Level of hepatitis B surface antigen might serve as a new marker to predict hepatocellular carcinoma recurrence following curative resection in patients with low viral load

To investigate the association between preoperative HBsAg (hepatitis B surface antigen) level and risk of HCC (hepatocellular carcinoma) recurrence following curative resection, we enrolled 826 HBV-related HCC patients who underwent curative resection and received long-term follow-up at the Eastern Hepatobiliary Surgery Hospital (Shanghai, China). Multivariate analyses showed that serum HBsAg ≥ 2000 S/CO, seropositive hepatitis B e antigen (HBeAg), γ-glutamyl transpeptidase > 61 U/L, prothrombin time > 13 s, multinodularity, lager tumor size, and major portal vein invasion were independently associated with a increased risk of HCC recurrence. Compared with HCC patients with HBsAg level < 2000 S/CO, HCC patients with HBsAg level ≥ 2000 S/CO had a higher prevalence of seropositive HBeAg, antiviral therapy, and cirrhosis; were younger; and had a higher levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and HBV viral load. Multivariable stratified analyses showed HCC patients with HBsAg level < 2000 S/CO tended to have a lower incidence of HCC recurrence in following subgroups of patients, including for noncirrhotic (HR, 0.561; 95% CI, 0.345-0.914), HBV DNA < 2000 IU/mL (HR, 0.604; 95% CI, 0.401-0.912), ALT ≤ 41 U/L (HR, 0.643; 95% CI, 0.440-0.942), AST ≤ 37 U/L (HR, 0.672; 95% CI, 0.459-0.983), and seronegative HBeAg (HR, 0.682; 95% CI, 0.486-0.958). When we evaluated HBeAg-negative patients with HBV DNA < 2000 IU/mL, HBsAg level still determined risk of HCC recurrence (p = 0.014), but not HBV DNA (p = 0.550) and ALT (p = 0.186). These results suggest high levels of HBsAg increase risk of HCC recurrence following curative resection. HBsAg level might serve as a new marker to complement HBV DNA level in predicting HCC recurrence, especially in HBeAg-negative patients with low viral load.     

Comparison of neoadjuvant regimens for resectable gastroesophageal junction cancer: a systematic review of randomized clinical trials across three decades

BackgroundThe optimal perioperative treatment for adenocarcinoma of gastroesophageal junction (GEJ) tumor remains uncertain. The systematic review aims to assess the best neoadjuvant modality, namely chemotherapy (CT) versus chemoradiotherapy (CRT) based on randomized controlled trials (RCTs) for resectable gastric, esophageal and GEJ tumors.MethodsWe performed a comprehensive PubMed database and Cochrane Library search to identify relevant RCTs related to neoadjuvant treatment for resectable GEJ adenocarcinoma. We included all published RCTs (phase 2 or 3) that tested specific neoadjuvant therapies (CT or CRT) if the patient population included GEJ tumors. We applied the Version 2 Cochrane risk-of-bias tool (RoB 2) to all the eligible studies. Outcomes examined included R0 resection and pathological response based on intention-to-treat (ITT) analysis, surgical outcomes, notable adverse events, and overall survival (OS). Each randomized group of every study was noted to be neoadjuvant CRT, CT, or surgery alone in order to compare the outcomes among these treatment approaches.ResultsWe identified 25 RCTs with 7,855 patients published from 1996 to 2019. Seven studies tested preoperative CT versus surgery alone, 7 tested preoperative radiotherapy (RT) or CRT versus surgery alone, 4 tested preoperative RT or CRT versus preoperative CT, and 7 tested other combinations. The R0 resection ranged 47–100% and the 3-year OS ranged 6–66.1% in all the study arms. In an exploratory analysis, CRT strategies showed a superior R0 resection rate [80.2%; 95% confidence interval (CI): 79.8–80.6%] to surgery alone (60.9%; 95% CI: 60.4–61.3%; P<0.01) and to preoperative CT (63.9%; 95% CI: 63.6–64.2%; P<0.01). When comparing 3- and 5-year OS, improvement was noted when comparing CRT to surgery alone (P<0.01), and perioperative CT to surgery alone (P<0.01), but no definite difference was noted between CRT versus CT.DiscussionPreoperative CRT showed improvement in R0 resection rate to surgery alone and preoperative CT. However, there is no significant difference in OS between CRT and CT. Both neoadjuvant strategies remain clinically meaningful options for patients with resectable GEJ tumors. Lack of patient-level data and inconsistent reporting of key outcomes across studies were the main limitations of our study.     

