Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Efficacy and safety of lenvatinib plus PD-1 inhibitor with or without transarterial chemoembolization in unresectable hepatocellular carcinoma.

PURPOSE: To compare the clinical benefit and tolerability of triple therapy of lenvatinib, programmed death 1 (PD-1) inhibitor, and transarterial chemoembolization (TACE) versus dual therapy of lenvatinib and PD-1 inhibitor in unresectable hepatocellular carcinoma (HCC) patients. METHODS: Between October 2018 and September 2021, patients with unresectable HCC who received triple therapy of lenvatinib, PD-1 inhibitor, and TACE or dual therapy of lenvatinib and PD-1 inhibitor participated in this study. The efficacy was evaluated by survival and therapeutic response, and the tolerability was evaluated by the frequency and severity of key adverse events (AEs). RESULTS: In total, 118 eligible patients with unresectable HCC who received combination therapy were included in this study. Among them, 60 patients received triple therapy of lenvatinib, PD-1 inhibitor, and TACE (L-P-T group), and 58 eligible patients received dual therapy of lenvatinib and PD-1 inhibitor (L-P group). Patients who received triple therapy had better overall survival (OS) [median, 29.0 vs. 17.8 months, p < 0.01] and progression-free survival (PFS) [median, 16.2 vs. 10.2 months, p < 0.01] than those who received dual therapy. The objective response rate (76.7 vs. 44.9%, p < 0.01) and disease control rate (96.7 vs. 75.9%, p < 0.01) in the L-P-T group were higher than in the L-P group, respectively. Multivariate analyses revealed that the treatment option and BCLC stage were independent prognostic factors for OS, while treatment option and tumor number were independent prognostic factors for PFS. The incidence and severity of AEs in the L-P-T group were comparable to those in the L-P group (any grade, 95.0 vs. 94.8%, p = 1.00; grade ≥ 3, 30.0 vs. 27.6%, p = 0.93). CONCLUSION: Triple therapy of lenvatinib, PD-1 inhibitor, and TACE may achieve more favorable survival benefits than dual therapy of lenvatinib and PD-1 inhibitor in unresectable HCC patients with manageable safety profiles.

Association between depressive symptoms and lung function in the United States adults without pulmonary diseases: A cross-sectional study from NHANES.

BACKGROUND: Depression is a severe and common mental disorder. The association between depressive symptoms and lung function remains unclear. To determine whether depressive symptoms are associated with lung function in U.S. adults without pulmonary diseases. METHODS: A cross-sectional study of National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2012 were used to estimate the relationship between depressive symptoms and lung function. Depressive symptoms were determined by a participant's score on the Patient Health Questionnaire-9. Forced Expiratory Volume 1st Second (FEV1) Forced Vital Capacity (FVC) were determined by the spirometry. Weighted multivariate linear regression was used to analyze this relationship and subgroup analyses were performed. RESULTS: Of 8027 participants, 576 (7.18 %) participants with depression. Depression group had significant lower FEV1 and FVC than non-depression group. After adjustment for all covariates, there was a significant negative association between depressive symptoms and FVC (ß -4.84, 95 % CI -9.10 to -0.57), especially in non-Hispanic White people (ß -9.03, 95 % CI -14.38 to -3.69). There was no independent association between depressive symptoms and FEV1 in all participants, whereas the association was significant in non-Hispanic White people (ß -4.91, 95 % CI -9.50 to -0.32). CONCLUSIONS: High depressive symptoms were independently associated with decline of FVC among U.S. adults without pulmonary diseases, especially in non-Hispanic White people. In addition, although it was not independently associated with FEV1 in all participants, depressive symptom score was also negatively associated with FEV1 in non-Hispanic White people.

Prognostic effect of albumin-to-alkaline phosphatase ratio on patients with hepatocellular carcinoma: a systematic review and meta-analysis.

The prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) in patients with hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aims to evaluate the prognostic role of AAPR in patients with HCC. The databases of Web of Science, Embase, Cochrane Library and PubMed were comprehensively searched from inception to April 25, 2022. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated with Stata 16.0 software for the assessment of the relationship between AAPR and overall survival (OS) as well as recurrence-free survival (RFS) in patients with HCC. A total of 2634 patients from 12 cohorts were included in this meta-analysis. The pooled results showed that lower AAPR predicted poorer OS (HR 2.02, 95% CI 1.78-2.30). Similarly, pooled results demonstrated that lower AAPR also predicted poorer RFS (HR 1.88, 95% CI 1.37-2.57). The heterogeneity for RFS by multivariate analytic results and the publication bias for OS existed, however, the subgroup analysis, meta-regression analysis as well as adjustment using trim-and-fill analysis confirmed an association between AAPR and OS as well as RFS. This meta-analysis proves that lower AAPR in patients with HCC predicted inferior survival outcomes, and AAPR might be a promising indicator for the prognosis of HCC.

Efficacy and safety of atezolizumab plus bevacizumab combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma.

Background: Atezolizumab plus bevacizumab has been proved to have promising antitumor activity and tolerable safety in patients with unresectable hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) also demonstrated high response rates and favorable survival for patients with advanced HCC. This study aimed to explore the preliminary clinical efficacy and safety of atezolizumab plus bevacizumab combined with HAIC for patients with treatment-naive advanced HCC. Methods: Between October 2020 and September 2021, patients with advanced HCC who initially received atezolizumab plus bevacizumab combined with HAIC of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) from three hospitals in China were reviewed for eligibility. The efficacy was evaluated by tumor response rate and survival, and the safety was evaluated by the frequency of key adverse events (AEs). Results: In total, 52 eligible patients with advanced HCC who received triple therapy were included in this study. The objective response rates (ORRs) based on mRECIST and RECIST1.1 criteria were 67.3% and 44.2%, respectively. The median progression-free survival (PFS) of patients was 10.6 months (95% CI, 8.37-13.8), and the overall survival (OS) was not reached. Extrahepatic metastasis was an independent risk factor associated with PFS. All AEs were controlled and no treatment-related deaths occurred. Conclusion: Atezolizumab plus bevacizumab combined with HAIC-FOLFOX had a significant therapeutic effect and manageable AEs in patients with advanced HCC, which may be a potential treatment option for advanced HCC.

Complete Response After Pre-Operative Transcatheter Arterial Chemoembolization for Unresectable Primary Hepatic Neuroendocrine Tumour: A Case Report and Literature Review.

Background: Primary hepatic neuroendocrine tumours (PHNET) are extremely rare. Currently, no evidence-based guidelines are available for PHNET treatment, especially for unresectable tumours. Case Presentation: We present the case of a 43-year-old man who was admitted to our hospital with complaints of backache for more than 1 month. The imaging examination showed a 5.5×5.3 cm lesion in the liver and no extrahepatic lesions, which was confirmed as a grade 2 PHNET by the pathological results and exclusion of non-hepatic origins. A multidisciplinary team (MDT) consultation revealed that the lesion was an unresectable primary hepatic neuroendocrine tumour (uPHNET) but could be potentially treated by conversion surgery. The patient was initially administered four cycles of chemotherapy with temozolomide, 5-fluorouracil, and ondansetron, and was evaluated as stable disease (SD) according to the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Because of the limited clinical benefit of chemotherapy, the patient subsequently underwent transcatheter arterial chemoembolisation (TACE) treatment, which reduced the tumour size and converted uPHNET to resectable tumours. A complete response (CR) was achieved after surgery, and the patient has been disease-free. Conclusions: This case was reported by a patient with uPHNET who benefited from the pre-operative TACE, providing a potentially effective management strategy for refractory tumours.

Aspartate aminotransferase-to-platelet ratio index for predicting late recurrence of hepatocellular carcinoma after radiofrequency ablation.

