Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Subsequent locoregional therapy prolongs survival in progressive hepatocellular carcinoma patients under lenvatinib treatment.

BACKGROUND: Locoregional therapy and multi-kinase inhibitor agent have been the backbone of treatment for hepatocellular carcinoma (HCC) patients. However, the effect of combination or sequential use of locoregional therapy on HCC patients receiving multi-kinase inhibitor remain uncertain. Therefore, we aim to explore whether the subsequent locoregional therapy provides better survival in HCC patients under lenvatinib treatment. METHODS: From March 2018 to April 2020, a total of 78 unresectable HCC patients receiving lenvatinib were recruited. Image response was evaluated by dynamic image using the modified RECIST criteria. Among patients with tumor progression under lenvatinib treatment, whether receiving subsequent locoregional therapy or not were documented. Overall survival between two groups and the predictors for tumor progression were also analyzed. RESULTS: Among the 78 patients receiving lenvatinib, the median age was 67.8 years old, and 69.2 % were male. Forty-four patients (56.4 %) experienced tumor progression with time to progression 5.1 months (95 % confidence interval (CI): 4.7-6.8) months. In multivariable Cox regression analysis, albumin-bilirubin (ALBI) grade II (adjusted HR: 2.883, P = 0.0104), and treatment duration less than three months (adjusted HR: 3.801, P = 0.0014) were the independent predictive factors for tumor progression, while patients achieving objective response under lenvatinib treatment within 12 weeks was the independent protective factor for tumor progression (adjusted HR: 0.144, P = 0.0020). Among the 44 patients with tumor progression, twenty-six (59.1 %) patients received subsequent locoregional therapy after tumor progression. Comparing to those with tumor progression without locoregional treatment, patients who received subsequent locoregional therapy had significantly better survival (1st year cumulative survival rate 70 % vs 27 %, log-rank P = 0.003). CONCLUSION: ALBI grade, treatment duration of lenvatinib, and achieving objective image response within twelve weeks were the independent predictive factors for tumor progression. Furthermore, longer overall survival was observed in tumor progression patients with subsequent locoregional therapy and with better liver preserved function.

Using Arterial Pulse and Laser Doppler Analyses to Discriminate between the Cardiovascular Effects of Different Running Levels.

BACKGROUND AND AIMS: Running can induce advantageous cardiovascular effects such as improved arterial stiffness and blood-supply perfusion. However, the differences between the vascular and blood-flow perfusion conditions under different levels of endurance-running performance remains unclear. The present study aimed to assess the vascular and blood-flow perfusion conditions among 3 groups (44 male volunteers) according to the time taken to run 3 km: Level 1, Level 2, and Level 3. METHODS: The radial blood pressure waveform (BPW), finger photoplethygraphy (PPG), and skin-surface laser-Doppler flowmetry (LDF) signals of the subjects were measured. Frequency-domain analysis was applied to BPW and PPG signals; time- and frequency-domain analyses were applied to LDF signals. RESULTS: Pulse waveform and LDF indices differed significantly among the three groups. These could be used to evaluate the advantageous cardiovascular effects provided by long-term endurance-running training, such as vessel relaxation (pulse waveform indices), improvement in blood supply perfusion (LDF indices), and changes in cardiovascular regulation activities (pulse and LDF variability indices). Using the relative changes in pulse-effect indices, we achieved almost perfect discrimination between Level 3 and Level 2 (AUC = 0.878). Furthermore, the present pulse waveform analysis could also be used to discriminate between the Level-1 and Level-2 groups. CONCLUSIONS: The present findings contribute to the development of a noninvasive, easy-to-use, and objective evaluation technique for the cardiovascular benefits of prolonged endurance-running training.

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.

A GALNT14 rs9679162 genotype-guided therapeutic strategy for advanced hepatocellular carcinoma: systemic or hepatic arterial infusion chemotherapy.

