Α-fetoprotein Level Research Articles

An observational study of donafenib as adjuvant therapy to prevent hepatocellular carcinoma recurrence after curative surgery.

e16227 Background: The five-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection is as high as 70% and remains a major clinical challenge. Many investigators have suggested adjuvant therapy to prevent HCC recurrence, and several promising outcomes have been reported. Donafenib has been approved as a standard treatment for patients with unresectable HCC in China. Here, we describe our preliminary results regarding the efficacy and safety of donafenib as an adjuvant therapy for patients with HCC after hepatectomy. Methods: This was an observational study of patients with HCC following hepatectomy treated with donafenib in routine practice at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. The enrolled patients were 75 years or younger, had been diagnosed with HCC, showed no evidence of recurrence at radiological follow-up within one month after hepatectomy, and had at least one high recurrence risk factor, such as tumor diameter ≥5 cm, tumor number ≥2, microvascular invasion, or serum a-fetoprotein level before surgery ≥400 ng/mL. All of the patients had adequate hematologic, hepatic, and renal functions. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included 6- and 12-month RFS rates, overall survival, and adverse events. Results: Seventeen patients were enrolled in this study. The median age was 56 years (range, 40–72), 88.2% were males, 82.4% with HBV, 17.6% had preoperative serum a-fetoprotein levels ≥400 ng/mL, 35.3% had tumor diameters ≥5 cm, 29.4% had tumor numbers ≥2, and 29.4% had microvascular invasion. The median follow-up time for the entire patient cohort was 16 months (95% confidence interval [CI], 11.9–20.1), and 5 of 17 patients relapsed, with a recurrence rate of 29.4%. The median RFS was not reached; the 6- and 12-month RFS rates were 88.2% and 70.1%, respectively. Treatment-related adverse events (TRAEs) occurred in 82.4% of the patients, most of which were grades 1–2. Grade 3 TRAEs, including hand-foot skin reaction and rash, were observed in three (16.4%) patients. No grade 4 or 5 TRAEs occurred. Conclusions: The findings of the present study suggest that donafenib as adjuvant therapy may be a potentially effective way to prevent HCC recurrence after curative surgery. Our findings should be validated in a larger, prospectively evaluated sample. Clinical trial information: ChiCTR2200064030 .

Comparative Study of Long-Term Outcomes of Laparoscopic Liver Resection versus Radiofrequency Ablation for Single Small Hepatocellular Carcinoma Located in Left Lateral Segments of the Liver.

Background and Objectives: Laparoscopic liver resection (LLR) is now widely recognized as the primary surgical option for hepatocellular carcinomas (HCC) smaller than 3 cm located in the left lateral segment of the liver. Nevertheless, there is a scarcity of studies comparing laparoscopic liver resection with radiofrequency ablation (RFA) in these cases. Materials and Methods: We retrospectively compared the short- and long-term outcomes of Child-Pugh class A patients who underwent LLR (n = 36) or RFA (n = 40) for a newly diagnosed single small (≤3 cm) HCC located in the left lateral segment of the liver. Results: Overall survival (OS) was not significantly different between the LLR and RFA groups (94.4% vs. 80.0%, p = 0.075). However, disease-free survival (DFS) was better in the LLR group than in the RFA group (p < 0.001), with 1-, 3-, and 5-year DFS rates of 100%, 84.5%, and 74.4%, respectively, in the LLR group vs. 86.9%, 40.2%, and 33.4%, respectively, in the RFA group. The hospital stay was significantly shorter in the RFA group than in the LLR (2.4 vs. 4.9 days, p < 0.001). The overall complication rate was higher in the RFA group than in the LLR group (15% vs. 5.6%). In patients with an α-fetoprotein level of ≥20 ng/mL, the 5-year OS (93.8% vs. 50.0%, p = 0.031) and DFS (68.8% vs. 20.0%, p = 0.002) rates were greater in the LLR group. Conclusions: LLR showed superior OS and DFS compared to RFA in patients with a single small HCC situated in the left lateral segment of the liver. LLR can be considered for patients with an α-fetoprotein level of ≥20 ng/mL.