BACKGROUND: Our study aimed to explore the prognostic value of the aspartate aminotransferase-platelet ratio index (APRI) and to develop a new nomogram for patients with hepatocellular carcinoma (HCC) who experience late recurrence after radiofrequency ablation (RFA). To date, no study has explored the value of APRI for assessing the late recurrence of HCC after RFA. MATERIALS AND METHODS: The prognostic value of APRI was evaluated and validated in our multicenter retrospective analysis. A total of 466 HCC patients undergoing RFA were reviewed as a training cohort, and 234 HCC patients were included in the external validation cohort. The nomogram was built based on significant prognostic factors in a multivariate analysis and validated in the external validation cohort. RESULTS: The cutoff APRI score was 0.78, and it appropriately discriminated between low- and high-risk groups for late recurrence in HCC patients. The cumulative recurrence-free survival rates of the low-risk group were significantly higher than those of the high-risk group (p < 0.001), according to the Kaplan-Meier curves. Late recurrence in HCC patients after RFA was associated with APRI, sex and multiple tumors. The nomogram based on potential risk factors (APRI score, sex and multiple tumors) as indicated by multivariate Cox regression analysis showed good discrimination and calibration in the training and external verification groups. CONCLUSIONS: The APRI score is a feasible independent prognostic factor for the late recurrence of HCC after RFA. The proposed nomogram could aid clinicians in following disease progression and providing tailored therapy for patients.

The effectiveness of radiofrequency ablation for patients with BCLC B1 stage hepatocellular carcinoma downgraded by transarterial chemoembolization.

PURPOSE: To evaluate the effectiveness of radiofrequency ablation (RFA) as a curative therapy for BCLC B1 stage (beyond Milan criteria but within up-to-seven criteria) hepatocellular carcinoma (HCC) followed by downstageing by using transarterial chemoembolization (TACE). METHODS: We retrospectively recruited patients underwent RFA alone and who underwent RFA following downstaging into BCLC B1 stage using TACE between April 2011 and August 2017. Overall survival (OS) and recurrence-free survival (RFS) were compared using the Kaplan-Meier method. A propensity score analysis was performed to reduce potential bias. RESULTS: The downstaging TACE+RFA and RFA alone group comprised 50 and 110 patients, respectively. After propensity score matching, the 1-, 2-, and 3-year OS rates were 100%, 92%, 74%, respectively, the 1-, 2-, and 3-year RFS rates were 40%, 36%, and 20%, respectively, for patients in the downstaging TACE+RFA group. The 1-, 2-, and 3-year OS rates were 96%, 90%, and 82%, respectively, the 1-, 2-, and 3-year RFS rates were 51%, 32%, and 32%, respectively, for patients in the RFA group. No statistical differences were observed between the two groups in terms of OS and RFS before and after matching. CONCLUSION: RFA after downstaging into BCLC B1 stage using TACE offered a safe and effective treatment regime for patients with HCC beyond the up-to-seven criteria. The intermediate-term OS and RFS of RFA following downstaging into BCLC B1 stage using TACE for HCC were similar to that of patients who were initially in BCLC B1stage.

A Systemic Inflammation Response Index (SIRI)-Based Nomogram for Predicting the Recurrence of Early Stage Hepatocellular Carcinoma After Radiofrequency Ablation.

OBJECTIVE: To explore the prognostic value of the systemic inflammation response index (SIRI) defined as neutrophil count × monocyte count/lymphocyte count in the patients with early stage hepatocellular carcinoma (HCC) within the Milan criteria after radiofrequency ablation (RFA). MATERIALS AND METHODS: The prognostic value of SIRI was evaluated in a primary cohort (n = 403) and then further validated in an independent test cohort (n = 140). A novel preoperative prognostic nomogram was constructed from a multivariate analysis and validated in an external validation cohort. RESULTS: The optimal cutoff value of SIRI for patient stratification into a low SIRI group and a high SIRI group was 1.36. Survival analysis showed that the median overall survival (OS) and recurrence-free survival (RFS) were significantly higher in patients with a low SIRI compared to those with a high SIRI. The alpha-fetoprotein (AFP), SIRI, tumor number and size were independent predictors of RFS based on multivariate analysis. The nomogram including the SIRI, tumor number, tumor size, AFP could more accurately determine the prognosis of HCC patients than BCLC stage (0.74 vs. 0.62, P < 0.001). In addition, the dynamic changes in post-RFA SIRI also had prognostic significance and patients with a reduction in the SIRI by > 75% had a better prognosis. CONCLUSION: Preoperative SIRI was an independent predictor for RFS in patients with early stage HCC within the Milan criteria. The comprehensive nomogram can objectively and reliably help clinicians identify high-risk patients and develop individualized treatment plans.

