Ultrasound tissue scatterer distribution imaging: An adjunctive diagnostic tool for shear wave elastography in characterizing focal liver lesions.

OBJECTIVES: Focal liver lesion (FLL) is a prevalent finding in cross-sectional imaging, and distinguishing between benign and malignant FLLs is crucial for liver health management. While shear wave elastography (SWE) serves as a conventional quantitative ultrasound tool for evaluating FLLs, ultrasound tissue scatterer distribution imaging (TSI) emerges as a novel technique, employing the Nakagami statistical distribution parameter to estimate backscattered statistics for tissue characterization. In this prospective study, we explored the potential of TSI in characterizing FLLs and evaluated its diagnostic efficacy with that of SWE. METHODS: A total of 235 participants (265 FLLs; the study group) were enrolled to undergo abdominal examinations, which included data acquisition from B-mode, SWE, and raw radiofrequency data for TSI construction. The area under the receiver operating characteristic curve (AUROC) was used to evaluate performance. A dataset of 20 patients (20 FLLs; the validation group) was additionally acquired to further evaluate the efficacy of the TSI cutoff value in FLL characterization. RESULTS: In the study group, our findings revealed that while SWE achieved a success rate of 49.43 % in FLL measurements, TSI boasted a success rate of 100 %. In cases where SWE was effectively implemented, the AUROCs for characterizing FLLs using SWE and TSI stood at 0.84 and 0.83, respectively. For instances where SWE imaging failed, TSI achieved an AUROC of 0.78. Considering all cases, TSI presented an overall AUROC of 0.81. There was no statistically significant difference in AUROC values between TSI and SWE (p > 0.05). In the validation group, using a TSI cutoff value of 0.67, the AUROC for characterizing FLLs was 0.80. CONCLUSIONS: In conclusion, ultrasound TSI holds promise as a supplementary diagnostic tool to SWE for characterizing FLLs.

Nasopharyngeal carcinoma patient-derived xenograft mouse models reveal potential drugs targeting cell cycle, mTOR, and autophagy pathways.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) infection. To test preclinical NPC drugs, we established two patient-derived xenograft (PDX) mouse models, EBV-positive PDX-B13 and EBV-negative PDX-Li41, for drug screening. METHODS: Based on next generation sequencing (NGS) studies, PDX-B13 had CCND1 copy number (CN) gain but CDKN2A CN loss, whereas PDX-Li41 had CDKN2A and RB1 CN loss, TSC1 (negative regulator of mTOR) frameshift deletion mutation, and increased activation of mTOR, a serine/threonine kinase that governs metabolism, autophagy, and apoptosis. Increased mTOR was also associated with poor NPC prognosis. RESULTS: Everolimus, an mTOR inhibitor, suppressed tumor growth in the two PDX NPC models and had an additive antitumor effect with palbociclib, a CDK4/6 inhibitor. PDX tumors treated with various drugs or untreated were subjected to RNA sequencing, transcriptome profile analysis, and selective Western blotting to understand the interactions between these drugs and gene expression profiles. Palbociclib also suppressed EB viral nuclear antigen (EBNA1) expression in PDX-B13. Everolimus together with autophagy inhibitor, hydroxychloroquine, had additive anti-tumor effect on PDX-B13 tumor. Immunohistochemistry revealed that high mTOR levels were correlated with poor overall survival in patients with metastatic NPC (N = 90). CONCLUSIONS: High mTOR levels are a poor prognostic factor in NPC, and cell cycle, mTOR and autophagy pathways may serve as therapeutic targets in NPC. In addition, PDX models can be used for efficiently testing potential NPC drugs.

Dynamic Change of Albumin-Bilirubin Score Is Good Predictive Parameter for Prognosis in Chronic Hepatitis C-hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization.