Sarcopenia as a Prognostic Factor in Patients with Hepatoblastoma: Does It Influence Surgical Outcomes and Survival? Preliminary Retrospective Study

AimSarcopenia is associated with poor prognosis in adult oncologic patients, with little evidence of this association in pediatric population, including hepatoblastoma. MethodsRetrospective study in patients with hepatoblastoma, divided into those with or without sarcopenia. Sarcopenia was assessed by measuring psoas muscle area (PMA) at L4-L5 level on the CT/MR and defined as z-score values ≤ 2. Relapse and mortality were analyzed. ResultsTwenty-one patients (57.1% male) were included, with median age 35.7 months (IQR: 23.5–58.5). Seven (33.3%) had sarcopenia on initial studies compared to 14 (66.7%) who did not. No differences were found between groups in age, weight, PRETEXT, surgical treatment or. α-fetoprotein levels. Sarcopenia was associated with a higher rate of metastases at diagnosis (49.2% vs 0.0%; p = 0.026) and surgical complications (57.1% vs 21.4%, p = 0.047). After a median follow-up of 65.1 months (1.7–144.8), 2 patients (28.6%) had tumor relapse in sarcopenic group compared to 1 (7.1%) in non-sarcopenic group. Two patients died in sarcopenic group and 1 in non-sarcopenic group. Median event-free survival (EFS) was lower in sarcopenic group (100.38 ± 25.63 vs 118.91 ± 11.52 months) as well as overall survival (OS) (101.72 ± 24.86 vs 121.78 ± 8.75 months) with no statistical significance. Five-year EFS was also lower in sarcopenic group (71% vs 93%) as well as 5-year OS (71% vs 87%). ConclusionsSarcopenia at diagnosis was associated with a higher rate of metastases and surgical complications in hepatoblastoma. Our data shows the first evidence of its role as a possible poor prognostic factor, influencing survival and risk of relapse. Level of EvidenceII. Type of StudyOriginal article. Retrospective study

Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis

The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis. We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through2021. We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73-0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65-0.85) at 1 year and 0.77 (95% CI, 0.71-0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration. The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification.

Overall Survival Rates Become Similar Between Percutaneous Ablation and Hepatic Resection With Increasing Age Among Elderly Patients With Early Hepatocellular Carcinoma

This study aimed to investigate the efficacy and safety of percutaneous ablation versus hepatectomy in an elderly population with hepatocellular carcinoma (HCC).Retrospective data on patients aged ≥ 65 years with very-early/early stages of HCC (≤ 50 mm) were obtained from three centers in China. Inverse probability of treatment weighting analysis was performed after stratifying the patients by age (65 - 69, 70 - 74 and ≥ 75 years).Of the 1,145 patients, 561 and 584 underwent resection and ablation, respectively. For patients aged 65 - 69 and 70 - 74 years, resection resulted in significantly better overall survival (OS) than ablation (age 65 - 69, P < 0.001, hazard ratio (HR) = 0.27; age 70 - 74, P = 0.012, HR = 0.64). However, in patients aged ≥ 75 years, resection and ablation resulted in a similar OS (P = 0.44, HR = 0.84). An interactive effect existed between treatment and age (effect of treatment on OS, age 65 - 69 as the reference, for age 70 - 74, P = 0.039; for age ≥ 75, P = 0.002). The HCC-related death rate was higher in patients aged 65 - 69, and the liver/other cause-related death rate was higher in patients aged > 69. Multivariate analyses showed that the type of treatment, number of tumors, α-fetoprotein level, serum albumin level and associated diabetes mellitus were independent factors associated with OS, but not hypertension or heart diseases.With increasing patient age, the treatment outcomes of ablation become similar to those of resection. A higher liver/other cause-related death rate in very elderly patients may shorten the life expectancy, which may lead to the same OS regardless of whether resection or ablation is chosen.

Association between Posttreatment Serum Platelet-to-Lymphocyte Ratio and Distant Metastases in Patients with Hepatocellular Carcinoma Receiving Curative Radiation Therapy.