经皮肝穿刺射频热凝治疗肝脏恶性肿瘤

Objective To study the therapeutic efficay of percutaneous radiofrequency ablation(PRFA)for hepatic malignancies and to definr its indications and its criteria of the curative effect.Methods In 100 patients with histologically of clinically confirmed hepatocellular carcinoma(HCC)or liver metastases we performed PRFA under ultrasound guidance using Le Veen multipolar array meedle electrode and RF 2000 generator.All patients were followed to identify complications and to assess treatment response.Results PRFA was performed in 76 patients with HCC and in 24 with liver metastases.The Alpha-fetoprotein(AFP)levles of the AFP positive HCC patients with inoperable small HCCs decreased to normal in 75.0%(21/28)and decreased markedly in 21.4%(6/28).Complete necrosis of small hepatic malignancies,documented by magnetic resonance imaging(MRI)was achieved in 85.9%(61/71).If the tumor shows iso-or hyper-intensity on Ti-weighted images,and relative hypointensity on T2-weighted images,and no enhanced intensity on dynamic contrast-enhanced MR imaging,it is considered completely coagulated.Conclusion PRFA is a novel local thermal palliative therapy for small hepatic malignancies that is minimally invasive,safe and effective.In patients with large lesions it can be combined with transarterial chemoembolization(TACE).Critera for curative treatment are normalization of serum AFP and /or MRI or CT scan findings showing complete necrosis.     

Gadoxetic acid-enhanced 3.0 T MR imaging versus multidetector-row CT in the detection of colorectal metastases in fatty liver using intraoperative ultrasound and histopathology as a standard of reference

Objective

To compare the diagnostic value of gadoxetic acid-enhanced MRI at 3.0 T with 64-row MDCT in the detection of colorectal liver metastases in diffuse fatty infiltration of the liver after neoadjuvant chemotherapy.

Methods

Twenty-three patients with colorectal liver metastases and at moderate to severe steatosis (25–90%) underwent prospectively preoperative tri-phasic MDCT (Somatom Sensation 64, Siemens) and gadoxetic acid-enhanced MRI (3-T Magnetom Trio, Siemens). All patients underwent surgical resection of liver metastases. Intraoperative ultrasound (IOUS) was carried out, which served as the standard of reference, together with histopathology.

Results

Overall, 68 metastases (range, 0.4–6 cm; 31/68 metastases [46%] ≤ 1 cm) were found at histology. MDCT detected 49/68 lesions (72%), and MRI 66/68 (97%, p < 0.001). For lesions ≤1 cm, MDCT detected only 13/31 (41.9%) and MRI 29/31 (93%, p < 0.001). Eight false-positive lesions were detected by MDCT, seven small lesions by MRI. There was no statistically significant difference between the two modalities in the detection of lesions >1 cm (p = 0.250). IOUS detected all metastases and revealed two false-positive diagnoses.

Conclusion

Gadoxetic acid-enhanced 3.0 T MRI is superior to 64-row MDCT in detecting colorectal liver metastases ≤1 cm during preoperative staging in patients with liver steatosis. A combination of MRI and IOUS may further improve the outcome of surgical treatment.     

Prediction of early recurrence of hepatocellular carcinoma after resection based on Gd-EOB-DTPA enhanced magnetic resonance imaging: a preliminary study