Background and Aims: The Albumin-Bilirubin (ALBI) grade is a good index for liver function evaluation and is also associated with the outcomes of hepatocellular carcinoma patients receiving TACE. However, the correlation between the dynamic change to the ALBI score and clinical outcome is seldom discussed. Therefore, this study aimed to investigate the application of ALBI grade and dynamic change of ALBI grade (delta ALBI grade) after first TACE for prognosis prediction in HCC patients with chronic hepatitis C infection. Method: From January 2005 to December 2015, newly diagnosed naive chronic hepatitis C-hepatocellular carcinoma (CHC-HCC) patients who were treated with TACE as the initial treatment at the Chang Gung Memorial Hospital, Linkou Medical Center, were retrospectively recruited. The pre-treatment host factors, tumor status and noninvasive markers were collected. The Cox regression model was used to identify independent predictors of overall survival and tumor recurrence. Results: Among 613 treatment-naive CHC-HCC patients, 430 patients died after repeated TACE during a median follow-up of 26.9 months. Complete remission after repeated TACE occurred in 46.2% patients, and 208 patients (33.9%) had tumor recurrence, with a median recurrence-free interval of 8.5 months. In Cox regression analysis, ALBI grade II/III (aHR: 1.088, p = 0.035) and increased delta ALBI grade (aHR: 1.456, p = 0.029) were independent predictive factors for tumor recurrence. Furthermore, ALBI grade II/III (aHR: 1.451, p = 0.005) and increased delta ALBI grade during treatment (aHR: 1.436, p = 0.006) were predictive factors for mortality, while achieving complete response after repeated TACE (aHR: 0.373, p < 0.001) and anti-viral therapy (aHR: 0.580, p = 0.002) were protective factors for mortality. Conclusion: Both ALBI and delta ALBI grade are independent parameters to predict survival and tumor recurrence of CHC-HCC patients receiving TACE treatment.

Complete response at first transarterial chemoembolization predicts favorable outcome in hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is the mainstay of treatment for patients with intermediate/advanced stage or unresectable hepatocellular carcinoma (HCC). Despite the palliative nature of TACE treatment, embolizing the tumor feeding vessels and leading to progressive tumor necrosis, complete response (CR) after TACE could still be observed in a certain population. Thus, this study aimed to investigate both the predictors for CR and the long-term prognosis of the patients with CR after TACE. The study recruited new diagnosed HCC patients initially treated with TACE from 2010 to 2013. Post TACE response was assessed by scheduled image studies according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Then, pre-TACE factors were compared between patients with and without CR. After the first session of TACE, 22.3% of the 669 TACE treated patients achieved CR. During a median of 26.6 months follow-up, patients with CR had better overall survival than those without (median: 35.8 vs. 24.0 months, P<0.001). By multivariate logistic regression analysis, Child-Turcotte-Pugh class B (OR: 0.419, P=0.005), tumor burden beyond up-to-7 criteria (OR: 0.118, P<0.001), bilobar tumor extent (OR: 0.236, P<0.001), higher alpha-fetoprotein (AFP) level (≥20 ng/ml, OR: 0.614, P=0.039) and higher platelet counts (>150 k/µl, OR: 0.482, P=0.002) were unfavorable predictors for CR after first TACE. In addition, macrovascular invasion (HR: 3.113, P=0.001) and higher AFP levels (≥15 ng/ml, HR: 2.601, P=0.007) were predictors for early HCC recurrence whereas diabetes mellitus (DM) (HR: 2.166, P=0.006) was the only significant predictor for late HCC recurrence in CR patients. In conclusion, more than one-fifth of HCC patients achieved CR after first TACE and these patients had favorable prognosis. Furthermore, tailored post-TACE follow-up strategies shall be considered in patients with different risk factors of early or late recurrence after CR.

MELD score is the better predictor for 30-day mortality in patients with ruptured hepatocellular carcinoma treated by trans-arterial embolization.