Nomograms including the controlling nutritional status score in patients with hepatocellular carcinoma undergoing transarterial chemoembolisation for prediction survival: a retrospective analysis.

This retrospective study investigated the predictive value of the Controlling Nutritional Status (CONUT) score in patients with intermediate-stage hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE). Nomograms were developed to predict progression-free and overall survival (PFS, OS). The medical data of 228 patients with HCC and treated with TACE were collected. The patients were apportioned to 2 groups according to CONUT score: low or high (<4, ≥4). Univariate and multivariate analyses were performed using Cox regression for OS and PFS. OS and PFS were estimated by the Kaplan-Meier curve and compared with the log-rank test. Nomograms were constructed to predict patient OS and PFS. The nomograms were evaluated for accuracy, discrimination, and efficiency. The cut-off value of CONUT score was 4. The higher the CONUT score, the worse the survival; Kaplan-Meier curves showed significant differences in OS and PFS between the low and high CONUT score groups (P = 0·033, 0·047). The nomograms including CONUT, based on the prognostic factors determined by the univariate and multivariate analyses, to predict survival in HCC after TACE were generated. The CONUT score is an important prognostic factor for both OS and PFS for patients with intermediate HCC who underwent TACE. The cut-off value of the CONUT score was 4. A high CONUT score suggests poor survival outcomes. Nomograms generated based on the CONUT score were good models to predict patient OS and PFS.

Using the aMAP Risk Score to Predict Late Recurrence Following Radiofrequency Ablation for Hepatocellular Carcinoma in Chinese Population: A Multicenter Study.

OBJECTIVE: This study was conducted to explore the application of age-male-ALBI-platelets (aMAP) score for predicting late recurrence of hepatocellular carcinoma (HCC) following radiofrequency ablation (RFA) and develop an aMAP score based-nomogram to predict prognosis in Chinese population. MATERIALS AND METHODS: HCC patients who developed late recurrence following RFA at National Cancer Center (NCC) of China, First Hospital of Shanxi Medical University and Beijing Hospital of Traditional Chinese Medicine from January 2011 to December 2016 were included as a training cohort, and patients who were treated at Affiliated Cancer Hospital of Zhengzhou University between January 2012 and December 2016 were included as an external validation cohort. The optimal cut-off value for aMAP score was determined using X-tile software to discriminate the performance of recurrence-free survival (RFS). RESULTS: A total of 339 eligible patients were included in this study. Patients were grouped into low-risk (aMAP score ≤64.2), medium-risk (64.3 ≤aMAP score ≤68.6) and high-risk (aMAP score ≥68.7) groups by X-tile plots. The prognostic factors that affected RFS were the number of lesions and aMAP score. A nomogram was constructed to predict the RFS with a C-index of 0.793 (95% CI: 0.744-0.842). The time-dependent receiver operating characteristic curves (t-AUCs) of the nomogram to predict 3, 4 and 5-year RFS were 0.808, 0.820 and 0.764, respectively. The model was then tested with data from an external validation cohort. The calibration curve confirmed the optimal agreement between the predicted and observed values. CONCLUSION: The aMAP score provided a well-discriminated risk stratification and is an independent prognostic factor for the late recurrence of HCC following RFA. The aMAP score-based nomogram could help to strengthen prognosis-based decision making and formulate adjuvant therapeutic and preventive strategies.

A multicenter, hospital-based and non-inferiority study for diagnostic efficacy of automated whole breast ultrasound for breast cancer in China.