BackgroundEarly recurrence (ER) after radical resection of hepatocellular carcinoma (HCC) affects the prognosis of patients. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can improve the detection rate of small HCC. This study innovatively introduces a new quantitative index combined with qualitative index to compare the differences in clinical and imaging characteristics between ER and non-ER groups and evaluate the feasibility of Gd-EOB-DTPA-enhanced MRI in predicting ER.MethodsA total of 68 patients with HCC confirmed by operation and pathology in the Shandong Cancer Hospital and Institute were included retrospectively. All participants were examined by Gd-EOB-DTPA-enhanced MRI within 3 weeks before surgery. Regular follow-up was performed every 2 months within 1 year after operation. Among them, 18 cases with new lesions were in ER group, and 50 cases without new lesions were in non-ER group. The clinical and imaging data of the 2 groups were collected, and the differences of clinical data and preoperative MRI signs between the ER group and non-ER group were compared. The predictive factors of ER after HCC were analyzed by multivariate logistic regression.ResultsThe quantitative parameter lesion-to-liver contrast enhancement ratio (LLCER) can predict the pathological grade of HCC (P=0.023). The results of univariate analysis between the ER group and non-ER group showed that there were significant differences in pathological grade (P=0.008), lesion morphology (P=0.011), peritumoral low signal intensity in hepatobiliary phase (HBP) (P<0.001), satellite nodules (P<0.001), and LLCER (P<0.001) between the 2 groups. Multivariate logistic regression analysis showed that HBP peritumoral low signal intensity [odds ratio (OR) =7.214, 95% confidence interval (CI): 1.230–42.312, P=0.029], satellite nodules (OR =9.198, 95% CI: 1.402–60.339, P=0.021), and parameter LLCER value (OR =0.906, 95% CI: 0.826–0.995, P=0.039) were independent predictors of ER of HCC after resection.ConclusionsPreoperative Gd-EOB-DTPA enhanced MRI has important predictive value for early recurrence after radical resection of hepatocellular carcinoma.     

Higher Efficiency of Percutaneous Microwave (MWA) Than Radiofrequency Ablation (RFA) in Achieving Complete Response in Cirrhotic Patients with Early Hepatocellular Carcinoma

Background: Contrasting data are available in the literature regarding the superiority of percutaneous microwave ablation (MWA) or radiofrequency ablation (RFA) in very early or early (BCLA 0 or A) hepatocellular carcinoma (HCC). Aims: The primary outcome was to compare the efficacy of RFA and MWA in achieving complete response in cirrhotic patients with early and very early HCC. The secondary outcomes were to evaluate the overall survival and the recurrence rate. Methods: A retrospective, observational, single-center study was performed. Inclusion criteria were liver cirrhosis, new diagnosis of a single node of HCC measuring a maximum of 50 mm or up to three nodules with diameter up to 35 mm, treatment with RFA or MWA. Radiological response was evaluated with multiphasic contrast-enhanced Computed Tomography or Magnetic Resonance Imaging at 5–7 weeks after thermal ablation. Complete response was defined when no vital tissue was detected after treatment. Results: Overall, 251 HCC patients were included in this study; 81 patients were treated with MWA and 170 with RFA. The complete response rate was similar in MWA and RFA groups (out of 331 nodules, 87.5% (91/104) were treated with MWA and 84.2% (186/221) were treated with RFA, p = 0.504). Interestingly, a subanalysis demonstrated that for 21–35 mm nodules, the probability to achieve a complete response using MWA was almost 5 times higher than for RFA (OR = 4.88, 95% CI 1.37–17.31, p = 0.014). Moreover, recurrence rate in 21–35 mm nodules was higher with RFA with respect to MWA (31.9% versus 13.5%, p = 0.019). Overall survival was 80.4% (45/56) when treated with MWA and 62.2% (56/90) when treated with RFA (p = 0.027). No significant difference was observed between MWA and RFA treatment in the 15–20 mm nodules group. Conclusion: This study showed that MWA is more efficient than RFA in achieving complete response in HCC nodules with 21 to 35 mm diameter.     

A novel mono-modality fusion imaging method based on three-dimensional contrast-enhanced ultrasound for the evaluation of ablation margins after microwave ablation of hepatocellular carcinoma

BackgroundTo investigate the feasibility and accuracy of using preoperative and postoperative three-dimensional contrast-enhanced ultrasound (3D CEUS) fusion imaging in the evaluation of safety margins after thermal ablation of hepatocellular carcinoma (HCC).MethodsA total of the 24 patients with HCC who underwent microwave ablation (MWA) between June 2020 and December 2020 were enrolled in this study. All patients received preoperative and postoperative 3D CEUS. The preoperative and postoperative 3D CEUS images were then fused. The success rate and evaluation time were recorded. The ablation margin and whether or not the safety margin was reached were calculated and recorded. If the ablation safety margin was not reached, the residual ablation volume needed to cover the safety margin was calculated automatically. The agreement between contrast-enhanced computed tomography(CECT) and 3D CEUS fusion imaging in the evaluation of ablation margins was explored using the kappa coefficient.ResultsThe 3D CEUS fusion success rate was 95.8% (23/24), with a mean fusion time of (4.1±1.8) minutes. Twenty-three tumors were completely ablated, and the safety margin was achieved for 9 tumors. The ablation margin of 14 tumors was <5 mm. The mean uncovered safety margin volume was (2.27±2.11) mL, and the mean proportion of the uncovered safety margin to the whole safety margin was 16.8%. According to the results of preoperative and postoperative CECT fusion imaging, the ablation margin of 13 tumors was <5 mm, and the ablation margin of 10 tumors was >5 mm. The 2 methods showed excellent consistency, with a Kappa value of 0.911 (P=0.000012).ConclusionsThis study has presented a novel mono-modality fusion imaging method based on CEUS. We demonstrated that 3D CEUS fusion has a short fusion time and a high success rate, as well as good consistency with enhanced CT fusion. Therefore, 3D CEUS fusion is a feasible and accurate tool for evaluating the immediate efficacy of thermal ablation of HCC.     