BACKGROUND AND AIMS: Spontaneous hepatocellular carcinoma (HCC) rupture is a catastrophic life-threatening complication that could be rescued by trans-arterial embolization (TAE). However, deteriorated liver function with total bilirubin more than 3 mg/dL was deemed as a relative contraindication. This study was aimed to re-evaluate this relative contraindication. METHODS: Patients with ruptured HCC and treated by TAE between February 2005 and December 2016 in Chang Gung Memorial Hospital, Linkou branch were recruited. Pre-TAE characteristics including age, gender, etiology, liver biochemistry, Child-Pugh classification, Model for End-Stage Liver Disease (MELD) score, the presence of shock, tumor staging and post TAE liver function were compared between patients with and without post-TAE 30-day mortality. RESULTS: A total of 186 patients were enrolled. The successful hemostatic rate after embolization was 91.4% and the median overall survival was 224 days. The 30-day cumulative mortality rate is 20.4%. By multivariate logistic regression analysis, male [aOR: 0.25, P=0.034] MELD score [aOR: 13.61, P<0.001], tumor size [aOR: 1.21, P=0.023] are the independent predictors for 30-day mortality. MELD score has better predictability of post-TAE 30-day mortality than total bilirubin level (AUROC: 0.818 vs. 0.668). The cut-off points of MELD score 13 has higher negative predictive value of 95% for post-TAE 30-day mortality. CONCLUSION: TAE is effective for the initial hemostasis in patients with HCC rupture. MELD score ≥13 rather than only total bilirubin level >3 mg/dL be more predictive of post TAE 30-day mortality.

Prospective comparison of early interim 18F-FDG-PET with 18F-FLT-PET for predicting treatment response and survival in metastatic breast cancer.

BACKGROUND: To compare the value of interim 18F-FLT-PET and 18F-FDG-PET for predicting treatment outcomes in patients with metastatic breast cancer after salvage therapy. METHODS: Patients with metastatic breast cancer received PET/CT using 18F-FLT and 18F-FDG at baseline, after the 1st and 2nd cycle of systemic chemotherapy. The clinical response was classified according to Response Evaluation Criteria in Solid Tumors 1.1 based on contrast-enhanced CT after 3 months of systemic chemotherapy. The metabolic response on PET was assessed according to European Organization for Research and Treatment of Cancer criteria or PET Response Criteria in Solid Tumors (PERCIST) and was correlated to the clinical response, overall survival (OS), and progression-free survival (PFS). RESULTS: Twenty-five patients entered final analysis. On 18F-FDG-PET, clinical responders after 2 chemotherapy cycles (post-2c) had a significantly greater reduction of maximal standardized uptake value (SUV) and the peak SUV corrected for lean body mass (SULpeak) of the tumor than non-responders (P = 0.030 and 0.003). Metabolic response determined by PERCIST on post-2c 18F-FDG-PET showed a high area under the receiver operating characteristics curve of 0.801 in predicting clinical response (P = 0.011). Patients who were metabolic responders by PERCIST on post-2c 18F-FDG-PET had a significantly longer PFS (53.8% vs. 16.7%, P = 0.014) and OS (100% vs. 47.6%, P = 0.046) than non-responders. Survival differences between responders and non-responders in the interim 18F-FLT-PET were not significant. CONCLUSIONS: 18F-FLT-PET failed to show an advantage over 18F-FDG-PET in predicting the treatment response and survival in patients with metastatic breast cancer. Assessment of treatment outcome by interim 18F-FDG-PET may aid treatment. TRIAL REGISTRATION: The study was retrospectively registered on 02/06/2020 on Clinicaltrials.gov (identifier NCT04411966 ).

Combination of Epithelial Growth Factor Receptor Blockers and CDK4/6 Inhibitor for Nasopharyngeal Carcinoma Treatment.

BACKGROUND: Nasopharyngeal carcinoma (NPC) involves host genetics, environmental and viral factors. In clinical observations, patients of young and old ages were found to have higher recurrence and metastatic rates. METHODS: Cytokine array was employed to screen druggable target(s). The candidate target(s) were confirmed through patient-derived xenografts (PDXs) and a new EBV-positive cell line, NPC-B13. RESULTS: Overexpression of epithelial growth factor (EGF) and EGF receptor (EGFR) was detected in young patients than in older patients. The growth of NPC PDX tumors and cell lines was inhibited by EGFR inhibitors (EGFRi) cetuximab and afatinib when used separately or in combination with the cell cycle blocker palbociclib. Western blot analysis of these drug-treated PDXs demonstrated that the blockade of the EGF signaling pathway was associated with a decrease in the p-EGFR level and reduction in PDX tumor size. RNA sequencing results of PDX tumors elucidated that cell cycle-related pathways were suppressed in response to drug treatments. High EGFR expression (IHC score ≥ grade 3) was correlated with poor survival in metastatic patients (p = 0.008). CONCLUSIONS: Our results provide encouraging preliminary data related to the combination treatment of EGFRi and palbociclib in patients with NPC.