We sought to investigate whether serum immune and inflammatory parameters can help to predict distant metastasis (DM) in patients with unresectable hepatocellular carcinoma (HCC) undergoing curative radiation therapy (RT). A total of 76 RT courses were analyzed. The following variables were included in the analysis: systemic inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), absolute lymphocyte count, lymphocyte-to-monocyte ratio, albumin, albumin-to-alkaline phosphatase ratio, RT-related parameters, and levels of total protein, hemoglobin, α-fetoprotein, and PIVKA-II. Distant control (DC) and overall survival (OS) rates were calculated and compared. The mean age was 61.4 years, and most patients were men (n = 62, 81.6%). The median RT fraction number and fractional doses were 12 (range, 4-30) and 5 (range, 2-12) Gy, respectively. With a median follow-up of 12 (range, 3.1-56.7) months, the 1-year DC and OS rates were 64.4% and 55.2%, respectively. The development of DM significantly deteriorated OS (p = 0.013). In the multivariate analysis, significant independent prognostic indicators for DC and OS rates were the highest posttreatment PLR (≤235.7 vs. >235.7, p = 0.006) and the lowest posttreatment PNI (≤25.4 vs. >25.4, p < 0.001), respectively. Posttreatment serum PLR might be helpfully used as a predictive biomarker of DM in unresectable HCC patients undergoing RT. Future research is necessary to confirm our findings.

Comparison of Four Albumin-Based Liver Reserve Models (ALBI/EZ-ALBI/PALBI/PAL) against MELD for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

(1) Background: The severity of liver functional reserve plays an important role in the management of hepatocellular carcinoma (HCC). Noninvasive models such as the model for end-stage liver disease (MELD), albumin-bilirubin (ALBI) grade and easy (EZ)-ALBI grade, platelet-albumin-bilirubin (PALBI) and platelet-albumin (PAL) are used to evaluate liver dysfunction. We aimed to compare the prognostic performance of these four albumin-based models against MELD in HCC patients undergoing transarterial chemoembolization (TACE). (2) Methods: A total of 1038 treatment naïve HCC patients who received TACE as the primary treatment were enrolled. A multivariate Cox model was used to determine independent survival predictors. (3) Results: Multivariate analysis revealed that higher serum creatinine and α-fetoprotein level, vascular invasion, large tumor size, ALBI grades 2-3, EZ-ALBI grades 2-3, PALBI grades 2-3, PAL grades 2-3, but not the MELD score, were independent predictors associated with decreased survival in different Cox models. Among these models, the PALBI grade had the highest homogeneity and lowest corrected Akaike information criteria value, followed by EZ-ALBI, PAL, ALBI and, lastly, MELD. (4) Conclusions: All four albumin-based liver reserve models are better prognostic tools than MELD score in HCC patients undergoing TACE. Of these, the PALBI score is the best model to evaluate the liver reserve and should be considered a surrogate marker in these patients.

The investigation on the hypercoagulability of hepatocellular carcinoma‐related cerebral infarction with thromboelastography

To investigate the hypercoagulability of hepatocellular carcinoma (HCC)-related cerebral infarction (HCRCI) with thromboelastography (TEG). A multicenter prospective study was conducted in HCRCI patients, HCC patients without cerebral infarction, and acute cerebral infarction (ACI) patients without HCC between January 2016 and December 2019. TEG parameters and laboratory and clinical data were collected and compared among the three groups. To confirm the independent risk factors of HCRCI, multivariate analyses were conducted. Receiver operating characteristic (ROC) curves were utilized to evaluate the area under the curve (AUC) plotted by each independent risk factor. There were 38 patientsrecruited in the HCRCI group, and 152 patients were recruited to the HCC group and the ACI group. The levels of plasma neutrophil count, D-dimer, α-fetoprotein (AFP), carcinoembryonic antigen, and maximum amplitude (MA)-a parameter of TEG-were significantly higher in the HCRCI group than HCC and ACI groups. Multivariate logistic regression analysis showed that increased neutrophile count, D-dimer, AFP, and MA were independently associated with HCRCI. ROC curve analysis showed firstthat AUC of MA for HCRCI was .875, which was larger than the other risk factors, and second that the optimal cutoff value for MA was 61.35, with a sensitivity of 89.50% and specificity of 66.40%. It was suggested that TEG disclosed that the pathogenesis of HCRIC is exactly related to the hypercoagulability. And with a cutoff value of MA equaling to 61.35, TEG facilitatesclinicians to identify HCC patients at high risk of HCRIC.

Diffusion-Weighted Imaging as a Quantitative Imaging Biomarker for Predicting Proliferation Rate in Hepatocellular Carcinoma: Developing a Radiomics Nomogram.