Computed tomography chest imaging offers no advantage over chest X-ray in the initial assessment of gestational trophoblastic neoplasia

Background The International Federation of Gynaecology and Obstetrics (FIGO) score identifies gestational trophoblastic neoplasia (GTN) patients as low- or high-risk of single-agent chemotherapy resistance (SACR). Computed tomography (CT) has greater sensitivity than chest X-ray (CXR) in detecting pulmonary metastases, but effects upon outcomes remain unclear.Methods Five hundred and eighty-nine patients underwent both CXR and CT during GTN assessment. Treatment decisions were CXR based. The number of metastases, risk scores, and risk category using CXR versus CT were compared. CT-derived chest assessment was evaluated as impact upon treatment decision compared to patient outcome, incidence of SACR, time-to-normal human chorionic gonadotrophin hormone (TNhCG), and primary chemotherapy resistance (PCR).Results Metastasis detection (p < 0.0001) and FIGO score (p = 0.001) were higher using CT versus CXR. CT would have increased FIGO score in 188 (31.9%), with 43 re-classified from low- to high-risk, of whom 23 (53.5%) received curative single-agent chemotherapy. SACR was higher when score (p = 0.044) or risk group (p < 0.0001) changed. Metastases on CXR (p = 0.019) but not CT (p = 0.088) lengthened TNhCG. Logistic regression analysis found no difference between CXR (area under the curve (AUC) = 0.63) versus CT (AUC = 0.64) in predicting PCR.Conclusions CT chest would improve the prediction of SACR, but does not influence overall treatment outcome, TNhCG, or prediction of PCR. Lower radiation doses and cost mean ongoing CXR-based assessment is recommended.Subject terms: Outcomes research, Endometrial cancer     

Comparison of portal and capsular microscopic vascular invasion in the outcomes of early HCC after curative resection

Microscopic vascular invasion (MVI) is a strong risk factor associated with tumor recurrence and poor overall survival (OS) among hepatocellular carcinoma (HCC) patients after resection. Two types of MVI are identified: portal vein and capsular vein invasion. However, little is known about the impact of different types of MVI on HCC recurrence. The present study aimed to compare HCC recurrence and OS between the portal vein and capsule vein MVI. Patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 were consecutively recruited. Factors that influenced OS and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. Of the 857 eligible patients, 327 (38.2%) had MVI, and 530 (61.8%) were without MVI. Of the 327 patients with MVI, 85 (26.0%) were with portal vein, 178 (54.4%) with capsular vein, and 64 (19.6%) with both-MVI type. Patients with both-MVI type suffered from a higher proportion of BCLC stage A (P < 0.001), capsular invasion (P = 0.002), and satellite nodules (P < 0.001). Both-MVI type is an independent risk factor for HCC recurrence (hazard ratio [HR]: 1.69; 95% CI, 1.22-2.36, P = 0.002) and mortality (HR: 2.29; 95% CI, 1.59-3.29, P < 0.001) compared with non-MVI. We further found that both-MVI type was significantly associated with a higher risk of extrahepatic recurrence (EHR) (HR: 8.74; 95% CI, 2.38-32.03, P = 0.001). Among HCC patients after curative resection, concurrent portal and capsular MVI is a risk factor for HCC recurrence, especially for EHR, in comparison with non-MVI or only portal or capsular MVI alone.     