Alpha-fetoprotein response at different time-points is associated with efficacy of nivolumab monotherapy for unresectable hepatocellular carcinoma.

Nivolumab monotherapy has a modest objective response rate (ORR) in hepatocellular carcinoma (HCC). To overcome the lack of biomarkers that predict delayed alpha-fetoprotein (AFP) response beyond 4 weeks, we applied a novel 50-10 rule of AFP response for unresectable HCC patients under nivolumab monotherapy and proposed an algorithm based on on-treatment AFP reduction at different time-points. Ninety unresectable HCC patients who underwent nivolumab monotherapy in 2015-2019 were retrospectively recruited and divided into four classes: rapid AFP decrease of ≥ 50% of baseline at week 4 (class I), AFP changes within ± 50% of baseline at week 4 that later decreased to ≥ 10% of baseline (class II) or not (class III) at week 12, and rapid AFP increase of ≥ 50% of baseline at week 4 (class IV). ORR was 47.4%, 36.0%, 7.7%, and 5.0% in class I-IV patients, respectively. Rapid (class I) and delayed (class II) AFP responders had significantly higher ORR, overall survival (OS) and progression-free survival (PFS) than non-responders (class III and IV) (ORR: 40.9% vs. 6.5%, P<0.001; median OS: not reached vs. 9.6 months, log-rank P<0.001; median PFS: 9.6 vs. 2.8 months, log-rank P<0.001). In multivariate analysis, AFP response was an independent factor associated with good OS (hazard ratio [HR]=0.301, P=0.001) and PFS (HR=0.332, P<0.001). Moreover, AFP responders had higher ORR and better OS as well as PFS than non-responders, regardless of nivolumab as a first- or more than a second-line therapy (all P<0.05). In conclusion, the novel 50-10 rule of AFP response provides practical guidance for nivolumab monotherapy in unresectable HCC patients. However, this algorithm remains to be verified in a large prospective cohort.

Switching monopolar radiofrequency ablation improves long-term outcomes of medium-sized hepatocellular carcinoma.

OBJECTIVES: Radiofrequency ablation (RFA) of medium-sized (3-5 cm) hepatocellular carcinoma (HCC) is suboptimal. Switching monopolar RFA (SW-RFA) enlarges the ablative volume to better cover larger tumors. This study aims to compare the long-term outcomes of medium-sized HCC treated by either SW-RFA or single-monopolar RFA (S-RFA). METHODS: We retrospectively reviewed 139 cases (147 medium-size HCC) between 2008 and 2014. Under propensity score matching, a total of 43 paired patients with medium-size HCC and balanced clinical variables treated by either SW-RFA or S-RFA were selected for comparison. RESULTS: SW-RFA showed a higher rate of achieving an adequate safety margin (p = 0.002). After a mean follow-up period of 40.4 months, SW-RFA produced significantly lower global RFA failure rates (p < 0.001) and better overall survival (p = 0.005) compared to S-RFA. SW-RFA was independently associated with a decreased risk of global RFA failure (hazard ratio [HR]: 0.136, 95% confidence interval [CI]: 0.030-0.607, p = 0.009) and improved overall survival (HR: 0.337, 95% CI: 0.152-0.747, p = 0.007). By last follow-up, the SW-RFA group maintained a superior tumor-free rate (p = 0.010) and fewer progressions to Barcelona Clinic Liver Cancer stage C (p = 0.011). Major complication rates were comparable in both groups (SW-RFA: 2.3% vs. S-RFA: 4.7%, p = 1.000). CONCLUSIONS: The switching multi-monopolar ablation technique could be beneficial for patients with medium-sized HCCs given sustained control of larger tumors with better overall survival. KEY POINTS: • Switching monopolar ablation could provide a sustained local tumor control and better overall survival than single-monopolar ablation for the medium-sized hepatocellular carcinoma. • Compared to single-monopolar ablation, switching monopolar ablation could create a larger homogeneous coagulation volume by using a shorter total ablation time to achieve a higher rate of adequate safety margin for a medium-sized HCC. • Patients with medium-sized HCC can be maintained at a higher rate of tumor-free status and at a lower risk of progression into BCLC stage C in the follow-up period after ablation by switching monopolar than by single-monopolar ablation.

