Circulating tumour cell counts and ultrasomics signature-based nomogram for preoperative prediction of early recurrence of hepatocellular carcinoma after radical treatment.

METHODS: Between December 2017 and December 2018, 153 HCC patients (134 males and 19 females; mean age, 56.0 ± 10.2 years; range, 28-78 years) treated with radical therapy were enrolled in our retrospective study and were divided into a training cohort (n = 107) and a validation cohort (n = 46). All patients underwent preoperative CTC tests and CEUS examinations before treatment. The ultrasomics signature was extracted and built from CEUS images. Univariate and multivariate logistic regression analyses were used to identify the significant variables related to ER, which were then combined to build a predictive nomogram. The performance of the nomogram was evaluated by its discrimination, calibration and clinical utility. The predictive model was further evaluated in the internal validation cohort. RESULTS: HBV DNA, serum AFP level, CTC status, tumour size and ultrasomics score were identified as independent predictors associated with ER (all p < 0.05). Multivariable logistic regression analysis showed that the CTC status (OR = 7.02 [95% CI, 2.07 to 28.38], p = 0.003) and ultrasomics score (OR = 148.65 [95% CI, 25.49 to 1741.72], p < 0.001) were independent risk factors for ER. The nomogram based on ultrasomics score, CTC status, serum AFP level and tumour size exhibited C-indexes of 0.933 (95% CI, 0.878 to 0.988) and 0.910 (95% CI, 0.765 to 1.055) in the training and validation cohorts, respectively, fitting well in calibration curves. Decision curve analysis further confirmed the clinical usefulness of the nomogram. CONCLUSION: The nomogram incorporating CTC, ultrasomics features and independent clinical risk factors achieved satisfactory preoperative prediction of ER in HCC patients after radical treatment. ADVANCES IN KNOWLEDGE: 1. CTC status and ultrasomics score were identified as independent predictors associated with ER of HCC after radical treatment. 2. The nomogram constructed by ultrasomics score generated by 17 ultrasomics features, combined with CTCs and independent clinical risk factors such as AFP and tumour size. 3. The nomogram exhibited satisfactory discriminative power, and could be clinically useful in the preoperative prediction of ER after radical treatment in HCC patients.

Preoperative prognostic value of alfa-fetoprotein density in patients with hepatocellular carcinoma undergoing radiofrequency ablation.

OBJECTIVES: To examine the prognostic value of preoperative alfa-fetoprotein (AFP) density and other clinical factors in patients undergoing percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS: From January 2010 to December 2018, a total of 543 patients undergoing RFA for HCC meeting the Milan criteria were included at our institution. AFP density was calculated as absolute AFP pre-ablation divided by the total volume of all HCC lesions. The survival rates according to AFP density were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazards regression analyses were used to assess predictors of overall survival (OS) and progression-free survival (PFS). RESULTS: The Kaplan-Meier 1-, 3-, and 5-year OS rates were 98.8%, 88.5%, and 70.4%, respectively, for the low AFP density group, and 98.3%, 74.9%, and 49.4%, respectively, for the high AFP density group. The corresponding PFS rates were 78.9%, 56.7%, and 40.9% (low AFP density group), and 63.6%, 40.8%, and 27.5% (high AFP density group). High AFP density was associated with significantly reduced PFS and OS (both p < 0.001). Multivariate analysis suggested that AFP density was a predictor of OS and PFS. CONCLUSIONS: Serum AFP density may serve as a promising predictor of survival in patients with HCC undergoing RFA. High AFP density could identify patients who might be prone to recurrence or progression and need close surveillance.

Percutaneous thermal ablation of hepatic tumors: local control efficacy and risk factors for artificial ascites failure.