This study aimed to explore the predictive performance of diffusion-weighted imaging with apparent diffusion coefficient map in predicting the proliferation rate of hepatocellular carcinoma and to develop a radiomics-based nomogram. This was a single-center retrospective study. A total of 110 patients were enrolled. The sample included 38 patients with low Ki67 expression (Ki67 ≤10%) and 72 with high Ki67 expression (Ki67 >10%) as demonstrated by surgical pathology. Patients were randomly divided into either a training (n = 77) or validation (n = 33) cohort. Diffusion-weighted imaging with apparent diffusion coefficient maps was used to extract radiomic features and the signal intensity values of tumor (SI tumor ), normal liver (SI liver ), and background noise (SI background ) from all samples. Subsequently, the clinical model, radiomic model, and fusion model (with clinical data and radiomic signature) were developed and validated. The area under the curve (AUC) of the clinical model for predicting the Ki67 expression including serum α-fetoprotein level ( P = 0.010), age ( P = 0.015), and signal noise ratio ( P = 0.026) was 0.799 and 0.715 in training and validation cohorts, respectively. The AUC of the radiomic model constructed by 9 selected radiomic features was 0.833 and 0.772 in training and validation cohorts, respectively. The AUC of the fusion model containing serum α-fetoprotein level ( P = 0.011), age ( P = 0.019), and rad score ( P < 0.001) was 0.901 and 0.781 in training and validation cohorts, respectively. Diffusion-weighted imaging as a quantitative imaging biomarker can predict Ki67 expression level in hepatocellular carcinoma across various models.

Factors Associated With Complete Pathologic Necrosis of Hepatocellular Carcinoma on Explant Evaluation After Locoregional Therapy: A National Analysis Using the UNOS Database.

BACKGROUND. Complete pathologic necrosis (CPN) is associated with improved survival in patients who undergo liver transplant (LT) after locoregional therapy (LRT) for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of this article was to identify patient, HCC, and transplant center characteristics associated with rates of CPN on explant evaluation using a large national sample of patients undergoing LT after LRT for HCC measuring 3 cm or smaller. METHODS. This retrospective study used data from the United Network for Organ Sharing database. The study included 6265 adults (median age, 62 years; 1505 women, 4760 men) who underwent LT after a single type of LRT (either transarterial chemoembolization [TACE], thermal ablation, or transarterial radioembolization [TARE]) for HCCs measuring 3 cm or smaller at one of 118 U.S. transplant centers from April 12, 2012, to March 31, 2020. Patients were classified as having CPN if explant evaluation showed 100% necrosis of all HCCs. Associations with CPN were explored. Centers were categorized into tertiles on the basis of center-level CPN rates, and tertiles were compared. RESULTS. LRT was performed by TACE in 69.5% (4352/6265), thermal ablation in 19.4% (1217/6265), and TARE in 11.1% (696/6265) of patients. CPN rate was 18.5% (805/4352) after TACE, 35.8% (436/1217) after thermal ablation, 33.6% (234/696) after TARE, and 23.5% (1475/6265) overall. In multivariable analysis incorporating age, sex, model for end-stage liver disease score, α-fetoprotein level before LRT, wait list time, number of HCCs, HCC size, and the transplant center (as a random factor), use of thermal ablation (OR, 2.19; 95% CI, 1.86-2.57; p < .001) or TARE (OR, 1.92; 95% CI, 1.57-2.36; p < .001), with TACE as reference, independently predicted greater likelihood of CPN. Center-level CPN rates ranged from 0.0% to 50.0%. With centers stratified by CPN rates, ablation was performed more frequently than TACE in 5.0% of centers in the first, 15.4% in the second, and 23.1% in the third tertiles (p = .07). CONCLUSION. CPN rate on explant evaluation was low. Thermal ablation or TARE, rather than TACE, was associated with higher likelihood of CPN in patient-level and center-level analyses. CLINICAL IMPACT. Findings from this large national sample support a potential role of thermal ablation or TARE for achieving CPN of HCC measuring 3 cm or smaller.

Combined serum CXCL8, CXCL9and CXCL13 tests for the prediction of microvascular invasion in hepatocellular carcinoma.