The incidence and predictors of post transarterial chemoembolization variceal bleeding in hepatocellular carcinoma patients.

BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC) patients. Variceal bleeding is a life-threatening complication and may alter the initial treatment plan. This study was aimed to elucidate the risk factors for variceal bleeding in HCC patients receiving TACE treatment. METHODS: From 2005 to 2016, a total of 1233 treatment-naive HCC patients receiving first time TACE treatment in Chang Gung Memorial Hospital, Linkou medical center were recruited. Pre-TACE status including baseline characteristics, prior history of ascites, and parameters for liver function evaluation were analyzed. All the variables were compared between patients with and without variceal bleeding. RESULTS: Among the 1233 patients, the median age was 63.7 (range 25.8-91.5) years old, and 73.5% were male. Variceal bleeding events were documented in 19 patients (1.5%) within 3 months post TACE treatment. Patients with younger age, cirrhosis, pre-treatment ascites and advanced fibrosis status (higher MELD score, CTP score, ALBI grade, FIB-4 and APRI score) were more likely to encounter post-treatment variceal bleeding. Multivariate Cox regression analysis revealed existence of ascites (adjusted HR: 4.859 (1.947-12.124), p = 0.001), and higher FIB-4 score (adjusted HR: 4.481 (1.796-11.179), p = 0.001) were the independent predictive factors for variceal bleeding. Patients with post-TACE variceal bleeding are more likely to encounter tumor progression (42.1% vs. 20.3%, p = 0.039) and mortality owing to GI bleeding (15.8% vs. 3%, p = 0.032). CONCLUSION: The incidence of post-TACE variceal bleeding was 1.5%. Patients with post-TACE variceal bleeding have poorer TACE treatment response. The pre-treatment ascites and FIB-4 score are the independent predictors for post-TACE variceal bleeding.

Add-on sorafenib is beneficial for hepatocellular carcinoma patients with transarterial chemoembolization refractoriness: a real-world experience.

BACKGROUND AND AIMS: Sorafenib is the first proved target therapy that shows significant survival benefit in advanced hepatocellular carcinoma. This study was aimed to investigate whether add-on sorafenib be beneficial for those experienced transarterial chemoembolization refractoriness. METHODS: From 2005 to 2016, a total of 656 treatment-naive hepatocellular carcinoma patients receiving transarterial chemoembolization treatment were recruited. Transarterial chemoembolization refractoriness was defined as progressive disease after two consecutive of transarterial chemoembolization treatment within 6 months. Patient's baseline characteristics, tumor burden, and parameters for liver function evaluation during treatment were analyzed. All the variables were compared between patients with and without transarterial chemoembolization refractoriness, as well as with and without add-on sorafenib. RESULTS: Among the 656 patients, the median age was 62.5 (range 27.3-91.5) years old, and 74.5% were male. Transarterial chemoembolization refractoriness events were documented in 202 patients (30.8%). After multivariate logistic regression analysis, tumor size ≧5 cm, baseline alpha-fetoprotein level ≧200 mg/dl, elevation of alpha-fetoprotein ≧20%, and elevation of Child-Turcotte-Pugh score ≧2 points after first transarterial chemoembolization were the independent predictive factors for transarterial chemoembolization refractoriness. Twenty-two patients (10.9%) received add-on sorafenib treatment and 146 (72.3%) patients continued transarterial chemoembolization treatment alone. After 1:2 propensity score matching, patients with add-on sorafenib therapy had significantly longer median overall survival than transarterial chemoembolization treatment alone (23.1 vs. 11.0 months, log-rank P = 0.001). CONCLUSION: The tumor size, baseline alpha-fetoprotein, and elevation of alpha-fetoprotein and Child-Turcotte-Pugh score after first transarterial chemoembolization were the predictors for transarterial chemoembolization refractoriness. For patients with transarterial chemoembolization refractoriness, add-on sorafenib achieved better survival benefit than transarterial chemoembolization treatment alone.