OBJECTIVE: To investigate the risk factors affecting the technical failure of artificial ascites (AA) formation and to evaluate the local control efficacy of percutaneous thermal ablation assisted by the AA for hepatic tumors. METHODS: A total of 341 patients with 362 hepatic tumors who underwent thermal ablation assisted by AA were reviewed retrospectively. The technical success of AA, the volume of liquid, and local efficacy after ablation were assessed. Predictive factors for the technical failure of AA formation and local tumor progression (LTP) were analyzed using univariate and multivariate analysis. RESULTS: The technical success rate of AA formation was 81.8% (296/362). The amount of fluid was higher when the tumor was located in the left lobe of the liver than when it was located in the right lobe (median 950 ml versus 700 ml, p < 0.001). Previous hepatic resection (OR: 12.63, 95% CI: 2.93-54.45, p < 0.001), ablation (OR: 6.48, 95% CI: 1.36-30.92, p = 0.019) and upper-abdomen surgery (OR: 11.34, 95% CI: 1.96-65.67, p = 0.007) were the independent risk factors of AA failure. In the AA success group, the complete ablation rate was higher and the LTP rate was lower than that in the AA failure group (98.7 versus 92.4%, p = 0.012; 8.8 versus 21.2%, p = 0.004). Multivariate analysis identified AA failure (p = 0.004), tumor size (>3.0 cm) (p = 0.002) and metastatic liver tumor (p = 0.008) as independent risk factors for LTP. CONCLUSION: History of hepatic resection, ablation and upper abdomen surgery were significant predictive factors affecting the technical failure of AA formation. Successful introduction of AA before thermal ablation can achieve better local tumor control efficacy.

Treatment effect of radiofrequency ablation versus liver transplantation and surgical resection for hepatocellular carcinoma within Milan criteria: a population-based study.

OBJECTIVES: Restricted mean survival time (RMST) has been increasingly used to assess the treatment effect. We aimed to evaluate a treatment effect of radiofrequency ablation (RFA) versus liver transplantation (LT) and surgical resection (SR) for hepatocellular carcinoma (HCC) within Milan criteria by using an adjusted RMST. METHODS: A total of 7,218 HCC patients (RFA, 3,327; LT, 2,332; SR 1,523) within Milan criteria were eligible for this retrospectively study. The RMST using inverse probability of treatment weighting (IPTW) adjustment were applied to estimate the treatment effect between RFA and LT, RFA, and SR groups. RESULTS: The 3-, 5-, and 10-year IPTW-adjusted difference in RMST of OS for LT over RFA were + 4.5, + 12.4, and + 36.3 months, respectively. For SR versus RFA group, the survival benefit was + 2.3, + 6.1, and + 15.8 months at 3, 5, and 10 years, respectively. But the incremental survival benefit of SR over RFA was only half than that of LT over RFA. In the subgroup of solitary tumor ≤ 2 cm, the adjusted RMST of RFA versus SR was comparable with no statistical differences. Beyond that, in comparison with RFA, a notably greater efficacy of LT and SR was consistently across all subgroups with solitary HCC > 2.0 cm, AFP positive or negative, and fibrosis score 0-4 or 5-6. CONCLUSIONS: RMST provides a measure of absolute survival benefit at a specific time point. Using IPTW-adjusted RMST, we showed that the incremental survival benefit of SR over RFA was about half than that of LT over RFA. KEY POINTS: • The restricted mean survival time offers an intuitive, clinically meaningful interpretation to quantify the treatment effect than the hazard ratio. • Liver transplantation and surgical resection provided better overall survival compared to radiofrequency ablation for HCC patients within Milan criteria, but RFA and SR provide equivalent long-term overall survival for solitary HCC ≤ 2 cm. • The incremental survival benefit of surgical resection over radiofrequency ablation was only half than that of liver transplantation over radiofrequency ablation.

Lesion outline and thermal field distribution of ablative in vitro experiments in myocardia: comparison of radiofrequency and laser ablation.