Although targeted agents are recommended as the first-line treatments for advanced hepatocellular carcinoma (aHCC), systemic chemotherapy or hepatic arterial infusion chemotherapy (HAIC) are still being used in Asian countries. Beside economic considerations, it was found that targeted drugs could not significantly prolong overall survival in aHCC patients with distant metastasis. In addition, chemotherapy could achieve complete response in a small proportion of patients. Here, we aimed to investigate whether combination of three previously identified single nucleotide polymorphism (SNP) predictors (GALNT14-rs9679162, WWOX-rs13338697, and rs6025211) could guide our choice between systemic chemotherapy, HAIC, and targeted agents in aHCC patients. A cohort of 237 real-world aHCC patients (171 receiving systemic chemotherapy followed by various anticancer treatments including sorafenib; 66 receiving HAIC) were included for outcome analysis. By combining the three SNP markers with or without addition of two clinical criteria (tumor diameter <8 cm, neutrophils <80%), small groups of patients were found to harbor high complete response rates to systemic chemotherapy (35.3% if the 3-SNP signature alone matched; 60.0% if clinical criteria also matched). Subsequent sorafenib treatment for chemotherapy non-responders was associated with longer overall survival (P < 0.001). In HAIC-treated patients, GALNT14-rs9679162 genotype "GG" was associated with longer overall survival (P = 0.019, median survival > 10.5 months). In conclusion, pre-test for the 3-SNP signature in aHCC patients could identify potential systemic chemotherapy or HAIC responders. Chemotherapy non-responders still benefited from subsequent sorafenib treatment. Accordingly, we propose a roadmap for aHCC patients when chemotherapy or HAIC is to be used.

Prolonged post-ablation fever may predict one-year tumor recurrence in hepatocellular carcinoma after radiofrequency ablation.

BACKGROUND: The impact of prolonged post-ablation fever (PAF) defined as persistent fever > 24 h after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) had not been described before. This study aims to investigate the impact of prolonged PAF on early tumor recurrence in HCC patients after RFA. METHODS: From 2013 to 2015, a total of 135 patients with HCC meeting Milan criteria and all the tumors having confirmed complete ablation after RFA were enrolled. Study endpoint was any HCC recurrence within 1 year after ablation. Cox regression analysis was applied for multivariate analysis to determine the independent predictors of 1-year tumor recurrence. RESULTS: Post-ablation fever occurred in 42 (31.1%) patients after RFA, while prolonged PAF was found in 22 (16.3%) patients. Fifty-eight (42.8%) patients occurred any tumor recurrence within 1 year after complete ablation. Patients with prolonged PAF had a significantly higher rate of HCC recurrence within 1 year (72.7% vs. 37.1%, p = 0.002) and had a significantly shorter time-to-recurrence interval (19.6 vs. 40.5 months, Log rank test, p = 0.002) than those who had no prolonged PAF. Multivariate analysis by Cox regression showed the previous HCC recurrence history (aHR: 1.792, p = 0.0284), baseline AFP > 20 ng/ml (aHR: 1.868, p = 0.0211) and prolonged PAF (aHR: 2.092, p = 0.0138) were associated with early recurrence. CONCLUSIONS: Prolonged PAF may associate with early HCC recurrence after complete ablation by RFA. Patients with prolonged PAF need to be more clinical attentions.

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.

Timely eradication of HCV viremia by PegIFN/RBV is crucial in prevention of post RFA recurrence in CHC-HCC patients.

BACKGROUND: Secondary prevention of hepatocellular carcinoma (HCC) among patients with chronic hepatitis C (CHC) who achieve sustained virologic response (SVR) with interferon-based therapy has been proved effective. However, tertiary prevention with PegIFN/RBV therapy of HCC recurrence seems limited effect in CHC-HCC patients post curative therapies. This study aims to investigate the timing and impact of PegIFN/RBV treatment on prevention of HCC recurrence in patients after RFA treatment. METHODS: From 2013 to 2016, a total of 137 CHC-HCC patients from a 508 patient based cohort receiving complete RFA treatment in Chang Gung Memorial Hospital, Linkou Medical Center were retrospectively recruited. Pre-RFA patient demographics were analyzed by cox regression analysis for prediction on tumor recurrence. Statistics analysis was performed with SPSS V.20 (IBM, USA). RESULTS: The mean age of the 137 patients were 69.6 year-old and 71.5% of patients were cirrhotic. After propensity score matching, one hundred and two patients were enrolled into the analysis. Fifty-one patients (50%) received PegIFN/RBV therapy and twenty-seven patients (52.9%) achieved SVR. Patients who could achieve SVR had lower tumor recurrence rate than non-SVR and untreated groups (29.6% vs. 66.7% vs. 49.0%, P = 0.030). The effect is more prominent in those achieve SVR prior to compared with after RFA despite not reach statistically significant (26.1% vs. 50.0%, P = 0.334). CONCLUSION: Timely treatment with SVR achievement has the lowest tumor recurrence rate in CHC-HCC patients. Secondary prevention might be even more important than tertiary prevention in CHC patients, especially regarding prevention of post RFA HCC recurrence.