Integrated genomic analyses in PDX model reveal a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for nasopharyngeal carcinoma.

BACKGROUND: Patient-derived xenograft (PDX) tumor model has become a new approach in identifying druggable tumor mutations, screening and evaluating personalized cancer drugs based on the mutated targets. METHODS: We established five nasopharyngeal carcinoma (NPC) PDXs in mouse model. Subsequently, whole-exome sequencing (WES) and genomic mutation analyses were performed to search for genetic alterations for new drug targets. Potential drugs were applied in two NPC PDX mice model to assess their anti-cancer activities. RNA sequencing and transcriptomic analysis were performed in one NPC PDX mice to correlate with the efficacy of the anti-cancer drugs. RESULTS: A relative high incident rate of copy number variations (CNVs) of cell cycle-associated genes. Among the five NPC-PDXs, three had cyclin D1 (CCND1) amplification while four had cyclin-dependent kinase inhibitor CDKN2A deletion. Furthermore, CCND1 overexpression was observed in > 90% FFPE clinical metastatic NPC tumors (87/91) and was associated with poor outcomes. CNV analysis disclosed that plasma CCND1/CDKN2A ratio is correlated with EBV DNA load in NPC patients' plasma and could serve as a screening test to select potential CDK4/6 inhibitor treatment candidates. Based on our NPC PDX model and RNA sequencing, Palbociclib, a cyclin-dependent kinase inhibitor, proved to have anti-tumor effects by inducing G1 arrest. One NPC patient with liver metastatic was treated with Palbociclib, had stable disease response and a drop in Epstein Barr virus (EBV) EBV titer. CONCLUSIONS: Our integrated information of sequencing-based genomic studies and tumor transcriptomes with drug treatment in NPC-PDX models provided guidelines for personalized precision treatments and revealed a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for NPC.

Investigations of organ and effective doses of abdominal cone-beam computed tomography during transarterial chemoembolization using Monte Carlo simulation.

BACKGROUND: To investigate the organ dose, effective dose (ED), conversion factor, and the C-arm rotation angle effects on dose variations of abdominal C-arm cone-beam computed tomography (CBCT) during transarterial chemoembolization (TACE). METHODS: The organ doses and EDs for abdominal C-arm CBCT were retrospectively calculated according to a Monte Carlo technique for 80 patients. Dose variations from projections, ED to dose-area product (DAP) ratios, and effects of body mass index (BMI) on the ED and ED to DAP ratios were also analyzed. RESULTS: The kidney received the highest dose (14.6 ± 1.2 mSv). Organ dose deviations among C-arm rotation angles was highest for stomach (CV = 0.71). The mean ED of the the CBCT run during TACE was 3.5 ± 0.5 mSv, and decreased with increased BMI (R2 = 0.45, p < 0.001). The mean ED to DAP ratio was 0.27 ± 0.04 mSv·Gy- 1·cm- 2 and tended to decrease with increased BMI (R2 = 0.55, p < 0.001). The mean ED to DAP ratios were 0.29 ± 0.02, 0.26 ± 0.02, and 0.23 ± 0.03 mSv·Gy- 1·cm- 2 for patients with BMI < 25 kg/m2, 25-30 kg/m2, and ≥30 kg/m2, respectively. CONCLUSIONS: Suitable conversion factors for C-arm CBCT facilitate the use of DAPs for estimating the ED. The patient dose can be varied by adjusting the CBCT rotation angle setting, and dose reduction strategies can be further manipulated.

Correlation between overall survival and differential plasma and tissue tumor marker expression in nasopharyngeal carcinoma patients with different sites of organ metastasis.