Aim: This work is to explore the predictive and diagnostic value of chemokine C-X-C motif ligand 8 (CXCL8), CXCL9and CXCL13 combined detections for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. Materials & methods: A total of82 HCC patients with MVI were recruited as the MVI group and 154 patients with nonMVI were recruited as the non MVI group. Results: In HCC patients with MVI, CXCL8, CXCL9, CXCL13 levels were significantly elevated. Child-Pugh scores and serum α-fetoprotein level had positive correlation with CXCL8, CXCL9and CXCL13 levels. The serum levels of CXCL8, 9and 13 were effective in predicting MVI in HCC patients. Conclusion: CXCL8, CXCL9 and CXCL13 levels in HCC patients are valuable parameters in the prediction of MVI.

FOXP3 and SQSTM1/P62 correlate with prognosis and immune infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common highly malignant tumours worldwide. FOXP3 and SQSTM1/P62 have been shown to be abnormally expressed in tumour cells, but their function in different tumours remains controversial. The present study was designed to evaluate the expression of FOXP3 and P62 in HCC and their prognostic value as well as their relationship with immune infiltration in HCC patients. The Gene Expression Omnibus (GEO) database and TNMplot.com platform were used to analyse the expression of FOXP3 and P62. The Cancer Genome Atlas (TCGA) database and Kaplan-Meier plotter were used to assess the impacts of FOXP3 and P62 on clinical prognosis. In addition, TCGA database was also used to examine the correlation between the expression of FOXP3 and P62 and tumour immune infiltration using the CIBERSORT algorithm. Finally, immunohistochemistry (IHC) was used to determine expression levels of FOXP3 and P62 in 89 HCC and adjacent normal liver tissues, and their effects on clinicopathological features and prognosis were verified. FOXP3 expression was downregulated in HCC tissues, while P62 expression was upregulated. FOXP3 underexpression and P62 overexpression were closely related to decreased overall survival (OS) in HCC patients. Additionally, the abnormal expression of FOXP3 and P62 was closely related to the infiltration levels of 12 types of immune cells, including regulatory T cells (Tregs), M2 macrophages, M0 macrophages, and CD8 T cells. Notably, in the validation model, abnormal FOXP3 and P62 expression was significantly associated with adverse clinicopathological factors in HCC patients, including elevated α-fetoprotein (AFP) levels, poor tumour differentiation, and increased Ki67 levels. Furthermore, low FOXP3 and high P62 expression were independent risk factors for predicting OS prognosis in HCC patients. FOXP3 and P62 have been shown to be important prognostic factors in HCC patients and are associated with immune cell infiltration in HCC. These findings suggest that FOXP3 and P62 may be valuable prognostic biomarkers and potential therapeutic targets for HCC treatment.

Risk factors for liver-related and non-liver-related mortality following a sustained virological response after direct-acting antiviral treatment for hepatitis C virus infection in a real-world cohort.

A direct-acting antiviral (DAA)-induced sustained virological response (SVR) reduces the risk of mortality. However, the risk factors associated with liver-related and non-liver-related mortality following a SVR after DAA treatment are unclear. We assessed the incidence and risk factors of liver-related and non-liver-related mortality in 1180 patients who achieved a SVR after DAA treatment. During the follow-up period after DAA treatment (median duration, 1099 [range: 84-2345] days), 53 (4.5%) patients died: 15 due to liver-related mortality, 25 due to non-liver-related mortality and 13 due to unknown causes. The all-cause, liver-related and non-liver-related mortality rates were 14.9, 4.2 and 7.0/1000 person-years, respectively. In a multivariate analysis, the development of hepatocellular carcinoma (HCC) after DAA treatment (p=.009; hazard ratio [HR], 31.484), an estimated glomerular filtration rate (eGFR) at baseline ≤61.68 ml/min/1.73 m2 (p=.015; HR, 6.607), and an α-fetoprotein level post-treatment ≥7.6ng/ml (p=.041; HR, 18.490) were significantly associated with liver-related mortality. Furthermore, eGFR ≤67.94 ml/min/1.73 m2 at baseline (p=.012; HR, 3.407) and albumin-bilirubin (ALBI) grade ≥ 2 at SVR (p=.024; HR, 3.449) were significantly associated with non-liver-related mortality. Early diagnosis and therapeutic interventions for HCC development after DAA treatment are important to reduce liver-related mortality. The ALBI grade, which reflects the hepatic functional reserve, is a useful predictor of non-liver-related mortality after a SVR induced by DAA treatment. Furthermore, the renal dysfunction caused by metabolic syndrome may affect prognosis even after eliminating hepatitis C virus.