Preoperative Leukocyte Counts Increase Risk of Adverse Outcomes in Obese Patient Undergoing Cardiac Surgery.

Obesity is a chronic inflammatory state associated with increased postoperative morbidity in patients undergoing cardiac surgery. In this study, we sought to determine whether the white blood cell (WBC) response may be an additional predictor for postoperative morbidities in obese patients undergoing cardiac surgery. A total of 1,171 consecutive patients who underwent cardiac surgery were retrospectively reviewed. Patients were divided into three groups based on their body mass index (BMI): non-obese (BMI < 30 kg/m²), obese (BMI 30-34.9 kg/m²) and severely obese (BMI ≥ 35 kg/m²). We used serial WBC count as an index of inflammation. Postoperative infection rate and postoperative hospital and intensive care unit (ICU) lengths of stay (LOS) were the primary endpoints. Obese and severely obese patients had significantly higher preoperative WBC counts and greater changes from the baseline at 24 h post-operation (P < 0.01). Obese and severely obese patients had significantly higher postoperative infection rate (P < 0.01). The postoperative LOS was significantly longer in severely obese patients (P = 0.03), and the ICU LOS was significantly longer in severely obese patients compared to non-obese patients (P = 0.02). Using logistic regression analysis, we identified the preoperative WBC count as an independent predictor for longer ICU stay and higher postoperative infection rate, and changes in WBC from preoperative baseline as a predictor for postoperative length of hospital stay in addition to BMI. Obese patients have increased postoperative morbidity after cardiac surgery. In addition to BMI, preoperative WBC count and the increase in WBC from the baseline in the immediate postoperative period are independent predictors for postoperative adverse outcomes.

The miR-200b-ZEB1 circuit regulates diverse stemness of human hepatocellular carcinoma.

Accumulating evidence suggests that human hepatocellular carcinoma (HCC) can be derived from cancer stem cells (CSCs), which contribute to tumor initiation, metastasis, chemoresistance, and recurrence. A great variety of HCC CSCs resulting in diverse clinical manifestations have been reported. However, how CSC diversity is regulated and generated remains unclear. Here we report that the miR-200b-ZEB1 circuit is closely involved with the induction and maintenance of a diverse group of CSCs. We found that miR-200b downregulation occurred in early HCC and associated with poor prognosis. The downregulation was attributable to genome deletion and promoter methylation of the miR-200a/b/429 gene. Ectopic expression of miR-200b or silencing of ZEB1 led to a decrease in CD13+ and CD24+ HCC CSCs and an increase in EpCAM+ HCC CSCs. Mechanistically, miR-200b directly suppressed BMI1 and ZEB1 expressions. ZEB1 recognized promoters of CD13, CD24, and EpCAM genes resulting in CD13 and CD24 upregulation and EpCAM downregulation. Neither miR-200b nor ZEB1 had obvious effects on CD133 or CD90 expression. Silencing CD13 or CD24 expression suppressed tumorigenicity of HCC cells. Ectopic expression of CD24 reversed the suppression of tumorigenicity by ectopic expression of miR-200b. Clinically, miR-200b downregulation was coupled with ZEB1 upregulation in approximately two-thirds of HCC patients. ZEB1 expression was positively correlated with CD13 and CD24 expressions in HCCs, while miR-200b expression was positively correlated with EpCAM. Our findings suggest that the miR-200b-ZEB1 circuit is a master regulator of diverse stemness of HCC, which differentiates HCCs into those containing CD13+ /CD24+ CSCs from those containing EpCAM+ CSCs.

Acute exacerbation of hepatitis C in hepatocellular carcinoma patients receiving chemotherapy.