This study is the first multi-center non-inferiority study that aims to critically evaluate the effectiveness of HHUS/ABUS in China breast cancer detection. This was a multicenter hospital-based study. Five hospitals participated in this study. Women (30-69 years old) with defined criteria were invited for breast examination by HHUS, ABUS or/and mammography. For BI-RADS category 3, an additional magnetic resonance imaging (MRI) test was provided to distinguish the true negative results from false negative results. For women classified as BI-RADS category 4 or 5, either core aspiration biopsy or surgical biopsy was done to confirm the diagnosis. Between February 2016 and March 2017, 2844 women signed the informed consent form, and 1947 of them involved in final analysis (680 were 30 to 39 years old, 1267 were 40 to 69 years old).For all participants, ABUS sensitivity (91.81%) compared with HHUS sensitivity (94.70%) with non-inferior Z tests, P = 0.015. In the 40-69 age group, non-inferior Z tests showed that ABUS sensitivity (93.01%) was non-inferior to MG sensitivity (86.02%) with P < 0.001 and HHUS sensitivity (95.44%) was non-inferior to MG sensitivity (86.02%) with P < 0.001. Sensitivity of ABUS and HHUS are all superior to that of MG with P < 0.001 by superior test.For all participants, ABUS specificity (92.89%) was non-inferior to HHUS specificity (89.36%) with P < 0.001. Superiority test show that specificity of ABUS was superior to that of HHUS with P < 0.001. In the 40-69 age group, ABUS specificity (92.86%) was non-inferior to MG specificity (91.68%) with P < 0.001 and HHUS specificity (89.55%) was non-inferior to MG specificity (91.68%) with P < 0.001. ABUS is not superior to MG with P = 0.114 by superior test. The sensitivity of ABUS/HHUS is superior to that of MG. The specificity of ABUS/HHUS is non-inferior to that of MG. In China, for an experienced US radiologist, both HHUS and ABUS have better diagnostic efficacy than MG in symptomatic individuals.

Nomogram Based on Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio to Predict Recurrence in Patients with Hepatocellular Carcinoma after Radiofrequency Ablation.

OBJECTIVES: To investigate the prognostic value of pre-procedure neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and construct a nomogram to predict disease-free survival (DFS) in patients receiving radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) within Milan criteria. METHODS: The data of 515 patients of HCC within Milan criteria receiving RFA were retrospectively collected. The patients were divided into two groups: the training group (n = 382) and the validation group (n = 133). Several preprocedural variables were analyzed in the two groups to determine the prognostic factors. RESULTS: The median DFS time of the training and validation group was 28.4 months and 24.5 months, respectively. Multivariate analyses showed that number of lesions, alpha-feto protein levels, NLR and PLR were independent risk factors of DFS. According to the time-dependent receiver operating characteristic curve (t-ROC), the optimal cutoff value of the NLR and PLR was 1.55 and 75.30, respectively, with sensitivity of 0.737 and 0.648 and specificity of 0.541 and 0.508, respectively. The area under curve (AUC) of the t-ROC curves for the NLR was 0.662 and PLR was 0.597. The DFS was significantly higher in the NLR ≤ 1.55 group compared to NLR > 1.55 group and the PLR ≤ 75.30 group compared to PLR > 75.30 group in both training and validation datasets. Nomogram was developed based on the prognostic factors indicated by the Cox regression to predict 1-, 2-, 3- and 5-year DFS probabilities. CONCLUSIONS: The cutoff value of the NLR and PLR was 1.55 and 75.30. This new nomogram based on NLR and PLR may provide good and individualized prediction of recurrence for HCC patients within Milan criteria after RFA.

Prognostic significance of systemic immune-inflammation index-based nomogram for early stage hepatocellular carcinoma after radiofrequency ablation.