OBJECTIVES: To explore the lesion outline and thermal field distribution of radiofrequency ablation (RFA) and laser ablation (LA) in myocardial ablation in vitro. MATERIALS AND METHODS: Twenty-four fresh porcine hearts were ablated with RFA or LA in vitro. The radiofrequency electrode or laser fiber and two parallel thermocouple probes were inserted into the myocardium under ultrasound guidance. The output power for RFA was 20 W/s and for LA was 5 W/s, and the total thermal energies were 1200 J, 2400 J, 3600 J, and 4800 J. The range of ablation lesions was measured, and temperature data were recorded simultaneously. RESULTS: All coagulation zones were ellipsoidal with clear boundaries. The center of LA was carbonized more obviously than that of RFA. With the accumulation of thermal energy and the extended time, all the ablation lesions induced by both RFA and LA were enlarged. By comparing the increase in thermal energy between the two groups, both the short-axis diameter and the volume change showed significant differences between the 1200 J and 3600 J groups and between the 2400 J and 4800 J groups (all P < 0.05). Both the short-axis diameter and the volume of the coagulation necrosis zone formed by LA were always larger than those of RFA at the same accumulated thermal energy. The temperatures of the two thermocouple probes increased with each energy increment. At the same accumulated energy, the temperature of LA was much higher than that of RFA at the same point. The initial temperature increase at 0.5 cm of LA was rapid. The temperature reached 43 °C and the accumulated energy reached 1200 J after approximately 4 min. After that the temperature increased at a slower rate to 70  C. For the RFA at the point of 0.5 cm, the initial temperature increased rapidly to 30 °C with the same accumulated energy of 1200 J after only 1 min. In the range of 4800 J of accumulated thermal energy, only the temperature of LA at the point of 0.5 cm exceeded 60 °C when the energy reached approximately 3000 J. CONCLUSIONS: Both RFA and LA were shown to be reliable methods for myocardial ablation. The lesion outline and thermal field distribution of RFA and LA should be considered when performing thermal ablation in the intramyocardial septum during hypertrophic obstructive cardiomyopathy.

Thermal ablation versus hepatic resection for the treatment of liver metastases from gastrointestinal stromal tumors: a retrospective study.

Objective: The study aimed to compare effectiveness and safety of thermal ablation and hepatic resection in patients with liver metastases of gastrointestinal stromal tumors (GISTs).Method: A total of 55 patients (27 in the ablation group and 28 in the surgery group) with liver metastases were included. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier's survival estimate curves. Univariate and multivariate regression analyses were carried out to identify potential prognostic factors.Results: The median OS was 102.0 months in the ablation group and 117.0 months in the surgery group (p = .875). The 1-, 3- and 5-year OS rates were 100%, 88.9% and 74.1% in the ablation group and 92.8%, 82.1% and 78.6% in the surgery group, respectively. The 1-, 3- and 5-year PFS rates were 48.1%, 25.9% and 18.5% in the ablation group and 67.8%, 64.3% and 64.3% in the surgery group, respectively. Multivariate analysis showed that preoperative tyrosine kinase inhibitor (TKI) treatment (progressive disease, PD) (HR, 13.985; 95% CI, 1.791-109.187; p = .012) was the only significant independent prognostic factor for OS. Tumor number (HR, 1.318; 95% CI, 1.021-1.702; p = .034) was identified as an independent predictor for PFS in multivariate analysis. There were fewer postoperative complications (18.5% vs. 78.6%, p = .001) and shorter lengths of hospital stay (8.0 vs. 16.5 days, p = .001) in the ablation group.Conclusion: Compared with resection, thermal ablation offered comparable OS for liver metastases of GISTs. Furthermore, thermal ablation had the advantages of fewer complications and shorter lengths of hospital stay.