Thioredoxin reductase: A novel,independent prognostic marker in patients with hepatocellular carcinoma

Here we found that hepatocellular carcinoma (HCC) patients with recurrence outcome and nonsurvivors had significantly increased thioredoxin reductase (TrxR) serum levels on reoperation (P < 0.0001 and P < 0.0001). Multivariate regression analysis adjusted for common risk factors showed that TrxR was an independent predictor of recurrence (hazard ratios [HR] = 4.19; 95% confidence intervals [CI]: 3.21–7.08) and overall survival (HR = 5.56; 95% CI: 3.42–10.21). The area under the receiver operating characteristic curve of TrxR was 0.837 (95% CI, 0.794–0.881) for recurrence outcome and 0.901 (95% CI, 0.869–0.933) for mortality, which was superior to high-sensitivity-C-reactive protein and a-fetoprotein (P < 0.001). The preoperative serum TrxR level is an independent and significant indicator predictive of poor prognosis and early recurrence in patients with HCC, which offering reliable information for predicting survival.     

Development of an AI system for accurately diagnose hepatocellular carcinoma from computed tomography imaging data

Background and aims Computed tomography (CT) scan is frequently used to detect hepatocellular carcinoma (HCC) in routine clinical practice. The aim of this study is to develop a deep-learning AI system to improve the diagnostic accuracy of HCC by analysing liver CT imaging data.Methods We developed a deep-learning AI system by training on CT images from 7512 patients at Henan Provincial Peoples’ Hospital. Its performance was validated on one internal test set (Henan Provincial Peoples’ Hospital, n = 385) and one external test set (Henan Provincial Cancer Hospital, n = 556). The area under the receiver-operating characteristic curve (AUROC) was used as the primary classification metric. Accuracy, sensitivity, specificity, precision, negative predictive value and F1 metric were used to measure the performance of AI systems and radiologists.Results AI system achieved high performance in identifying HCC patients, with AUROC of 0.887 (95% CI 0.855–0.919) on the internal test set and 0.883 (95% CI 0.855–0.911) on the external test set. For internal test set, accuracy was 81.0% (76.8–84.8%), sensitivity was 78.4% (72.4–83.7%), specificity was 84.4% (78.0–89.6%) and F1 (harmonic average of precision and recall rate) was 0.824. For external test set, accuracy was 81.3% (77.8–84.5%), sensitivity was 89.4% (85.0–92.8%), specificity was 74.0% (68.5–78.9%) and F1 was 0.819. Compared with radiologists, AI system achieved comparable accuracy and F1 metric on internal test set (0.853 versus 0.818, P = 0.107; 0.863 vs. 0.824, P = 0.082) and external test set (0.805 vs. 0.793, P = 0.663; 0.810 vs. 0.814, P = 0.866). The predicted HCC risk scores by AI system in HCC patients with multiple tumours and high fibrosis stage were higher than those with solitary tumour and low fibrosis stage (tumour number: 0.197 vs. 0.138, P = 0.006; fibrosis stage: 0.183 vs. 0.127, P < 0.001). Radiologists’ review showed that the accuracy of saliency heatmaps predicted by algorithms was 92.1% (95% CI: 89.2–95.0%).Conclusions AI system achieved high performance in the detection of HCC compared with a group of specialised radiologists. Further investigation by prospective clinical trials was necessitated to verify this model.Subject terms: Cancer imaging, Cancer screening     

Comparison between Computer Tomography and Magnetic Resonance Imaging in the Diagnosis of Small Hepatocellular Carcinoma

Background: Hepatocellular carcinomas (HCCs) less than 2 cm in diameter generally demonstrate a good outcome after curative therapy. However, the diagnosis of small HCC can be problematic and requires one or more dynamic imaging modalities. This study aimed to compare the sensitivity and agreement between CT and MRI for the diagnosis of small HCCs. Methods: CT and/or MRI scans of HCCs (1-2 cm) diagnosed by histopathology or typical vascular pattern according to the 2005 AASLD criteria were blindly reviewed by an abdominal radiologist. The reports were defined as conclusive/typical when arterial enhancement and washout during the portal/delayed phases were observed and as inconclusive when typical vascular patterns were not observed. The sensitivity and Cohen’s kappa (k) for agreement were calculated. Results: In 27 patients, 27 HCC nodules (1-2 cm) were included. Diagnosis with a single-imaging modality (CT or MRI) was 81 % versus 48 % (p = 0.01). The CT sensitivity was significantly higher than MRI (78 % versus 52 %, p = 0.04). Among 27 nodules that underwent both CT and MRI, a discordance in typical enhancement patterns was found (k = 0.319, p = 0.05). In cases with inconclusive CT results, MRI gave only an additional 3.7 % sensitivity to reach a diagnosis. In contrast, further CT imaging following inconclusive MRI results gave an additional 29.6 % sensitivity.Conclusions: A single typical imaging modality is sufficient to diagnose small HCCs. Compared with MRI, multiphasic CT has a higher sensitivity. The limitations of MRI could be explained by the greater need for patient cooperation and the types of MRI contrast agent.     