BACKGROUND: Radiofrequency ablation (RFA) is the recommended treatment for early stage hepatocellular carcinoma (HCC), and the prognostic value of systemic immune-inflammation index (SII) in early stage HCC is not discussed. Therefore, the purpose of the study is to explore the prognostic value of SII based on lymphocyte, neutrophil, and platelet counts in patients with HCC after RFA. METHODS: We retrospectively evaluated the prognostic value of the SII in training and validation cohorts, and then established an effective nomogram for HCC after RFA based on SII. The C-index, and area under the time-dependent receiver operating characteristic curve (t-AUC) were used to evaluate the discrimination and calibration value of the nomogram. RESULTS: An optimal cut-off value for the SII of 324.55×109 stratified the patients with HCC into high- and low-SII groups. Univariate and multivariate analyses revealed that SII was an independent predictor for overall survival (OS) and recurrence-free survival (RFS). Moreover, SII was an independent prognostic factor for early-stage HCC with normal alpha-fetoprotein (AFP) levels. The t-AUC of the SII was higher for OS and RFS than for neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR). A high preoperative SII was associated with multiple tumors, larger tumors, and higher levels of AFP. A well-discriminated and calibrated nomogram was constructed to predict the probability of 1-, 2-, 3-, and 5-year RFS with C-indexes of 0.80, which was significantly higher than that obtained with other prognostic clinical indexes. CONCLUSIONS: The SII is an independent prognostic factor affecting the survival outcomes of patients with early-stage HCC. The comprehensive nomogram based on SII presented in this study is a promising model for predicting RFS in HCC patients after RFA.

Early recurrence after radiofrequency ablation for hepatocellular carcinoma: a multicenter retrospective study on definition, patterns and risk factors.

OBJECTIVE: To define an optimal cutoff time to distinguish early and late recurrence in hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA), and to determine the risk factors and patterns of early recurrence. MATERIALS AND METHODS: This retrospective study included HCC patients who developed recurrence after RFA as the primary therapy at three Chinese hospitals from January 2011 to December 2016. The best cutoff time to define early and late recurrence was determined based on differences in post recurrence survival (PRS). The clinical variables were assessed by univariate and multivariate logistic regression analyses. RESULTS: A total of 279 eligible patients were included. The optimal cutoff time interval after RFA to differentiate early and late recurrence was identified as 12 months (p = 0.029). The independent risk factors of early recurrence were multiple tumors, alpha fetoprotein (AFP) levels, gamma-glutamyl transferase (γ-GT), and serum albumin (ALB) levels. A well-discriminated nomogram was constructed to predict risk of early recurrence. The incidence of intrahepatic distant recurrence (IDR) alone and IDR + extrahepatic recurrence (ER) in early recurrence group was significantly higher than those in late recurrence group (80.73% vs. 66.47%, p = 0.009). CONCLUSION: Twelve months was determined as the optimal cutoff time for differentiating early and late recurrence after RFA for HCC patients. The factors affecting early recurrence after RFA were multiple tumors, AFP levels, ALB level, and γ-GT level. Patients in early recurrence cohort were more likely to develop IDR alone or IDR + ER.

Predictors and patterns of recurrence after radiofrequency ablation for hepatocellular carcinoma within up-to-seven criteria: A multicenter retrospective study.

PURPOSE: To determine the risk factors and patterns of recurrence after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) meeting the up-to-seven criteria and to develop a nomogram to predict the recurrence free survival (RFS). MATERIALS AND METHODS: This retrospective study included 481 HCC patients meeting the up-to-seven criteria and who received RFA as the primary therapy at three Chinese hospitals from January 2013 to December 2016. All clinical variables were assessed by univariate and multivariate Cox regression analyses and a nomogram was constructed to predict the probability of RFS. RESULTS: The recurrence rate was 50.7 % (244/481). Age > 60 years, male gender, and multiple tumors were independent risk factors of recurrence. The incidence of early and late recurrence was 68.03 % (n = 166) and 31.97 % (n = 78), respectively. Seven patterns of spatial recurrence were identified: local tumor progression (LTP) alone (n = 18, 7.38 %), intrahepatic distant recurrence (IDR) alone (n = 136, 55.74 %), extrahepatic recurrence (ER) alone (n = 21, 8.61 %), IDR + ER (n = 45, 18.44 %), LTP + IDR (n = 16, 6.56 %), LTP + ER (n = 4, 1.64 %) and LTP + IDR + ER (n = 4, 1.64 %). The 1-, 2-, and 3-year RFS rates were 79.63 %, 65.23 %, and 51.03 %, respectively. A well-discriminated and calibrated nomogram was constructed. CONCLUSIONS: The factors affecting recurrence after RFA were age, gender, and the number of tumors. IDR was the most common type of recurrence after complete ablation.