Application of contrast-enhanced ultrasonography for large cell neuroendocrine carcinoma in the urinary bladder: a case report.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is an uncommon malignant bladder tumor, and the overall prognosis is poor. Contrast-enhanced ultrasound (CEUS) provides a new effective modality for tumor detection and diagnosis. CASE PRESENTATION: A 30-year-old man complained of repeated painless gross haematuria for half a month. Conventional ultrasound demonstrated a hypoechoic solitary lesion with hyperechoic margins measuring 3.4 × 3.1 cm in the anterior wall of the bladder. Superb microvascular imaging (SMI) showed a strong flow signal in the mass. CEUS revealed that the lesion was characterized by hyper-enhancement in the early phase and hypo-enhancement in the late phase. The entire bladder wall was disrupted by homogeneous hyper-enhanced tumor tissue on CEUS. Time-intensity curves (TICs) showed a rapid wash-in with a high maximum signal intensity (SI) and quick wash-out. Finally, partial cystectomy was performed and the pathological examination confirmed the diagnosis of LCNEC with invasion into the whole layer of the bladder wall. CONCLUSION: This case suggested that CEUS was a valuable imaging method to detect and diagnose LCNEC in the bladder, and that CEUS can provide information related to the depth of wall invasion and the microvasculature.

[Influence of warming needling technique on gastrointestinal reaction after hyperthermic intrape-ritoneal chemotherapy in patients with postoperation of colon cancer].

OBJECTIVE: To observe the effect of warming needling therapy on gastrointestinal reaction after hyperthermic intraperitoneal chemotherapy (HIPEC) in patients of spleen and stomach deficiency syndrome after colon cancer surgery. METHODS: A total of 120 cases of HIPEC were randomized into observation group and control group, 60 cases in each. The patients of the two groups all received HIPEC. In the observation group, 1 h before HIPEC, warming needling technique was applied to Zusanli (ST36), Sanyinjiao (SP6) and Yinlingquan (SP9) and the even-needing technique of acupuncture was applied to Neiguan (PC6) for 30 min, and then the intravenous injection with Ondansetron was given 30 min before HIPEC. In the control group, The intravenous injection with Ondansetron was given 30 min before HIPEC. In the two groups, the changes in nausea, vomiting, abdominal distention, diarrhea, total bilirubin (TB), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and KPS score, as well as the average hospitalization length of stay were observed. RESULTS: The total effective rates in the treatment of nausea, vomiting, abdominal distention and diarrhea were 91.67%(55/60), 93.33%(56/60), 80.00%(48/60) and 88.33%(53/60) in the observation group and were 78.33%(47/60), 78.33%(47/60), 63.33%(38/60) and 70.00%(42/60) in the control group respectively, and the total effective rate in the treatment of gastrointestinal reaction of HIPEC in the observation group was obviously higher than that in the control group(P<0.05). The KPS score and curative effect in the observation group was obviously higher than those of the control group(P<0.05), and the average hospitalization length of stay in the observation group was obviously reduced as compared with the control group (P<0.05). There were no significant differences in serum TB, ALT and ALP contents between the two groups after treatment (P>0.05). CONCLUSION: The warming needling technique of acupuncture and moxibustion alleviates the gastrointestinal reaction, improves KPS score and reduces the hospitalization length of stay in HIPEC patients after the surgery of colon cancer and differentiated as the spleen and stomach deficiency in traditional Chinese medicine.

Sorafenib versus hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The clinical benefits and safety of Sorafenib versus hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) are inconsistent in some studies. This meta-analysis aims to evaluate the effectiveness and safety of Sorafenib versus HAIC for patients with advanced HCC. METHODS: An electronic search was performed from PubMed, Embase, the Cochrane Library and Web of Science to identify comparative studies evaluating Sorafenib versus HAIC for HCC. Objective response rate, disease control rate, overall survival, progression-free survival and adverse events were evaluated using meta-analytical techniques. RESULTS: Fourteen retrospective studies with 1779 patients (Sorafenib = 773, HAIC = 1006) were included in the meta-analysis. HAIC delivered favorable outcomes in objective response rate (odds ratio 0.13; 95%CI, 0.07-0.24) and disease control rate (odds ratio 0.48; 95%CI 0.26-0.87) assessed by the Response Evaluation Criteria in Solid Tumors. The pooled hazard ratio for overall survival at 0.60 (95% CI 0.39-0.91) and the pooled hazard ratio for progression-free survival at 0.69(95% CI 0.51-0.95), further indicates that HAIC was superior to Sorafenib. There was a higher incidence of adverse events, including hypertension (odds ratio 13.07; 95% CI 2.37-71.67), fatigue (odds ratio 6.72; 95% CI 2.14-21.13), dermatological disorders (odds ratio 15.87; 95% CI 5.58-45.16) and gastrointestinal disorders (odds ratio 3.20; 95% CI 2.02-5.07) in patients receiving Sorafenib than in those receiving HAIC. CONCLUSION: HAIC offers a safe and effective alternative to Sorafenib with better tumor response and longer overall survival and progression-free survival, hence HAIC should be recommended for the patients with advanced HCC.