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

BackgroundLong-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).MethodsA 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.ResultsPatients 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)].ConclusionsThis 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.     

Ablative radiation therapy for hepatocellular carcinoma is associated with reduced treatment- and tumor-related liver failure and improved survival

BackgroundMore than 70% of patients with hepatocellular carcinoma (HCC) are not candidates for curative therapy or recur after curative-intent therapy. There is growing evidence on the use of ablative radiation therapy (RT) for liver tumors. We aimed to analyze outcomes of HCC patients treated with conventional versus ablative RT.MethodsWe retrospectively analyzed medical records of HCC patients treated with liver RT from 2001 to 2019. We defined ablative RT as biologically effective dose (BED) ≥80 Gy. RECIST 1.1 was used to define early responses at 3–6 months after RT, and local control (LC) at last follow-up (FU). Data was analyzed using Fisher exact test, Kaplan-Meier, cumulative incidence rates, Cox proportional hazards model and Fine-Gray competing risks.ResultsForty-five patients were identified, of whom 14 (31.1%) received ablative RT using a stereotactic technique. With median FU of survivors of 10.1 months, 1-year cumulative incidence of LC was 91.7% for ablative and 75.2% for BED <80 Gy. At early FU, patients treated with ablative RT had better responses compared to BED <80 Gy, with 7% progressing versus 19%, and 21.4% with complete response versus none (P=0.038). On univariate analysis (UVA), Child-Pugh (CP) score [hazard ratio (HR): 3 for CP-B, HR: 16 for CP-C] and BED (HR: 7.69 for BED <80 Gy) correlated with deterioration of liver function, leading to liver failure. Most liver failure cases were due to disease progression. No RT-related liver failure occurred in the ablative RT group. On UVA, only BED ≥80 Gy was associated with improved overall survival (OS) (HR: 0.4; P=0.044). Median OS (mOS) and 1-year OS were 7 months and 35% respectively for BED <80 Gy compared to 28 months and 66% for BED ≥80 Gy. No grade 3+ bowel toxicity was reported in either group.ConclusionsGreater than 90% LC was achieved after stereotactic ablative RT, which was associated with minimized tumor- and treatment-related liver failure and improved survival for highly selected inoperable HCC patients.     

Predictive Value of Interferon γ Receptor Gene Polymorphisms for Hepatocellular Carcinoma Susceptibility

Background:Recent reports suggested relation between Interferon Gamma (IFN-γ) gene polymorphism and the risk of development of HCC on top of hepatic cirrhosis. The aim of this study was to address the predictive value of Interferon Gamma gene receptor (IFN-γR) polymorphisms for the occurrence of hepatocellular carcinoma on top of liver cirrhosis. Patients and Methods:This is a case control study performed on patients selected from the outpatient hepatology clinic, specialized medical hospital, Mansoura University, Egypt, from August 2017 to February 2019. The included patients were categorized into two groups; 60 patients with HCC on top of cirrhosis and 20 patients with hepatic cirrhosis. For all patients IFN-γR polymorphism was identified by RFLP. Results:Our study showed that HCC patients had male predominance. Additionally, diabetes mellitus (DM) was found in 28.3% of total HCC patients. Half of HCC patients in this study were from rural areas (50%). The frequency of AA at position -611 in the IFN-γR (-611 IFN-γR) was significantly higher in the HCC group as compared to cirrhotic group (P=0.021). Moreover; the frequency of CC and CT genotypes of IFN-γR -56 was not significantly different in HCC group as compared to control group (P>0.05). The IFN-γR (-611 IFN-γ) AA genotype significantly increased risk of HCC (OR= 0.78, 95% CI= 0.10-6.39; P= 0.042).Conclusion:The analysis of IFN-γR -611 single nucleotide gene polymorphism could be a valuable marker for predicting subgroup of cirrhotic patients with high risk of developing HCC. Cirrhotic patients have AA genotype of IFN-γR-611 recommended to be under close follow up.Key Words: Cirrhosis, HCC, interferon gamma receptor, polymorphism     