Clinical characteristics and risk factors analysis for the recurrence of pelvic endodermal sinus tumors

This study investigated the clinicopathological characteristics and factors influencing the recurrence of pelvic endodermal sinus tumor (PEST). 54 cases were retrospectively analyzed from at the Zhejiang Cancer Hospital. Progression-free survival (PFS) and related factors on disease recurrence were evaluated. Six patients had extragonadal endodermal sinus tumor, and four had histological features of endodermal sinus tumor (EST) combined with embryonal carcinoma (EC). 39 patients underwent fertility-preserving surgery, 18 patients had a childbearing history, and eight patients had residual tumor after initial treatment as surgery or chemotherapy. 26 patients had a tumor diameter of more than 15 cm, and 30 patients had a serum αfetoprotein (AFP) level greater than 10,000 ng/mL before initial management. The median follow-up was 47.5 months (range, 14–212 months). During follow-up, 15 patients experience recurrence, with a recurrence rate of 27.8% and a 5-year PFS rate of 61.1%. In univariate analysis, the FIGO (International Federation of Gynecology and Obstetrics) stage (stage III–IV vs. I–II; hazard ratio (HR) = 9.73, p &lt; 0.001), residual tumor (yes vs. no for the first surgery; HR = 4.86, p = 0.001), histological features (EST combined with EC vs. EST; HR = 4.08, p = 0.017), and use of platinum-based chemotherapy (courses ≥3 vs. courses &lt;3; HR = 0.19, p = 0.004) were independent factors influencing recurrence. In multivariate analysis, only stage was an independent risk factor for PFS (stage III–IV vs. I–II; HR = 6.92, p = 0.02). Stage is a prognostic factor for recurrence of PEST. The aim of the initial surgery is to maximally debulk all grossly visible tumor and the post-operative treatment should include a sufficient dose and full course of platinum-based chemotherapy, which may reduce the recurrence rate. Maybe some gene expression that could be associate with PEST.

Yttrium-90 Radioembolization as the Major Treatment of Hepatocellular Carcinoma.

The purpose of this study was to assess the safety and efficacy of Yttrium-90 radioembolization using in unresectable hepatocellular carcinoma. From 2017 to 2021, 32 patients with unresectable hepatocellular carcinoma, with mean tumor diameter about 7cm (21 males, 11 females; median age, 57.5 years of age), treated with Yttrium-90 radioembolization using resin microspheres were reviewed at pre-Yttrium-90 and post-Yttrium-90 follow-up. Tumor response was assessed according to the modified Response Evaluation Criteria in Solid Tumors. Outcomes including overall survival and progression-free survival were reported. Median follow-up was 18 months. At follow-up examinations at 3-, 6-, and 12-months follow-up, the overall survival rates were 94%, 87% and 59%, and the progression-free survival rates were 78%, 64% and 60%, respectively. Complete response, partial response, stable disease, and progressive disease were noted in 7 (21.9%), 14 (43.7%), 4 (12.5%), and 7 (21.9%) patients, respectively. The disease control rate was 78.1%, the objective response rate was 65.6%, and the successful downstage rate was 34.4% (11 of 32). Nine of thirty-two patients underwent resection or transplantation after Yttrium-90 radioembolization with 2-year overall survival being 100%. No serious adverse events occurred after Yttrium-90 treatment. Worse overall survival was related to the larger tumor, higher stage, Eastern Cooperative Oncology Group performance status, and Child-Pugh score. And worse progression-free survival was related to the higher tumor burden, and pre-Yttrium-90 serum α-fetoprotein level >100. Yttrium-90 Radioembolization can control hepatocellular carcinoma well even in advanced diseases. Patients successfully downstaging/bridging to resection or transplantation have excellent overall survival.

Serum biomarkers of colonic polyps in patients with acromegaly: a meta-analysis and systematic review.