Intra-Cavitary Contrast-Enhanced Ultrasound: A Novel Radiation-Free Method for Detecting Abscess-Associated Penetrating Disease in Crohn's Disease.

BACKGROUND AND AIM: Penetrating disease is a common condition complicating Crohn's disease [CD]. Establishing the presence of a fistula and the anatomical definition of the fistulous tracts are essential for deciding on appropriate treatment strategies. We aimed to assess the diagnostic accuracy of intra-cavitary contrast-enhanced ultrasound [IC-CEUS] for the detection of a fistulous tract associated with abscesses in CD patients. METHODS: In this prospective cohort study, consecutive CD patients suspected of having an intra-abdominal abscess, who were referred for US-guided aspiration were recruited. IC-CEUS was performed by injecting diluted contrast agent [SonoVue] into the abscess cavity immediately following the ultrasound-guided needle abscess aspiration and drainage. The diagnostic accuracy of IC-CEUS in demonstrating the presence of fistulous tracts was compared with that of computed tomography enterography/magnetic resonance enterography [CTE/MRE], using surgical and gross pathological findings as the reference standard. RESULTS: Thirty-one patients who underwent IC-CEUS and subsequent surgery were included in the final analysis. IC-CEUS demonstrated fistulous/sinus tracts in 26 of 31 participants with a sensitivity and specificity of 86.7 % (95% confidence interval [CI], 68.4-95.6%) and 100% [95% CI, 5.5-100.0%], respectively. Moreover, IC-CEUS correctly demonstrated fistulous/sinus tracts in 13 participants without delineation of fistulous/sinus tracts on CTE/MRE. Combining IC-CEUS and CTE/MRE, the fistula/sinus tract was clearly demonstrated in 29 patients [93.5%, 29/31]. The mean duration of the IC-CEUS procedure was 8.6 min [range 5.0-12.0]. No severe adverse events occurred during the IC-CEUS procedure. CONCLUSION: In this pilot study, IC-CEUS accurately delineated the anatomical definition of fistulous/sinus tracts associated with intra-abdominal abscesses in CD patients. As a radiation-free and safe technique, IC-CEUS may be used as an alternative/adjunctive method to CTE/MRE for detecting penetrating disease in patients with CD.

Multiple cavernous hemangiomas of the lung and liver mimicking metastasis: A case report and literature review.

RATIONALE: Cavernous hemangiomas are benign vascular malformations that usually involve the skin, subcutaneous tissue, and liver. Described herein was multiple masses in the lung and liver mimicking metastasis, which was proved to be cavernous hemangiomas histologically. PATIENT CONCERNS: A 78-year-old man with complaint of dizziness for 3 days was referred to the local hospital for medical attention. DIAGNOSES: Multiple masses in the lung and liver was diagnosed pathologically as cavernous hemangioma. INTERVENTIONS: Because of the benign pathological characteristic and multiple distribution, no treatment except some symptomatic treatment for dizziness was administered. OUTCOME: After more than 2 years of follow-up visits, the patient had no apparent symptoms and was healthy. LESSONS: Proper diagnosis of multiple cavernous hemangiomas is essential. The final diagnosis depends on the pathology results. The most appropriate management is follow-up. Surgical treatment is suitable for large or symptomatic lesions which can result in satisfactory prognoses.