Acute hepatitis C exacerbations can occur in cancer patients carrying hepatitis C virus (HCV) when receiving systemic chemotherapy. However, clinical studies evaluating these complications remain rare due to the lack of clinically proven effective and tolerable anti-HCV treatments at late cancer stages. Furthermore, no data were available regarding hepatitis C exacerbation in advanced hepatocellular carcinoma (HCC) patients receiving chemotherapy. To address this issue, 48 patients with HCV-related advanced HCC, who underwent systemic chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone from 2008 to 2014 were analyzed. Nine patients developed acute hepatitis exacerbations defined by HCV-RNA elevation ≥10-fold and alanine transaminase (ALT) elevation ≥5-fold of the upper normal limit. Six were genotype 1b and 3 were genotype 2. Three patterns of clinical courses were observed including single episode of exacerbation (n = 5), fluctuated flares (n = 3), and delayed exacerbation (n = 1). Hepatic failure developed in five patients. Patients with acute exacerbations were less likely to have pretreatment ascites (11.1% vs. 53.8%; P = 0.028) and displayed a lower baseline ALT (44.1 ± 28.5 U/L vs. 72.6 ± 19.2 U/L; P = 0.007). Paradoxically, despite a high risk of hepatic failure, occurrence of hepatitis C exacerbation was associated with a favorable overall survival (P = 0.027; 22.8 vs. 5.4 months). In conclusion, hepatitis C exacerbation can occur in HCC patients receiving chemotherapy, leading to liver failure. However, the flare was associated with a better overall survival, possibly due to its association with a better baseline liver function. J. Med. Virol. 89:153-160, 2017. © 2016 Wiley Periodicals, Inc.

Perceptions of problem-drinker patients' family members about their own hazardous-drinking behaviours in Chinese general hospitals: a qualitative study.

BACKGROUND: Excessive alcohol use has been associated with health, social and legal problems. Alcohol-related problems have been studied primarily in problem-drinker patients, with few studies on their family members, particularly about their own hazardous or harmful alcohol-drinking behaviours. METHOD: In this qualitative descriptive study, participants were recruited from three hospitals randomly selected from northern and central Taiwan (2:1). Hazardous-drinker patients and their family members were screened using the Chinese version Alcohol Use Disorders Identification Test (scores ≥8 indicate harmful or hazardous drinkers). Data were collected in individual, audiotaped, in-depth interviews using an interview guide. Verbatim interview transcripts were analysed using ATLAS.ti, version WIN 7.0. RESULTS: The sample of 35 family members with hazardous or harmful drinking behaviours perceived that their own alcohol-drinking behaviours were related to six major patterns: family habits, leisure activities with friends, work pressures, personal taste, a way to forget one's problems and to express happiness. CONCLUSION: We recommend that programmes targeting harmful or hazardous drinking among problem-drinker patients' family members should educate participants about the standard amounts of alcohol in alcoholic beverages, recommended amounts of alcohol consumption for males and females, the long-term effects of excessive alcohol consumption; address sources of risk factors at work; offer strategies to resist social pressures to drink; and build positive strategies for coping with stress.

Pretreatment platelet count early predicts extrahepatic metastasis of human hepatoma.

BACKGROUND & AIMS: Thrombocytosis is associated with metastasis in many human cancers. Most hepatocellular carcinomas (HCC) develop in cirrhotic livers, which are characterized by thrombocytopenia. We aimed to elucidate the pretreatment platelet count in prediction of extrahepatic metastasis of HCC during the follow-up. METHODS: Three cohorts containing 1660, 480 and 965 HCC patients enrolled from three hospitals were used for discovery and validation respectively. Pretreatment clinical factors associated with extrahepatic metastasis during follow-up up to 5 years were identified using multivariate Cox regression model. RESULTS: In early-stage HCC (BCLC stage 0-A), pretreatment platelet count (hazard ratio [HR], 1.04 per 10,000/µl; 95% CI, 1.01-1.07; P = 0.010) and serum alpha-foetoprotein (AFP) >100 ng/ml (HR, 1.70; 95% CI, 1.04-2.78; P = 0.033) were the only two independent factors associated with extrahepatic metastasis. Receiver operating characteristic evidenced that pretreatment platelet count predicted metastasis better than AFP did. Survival tree analysis identified platelet counts <118,000/µl (HR, 0.49; 95% CI, 0.38-0.63; P < 0.001) or >212,000/µl (HR, 2.12; 95% CI, 1.67-2.70; P < 0.001) to categorize patients into low and high risk of metastasis subgroups, which were verified using both validation cohorts. CONCLUSIONS: Pretreatment platelet count is a reliable marker to predict extrahepatic metastasis of early-stage HCC following curative treatment. Cirrhotic thrombocytopenia contributes to relatively low metastasis incidence of HCC than many other cancers. High platelet count identifies a subgroup of HCC patients at high risk of metastasis, who might benefit from adjuvant therapies following initial curative treatment.