Differential overall survival of nasopharyngeal carcinoma (NPC) with different organ site metastases has been documented. Here, we attempted to determine the underlying mechanisms by assessing plasma and tumor tissue markers in relation to patient survival. Pretreatment plasma Epstein-Barr virus (EBV) DNA concentrations, cytokines and tissue macrophages, proliferation and apoptosis markers were determined in 178 patients with metastatic NPC. The median overall survival (OS) was 19 months. Patients with single organ metastases had better outcomes than those with multiple organ metastases (median OS: 26 months vs. 16 months), with statistical significance. Among the single organ involvement cases, patients with lung metastasis only showed longer survival than those with bone or liver involvement (median OS: 50 months vs. 21 months vs. 18 months; P < 0.001). Pretreatment plasma EBV DNA concentrations were lower in patients with lung metastasis than bone or liver metastasis among single organ site groups. Plasma interferon-γ-inducible protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1) expression levels were correlated with differential single organ site metastasis OS and EBV DNA load. Liver metastatic tissue had higher density of infiltrating macrophages and proliferative index than the lung metastatic group. Low pretreatment plasma EBV DNA load, expression of cytokines, such as IP-10 and MCP-1, tissue macrophage infiltration, and proliferative index may contribute to the differences in overall survival.

Impact of spontaneous tumor rupture on prognosis of patients with T4 hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Compare the outcomes of three groups of patients with T4 hepatocellular carcinoma (HCC): tumor rupture with shock (RS group), tumor rupture without shock (R group), and no tumor rupture (NR group). MATERIALS AND METHODS: We retrospectively reviewed 221 patients with T4 HCC from 2010 to 2012. The clinical background and prognosis were analyzed. RESULTS: Overall in-hospital mortality rate was 18.1%; overall median survival time was 4 months. The NR group were more likely to have multiple and infiltrative tumors (P < 0.001). Relative to the NR group, the R + RS group had better survival rates at 6 months (49.2% vs. 32.2%), 1 year (35.3% vs. 21.0%), 3 years (22.5% vs. 11.0%), and 5 years (17.7% vs. 5.5%) (P = 0.010). Patients in the RS group had a higher in-hospital mortality rate, but significantly better long-term survival than the NR and R group (P < 0.001). Multivariate analysis indicated that Child-Pugh class B or C, presence of portal venous thrombosis, and absence of shock were significantly associated with poor survival. CONCLUSION: Patients with tumor rupture and shock had worse in-hospital survival. However, patients without decompensated liver cirrhosis and portal venous thrombosis, and eligible for curative treatment had favorable long-term outcome. J. Surg. Oncol. 2016;113:789-795. © 2016 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc.

Application of a patient-derived xenograft model in cytolytic viral activation therapy for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an Epstein Barr virus (EBV)-related malignancy in which the tumor microenvironment plays a pivotal role in tumor progression. Here, we developed two patient-derived xenograft (PDX) mouse lines from engrafted NPC metastatic tumors. Positive staining for EBV-encoded small RNAs confirmed that these tumors harbored EBV, and gene expression profile analyses further showed that the PDX was highly similar to the primary parent tumor. In vivo drug screening using the PDX system demonstrated that gemcitabine had the best antitumor effect among the tested drugs. The donor of this PDX also showed excellent responsiveness to gemcitabine treatment. The combination of gemcitabine and valproic acid exerted synergistic antitumor effects. Further addition of ganciclovir to this two-drug combination regimen enhanced cytolytic viral activation, yielding the best antitumor response among tested regimens. Treatment with this three-drug combination regimen decreased plasma EBV-DNA load, tumor viral concentration, and the number of viable tumor cells to a greater extent than the two-drug gemcitabine and valproic acid combination. These results highlight the value of PDX models in the development of EBV-targeted strategies to treat NPC.

Complications of fluoroscopically guided percutaneous gastrostomy with large-bore balloon-retained catheter in patients with head and neck tumors.

BACKGROUND/PURPOSE: To review the complications, mortality rate and nutritional status of patients with head and neck cancer after fluoroscopically guided percutaneous gastrostomy (FPG). METHODS: We retrospectively recruited 110 patients who had undergone FPG using 14-French balloon-retained catheters. The mortality rate, procedural and catheter-related complications, and Eastern Cooperative Oncology Group performance status were reviewed. Peritonitis, abscess, septicemia and bleeding were defined as major complications. Tube-related problems, including dislodgment, obstruction, leakage, vomiting and infection, were classified as minor complications. RESULTS: Patients were stratified according to Eastern Cooperative Oncology Group performance status as follows: grade 0 (n=6); grade 1 (n=22); grade 2 (n=44); grade 3 (n=29); and grade 4 (n=7). The respective complication rates were 21%, 24%, 26%, and 29% for grades 1-4; however, there were no significant intergrade differences. The rates of major and minor complications were 1.9% and 20.0%, respectively. A total of 47 (43.5%) patients succumbed due to cancer deterioration; however, there was no gastrostomy-induced mortality. The catheter-occlusion rate of 3.7% in this cohort was significantly lower than that reported in other pigtail-retained gastrostomy studies. CONCLUSION: FPG is a safe method with low mortality and complication rate for constructing long-term enteral access in patients with head and neck cancer and esophageal abnormalities, who have no endoscopic access to the stomach.