[Effect of fracture of lower limbs with hemorrhage on myocardial injury and its mechanism in rats].

OBJECTIVES: To test whether myocardial apoptosis can be induced by traumatic fracture of lower limbs with hemorrhage, in order to lay a foundation of myocardial injury after traumatic fracture for the follow-up study. METHODS: Twenty SD rats were randomly divided into two groups, i. e. control group and trauma group(n=10). A rat model of traumatic hemorrhage was establish, and a traumatic model of the original generation of myocardial cell culture was constructed in vitro. The level of interleukin-2(IL-2),IL-6,IL-10 and tumor necrosis factor-α(TNF-α) in rat serum was detected by ELISA at 0, 1, 2, 4, 8, 12, 16, 24 and 48 hour to find the most significant point. The pathological cardiac injury in rats was observed by HE staining under a microscope, and the apoptosis of cultured cardiomyocyte in vitro was detected by TUNEL methods. The expressions of apoptosis gene,(Bcl-2) and Bax, in myocardium of rat and cultured cardiomyocyte in vitro were detected by Western blot and RT-PCR. RESULTS: At the 4th hour after trauma, IL-6 and IL-10 in the serum of rats reached its highest, IL-2 reached its lowest at the 8th hour after trauma, and TNF-αreached its highest at 1 hour after trauma, then all recovered to their normol level gradually. Myocardial HE staining indicated that cardiomyocyte was swelling, disordered derangement, inflammatory cell infiltrated; a large number of myocardial cell nuclei was dyedbrown in TUNEL test which proved that the apoptosis index increased (P<0.05). Western blot and RT-PCR results showed that the expression of pro-apoptotic gene Bax was up-regulated (P<0. 05), while expression of anti apoptosis gene Bcl-2 down-regulated (P<0.05). CONCLUSIONS: The myocardial apoptosis can be induced by traumatic fracture of lower limbs with hemorrhage in rats, and then lead to myocardial injury.

Diagnostic nomogram for gallbladder wall thickening mimicking malignancy: using contrast-enhanced ultrasonography or multi-detector computed tomography?

OBJECTIVES: To establish a diagnostic nomogram using contrast-enhanced ultrasonography (CEUS) in gallbladder wall thickening mimicking malignancy and compare with multi-detector computed tomography (MDCT). METHODS: Seventy-two patients with gallbladder wall thickening on B-mode ultrasonography (BUS) were examined by CEUS to develop independent predictors for diagnosing gallbladder carcinoma. Among the 72 cases, 48 patients underwent both CEUS and MDCT. The diagnostic performances of different sets of CEUS criteria and MDCT were compared. A prediction model of malignancy using CEUS was developed. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. RESULTS: Multivariate logistic regression indicated that inhomogeneous enhancement in the arterial phase was the strongest independent predictor of malignancy (odds ratio, OR 51.162), followed by interrupted inner layer (OR 19.788), washout time ≤40 s (OR 16.686), and wall thickness >1.6 cm (OR 3.019), which were all selected into the nomogram. Combined with the above significant features, the diagnostic performance of CEUS (AUC = 0.917) was higher than that of MDCT (AUC = 0.788, P = 0.070). The predictive model using CEUS showed good discrimination, with a concordance index of 0.974 (0.950 through internal validation), and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: CEUS could accurately differentiate between malignant and benign gallbladder wall thickening with equivalent efficacy compared to MDCT. The proposed nomogram could be conveniently used to facilitate the preoperative individualized prediction of malignancy in patients with gallbladder wall thickening.

Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth.

FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam20A-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM20A. By breeding K14-Cre mice with Fam20A(flox/flox) mice, we created K14-Cre;Fam20A(flox/flox) (conditional knock out, cKO) mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography, histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam20A-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice. The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.

Sorafenib suppresses the rapid progress of hepatocellular carcinoma after insufficient radiofrequency ablation therapy: an experiment in vivo.