A single nucleotide polymorphism on the GALNT14 gene as an effective predictor of response to chemotherapy in advanced hepatocellular carcinoma.

Previously, a pilot genome-wide association study has identified candidate single nucleotide polymorphism predictors for the therapeutic response of 5-fluorouracil, mitoxantrone and cisplatin (FMP) combination chemotherapy in advanced hepatocellular carcinoma (HCC). Here, we conducted a prospective confirmatory study to examine the predictive value of rs9679162 (located on GALNT14 gene) for the therapeutic responses using a split-dose FMP protocol. One hundred and seven advanced HCC patients receiving split-dose FMP therapy were enrolled. All patients were in Barcelona Clinical Liver Cancer Stage C with either main portal vein thrombosis and/or distant metastasis. Of them, 105 (98.1%) were Child-Pugh classification B. GALNT14 genotype was determined before therapy. Of the patients included, 28 were rs9679162 "TT" and 79 were "non-TT" ("GG" + "GT") genotype. The median overall survival, time-to-progression, response rate and disease control rate were ("TT" versus "non-TT") 6.8 versus 3.9 months (p < 0.001), 3.9 versus 2.1 months (p < 0.001), 28.6% versus 10.1% (p = 0.029) and 35.7% versus 15.2% (p = 0.030), respectively. Multivariate analysis indicated that rs9679162 genotype was an independent predictor for overall survival (p = 0.002). Categorical analysis showed that 17 patients with "TT" genotype, tumor size < 10 cm and neutrophils < 74% had a median overall survival of 25.5 months and a therapeutic response rate of 47.1%. In conclusion, this prospective study confirmed that GALN14 genotype (rs9679162) was an effective predictor for therapeutic outcome in advanced HCC patients treated by FMP chemotherapy. Combining GALNT14 genotype and clinical parameters, a subgroup of patients with excellent outcome was identified.

Adjuvant therapy for hepatocellular carcinoma after curative treatment.

Hepatocellular carcinoma (HCC) is a common malignancy in the world. Although resection and various locoregional therapies can achieve eradication or complete ablation of small HCC, HCC recurrence after these therapies is still common. Although candidates for medical ablation usually exhibit compensated hepatic functional status, the frequent recurrence of HCC after successful ablation contributes to short survival. Therefore, attempts to prevent HCC recurrence are essential to prolong survival. Efforts in preventing HCC recurrence after curative therapies include prevention of early recurrence by improving liver immunity and eliminating microscopic tumor foci or micrometastases, and prevention of late recurrence by reducing the hepatitis activity and using antiviral therapies based on viral suppression/eradication. In HCC with vascular invasion, adjuvant transcatheter arterial chemoembolization should be considered to provide better control. Whether the adjuvant use of sorafenib may suppress microscopic tumor foci or micrometastases may be unveiled in the near future. This review article will update the algorithms, novel medication or study drugs in the prevention of HCC after curative therapies.

Crystal amphetamine smoking-induced acute eosinophilic pneumonia and diffuse alveolar damage: a case report and literature review.

Eosinophilic pneumonia (EP) is a disease characterized by prominent infiltration of lung structures by eosinophils. The lung interstitium is infiltrated by eosinophils, and essentially the alveolar spaces are filled with eosinophils and a fibrinous exudate, with conservation of the global architecture of the lung. Diagnosis of EP relies on pathological demonstration of alveolar eosinophilia along with characteristic clinical manifestations of nonproductive cough, dyspnea, chest pain and/or unique imaging features. EP may be categorized according to the origin: EP of undetermined origin may overlap with well-individualized syndromes, while EP with a definite cause are mainly due to infections or drug abuse. Here, we report a case of an amphetamine abuser who developed acute EP and acute respiratory distress syndrome after amphetamine inhalation. Related studies on the pathogenesis of stimulant-related lung injury and treatment strategies are also discussed.