Triphasic dynamic CT findings of 63 hepatic focal nodular hyperplasia in 46 patients: correlation with size and pathological findings.

BACKGROUND: To correlate the dynamic computed tomography (CT) of hepatic focal nodular hyperplasia (FNH) with its size and pathology. METHODS: The clinical data, pathological and dynamic CT findings of 36 FNHs in 24 males and 27 lesions in 22 females were reviewed. The pathological and CT findings of the 32 small FNHs (diameter < 3 cm) and 31 large FNHs (diameter >or= 3 cm) were compared and analyzed. RESULTS: All FNHs were hypervascular at arterial phase except for central scarring. The mean diameter of FNHs with hypoattenuating, isoattenuating, hyperattenuating on delayed scans were 5.05 cm, 3.06 cm, and 2.70 cm, respectively (p = 0.026). As compared with small FNHs, large ones were significantly more likely to reveal central scarring (p = 0.005), vascular displacement (p < 0.001), and abnormal vessels around lesions (p < 0001). Coexistent bile ductile proliferation and bridging septa were more commonly observed in small FNHs (p = 0.028 for both). FNHs without aberrant vessels tended to feature hyperattenuating during the portal venous phase (p = 0.041). CONCLUSIONS: FNHs with different tumor sizes may manifest various dynamic CT findings that are more or less related to the different pathological findings.

T-fastener gastropexy and percutaneous gastrostomy under CT-fluoroscopic guidance in a patient with partial gastrectomy.

The real-time images of computed tomography (CT)-fluoroscopy provide an excellent means of guidance for percutaneous interventions. We describe the performance of T-fastener gastropexy and percutaneous gastrostomy under CT-fluoroscopic guidance in a 59-year-old woman who had received total pharyngolaryngectomy for hypopharyngeal cancer and partial gastrectomy with Billroth II anastomosis for bleeding gastric ulcer 10 years before this operation. The previous gastric operation altered the gastrointestinal anatomy and made conventional fluoroscopic-guided percutaneous gastrostomy extremely difficult and risky. The T-fastener gastropexy and percutaneous gastrostomy were accomplished smoothly in a single session using CT-fluoroscopic guidance. This modified method of percutaneous gastrostomy may be useful in patients with anatomic distortion due to previous gastric surgery.

Gallbladder polyp as a manifestation of hemobilia caused by arterial-portal fistula after percutaneous liver biopsy: a case report.

Outpatient percutaneous liver biopsy is a common practice in the differential diagnosis and treatment of chronic liver disease. The major complication and mortality rate were about 2-4% and 0.01-0.33% respectively. Arterio-portal fistula as a complication of percutaneous liver biopsy was infrequently seen and normally asymptomatic. Hemobilia, which accounted for about 3% of overall major percutaneous liver biopsy complications, resulted rarely from arterio-portal fistula We report a hemobilia case of 68 years old woman who was admitted for abdominal pain after liver biopsy. The initial ultrasonography revealed a gallbladder polypoid tumor and common bile duct (CBD) dilatation. Blood clot was extracted as endoscopic retrograde cholangiopancreatography (ERCP) showed hemobilia. The patient was shortly readmitted because of recurrence of symptoms. A celiac angiography showed an intrahepatic arterio-portal fistula. After superselective embolization of the feeding artery, the patient was discharged uneventfully. Most cases of hemobilia caused by percutaneous liver biopsy resolved spontaneously. Selective angiography embolization or surgical intervention is reserved for patients who failed to respond to conservative treatment.