Safety and efficacy of ultrasound-guided percutaneous coaxial core biopsy of pancreatic lesions: a retrospective study.

BACKGROUND AND OBJECTIVE: Pancreatic cancer tumors are difficult to access for biopsy. The use of coaxial needles during ultrasound (US)-guided coarse needle biopsy (CNB) may help to improve specimen collection yields and avoid tissue damage. In this retrospective study, the safety, efficacy, and clinical benefits of US-guided percutaneous coaxial CNB of pancreatic masses were evaluated and compared to those of non-coaxial CNB. METHODS: A total sample of 220 biopsies performed from August 2015 to August 2019 were analyzed, including 114 performed with a coaxial needle (17-gauge coaxial coarse needle combined with an 18-gauge coarse biopsy needle) and 106 performed with a non-coaxial needle (18-gauge coarse biopsy needle without a coaxial sheath). The coaxial CNB group was stratified by lesion location to further evaluate the applicability of coaxial core needles. The satisfactory specimen rate, diagnostic efficiency, operating time, and complication rate were compared statistically between groups and subgroups. RESULTS: Compared to the non-coaxial CNB group, the coaxial CNB group had a greater satisfactory specimen rate (98.3% vs. 92.3%; p = 0.048), a lesser mean operating time (8.9 ± 3.27 min vs. 16.8 ± 5.77 min; p < 0.001), and a lower complication rate (2.6% vs. 9.6%, p =0 .04). A better diagnostic efficiency was obtained for coaxial CNBs in the head of pancreas (98.7%) than in the body or tail of the pancreas (90%, p = 0.047). CONCLUSION: For pancreatic masses, coaxial CNB can yield a higher satisfactory sample rate, lower complication rate, and shorter operating time than non-coaxial biopsy. US-guided percutaneous coaxial CNB is a safe and efficient puncture technique for pancreatic lesion diagnosis.

Prediction of late recurrence after radiofrequency ablation of HBV-related hepatocellular carcinoma with the age-male-albumin-bilirubin-platelets (aMAP) risk score: a multicenter study.

BACKGROUND: Long-term survivals of patients with HBV-related hepatocellular carcinoma are limited by the high incidence of tumor recurrence after radiofrequency ablation (RFA), identification of the risk factors and understanding the patterns of recurrence can help to improve the comprehensive management of patients after RFA. Therefore, the purpose of the study is to explore the prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in patients with early-stage HBV-related hepatocellular carcinoma (HCC) receiving RFA; investigate the risk factors and patterns of late recurrence (LR); and develop a nomogram to predict recurrence-free survival (RFS). METHODS: A retrospective review of HBV-related HCC patients who underwent primary RFA from March 2012 to December 2020 was conducted. The prognostic value of the aMAP score was evaluated in a primary cohort (n=302) and then further validated in an independent validation cohort (n=143). The optimal threshold of aMAP scores was calculated by X-tile 3.6.1 software. A prognostic nomogram was constructed from multivariate analysis and validated in an external validation cohort. RESULTS: Patients with aMAP scores ≤63.8, 63.8-67.8, and >67.8 were classified into low-, medium-, and high-recurrence risk groups, respectively. The C-index to predict LR was 0.76 (95% CI: 0.700-0.810). The high-risk group was associated with the worst RFS (HR: 5.298; 95% CI, 2.697-10.408; P<0.001) and overall survival (OS) (HR: 2.639; 95% CI, 1.097-6.344; P=0.03) compared with medium- and low-risk groups. The aMAP score, multiple tumors and preoperative HBV DNA level were independent risk factors for LR. The proposed nomogram had excellent performance in predicting LR of HBV-related HCC [C-index: 0.82 (95% CI: 0.772-0.870)]. CONCLUSIONS: This study demonstrated that the aMAP score can serve as an objective predictor of LR for HBV-related HCC patients after RFA. The nomogram based on preoperative HBV DNA level, aMAP score, and number of tumors can reliably help clinicians to stratify the recurrence risk of HCC patients after RFA.