Locoregional treatment improves overall survival for liver cancer during second-line regorafenib or immune checkpoint inhibitor.

For advanced hepatocellular carcinoma (HCC), the best second-line treatment after first-line treatment with sorafenib is unclear. This study aimed to compared the efficacy of second-line regorafenib (a tyrosine kinase inhibitor) and immune checkpoint inhibitors (ICIs) in patients with advanced HCC after sorafenib therapy. This retrospective study included 89 patients with HCC treated with sorafenib, and then regorafenib (n = 58) or an ICI (n = 31). Treatment response, overall survival (OS) and progression-free survival (PFS) of the 2 groups were compared, and factors associated with post-treatment mortality or disease progression were evaluated. During follow-up period, compared to regorafenib, treatment with an ICI results in a slight increase in a 20% decrease of AFP (35.7% vs. 31.8%), complete response rate (6.5% vs. 0%), objective response rate (16.1% vs. 6.9%), median overall survival (13.3 vs. 5 months), and median PFS (3.0 vs. 2.6 months). Combined locoregional treatment (LRT) (hazard ratio [HR] = 0.40, 95% confidence interval [CI]: 0.15-0.99) during second-line treatment was associated with a decreased risk of post-treatment mortality. After propensity scoring matching, combined LRT during second-line treatment had longer post-treatment OS than patients without combined LRT. A 20% decrease of AFP (HR = 0.54, 95% CI: 0.31-0.94) was associated with a decreased risk of post-treatment disease progression. In conclusions, second-line treatment with regorafenib or ICI prolongs OS in patients with advanced HCC treated with sorafenib. Combined LRT during second-line treatment is associated with decreased post-treatment mortality. A 20% decrease of AFP level may be predictive of a lower rate of disease progression.

Clinical and Dosimetric Results of Proton or Photon Radiation Therapy for Large (>5 cm) Hepatocellular Carcinoma: A Retrospective Analysis.

PURPOSE: Our purpose was to report the clinical and dosimetric attributes of patients with large unresectable hepatocellular carcinoma (HCC) undergoing proton or photon radiation therapy. METHODS AND MATERIALS: We retrospectively analyzed the outcomes and dosimetric indices of 159 patients with >5 cm nonmetastatic HCC who underwent definitive radiation therapy using either protons (N = 105) or photons (N = 54) between 2014 and 2018. Additional photon plans were performed in the 105 proton-treated patients using the same dose prescription criteria for intragroup dosimetric comparison. RESULTS: After a median follow-up of 47 months, patients with biologically effective dose (BED10) ≥ 75 Gy exhibited significantly better local control (LC; 2-year: 85.6% vs 20.5%; P < .001), progression-free survival (PFS; median, 7.4 vs 3.2 months; P < .001), and overall survival (OS; median, 18.1 vs 7.3 months; P < .001) compared with those with BED10 < 75 Gy. Notably, proton-treated patients had a significantly higher BED10 (96 vs 67 Gy; P < .001) and improved LC (2-year: 88.5% vs 33.8%; P < .001), PFS (median, 7.4 vs 3.3 months; P = .001), and OS (median, 18.9 vs 8.3 months; P < .001) than those undergoing photon radiation therapy. Furthermore, patients treated with protons had significantly lower V1 of the liver (P < .001), mean upper gastrointestinal tract dose (P < .001), and mean splenic dose (P < .001), with significantly decreased incidences of radiation-induced liver disease (P = .007), grade ≥3 upper gastrointestinal bleeding (P = .001), and grade ≥3 lymphopenia (P = .003). On multivariate analysis, proton radiation therapy consistently correlated with superior LC (P < .001), PFS (P < .001), and OS (P < .001). In intragroup dosimetric comparison, photon plans demonstrated significantly higher mean liver dose (P < .001) compared with actually delivered proton treatments, and 72 (69%) of them had mean liver dose exceeding 28 Gy, which necessitated target dose de-escalation. CONCLUSIONS: In the context of large HCC radiation therapy, a higher target BED10 was associated with improved outcomes. Notably, proton therapy has demonstrated the capability to deliver ablative doses while also being accompanied by fewer instances of severe toxicity.