In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of serum biomarkers of colonic polyps in patients with acromegaly. We reviewed studies on serum biomarkers of colonic polyps in patients with acromegaly, published on PubMed, Embase, Cochrane Library, Medline, and Chinese databases from January 1, 1966, to May 8, 2022. Meta-analysis and systematic review were conducted using Stata MP 14.0. Eight articles were included in this study. The mean (standard deviation) concentrations of serum biomarkers for acromegaly with and without colorectal polyps were extracted from these studies. Meta-analysis results showed that, compared to patients without colonic polyps, the levels of insulin-like growth factor-1 × upper limit of normal range (IGF-1 × ULN) and fasting insulin were significantly increased; while the levels of growth hormone (GH) were significantly decreased in patients with acromegaly and colonic polyps (IGF-1 × ULN: SMD 0.23; 95% CI 0.03-0.42, p < 0.05) (fasting insulin: SMD 0.95; 9 5% CI 0.11-1.8, p < 0.05) (GH: SMD - 0.25; 95% CI - 0.41 to - 0.08, p < 0.05). IGF-1 and FPG levels did not differ significantly (IGF-1: SMD -0.03; 95% CI - 0.22 to 0.17, p > 0.05) (FPG: SMD 0.14; 95% CI - 0.23 to 0.52, p > 0.05). The systematic review results suggest no significant differences in hemoglobin A1C, TSH, free thyroxine, FT4, T3, PRL, total cholesterol, HDL, LDL, fibrinogen, clathrate antigen, serum antigen 19-9, and α-fetoprotein levels, but serum Klotho levels. We present the first meta-analysis and systematic review of serum biomarkers in patients with acromegaly or colonic polyps. The prevalence of colonic lesion polyps, is associated with higher IGF-1 × ULN levels, higher insulin levels in acromegaly. Further research is required to confirm GH and serum soluble Klotho levels as biomarkers of colonic polyps. When IGF-1 × ULN, fasting insulin levels change in patients with acromegaly, the occurrence of colonic polyps should be monitored. Early detection may reduce the possibility of developing malignant colon neoplasms.

New prognostic system based on inflammation and liver function predicts prognosis in patients with advanced unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab: A validation study.

Recently, the neo-Glasgow prognostic score (GPS), a composite biomarker determined by the C-reactive protein level and albumin-bilirubin grade, was developed to predict outcomes in hepatocellular carcinoma (HCC) patients who undergo hepatic resection. The present research investigated whether the neo-GPS could predict prognosis in HCC patients treated with atezolizumab plus bevacizumab (Atez/Bev). A total of 421 patients with HCC who were treated with Atez/Bev were investigated. Multivariate Cox hazards analysis showed that a GPS of 1 (hazard ratio (HR), 1.711; 95% confidence interval (CI), 1.106-2.646) and a GPS of 2 (HR, 4.643; 95% CI, 2.778-7.762) were independently associated with overall survival. Conversely, multivariate Cox hazards analysis showed that a neo-GPS of 1 (HR, 3.038; 95% CI, 1.715-5.383) and a neo-GPS of 2 (HR, 5.312; 95% CI, 2.853-9.890) were also independently associated with overall survival in this cohort. Additionally, cumulative overall survival rates differed significantly by GPS and neo-GPS (p < 0.001). The neo-GPS, compared with the GPS, had a lower Akaike information criterion (1207 vs. 1,211, respectively) and a higher c-index (0.677 vs. 0.652, respectively) regarding to overall survival. In a subgroup analysis of patients considered to have a good prognosis as confirmed using a Child-Pugh score of 5 (p=0.001), a neutrophil-to-lymphocyte ratio <3 (p=0.001), or an α-fetoprotein level < 100 ng/mL (p < 0.001), those with a high neo-GPS (≥1) had a statistically poorer overall survival than those with a low neo-GPS. The neo-GPS can predict prognosis in advanced unresectable HCC patients treated with Atez/Bev.

Surgical Outcomes for Hepatocellular Carcinoma in Patients with Child–Pugh Class B: a Retrospective Multicenter Study