Late recurrence of hepatocellular carcinoma after radiofrequency ablation: a multicenter study of risk factors, patterns, and survival.

OBJECTIVE: This study aims to determine the risk factors, patterns, and long-term survival outcomes of late recurrence after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) within the Milan criteria and develop a nomogram to predict the recurrence-free survival (RFS). MATERIALS AND METHODS: This retrospective study included patients with HCC within the Milan criteria, who received RFA at three hospitals in China from January 2011 to December 2016. The clinical variables were assessed by univariate and multivariate Cox regression analyses. RESULTS: A total of 398 patients were included. The median follow-up was 58.7 months (range: 24.1-96.0). Ninety-eight patients had late recurrence. Furthermore, 14 patients (14.29%) had local tumor progression (LTP) alone, 43 patients (43.88%) had intrahepatic distant recurrence (IDR) alone, 15 patients (15.31%) had extrahepatic recurrence (ER) alone, three patients (3.06%) had both LTP and IDR, six patients (6.12%) had both LTP and ER, and 17 patients (17.35%) had both IDR and ER. Patients without late recurrence had better long-term overall survival (OS) compared to those with late recurrence (p < 0.001). Male gender, multiple tumors, and cirrhosis were the independent risk factors of late recurrence. A well-discriminated and calibrated nomogram was constructed to predict the probability of RFS. CONCLUSION: Male gender, multiple tumors, and cirrhosis are the independent risk factors of late recurrence after RFA for HCC within the Milan criteria. Late recurrence might mainly occur from de novo HCC under the background of cirrhosis. An individualized surveillance and prevention strategy for HCC patients after RFA should be developed. KEY POINTS: • In the present retrospective study of 398 patients, male gender, multiple tumors, and cirrhosis were the independent risk factors of late recurrence (> 2 years) of HCC after RFA. • The most common pattern of late recurrence was intrahepatic distant recurrence alone (n = 43, 43.88%). Late recurrence might mainly occur from de novo HCC under the background of cirrhosis. • A prognostic nomogram was built to predict the individualized recurrence-free survival after RFA, which achieved good calibration and discriminatory ability with a concordance index of 0.763.

Prognostic significance of controlling nutritional status score-based nomogram for hepatocellular carcinoma within Milan criteria after radiofrequency ablation.

BACKGROUND: Radiofrequency ablation (RFA) is a curative therapy for hepatocellular carcinoma (HCC) within Milan criteria. This study was conducted to evaluate the association between controlling nutritional status (CONUT) score and oncological outcomes in HCC patients within Milan criteria after RFA. Nomograms were constructed for the prediction of prognosis. METHODS: The study included 403 HCC patients within Milan criteria who underwent RFA at National Cancer Center and the First Hospital of Shanxi Medical University from January 2010 to December 2014. Oncological outcomes included disease-free survival (DFS) and overall survival (OS). The clinical variables were assessed by univariate and multivariate Cox regression analyses. C-index, time-dependent receiver operating characteristic (t-ROC) curve (t-AUC) and calibration plots were used to evaluate discrimination and calibration of the nomograms. RESULTS: Patients were divided into CONUT ≤4 and ≥5 groups. The common prognostic factors affecting DFS and OS were number of lesions, tumor differentiation, and CONUT score. Age and total bilirubin (TBIL) were prognostic factors for OS only. Both DFS and OS rates in CONUT ≤4 group were significantly higher than those in CONUT ≥5 group (P=0.033, P<0.001). Two well-discriminated and calibrated nomograms were constructed to predict the probability of 1-, 2-, and 3-year DFS and 1-, 2-, 3-, 5-year OS with C-indexes of 0.798 and 0.757, respectively. CONCLUSIONS: CONUT score is an independent prognostic factor for HCC after RFA treatment and a reliable indicator for nutritional interventions. Higher CONUT scores were associated with poor oncological outcomes. Nomograms based on CONUT score could efficiently predict DFS and OS for HCC patients within Milan criteria after RFA.