Effectiveness of high-flow nasal cannulae compared with noninvasive positive-pressure ventilation in preventing reintubation in patients receiving prolonged mechanical ventilation.

Many intensive care unit patients who undergo endotracheal extubation experience extubation failure and require reintubation. Because of the high mortality rate associated with reintubation, postextubation respiratory management is crucial, especially for high-risk populations. We conducted the present study to compare the effectiveness of oxygen therapy administered using high-flow nasal cannulae (HFNC) and noninvasive positive pressure ventilation (NIPPV) in preventing reintubation among patients receiving prolonged mechanical ventilation (PMV). This single-center, prospective, unblinded randomized controlled trial was at the respiratory care center (RCC). Participants were randomized to an HFNC group or an NIPPV group (20 patients in each) and received noninvasive respiratory support (NRS) administered using their assigned method. The primary outcome was reintubation within7 days after extubation. None of the patients in the NIPPV group required reintubation, whereas 5 (25%) of the patients in the HFNC group required reintubation (P = 0.047). The 90-day mortality rates of the NIPPV and HFNC groups (four patients [20%] vs. two patients [10%], respectively) did not differ significantly. No significant differences in length of RCC stay, length of hospital stay, time to liberation from NRS, and ventilator-free days at 28-day were identified. The time to event outcome analysis also revealed that the risk of reintubation in the HFNC group was higher than that in the NIPPV group (P = 0.018). Although HFNC is becoming increasingly common as a form of postextubation NRS, HFNC may not be as effective as NIPPV in preventing reintubation among patients who have been receiving PMV for at least 2 weeks. Additional studies evaluating HFNC as an alternative to NIPPV for patients receiving PMV are warranted.ClinicalTrial.gov ID: NCT04564859; IRB number: 20160901R.Trial registration: ClinicalTrial.gov ( https://clinicaltrials.gov/ct2/show/NCT04564859 ).

Combination of systemic immune-inflammation index and albumin-bilirubin grade predict prognosis of regorafenib in unresectable hepatocellular carcinoma.

Regorafenib improved prognosis for unresectable hepatocellular carcinoma (uHCC) after sorafenib treatment failure. We aimed to investigate prognostic value of combining systemic inflammatory markers with liver function evaluation in patients receiving sorafenib-regorafenib sequential therapy. A total of 122 uHCC patients who received sorafenib-regorafenib sequential therapy were retrospectively enrolled for analysis. The pre-treatment preserving liver function and six inflammatory indexes were collected. The Cox regression model was used to identify independent predictors of progression-free survival (PFS) and overall survival (OS). Baseline ALBI grade I (hazard ratio (HR) = 0.725, P = 0.040 for PFS; HR = 0.382, P = 0.012 for OS) and systemic inflammatory index (SII) ≤ 330 (HR = 0.341, P = 0.017 for OS; HR = 0.485, P = 0.037 for OS) were identified as independent prognostic factors in multivariable analysis and were used to develop the scoring system. Patients who fulfilled both criteria (2 points; score-high) had the longest median PFS (not-reached) and OS (not-reached), followed by fulfilling 1 criterion (1 point; score-intermediate; PFS: 3.7 months and OS: 17.9 months), and patients fulfilled no criterion (0 point; score-low; PFS: 2.9 months, overall log-rank P = 0.001 and OS: 7.5 months, overall log-rank P = 0.003). Additionally, best radiological response was significantly higher in patients with score-high (complete response/partial response/stable disease/progressive disease: score-high: 5.9%/5.9%/58.8%/29.4% vs. score-intermediate: 0%/14.0%/44.2%/41.9% vs. score-low: 0%/0%/25.0%/75.0%; P = 0.011). In conclusion, a combination of baseline ALBI grade and SII index can be used as a simple and powerful parameter to predict prognosis of uHCC patients receiving regorafenib after sorafenib-refractory treatment. The score may help with patient counseling but requires prospective validation.