Diagnosis of hepatocellular carcinoma: newer radiological tools

With the recent dramatic advances in diagnostic modalities, the diagnosis of hepatocellular carcinoma (HCC) is primarily based on imaging. Ultrasound (US) plays a crucial role in HCC surveillance. Dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI) are the standard diagnostic methods for the noninvasive diagnosis of HCC, which can be made based on hemodynamic features (arterial enhancement and delayed washout). The technical development of MDCT and MRI has made possible the fast scanning with better image quality and resolution, which enables an accurate CT hemodynamic evaluation of hepatocellular tumor, as well as the application of perfusion CT and MRI in clinical practice. Perfusion CT and MRI can measure perfusion parameters of tumor quantitatively and can be used for treatment response assessment to anti-vascular agents. Besides assessing the hemodynamic or perfusion features of HCC, new advances in MRI can provide a cellular information of HCC. Liver-specific hepatobiliary contrast agents, such as gadoxetic acid, give information regarding hepatocellular function or defect of the lesion, which improves lesion detection and characterization. Diffusion-weighted imaging (DWI) of the liver provides cellular information of HCC and also has broadened its role in lesion detection, lesion characterization, and treatment response assessment to chemotherapeutic agents. In this article, we provide an overview of the state-of-the art imaging techniques of the liver and their clinical role in management of HCC.     

Microwave ablation vs. surgical resection for treatment naïve hepatocellular carcinoma within the Milan criteria: a follow-up of at least 5 years

Objective:Thermal ablation poses challenges in the surgical resection (SR) of small hepatocellular carcinoma (HCC), and its therapeutic outcomes for larger lesions remain debated.Methods:This retrospective study evaluated 729 patients with HCC meeting the Milan criteria, who were treated with curative SR or microwave ablation (MWA) between 2008 and 2014. Overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and local tumor progression (LTP) were compared after propensity score matching (PSM). Co-variates associated with OS, CSS, LTP, and DFS were identified. The risk of death and tumor progression were compared.Results:During the median follow-up of 78.6 months, 253 patients were included in each group after PSM. For tumors ≤ 3.0 cm and 3.1–4.0 cm, MWA achieved comparable results in terms of OS, CSS, DFS, and LTP. For tumors 4.1–5.0 cm, MWA had lower OS, CSS, and DFS rates (all P < 0.05) than SR. Higher LTP rates were observed in the MWA group for tumors 4.1–5.0 cm, although the difference was not significant (P = 0.18). Complication rates (P = 0.41) were similar, but MWA led to less estimated blood loss (P < 0.01) and shorter postoperative hospitalization times (P < 0.01).Conclusions:MWA achieved comparable long-term oncologic outcomes with SR for ≤ 4 cm HCC, with lower complication rates and faster recovery.     

Impact of surveillance among patients with resected pancreatic cancer following adjuvant chemotherapy

BackgroundPancreatic adenocarcinoma carries a high risk of recurrence even after surgery and adjuvant chemotherapy. Current guidelines do not endorse routine surveillance imaging due to lack of evidence supporting a survival benefit. With current first-line palliative chemotherapy options, it is unclear whether surveillance allows for early detection of asymptomatic disease and therefore an improved opportunity to offer chemotherapy to fit patients. We sought to describe patterns of surveillance of resected pancreatic cancer at British Columbia (BC) Cancer and determine whether utilization of computerized tomography (CT) scans affected likelihood of receiving palliative chemotherapy at the time of recurrence.MethodsA retrospective review was completed to identify patients treated at BC Cancer centres between 2010–2016 who had undergone curative intent resection and received at least one cycle of adjuvant chemotherapy. Information was collected on baseline characteristics, imaging scans done between adjuvant chemotherapy and recurrence, and receipt of palliative chemotherapy. Two cohorts were defined based on number of scans done between completion of adjuvant chemotherapy and recurrence: those with only 1 scan were defined as “symptomatic” recurrences and patients who had undergone more than 1 scan were considered “surveillance” recurrences.ResultsIn total, 142 patients were included of which 115 (81%) patients developed recurrence. There were 22 patients (19%) in the “symptomatic” cohort and 93 patients (81%) in the “surveillance” cohort. Median time to recurrence 274 days (9.1 months) in the symptomatic cohort compared to 471 days (15.7 months) in the surveillance group. Patients who underwent surveillance scans were more likely to receive palliative chemotherapy at the time of recurrence, though statistical significance was not reached: 51% in surveillance group versus 27% in symptomatic group [odds ratio (OR) 2.11, 95% confidence interval (CI): 0.75–6.58, P=0.17].ConclusionsDespite the absence of surveillance recommendations, the majority of patients underwent surveillance imaging. We demonstrated a non-significant increase in the likelihood of receiving palliative chemotherapy among patients who underwent surveillance scans. With more efficacious palliative chemotherapy options available, studies to determine whether receipt of chemotherapy in asymptomatic recurrences translates into improved survival and/or quality of life are warranted.     