BackgroundsLiver resection for hepatocellular carcinoma (HCC) in patients with Child–Pugh class (CPC) B increases the incidence of postoperative complication and in-hospital death and decreases the disease-free survival (DFS) and overall survival (OS) compared with those with CPC A. Conversely, some selected patients possibly gained benefits for liver resection. MethodsClinical records of 114 patients with CPC B who underwent liver resection for HCC were retrospectively reviewed. The risk of postoperative complications (Clavien–Dindo classification grade of ≥ II), postoperative recurrence, and death was analyzed. ResultsPostoperative complications occurred in 36 patients (31.6%), and 2 died within 90 days postoperatively due to the liver and respiratory failure, respectively. Multivariate analysis indicated that albumin-bilirubin (ALB) grade III and extended operation time were found as independent risk factors for postoperative complications. The DFS and OS rates at 3/5 years after liver resection were 30.8%/25.3% and 68.4%/48.9%, respectively. Multivariate analysis indicated that the extended blood loss, high α-fetoprotein (AFP) level (≥ 200 ng/mL), and Barcelona Clinic Liver Cancer stage C were found to be independent risk factors for postoperative recurrence. The high AFP level was also an independent prognostic factor for OS. Patients with high AFP levels had postoperative recurrence within 2 years and a higher number of extrahepatic recurrences than those with low AFP levels (< 200 ng/mL). ConclusionFor patients with HCC with CPC B who were scheduled for liver resection, ALBI grade III and high AFP level should be considered as unfavorable outcomes after liver resection.

Nutritional Status Is Associated with Prognosis in Patients with Advanced Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab

Introduction: This study investigated the relationship between nutritional status, as determined by the prognostic nutritional index (PNI), and outcomes in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atez/bev). Methods: The study analyzed 485 HCC patients treated with Atez/bev. Results: There were 342 patients with a low PNI (<47) and 143 patients with a high PNI (≥47). The median follow-up duration was 9.4 (6.0–14.3) months. Multivariate Cox hazards analysis showed that an α-fetoprotein level ≥100 ng/mL (hazard ratio (HR), 2.217; 95% confidence interval (CI), 1.588–3.095; p < 0.001), and PNI ≥47 (HR, 0.333; 95% CI, 0.212–0.525; p < 0.001) were independently associated with overall survival. Multivariate analysis showed that an α-fetoprotein level ≥100 ng/mL (HR, 1.690; 95% CI, 1.316–2.170; p < 0.001) and PNI ≥47 (HR, 0.696; 95% CI, 0.528–0.918; p = 0.010) were independently associated with progression-free survival. Cumulative overall and progression-free survival rates differed significantly by PNI (p < 0.001 and p < 0.002, respectively). In a subgroup analysis using inverse probability weighting adjustment in patients with albumin-bilirubin grade 1 (n = 173), univariate Cox hazards analysis showed that a PNI ≥47 (HR, 0.502; 95% CI, 0.260–0.991; p = 0.047) was significantly associated with overall survival. Spline curve analysis revealed that a PNI of approximately 34–48 is an appropriate cutoff for predicting good overall and progression-free survival. Conclusion: The PNI, a biomarker of nutritional status, can predict prognosis in patients with HCC treated with Atez/bev, even those who are considered to have a good prognosis due to good liver function.

Preoperative identification of cytokeratin 19 status of hepatocellular carcinoma based on diffusion kurtosis imaging.

To explore the potential value of diffusion kurtosis imaging (DKI) for identification of cytokeratin 19 (CK19) status of HCCs. This study was approved by the local institute review board and written informed consent was obtained. 73 patients with pathologically confirmed HCCs were included in this prospective study. All the diffusion-weighted (DW) images were acquired using a 3.0-T MR scanner with 4 b-values (0, 800, 1500 and 2000s/mm2). The mean diffusion value (MD) and mean kurtosis coefficient (MK) from DKI, apparent diffusion coefficient (ADC) from DW imaging (b = 0, 500s/mm2), and tumor-to-liver signal intensity ratios on ADC map (SIRADC) and DW images with b-value of 500s/mm2 (SIRb500) were calculated and compared between CK19-positive (n = 23) and CK19-negative (n = 50) HCC groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for the positive expression of CK19. Increased a-fetoprotein level (p = 0.021) and SIRb500 (p = 0.006) and decreased ADC (p = 0.021) and MD (p < 0.001) were significantly correlated with CK19-positive HCCs at univariate analysis. Decreased MD value (odds ratio: 0.042, p = 0.002) and a-fetoprotein level (odds ratio: 5.139, p = 0.015) were the independent risk factors for CK19-positive HCCs at multivariate analysis. The area under the curve of MD value by receiver operating characteristic analysis was 0.823 with a sensitivity of 86.96% and a specificity of 76% for the prediction of CK19-positive HCCs. The decreased MD value derived from DKI is potential quantitative biomarker for predicting CK19-positive HCCs.