoperative diagnosis of hepatobiliary lesions•Pathologists should pay close attention to some pitfalls of discordant diagnoses
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