BACKGROUND: Radiofrequency ablation (RFA) is a widely applied treatment for hepatocellular carcinoma (HCC), but insufficient RFA can promote rapid progression of the residual tumor through the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) pathway. Although sorafenib has been successfully applied to advanced HCC, the use of sorafenib in residual tumor cells after RFA has rarely been tested. PURPOSE: To evaluate the potential role of sorafenib as an adjunct to RFA to reduce the recurrence rate after insufficient RFA. MATERIAL AND METHODS: Xenograft tumors of SMMC 7721 were created by subcutaneously inoculating nude mice with hepatoma cells (5 × 10(6) cells per mouse). Fourteen days after inoculation, all mice were divided into three groups (control group [sham puncture], RFA group, and RFA combined with sorafenib treatment group) with six mice in each group. Each group was given a different treatment procedure. After treatment, the volume of the tumors was calculated from the resected specimens. The mRNA and protein expression of HIF-1α and VEGFA was quantified by real-time PCR and immunohistochemistry analysis. The micro-vessel density (MVD) was determined by CD34 immunohistochemistry. RESULTS: Real-time PCR and immunohistochemistry analysis showed that, compared to the RFA group, HIF-1α and VEGFA expression were significantly decreased in the group that received RFA combined with sorafenib treatment (P < 0.05). By comparing the control group with the RFA group, we found that insufficient RFA promoted HIF-1α and VEGFA expression (P < 0.05). Similar results were obtained for MVD expression. Additionally, the combination of RFA with sorafenib therapy resulted in a synergistic reduction in tumor growth compared to insufficient RFA and sham puncture (P < 0.05). CONCLUSION: Sorafenib was able to inhibit the expression of HIF-1α and VEGFA, and sorafenib was able to increase time to recurrence when used as an adjunct to RFA.

Differential diagnosis between benign and malignant gallbladder diseases with real-time contrast-enhanced ultrasound.

The value of contrast-enhanced ultrasound (CEUS) in differential diagnosis between benign and malignant gallbladder diseases was investigated. Thirty-three patients with gallbladder carcinomas and 47 with benign gallbladder diseases underwent CEUS. The lesion enhancement time, enhancement extent, pattern, dynamic change of enhancement and the intactness of gallbladder wall were evaluated. In the early phase at CEUS, hyper-, iso-, hypo-, and non-enhancement were found in 84.8% (28/33), 9.1% (3/33), 6.1% (2/33), and 0% (0/33) of gallbladder carcinomas, and 70.3% (33/47), 17.0% (8/47), 2.1% (1/47), and 10.6% (5/47) of benign diseases (p > 0.05). Hyper-enhancement or iso-enhancement in the early phase and then fading out to hypo-enhancement within 35 s after contrast agent administration was found in 90.9% (30/33) of carcinomas and 17.0% (8/47) of benign lesions (p < 0.001). Destruction of the gallbladder wall intactness was absent in benign diseases, whereas it was present in 28 (84.8%) of the 33 carcinomas (p < 0.001). Destruction of gallbladder wall intactness on CEUS yielded the highest capability in differential diagnosis, with sensitivity, specificity, and Youden's index of 84.8% (28/33), 100% (47/47), and 0.85, respectively. Conventional US made correct original diagnoses in 55 (68.8%) patients, whereas CEUS in 77 (96.3%). Thus, CEUS is useful in differential diagnosis between malignant and benign gallbladder diseases.

Intrahepatic cholangiocarcinoma and hepatocellular carcinoma: differential diagnosis with contrast-enhanced ultrasound.