Comparable benefits of HCV eradication by direct acting antivirals and interferon-based therapy in patients with hepatocellular carcinoma undergoing surgical resection

Whether direct-acting antivirals (DAA) provide comparable survival benefit with interferon (IFN)-based therapy remains unclear. The aim of this study was to compare the outcomes after achieving SVR by IFN-based and DAA therapy after resection of HCV-related hepatocellular carcinoma (HCC). Consecutive 285 patients receiving curative resection for HCV-related HCC were retrospectively enrolled, including 103 (36.1%) and 69 (24.2%) patients with IFN-based and DAA therapy, respectively. Factors associated with recurrence, overall survival (OS) and hepatic decompensation-free survival were evaluated. The SVR rate of DAA was 95.7% in HCC patients. During a median follow-up period of 49.6 months, 102 (35.8%) patients died and 63 (24%) developed hepatic decompensation. By multivariate analysis, SVR by DAA or IFN-based therapy was not associated with early or late HCC recurrence. Achieving SVR (by IFN-based therapy: HR=0.321, P<0.001; by DAA: HR=0.396, P=0.011), BCLC stage B-C (HR=1.914, P=0.024), FIB-4 score >3.25 (HR=1.664, P=0.016) and microvascular invasion (HR=1.603, P=0.048) were independent predictors of OS. Achieving SVR (by IFN-based therapy: HR=0.295, P<0.001; by DAA: HR=0.193, P=0.002), BCLC stage B-C (HR=2.975, P=0.001), GGT >70 U/L (HR=1.931, P=0.015) and cirrhosis (HR=2.035, P=0.007) were independent predictors of decompensation-free survival. The benefit of achieving SVR was consistently observed in cirrhotic and non-cirrhotic patients, and in patients with and without HCC recurrence. In conclusion, achieving SVR by either DAA or IFN-based therapy provide comparable and significant reduction of mortality and hepatic decompensation after surgical resection of HCV-related HCC. DAA therapy should be prescribed for all HCC patients after curative surgical resection.     

The diagnosis and outcome of Krukenberg tumors

BackgroundAccurate diagnostic tools are crucial to distinguish patients with Krukenberg tumors from those with ovarian cancers before decision on initial management. To address this unmet need, we aimed to evaluate the diagnostic utility of clinical, biochemical, and radiographic factors in this patient population.MethodsPatients with Krukenberg tumors or primary ovarian cancers were retrospectively identified from institutional cancer registry. Kaplan-Meier method and Cox proportional hazards models were used for survival analysis. Logistic regression evaluated clinical, biochemical, and radiographic factors; residual deep neural network model evaluated features in computed tomography images as predictors to distinguish Krukenberg tumors from ovarian cancers. Model performance was summarized as accuracy and area under the receiver operating characteristic curve (AUC).ResultsThis study included 214 patients with Krukenberg tumors with median age of 52 years. Among 104 (48.6%) patients with colorectal cancer, those who received palliative surgery had significantly higher median overall survival (48.1 versus 30.6 months, P=0.015) and progression-free survival (22.2 versus 6.7 months, P<0.001) than those with medical management only. The accuracy of radiology reports to make either diagnosis of Krukenberg tumors or primary ovarian cancers was 60.7%. In contrast, multivariable logistic regression model with age [odds ratio (OR) 2.98, P<0.001], carbohydrate antigen 125 (OR 1.57, P=0.004), and carcinoembryonic antigen (OR 0.03, P=0.031) had 87.5% [95% confidence interval (CI): 75.0–100.0%] accuracy with AUC 0.96 (95% CI: 0.87–1.00). The neural network model had 62.8% (95% CI: 51.8–74.5%) accuracy with AUC of 0.61 (95% CI: 0.53–0.72).ConclusionsWe developed a diagnostic model with clinical and biochemical features to distinguish Krukenberg tumors from primary ovarian cancers with promising accuracy.