OBJECTIVE: We assessed the usefulness of contrast-enhanced ultrasound (CEUS) in the differentiation of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). METHODS: The CEUS enhancement patterns of 50 ICCs were retrospectively analysed and compared with 50 HCCs. Two readers independently reviewed the baseline ultrasound (BUS) and CEUS images and the diagnostic performances were evaluated by receiver operating characteristic (ROC) analysis. Time-intensity curves (TIC) were plotted for quantification analysis. RESULTS: In the arterial phase, peripheral rim-like hyperenhancement, heterogeneous hyperenhancement, homogeneous hyperenhancement and heterogeneous hypoenhancement were found in 25, 10, 3 and 12 of the ICCs versus 2, 29, 19 and 0 of the HCCs (P < 0.001), respectively. The diagnostic performance of both readers in terms of the area under the ROC curve (0.745 vs. 0.933 for reader 1, and 0.803 vs. 0.911 for reader 2), sensitivity (28% vs. 90%, and 44% vs. 82%) and accuracy (64% vs. 90%, and 71% vs. 90%) improved significantly after CEUS (all P < 0.05). The interobserver agreement increased from kappa = 0.575 at BUS to kappa = 0.720 after CEUS. TICs demonstrated that the intensities of the peripheral and central portions of the ICCs were lower than those of HCCs (both P < 0.05). CONCLUSION: CEUS improves the diagnostic performance significantly in the differentiation between ICC and HCC.

Treatment response evaluation with three-dimensional contrast-enhanced ultrasound for liver cancer after local therapies.

OBJECTIVE: To investigate the potential usefulness of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in evaluating the treatment response for liver cancer after local therapies. METHODS: A total of 107 lesions in 95 consecutive patients with liver cancer underwent local therapies and thereafter received low acoustic power 3D-CEUS examination. The LOGIQ 9 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The image quality of 3D-CEUS images was evaluated and the influence of 3D-CEUS to clinical outcome was investigated. RESULTS: The image quality of 3D-CEUS was defined as high in 102 (102/107, 95.3%) lesions and common in 5 (5/107, 4.7%) lesions. 3D-CEUS did not change the diagnosis in any patient compared with 2D-CEUS. However, 3D-CEUS changed the management in 3 (2.8%) of 107 lesions, increased confidence but made no change in diagnosis in 85 (79.5%) lesions, added some information but did not change management or diagnosis in 15 (14.0%), and made no change in 4 (3.7%), respectively, in comparison with 2D-CEUS. CONCLUSION: 3D-CEUS enhances the diagnostic confidence in the majority of the patients and even changes the management in some patients. 3D-CEUS has potential usefulness in evaluating treatment response for liver cancer after local therapies.

Enhancement pattern of hilar cholangiocarcinoma: contrast-enhanced ultrasound versus contrast-enhanced computed tomography.

OBJECTIVE: To compare the enhancement pattern of hilar cholangiocarcinoma on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). METHODS: Thirty-two consecutive patients with pathologically proven hilar cholangiocarcinomas were evaluated by both low mechanical index CEUS and CECT. The enhancement feature of the tumor, portal vein infiltration, and lesion conspicuity on them was investigated. RESULTS: In the arterial phase, the numbers of the lesions showing hyperenhancement, isoenhancement, and hypoenhancement, were 14 (43.8%), 14 (43.8%), and 4 (12.6%), on CEUS, and 12 (37.5%), 9 (28.1%), and 11 (34.4%), on CECT (P=0.162). In portal phase, the numbers of the lesions showing hypoenhancement, isoenhancement, and hyperenhancement were 30 (93.8%), 1 (3.1%), and 1 (3.1%), on CEUS, and 23 (71.9%), 8 (25.0%), and 1 (3.1%), on CECT (P=0.046). The detection rates for portal vein infiltration were 84.2% (16/19) for baseline ultrasound, 89.5% (17/19) for CEUS, and 78.9% (15/19) for CECT (all P>0.05 between every two groups). CEUS significantly improved the lesion conspicuity in comparison with CECT. CEUS and CECT made correct diagnoses in 30 (93.8%) and 25 (78.1%) lesions prior to pathological examination (P=0.125). CONCLUSION: The enhancement pattern of hilar cholangiocarcinoma on CEUS was similar with that on CECT in arterial phase, whereas in portal phase hilar cholangiocarcinoma shows hypoenhancement more likely on CEUS. CEUS and CECT lead to similar results in evaluating portal vein infiltration and diagnosis of this entity.